Evaluation of telemedicine for slit lamp examination of the eye following cataract surgery.
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Cataract Extraction↗
Biomedical subjects
J Stevens
Publications and source records attributed to J Stevens.
Time and dose-dependent modulation of phase 1 and phase 2 gene expression in response to treatment of MCF-7 cells with a natural anti-cancer agent.
Several known anti-cancer agents have been shown to lead to increased expression of phase 2 metabolic enzymes without affecting phase 1 enzymes. Phase 1 cytochrome P450 (CYP) enzymes are relevant in cancer studies in that they are involved in oxidative metabolism, biotransformation and detoxification, whereas phase 2 enzyme catalysis leads to clearance. In this study, we obtained semi-quantitative measurements of cytochrome P450 (phase 1) and phase 2 microsomal epoxide hydrolase (mEH) gene expression levels in response to treatment of MCF-7 breast cancer cells with water-soluble Vernonia amygdalina (V.A.) extract. V.A., a vegetable grown in Nigeria, has potential as an anti-cancer agent. The results of Western blot and RT-PCR analyses show that V.A. extract acts as a monofunctional inducer within exposure times ranging from 2-16 hr and dose ranges from 3-100 microg/ml of V.A. Exposure of cells to low doses of V.A. did not affect expression levels of CYP1A1/1A2 mRNA, but lead to induction of mEH, thus supporting the chemotherapeutic potential of VA. However, in parallel studies, CYP3A4 gene expression was also induced, suggesting potential intermediates which influence drug-drug interactions. These data are useful toward further validating V.A. extract as a potential clinically useful natural anti-cancer agent and provide some support for the concept that modulation in CYP3A4 expression in response to treatment is relevant to prognosis.
Breast Neoplasms↗
Bilateral isolated hippocampal malformation in temporal lobe epilepsy.
Hippocampal malformations in patients with epilepsy usually are reported in the context of widespread cortical malformations. Isolated hippocampal malformations are more rarely identified in MRI studies with little documentation of their pathologic appearance. Postmortem examination revealed abnormal position and complex convolutional malformations isolated to the hippocampal formation in an adult with temporal lobe epilepsy in whom MRI demonstrated bilateral hippocampal abnormalities.
Epilepsy, Complex Partial↗
The effects of atrazine on the sexual maturation of female rats.
The mammalian hazard assessment of the herbicide atrazine (ATR) has focused on the induction of mammary tumors and accelerated reproductive aging of adult rats, and the relationship of these effects to the inhibition of leutinizing hormone (LH) release from the pituitary, an effect itself caused by inhibition of GnRH signaling by the adult rat hypothalamus. In earlier studies, Laws et al. (Toxicol. Sci., 58, 366-376, 2000) demonstrated a delay in female rat sexual maturation induced by ATR, effects that could equally have been caused by inhibition of hypothalamic GnRH release. The present studies were designed to compare the doses that interfere with GnRH signaling seen in previous studies in adult Sprague-Dawley (SD) rats (LH surge suppression) with doses that impair GnRH signaling in peripubertal rats, as indicated by delayed sexual maturation. The studies evaluated the effects of ATR treatment on the timing of uterine growth and vaginal opening (VO) in peripubertal female Wistar (Alderley Park, AP) and SD rats. Doses of 10, 30, and 100 mg/kg ATR were administered daily from postnatal day (pnd) 21 to up to pnd 46. Determinations of uterine weight were made at pnd 30, 33, 43 (AP), and 46 (SD) and the timing of VO was also assessed in the last two of these experiments. The centrally acting GnRH antagonist Antarelix (ANT) was used as a positive control agent as it has previously been shown to prevent uterine growth and to delay VO in peripubertal AP rats. Uterine growth and VO were completely prevented in AP rats exposed to ANT. Uterine growth was delayed at pnd 30 and 33 in AP rats exposed to 100 mg/kg ATR, but this growth inhibition had been overcome by pnd 43. VO was significantly delayed in AP rats for the 100 mg/kg ATR dose. By pnd 46, VO was significantly delayed in SD rats exposed to both 30 and 100 mg/kg ATR, but uterine weights were unaffected by that time (as for AP rats). It is concluded that the no-effect level for the effects of ATR on sexually immature rats (10 mg/kg in SD; 30 mg/kg AP) is approximately the same as reported previously by Laws et al. in peripubertal Wistar rats (25 mg/kg). However, the no-effect level in peripubertal female SD rats is nearly an order of magnitude greater than the no-observed effect level observed in female SD rats fed ATR for 6 months (1.8 mg/kg) where LH suppression was used as an indicator of effect on the pituitary/hypothalamic axis (USEPA, Atrazine-DACT Fourth Report of the Hazard Identification and Review Committee, April 5, 2002). These results support the conclusion that the pituitary/hypothalamic axis in peripubertal female SD rats is less sensitive than that in adult female SD rats.
Administration, Oral↗
Associations between weight gain and incident hypertension in a bi-ethnic cohort: the Atherosclerosis Risk in Communities Study.
OBJECTIVE: To examine associations between weight gain and changes in blood pressure and the incidence of hypertension in four ethnicity-gender groups. DESIGN: Longitudinal closed cohort studied over an average of 6 y. SUBJECTS: Total of 9309 white and African-American men and women 45-64 y of age who participated in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: Weight and blood pressure were measured at baseline and after an average of 3 and 6 y of follow-up. Proportional hazard models with weight gain as a time-dependent variable were used to examine the association between weight gain and changes in blood pressure and hypertension. Multivariate models were used with baseline SBP, DBP, age, BMI, height, WHR, smoking, physical activity, education, caloric intake, fat intake and study center as covariates. RESULTS: Weight gain was associated with increases in SBP and DBP in all groups. Hazard ratios for hypertension associated with 1 kg annual weight gain were 1.36 (95% CI, 1.29, 1.45) in white women, 1.12 (95% CI, 1.03, 1.21) in African-American women, 1.35 (95% CI, 1.27, 1.43) in white men and 1.43 (95% CI, 1.27,1.61) in African-American men. CONCLUSION: Weight gain was associated with increased blood pressure and increased incidence of hypertension. The association was weaker among African-American women compared to other ethnicity-gender groups.
Black People↗
Funding ideas for new research.
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Fatigue↗
Genetic relationships between blowflies (Calliphoridae) of forensic importance.
Phylogenetic relationships among blowfly (Calliphoridae) species of forensic importance are explored using DNA sequence data from the large sub-unit (lsu, 28S) ribosomal RNA (rRNA) gene, the study includes representatives of a range of calliphorid species commonly encountered in forensic analysis in Britain and Europe. The data presented provide a basis to define molecular markers, including the identification of highly informative intra-sequence regions, which may be of use in the identification of larvae for forensic entomology. Phylogenetic analysis of the sequences also provides new insights into the different evolutionary patterns apparent within the family Calliphoridae which, additionally, can provide a measure of the degree of genetic variation likely to be encountered within taxonomic groups of differing forensic utility.
Animals↗
Toward an understanding of the furoxan-dinitrosoethylene equilibrium.
The tautomerism of furoxan (1,2,5-oxadiazole-2-oxide) has been investigated by different computational methods comprising modern density functionals as well as single-reference and multi-reference ab initio methods. The ring-opening process to 1,2-dinitrosoethylene is the most critical step of the reaction and cannot be treated reliably by low-level computations. The existence of cis-cis-trans-1,2-dinitrosoethylene as a stable intermediate is advocated by perturbational methods, but high-level coupled-cluster calculations identify this as an artifact. In contrast to the analogous reaction in benzofuroxans, cis-cis-cis-1,2-dinitrosoethylene was found to be a transition state rather than a local minimum. Model potentials were used to explain the occurrence and the disappearing of transition states and local minima relative to the reaction of benzofuroxan. Low-lying triplet states that can be accessed due to spin-orbit coupling were investigated as taking part in alternative routes to a proposed singlet pathway. Barriers for rotations of the nitroso groups on the S(0) and T(1) surfaces are reported.
Journal Article↗
Peptide binding characteristics of the non-classical class Ib MHC molecule HLA-E assessed by a recombinant random peptide approach.
BACKGROUND: Increasing evidence suggests that the effect of HLA-E on Natural Killer (NK) cell activity can be affected by the nature of the peptides bound to this non-classical, MHC class Ib molecule. However, its reduced cell surface expression, and until recently, the lack of specific monoclonal antibodies hinder studying the peptide-binding specificity HLA-E. RESULTS: An in vitro refolding system was used to assess binding of recombinant HLA-E to either specific peptides or a nonamer random peptide library. Peptides eluted from HLA-E molecules refolded around the nonamer library were then used to determine a binding motif for HLA-E. Hydrophobic and non-charged amino acids were found to predominate along the peptide motif, with a leucine anchor at P9, but surprisingly there was no methionine preference at P2, as suggested by previous studies. CONCLUSIONS: Compared to the results obtained with rat classical class Ia MHC molecules, RT1-A1c and RT1-Au, HLA-E appears to refold around a random peptide library to reduced but detectable levels, suggesting that this molecule's specificity is tight but probably not as exquisite as has been previously suggested. This, and a previous report that it can associate with synthetic peptides carrying a viral sequence, suggests that HLA-E, similar to its mouse counterpart (Qa-1b), could possibly bind peptides different from MHC class I leader peptides and present them to T lymphocytes.
Amino Acid Motifs↗
Changes in body mass index prior to baseline among participants who are ill or who die during the early years of follow-up.
The association between body mass index (weight (kg)/height (m)(2)) and mortality may be confounded by preexisting illness. A method commonly used to control for this confounding is the exclusion of participants who have certain diseases at baseline and/or those who die during the early years of follow-up. The authors used data from the Atherosclerosis Risk in Communities (ARIC) Study (n = 14,088) to determine whether participants identified by these criteria had different changes in body mass index than other participants. Weight change was measured over a 3-year interval between study entry (1987-1989) and reexamination (1990-1993), and information on vital status was collected over the subsequent 5 years. Mean change in body mass index was -0.54 (95% confidence interval (CI): -0.90, -0.12) among participants who died in the first year of follow-up, -0.03 (95% CI: -0.18, 0.12) among those who died in the first 4 years of follow-up, and 0.36 (95% CI: 0.33, 0.39) among those who survived for at least 5 years. Participants who died during the first 4 years were over twice as likely as survivors to have changed from the obese category (body mass index >or=30) to the nonobese category (odds ratio = 2.14; 95% CI: 1.44, 3.17). Mean change in body mass index prior to baseline was not different among ill participants compared with those who were healthy, but the odds of converting from obese to nonobese were higher in ill participants than in healthy ones (odds ratio = 1.29; 95% CI: 1.01, 1.67).
Body Mass Index↗
Preimplantation genetic diagnosis of pericentric inversions.
Inversions are structural chromosome abnormalities that may be associated with infertility, multiple miscarriage and chromosomally unbalanced offspring. Preimplantation genetic diagnosis (PGD) with subtelomeric probes was used to select for transfer only those embryos that were normal or balanced for three pericentric inversions. In contrast to previous protocols the present procedure allows the detection of unbalanced embryos that might arise from U-recombination in the inverted region. Additionally, aneuploidy screening was carried out in two cases by a second round of fluorescent in situ hybridization (FISH) with centromeric probes. Of the three couples that underwent the procedure one became pregnant twice. The first pregnancy delivered a healthy and chromosomally normal baby and the second pregnancy is ongoing with triplets.
Adult↗
Noninvasive assessment of human embryo nutrient consumption as a measure of developmental potential.
OBJECTIVE: To determine the relationship between blastocyst development and morphology and embryo metabolism. DESIGN: Noninvasive assessment of carbohydrate uptake and ammonium production by individual embryos. SETTING: Private assisted reproductive technology unit. PATIENT(S): Patients donated, with consent, cryopreserved pronucleate embryos and noncryopreserved blastocysts. INTERVENTION(S): Culture of 60 thawed pronucleate embryos in sequential media to the blastocyst stage with concomitant noninvasive analysis of embryo metabolism and analysis of 13 blastocysts from noncryopreserved embryos. MAIN OUTCOME MEASURE(S): Pyruvate and glucose consumption as well as blastocyst formation and quality. RESULT(S): Pyruvate and glucose uptakes on day 4 were significantly higher by embryos that went on to form blastocysts than by embryos that failed to develop to the blastocyst stage. Glucose uptakes were greatest in those blastocysts of highest grade, whereas pyruvate uptakes were similar irrespective of blastocyst grade, indicating that glucose is the more important nutrient for the human blastocyst. Among blastocysts of the same grade from the same patient, there was considerable spread of glucose consumption, indicating that glucose consumption may be of use in identifying blastocysts for transfer. Ammonium production by individual embryos was also measured, reflecting amino acid transamination and use by the human embryo. CONCLUSION(S): The ability to identify in culture the embryo with the highest developmental potential will facilitate the move to single-embryo transfers.
Blastocyst↗
Long-term retrograde amnesia...the crucial role of the hippocampus.
For patients with hippocampal pathology, disagreement exists in the literature over whether retrograde amnesia is temporally limited or very extensive depending on whether the anatomical damage is restricted to this structure or also involves additional temporal cortex. We report a comprehensive assessment of retrograde and anterograde memory functions of a severely global amnesic patient (VC). We found that he presented with a remarkably extensive and basically ungraded retrograde amnesia. This impairment profoundly affected four decades preceding the onset of his amnesia and encompassed both non personal and personal facts and events. VC also presented with a severe anterograde amnesia and a deficit in the acquisition of new semantic knowledge in the post-morbid period. Detailed MRI volumetric measurements revealed gross abnormalities in both hippocampi which were markedly shrunken. Of relevance to the debate on retrograde amnesia were the observations that the volumes of both entorhinal cortices and the remainder of both temporal lobes were normal. These data suggest that the hippocampus is critical not only for the efficient encoding and hence normal recall of new information but also for the recall of episodic information acquired before the onset of amnesia. Our results are compatible with the view that retrograde amnesia is both extensive and ungraded when the damage is limited to the hippocampus.
Aged↗
Central chemosensitivity and breathing asleep in unilateral medullary lesion patients: comparisons to animal data.
The rostro-ventrolateral medulla (RVLM) is a site of chemosensitivity in animals; such site(s) have not been defined in humans. We studied the effect of unilateral focal lesions in the rostrolateral medulla (RLM) of man, on the ventilatory CO(2) sensitivity and during awake and sleep breathing. Nine patients with RLM lesions (RLM group), and six with lesions elsewhere (non-RLM group) were studied. The ventilatory CO(2) sensitivity was lower in the RLM compared with the non-RLM group (mean (S.D.), RLM, 1.4 (0.9), non-RLM 3.0 (0.6) L min(-1) mmHg(-1)). In both groups resting breathing was normal. During sleep all RLM patients had frequent arousals, four had significant sleep disordered breathing (SDB), only one non-RLM patient had SDB. Our findings in humans resemble those in animals with focal RVLM lesions. This review provides evidence that in humans there is an area of chemosensitivity in the RLM. We propose that in humans, dorsal displacement of the RVLM area of chemosensitivity in animals, arises from development of the olive plus the consequences of the evolution of the cerebellum/inferior peduncle.
Animals↗
Survey of PCDD/Fs and non-ortho PCBs in UK sewage sludges.
A survey of PCDD/F and non-ortho PCB concentrations in the mesophilic, anaerobically digested sludge of 14 UK wastewater treatment works was carried out. The range of total Cl1-Cl8DD/F concentrations in the sludges was 8880-428000 pg/g dw with a median of 23300 pg/g dw. The concentrations of the three non-ortho PCBs were in the range 272-63000 pg/g dw with a median of 695 pg/g dw. The PCDD/F I-TEQs of the sludges studied were comparable to those published in the literature with a range of 20-225 pg I-TEQ/g dw and a median of 40.4 pg/g dw. The non-ortho PCBs usually added 2-7 pg/g to the total TEQ with one notable exception which increased the TEQ value 20-fold. With three exceptions, the PCDD/F content of the sludges fell well below the draft EU limit values proposed on 27 April 2000. The homologue group pattern of the PCDD/Fs is dominated by the HpCDDs and OCDD and is consistent with that found in most sewage sludges. There appears to be no correlation between the degree of industrial input and the PCDD/F concentration. This suggests that trade effluent is not always the most significant source of PCDD/Fs to wastewater in the UK.
Bacteria, Anaerobic↗
Challenges with studies investigating longevity of dental restorations--a critique of a systematic review.
OBJECTIVES: A systematic review is a method of evaluating the published and unpublished literature relating to a specific area or topic. The objectives of this paper are to identify and discuss problems encountered in synthesising the available literature; and to make recommendations for the future conduct and reporting of clinical trials that aim to determine the longevity of dental restorations. DATA SOURCES: Studies were identified by a wide search of published and unpublished material in any language using a large number of general and specialist data bases, hand searching of key dental journals and searching of abstracts from conference proceedings. STUDY SELECTION: Pre-defined inclusion criteria based on objective outcome measures of restoration longevity and study designs were applied to determine study selection. CONCLUSIONS: A review of the longevity of dental restorations completed recently encountered substantial problems in designing an appropriate protocol to address this issue. The review found that many of the factors reported previously as affecting restoration longevity could not be confirmed using the agreed systematic review protocol that incorporated an objective study design. Further, the multiplicity of study designs, and reporting methods found in the literature made meta-analyses impossible. A proforma is proposed in order to aid the design of future research into the longevity of restorations.
Dental Materials↗
Calreticulin, PDI, Grp94 and BiP chaperone proteins are associated with retained COMP in pseudoachondroplasia chondrocytes.
Cartilage oligomeric matrix protein (COMP), a large pentameric glycoprotein and member of the thrombospondin (TSP) group of extracellular proteins, is found in the territorial matrix surrounding chondrocytes. More than 50 unique COMP mutations have been identified as causing two skeletal dysplasias: pseudoachondroplasia (PSACH); and multiple epiphyseal dysplasia (EDM1). Recent studies suggest that calcium-binding and calcium-induced protein folding differ between wild type and mutant proteins, and abnormal processing of the mutant COMP protein contributes to the characteristic enlarged lamellar appearing rER cisternae in PSACH and EDMI chondrocytes in vivo and in vitro. Towards the goal of delineating the pathogenesis of PSACH and EDM1, in-vivo PSACH growth plate and in-vitro PSACH chondrocytes cultured in alginate beads were examined to identify and localize the chaperone proteins participating in the processing of the retained extracellular matrix proteins in the PSACH rER. Aggrecan was localized to both the rER cisternae and matrix while COMP and type IX collagen were only found in the rER. Type II collagen was solely found in the ECM suggesting that it is processed and transported differently from other retained ECM proteins. Five chaperone proteins: BiP (Grp78); calreticulin (CRT); protein disulfide (PDI); ERp72; and Grp94, demonstrated immunoreactivity in the enlarged PSACH cisternae and the short rER channels of chondrocytes from both in-vivo and in-vitro samples. The chaperone proteins cluster around the electron dense material within the enlarged rER cisternae. CRT, PDI and GRP94 AB-gold particles appear to be closely associated with COMP. Immunoprecipitation and Western blot, and Fluorescence Resonance Energy Transfer (FRET) analyses indicate that CRT, PDI and GRP94 are in close proximity to normal and mutant COMP and BiP to mutant COMP. These results suggest that these proteins play a role in the processing and transport of wild type COMP in normal chondrocytes and in the retention of mutant COMP in PSACH chondrocytes.
Achondroplasia↗
Two different, highly exposed, bulged structures for an unusually long peptide bound to rat MHC class I RT1-Aa.
The rat MHC class Ia molecule RT1-Aa has the unusual capacity to bind long peptides ending in arginine, such as MTF-E, a thirteen-residue, maternally transmitted minor histocompatibility antigen. The antigenic structure of MTF-E was unpredictable due to its extraordinary length and two arginines that could serve as potential anchor residues. The crystal structure of RT1-Aa-MTF-E at 2.55 A shows that both peptide termini are anchored, as in other class I molecules, but the central residues in two independent pMHC complexes adopt completely different bulged conformations based on local environment. The MTF-E epitope is fully exposed within the putative T cell receptor (TCR) footprint. The flexibility demonstrated by the MTF-E structures illustrates how different TCRs may be raised against chemically identical, but structurally dissimilar, pMHC complexes.
Adenosine Triphosphatases↗