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Biomedical subjects

A Taylor

Publications and source records attributed to A Taylor.

At least 289 records · Page 16Linked to original sources
PubMed1997

Age-related decline in ubiquitin conjugation in response to oxidative stress in the lens.

Accumulation of damaged proteins is a major age-related change in lenses of virtually all species and is associated with lens opacification. Proteolytic removal of the damaged proteins may play an important role in maintaining the transparency of the lens. In many tissues, selective removal of abnormal or damaged proteins occurs via a ubiquitin-dependent proteolytic pathway. Ubiquitin, an 8.5 kDa polypeptide, selectively binds to proteins to form ubiquitin-protein conjugates. This ubiquitin-protein conjugate is, in most cases, a signal for protein degradation. In this work, age-related changes in rat lens in the following aspects were detected: (a) levels of the ubiquitin-protein conjugates, (b) some of the enzymes involved in ubiquitin conjugation in rat lenses, and (c) ability to respond to oxidative damage. Endogenous ubiquitin-protein conjugates were detected in epithelium, cortex and nucleus of lenses from young and old rats. The levels of endogenous high molecular weight (HMW) ubiquitin-protein conjugates in each developmental zone of the lenses from young rats were higher than that in the counterparts of lenses from old animals. Peroxide-treatment generally resulted in elevated levels of endogenous HMW ubiquitin-protein conjugates although masses of bulk proteins remain unchanged. The increases in ubiquitin-protein conjugates in the epithelial sections of young and old lenses upon oxidative stress were comparable. In the cortex of young lenses, there was a significant oxidation-related increase in ubiquitin-protein conjugates. There was a similar trend but diminished response in the cortex of old lenses. Nuclear fibers from young lenses also showed an oxidation-induced increase in the level of ubiquitin-protein conjugates. This response was not observed in nuclear fibers of old lenses. The ability to form HMW-ubiquitin conjugates with exogenous 125I-labeled ubiquitin in the lens also increased upon oxidative stress. The extent of the increase in the de-novo ubiquitin conjugating activity upon exposure to oxidation in old lens was much smaller than in young lens. Ubiquitin-activating enzyme (E1), and ubiquitin conjugating enzymes (E2(17k), E2(20k) and E2(25k) were detected by thiol ester assays or Western blot analysis. No significant age-related changes in the levels of E1, E2(17k), E2(20k) and E2(25k) were detected. The activity of E1 and E2(17k) increased upon exposure to H2O2. These data indicate that lens has the ability to increase ubiquitin conjugation activity in response to oxidative stress and this ability is attenuated upon aging. The age-related decrease in the ability to mount a ubiquitin-dependent response upon oxidation may contribute to the accumulation of damaged proteins in the old lenses.

Aging↗
PubMed1997

Adolescent friendships mediating childhood adversity and adult outcome.

This interview-based study compares the friendships of 50 girls, aged 15-16, identified on the basis of their childhood experiences as being at-risk for difficulties in early adult partnerships, with the friendships of 50 girls of the same age from an inner-city school. Key differences in the features of both romantic and non-romantic adolescent friendships between the two groups of girls give a clearer understanding of the processes linking childhood adversity and poor adult outcome.

Adolescent↗
PubMed1997

JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity: a review of its behavioural properties.

The search for an improved clozapine-like compound has resulted in the selection of a new molecule: JL13 (5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5] benzoxazepine fumarate). Like clozapine, JL13 did not antagonize apomorphine-induced stereotypy and did not produce catalepsy but antagonized apomorphine-induced climbing in rodents (ID50 = 3.9 mg kg-1 s.c.). It was inactive against d-amphetamine-induced stereotypy but antagonized d-amphetamine-induced hyperactivity in the mouse (ID50 = 4.4 mg kg-1 i.p.). JL13, like clozapine, was able to antagonize (+/-)-DOI-induced head-twitches in the mouse (ID50 = 2.0 mg kg-1 i.p.). In the open-field test in the rat and forced swimming test in the mouse a high similarity was noted between the two drugs in the same range of doses. In a complex temporal regulation schedule in the dog, JL13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats trained to discriminate clozapine, JL13 (10 mg kg-1 i.p.) induced a high level of generalization (70%) to clozapine. In a drug discrimination procedure in the squirrel monkey, JL13 (3-10 mg kg-1 i.m.) produced a full substitution of clozapine. On the basis of these preclinical data, it is thus predicted that JL13 would be a promising atypical antipsychotic drug.

Animals↗
PubMed1997

Renal artery stent placement in renal artery stenosis: technical and early clinical results.

We report the technical and early clinical results of renal artery stent placement in 29 consecutive patients treated at a single centre over a 30-month period, employing the Palmaz balloon-expandable stent. Of 32 arteries treated, 23 (72%) were atheromatous, ostial stenoses. Immediate technical success was achieved in all 29 patients. Follow-up angiography was performed on 25 patients at 6.7 months (mean) and demonstrated a patient restenosis rate of 16%. All surviving patients were followed up for a minimum of 6 months. Blood pressure control was improved in eight (50%) of hypertensive patients, and renal function improved in seven (33%) and stabilized in six (29%) patients with chronic renal impairment (serum creatinine > 150 mumols/l). Complications occurred in seven (24%) of patients, including one procedure-related death. Our experience indicates that stent placement has an initial high technical success rate in renal artery stenosis and that this patency is maintained at repeat angiography with a low restenosis rate. Renal artery stenting is likely to extend the role of percutaneous renal revascularization especially in atheromatous ostial lesions. A randomized trial will be required to evaluate its role compared with balloon angioplasty.

Adult↗
PubMed1997

The possible role of copper ions in atherogenesis: the Blue Janus.

It has been proposed that the oxidative modification of low density lipoprotein (LDL) is a key event in human atherogenesis. Copper ions can catalyse the oxidative modification of LDL in vitro and there is some evidence that they may also participate in the oxidation of LDL within the arterial wall. However, copper ions also form an intrinsic constituent of superoxide dismutase and caeruloplasmin, enzymes that may be involved in preventing oxidative injury. Atherosclerotic lesions frequently contain considerable quantities of extracellular matrix molecules. These may contribute to the expansion of the arterial neointima, causing luminal narrowing. They may also play a beneficial role by stabilising the plaque. Copper is an essential component of lysyl oxidase, an enzyme involved in the biosynthesis of collagen, which is a major constituent of the extracellular matrix. The impact of alterations in body copper status on atherogenesis is therefore difficult to predict. Experimental and epidemiological data are conflicting and therefore do not provide a clear resolution of this issue. We have reviewed the biochemical and cellular effects of copper ions that may play a role in atherogenesis.

Arteriosclerosis↗
PubMed1997

Conduct disorder with and without mania in a referred sample of ADHD children.

OBJECTIVE: To test the hypothesis that dysphoric and non-dysphoric types of CD could be distinguished from one another in their patterns of familiality, adversity, and comorbidity. METHODS: We examined 140 ADHD and 120 normal controls at baseline and 4 years later using assessments from multiple domains. We compared ADHD subgroups with and without conduct (CD) and bipolar (BPD) disorders on psychiatric outcomes at a 4-year follow-up, familial psychopathology and psychosocial functioning. RESULTS: We found that ADHD children with both disorders had higher familial and personal risk for mood disorders than those with CD only, who had a higher personal risk for antisocial personality disorder. Among ADHD probands, having both CD and BPD was associated with poorer functioning and an increased risk for psychiatric hospitalization. DISCUSSION: Although preliminary, our findings suggest that the distinction between dysphoric and non-dysphoric CD may be clinically meaningful. If confirmed, our findings could have important diagnostic and therapeutic implications for the management of antisocial youth.

Attention Deficit Disorder with Hyperactivity↗
PubMed1997

Cell-cycle-specific transcription termination within the human histone H3.3 gene is correlated with specific protein-DNA interactions.

In vitro studies using highly purified calf thymus RNA polymerase II and a fragment spanning the first intron of H3.3 as template DNA have demonstrated the existence of a strong transcription termination site consisting of thymidine stretches. In this study, nuclear run-on experiments have been performed to assess the extent to which transcription elongation is blocked in vivo using DNA probes corresponding to region 5' and 3' of the in vitro termination sites. These studies suggest that H3.3 expression is stimulated following the inhibition of DNA synthesis through the elimination of the transcription elongation block. Interestingly, both the in vivo and in vitro experiments have revealed that the transcriptional block/termination sites are positioned immediately downstream of a 73 bp region that has been over 90% conserved between the chicken and human H3.3 genes. The extreme conservation of this intronic region suggests a possible role in maintaining cis-acting function. Electrophoretic mobility shift experiments show that HeLa cell nuclear extracts contain protein factors that bind specifically to the region of transcription elongation block. Furthermore, we demonstrate a correlation between the protein binding activity and the transcriptional block in cells that have been either arrested at the initiation of S phase or were replication-interrupted by hydroxyurea. DNA footprinting experiments indicate that the region of protein binding is at the 3' end of the conserved region and overlaps with one of the three in-vitro-mapped termination sites.

Animals↗
PubMed1997

The anti-cancer agent distamycin A displaces essential transcription factors and selectively inhibits myogenic differentiation.

The anticancer drug, distamycin A, alters DNA conformation by binding to A/T-rich domains. We propose that binding of the drug to DNA alters transcription factor interactions and that this may alter genetic regulation. We have analyzed the effects of distamycin A upon expression of the muscle-specific cardiac and skeletal alpha-actin genes which have A/T-rich regulatory elements in their promoters. Distamycin A specifically inhibited endogenous muscle genes in the myogenic C2 cell line and effectively eliminated the myogenic program. Conversely, when 10T1/2C18 derived pleuripotential TA1 cells were induced to differentiate in the presence of distamycin A, adipocyte differentiation was enhanced whereas the numbers of cells committing to the myogenic program decreased dramatically. Using the mobility shift assay distamycin A selectively inhibited binding of two important transcription factors, SRF and MEF2, to their respective A/T-rich elements. The binding of factors Sp1 and MyoD were not affected. The inhibition of factor binding correlated with a repression of muscle-specific promoter activity as assayed by transient transfection assays. Co-expression of the myoD gene, driven by a distamycin A-insensitive promoter, failed to relieve the inhibition of these muscle-specific promoters by distamycin A. Additionally, SRF and MEF2 dependent promoters were selectively down regulated by distamycin A. These results suggest that distamycin A may inhibit muscle-specific gene expression by selectively interfering with transcription factor interactions and demonstrate the importance of these A/T-rich elements in regulating differentiation of this specific cell type.

Actins↗
PubMed1997

Bone augmentation at titanium implants using autologous bone grafts and a bioresorbable barrier. An experimental study in the rabbit tibia.

The aim of the present investigation was to compare the effect of using autologous bone particles covered with a bioresorbable matrix barrier with the use of bone particles alone on bone augmentation at titanium implants installed in the rabbit tibia. Two Brånemark System implants, one in each tibia, were inserted in each of 9 rabbits in such a way that 5 threads were not covered with bone. Autologous bone particles were harvested from the skull and placed over the exposed implant surfaces on each tibia. The bone graft on one tibia was covered with a Guidor Matrix Barrier, while the bone graft on the other tibia served as a control. After a healing period of 12 weeks, the animals were sacrificed and specimens taken for histomorphometrical analyses. The analyses showed that a significantly larger volume of augmented bone tissue had formed at the test sites. There were, however, no differences in the amount of mineralized bone. In fact, the difference in tissue volume was due to an increased amount of bone marrow at the test sites. The degree of mineralized bone to implant contact as well as the degree of mineralized bone within the threads at the test implants were similar to that at the controls. In conclusion, it was found that the coverage of particulate autologous bone grafts with a bioresorbable barrier resulted in a larger volume of augmented bone than the use of bone grafts not covered with a barrier.

Animals↗
PubMed1997

Augmentation of skull bone using a bioresorbable barrier supported by autologous bone grafts. An intra-individual study in the rabbit.

The aim of this experimental investigation was to compare the effect of using autologous particulate bone grafts with and without a bioresorbable barrier covering for augmentation of the rabbit skull bone. For this purpose, bilateral, circular, 8 mm wide and 1 mm deep skull bone defects were prepared and overfilled with particulate bone grafts. The grafts placed in the test sites were covered with a bioresorbable barrier (Guidor Matrix Barrier). The grafts placed in the control sites were covered only by the repositioned, cutaneous flap. 12 weeks later, the animals were sacrificed, the experimental sites were defleshed and the height and volume of the augmented bone in the test and control sites were measured clinically. Histologically, morphometrical measurements of the bone tissue were performed in decalcified vertical cross-sections of the experimental sites. Statistically significant differences were found in favour of the coverage of the bone graft particles with the barrier, both with respect to the height and the volume of the augmented bone.

Animals↗
PubMed1997

Vitamin C in human and guinea pig aqueous, lens and plasma in relation to intake.

PURPOSE: Given the recent correlation between nutrition and risk for eye disease, there is keen interest in a possible correlation between nutrient intake and eye-tissue nutrient levels. In this work, the objective was (1) to determine, for the first time, the relation between dietary intake of vitamin C and eye tissue levels of the vitamin in free-living humans, (2) to determine the relation between levels of the vitamin in plasma, lens and aqueous, and (3) to compare this information to data gathered for a carefully reared group of guinea pigs that were fed different levels of vitamin C. METHODS: Two hundred sixty-five cataract patients (mean age = 72 years) from a clinical practice were recruited for this study. One hundred thirty-two patients provided the dietary intake data via a food frequency questionnaire, which we used for this work. Plasma, aqueous humor, and lens samples were obtained at the time of lentectomy and preserved for vitamin C analysis. Comparable samples were obtained from male Hartley white guinea pigs that were fed known amounts of vitamin C. Linear and log10-linear statistical models were also used to characterize the relation between vitamin C intake and human ocular tissue levels of the vitamin and to examine potential confounding and the effect of modification by age and sex. RESULTS: In humans, plasma and aqueous vitamin C concentrations were related to intake in a log-linear fashion, with slopes of 0.03 mM plasma vitamin C/log10-mg daily vitamin C intake and 0.41 mM aqueous vitamin C/log10-mg daily vitamin C intake. The best fit of vitamin C levels in lens and diet predicts a linear relationship with a sex-adjusted slope of 0.00094 mM lens vitamin C/mg daily vitamin C intake, although a log-linear relation can also be modeled. In guinea pigs, diet was related to eye tissue and plasma levels of the vitamin by a log10 linear relationship in all cases. Vitamin C in human lens was linearly related to plasma and aqueous vitamin C with slopes of 8.8 and 0.23, respectively. Vitamin C in aqueous was related to plasma in a log10-linear fashion with a slope of 1.6 mM aqueous vitamin C/log10 mM plasma vitamin C. In guinea pigs, vitamin C in plasma was related to aqueous and lens vitamin C by log10-linear relationships, whereas lens and aqueous vitamin C were clearly linearly related. CONCLUSIONS: Plasma and aqueous appear to be saturated in humans with intakes of < 250 mg vitamin C/day. However, a saturating relationship between lens vitamin C and dietary intake in humans was not indicated in this study, although such a relationship is seen in guinea pigs. Intertissue relations between vitamin C levels in humans and guinea pigs are similar for some but not all relations.

Adult↗
PubMed1997

Long-term vitamin C supplement use and prevalence of early age-related lens opacities.

We designed the present study to examine the cross-sectional relation between age-related lens opacities and vitamin C supplement use over a 10-12-y period before assessment of lens status in women without diagnosed cataract or diabetes. This design avoids biased measurement of nutrient intake that results when knowledge of lens opacities influences nutrition-related behavior or its reporting. The participants were 247 Boston-area women aged 56-71 y selected from the Nurses' Health Study cohort with oversampling of women with high or low vitamin C intakes. Lens opacities were graded with the Lens Opacification Classification System II. Use of vitamin C supplements for > or = 10 y (n = 26) was associated with a 77% lower prevalence of early lens opacities (odds ratio: 0.23; 95% CI: 0.09, 0.60) at any lens site and a 83% lower prevalence of moderate lens opacities (odds ratio: 0.17; 95% CI: 0.03, 0.85) at any lens site compared with women who did not use vitamin C supplements (n = 141) after adjustment for age and other potentially confounding variables. Women who consumed vitamin C supplements for < 10 y showed no evidence of a reduced prevalence of early opacities. These data, together with data from earlier experimental and epidemiologic studies, suggest that long-term consumption of vitamin C supplements may substantially reduce the development of age-related lens opacities.

Adult↗
PubMed1997

The course of alcohol withdrawal in a general hospital.

We conducted an observational study of 539 episodes of alcohol withdrawal in a general hospital, to determine the natural history, the incidences of seizures, hallucinations and delirium, and the risk factors for these events. The reaction began soon after arrival, at a median time of 5 h, and resolved at a median time of 22 h. Patients with a blood alcohol level of zero were in withdrawal on arrival, and only four patients had reactions lasting 120 h or longer. Complications were observed in 113 patients (21%) during the admission. Seizures occurred on arrival, hallucinations usually in the first 24 h and delirium in the first 48 h. No mortality was associated with alcohol withdrawal itself, but complications did extend length of stay by a median of 4 days, with delirium contributing most to the increase. Patients over 70 years of age or admitted with seizures had an increased risk of complication, but the greatest risk was associated with a delay in assessment of > 24 h. We conclude that in general hospitals, the alcohol withdrawal reaction becomes established very early, and detection and monitoring of patients within the first 24 h is the most important element in management.

Adult↗