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Biomedical subjects

J Atkinson

Publications and source records attributed to J Atkinson.

At least 91 records · Page 5Linked to original sources

Validity of short food frequency questionnaires used in cancer chemoprevention trials: results from the Prostate Cancer Prevention Trial.

Here, we describe the measurement characteristics of a 13-item dietary screener used in the Prostate Cancer Prevention Trial. We used data from 10,913 men who completed the 13-item dietary screener, a food frequency questionnaire (FFQ), and questionnaires on demographic and health-related characteristics and from 146 men who also completed multiple 24-h dietary recalls in a substudy. The analyses in this report focused on percentage energy from fat and saturated fat and used the mean estimates from the dietary recalls as the criterion measures. Absolute nutrient estimates from the screener were about one-third of the estimates from the recalls and the FFQ. Validity was defined as the Pearson correlation of the criterion measures of fat with the corresponding measures from the FFQ and the screener. The FFQ was a statistically significantly more precise measure of percentage energy from fat (r = 0.71) and saturated fat (r = 0.72) than was the screener (r = 0.50 and 0.53, respectively). There were also statistically significant differences in how well these instruments could detect variation in dietary fat across various participant characteristics, suggesting that the screener may not perform as well as the FFQ across demographic strata such as education (P < 0.001). The results from this study suggest that the use of short dietary screeners as the sole assessment instrument may result in a serious loss of information regarding important exposures (e.g., fat intake) and lost opportunities to enhance our knowledge regarding dietary factors and cancer risk.

Aged↗

Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection.

BACKGROUND: Tuberculosis is a common complication of HIV-1 infection, especially in developing countries. Practical and effective chemoprophylaxis regimens for HIV-1-related tuberculosis are needed. Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals. METHODS: We compared the efficacy of 6 months of isoniazid with 2 months of rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive individuals. Eligible participants were aged 16-77 years, HIV-1 seropositive, had a positive purified-protein derivative (PPD) skin test reaction of at least 5 mm, and had a normal chest radiograph. Participants were randomly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the development of tuberculosis and survival. FINDINGS: Tuberculosis developed in 14 (3.8%) of 370 participants assigned isoniazid and 19 (5.0%) of 380 participants assigned rifampicin and pyrazinamide (Cox model rate ratio 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7% among participants who received rifampicin and pyrazinamide compared with 1.0% (p=0.03) among participants who received isoniazid, and 5.4% versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of tuberculosis were observed in people with baseline CD4 percentages (of total lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no significant differences in total mortality at any time. INTERPRETATION: Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults. The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD-positive individuals could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determined.

AIDS-Related Opportunistic Infections↗

Nitric oxide lowers the calcium sensitivity of tension in the rat tail artery.

1. Controversy exists as to whether a fall in the intracellular Ca2+ concentration ([Ca2+]i) is a requisite element of the vasodilatory response to nitric oxide (NO). 2. We studied the effect of NO on the coupling between [Ca2+]i and vasoconstriction in arterial segments loaded with the [Ca2+]i-sensitive, intracellular dye fura-2. As data interpretation is equivocal when fura-2 is loaded into both endothelial and smooth muscle cells, we compared results from in vitro experiments on segments of the rat tail artery in which fura-2 and noradrenaline were applied on the luminal or adventitial side, and endothelium was removed 'physically' (rubbing or air) or 'functionally' (Nomega-nitro-L-arginine methyl ester). The use of air perfusion to remove endothelium is of considerable benefit since it allows paired observations in a single tissue. 3. Fura-2 loaded into endothelial cells but endothelial 'contamination' of the smooth muscle cell [Ca2+]i signal was minimal. 4. Endogenous NO decreased vasoconstrictor responses to noradrenaline but had no effect on [Ca2+]i. 5. Nitroglycerine decreased vasoconstrictor responses in a concentration-dependent fashion but had no effect on [Ca2+]i. 6. In conclusion, NO causes vasodilatation via a mechanism which is downstream of [Ca2+]i mobilization.

Air↗

Comparison of chromosome telomere integrity in multiple tissues from subjects at different ages.

Telomere DNA, at the ends of each chromosome, is conserved in nature and required for chromosome replication and stability. Reduction in telomere length has been observed in several malignancies as well as in leukocytes from healthy persons with advancing age. There is a paucity of data regarding telomere length and the effects of in vivo aging in different tissues. These data could be helpful in interpreting telomere length and understanding the role of telomere integrity and telomerase activity in malignant cells. We report telomeric DNA integrity studies of blood and skin collected from eight Caucasians of both sexes representing each decade of life from the fetus to 72 years of age without exposure to chemotherapy or radiation. In addition, telomeric data from 15 other tissues from the fetus and 8 other tissues from the 72-year-old male were examined. No significant differences were found in the shortest telomere size, the average telomere size, or telomere size variation between blood and skin from subjects at different ages. The average telomere size was 11.7 +/- 2.2 kb for blood and 12.8 +/- 3.7 for skin in all subjects studied. The shortest telomere length was 5.4 +/- 1.9 kb for blood and 4.3 +/- 0.9 kb for skin. Significant differences (P < 0.001) were found in the overall length of the DNA hybridization signal representing the shortest telomere size and the length of the DNA peak migration hybridization signal representing variation in telomere size between the 20-week fetus and the 72-year-old male. The 72-year-old male showed the shortest telomeres and the most variation (heterogeneity) in telomere size for all tissues studied, but the greatest differences were observed in blood compared with other tissues (e.g., average telomere length was 12.2 kb in the fetus and 7.2 kb in the 72-year-old male). The size of the telomere was negatively correlated with age for all tissues studied.

Adolescent↗

Orientation-reversal and phase-reversal visual evoked potentials in full-term infants with brain lesions: a longitudinal study.

The onset and maturation of visual cortical mechanisms can be recorded by using steady-state visual evoked potentials. The aim of this study was to evaluate and compare orientation-reversal (OR) and phase-reversal (PH) VEP as indicators of the maturation of cortical function in a population of fullterm infants with brain lesions on neonatal MRI. Forty-six infants with brain lesions on neonatal MRI were tested on both PH and OR VEP at 8 reversals/second at the age of 5 months and, if the responses were not significant, at a lower temporal frequency (4 reversals/second). Children whose VEPs were not significant at 5 months were tested longitudinally at 6, 9, 12 and 18 months. The results showed that 23 of the 46 infants (50%) did not show significant responses at 5 months and that while in 7 of the 23 (14% of the whole cohort) the responses became significant between 5 and 12 months, in the other 16 infants (34%) the VEP responses were persistently abnormal. Children with focal lesions, such as focal infarction or haemorrhages, tended to show normal or only mildly delayed VEP while more generalised lesions, such as the ones seen in infants with hypoxic-ischaemic encephalopathy grade 2 and 3, tended to be associated with abnormal VEP responses. The involvement of the optic radiations and occipital cortex was not always associated with abnormal VEP responses but the concomitant involvement of the basal ganglia was always associated with abnormal VEP. We were also able to demonstrate that VEP can be also used as a prognostic indicator: while normal OR VEP are reliably associated with a normal visual and neurodevelopmental outcome, abnormal 4 OR or 8 PH at 5 months are consistently associated with abnormal outcome.

Brain Diseases↗

Melatonin improves cerebral circulation security margin in rats.

Because melatonin is a cerebral vasoconstrictor agent, we tested whether it could shift the lower limit of cerebral blood flow autoregulation to a lower pressure level, by improving the cerebrovascular dilatory reserve, and thus widen the security margin. Cerebral blood flow and cerebrovascular resistance were measured by hydrogen clearance in the frontal cortex of adult male Wistar rats. The cerebrovasodilatory reserve was evaluated from the increase in the cerebral blood flow under hypercapnia. The lower limit of cerebral blood flow autoregulation was evaluated from the fall in cerebral blood flow following hypotensive hemorrhage. Rats received melatonin infusions of 60, 600, or 60,000 ng . kg-1 . h-1, a vehicle infusion, or no infusion (n = 9 rats per group). Melatonin induced concentration-dependent cerebral vasoconstriction (up to 25% of the value for cerebrovascular resistance of the vehicle group). The increase in vasoconstrictor tone was accompanied by an improvement in the vasodilatory response to hypercapnia (+50 to +100% vs. vehicle) and by a shift in the lower limit of cerebral blood flow autoregulation to a lower mean arterial blood pressure level (from 90 to 50 mmHg). Because melatonin had no effect on baseline mean arterial blood pressure, the decrease in the lower limit of cerebral blood flow autoregulation led to an improvement in the cerebrovascular security margin (from 17% in vehicle to 30, 55, and 55% in the low-, medium-, and high-dose melatonin groups, respectively). This improvement in the security margin suggests that melatonin could play an important role in the regulation of cerebral blood flow and may diminish the risk of hypoperfusion-induced cerebral ischemia.

Animals↗

Sensitivity of norepinephrine-evoked vasoconstriction to pertussis toxin in the old rat.

In male Wistar rats, the in vitro vasoconstrictor response of the perfused tail artery elicited by norepinephrine or serotonin decreased with age (24 mo old vs. 3 mo old), whereas the fluorescent signal (fura 2) produced by intracellular calcium (Ca2+i) mobilization increased. Both vasoconstriction and the increase in intracellular calcium concentration elicited by a high-K+, depolarizing solution were unaffected by aging. Pertussis toxin, a G protein inhibitor, had no effect on vasoconstriction induced by high K+ but diminished vasoconstrictor responses to norepinephrine in 3- and 12-mo-old animals but not in 24-mo-old animals. Pertussis toxin had no effect on Ca2+i mobilization. The sensitivity of receptor activation to pertussis toxin in tail arteries from 24-mo-old animals was restored by pretreatment with the alpha-adrenoceptor antagonist nicergoline. Nicergoline had no effect on vasoconstriction induced by high K+. Plasma norepinephrine concentration rose with age; nicergoline had no effect on this rise. We suggest that aging leads to a decrease in the intracellular G protein-modulated amplification of vasoconstriction produced by receptor activation and that this could be linked to the hyperadrenergic state. Ca2+ sensitivity can be restored by chronic treatment with an alpha-adrenoceptor antagonist.

Adrenergic alpha-Antagonists↗

Pancardiac tuberculosis--a case report.

The authors report a very unusual and unique case of pancardiac tuberculosis in a 25-year-old man who presented initially with atrial flutter with 1:1 conduction. Echocardiographic findings, computerized tomography images, and pathology specimens are presented. After initiation of antituberculous therapy, the patient converted to normal sinus rhythm.

Adult↗

Regional hemodynamic responses to visual stimulation in awake infants.

This study presents the first measurements using near infrared spectroscopy of changes in regional hemodynamics as a response to a visual stimulus in awake infants. Ten infants aged 3 d to 14 wk viewed a checkerboard with a 5-Hz pattern reversal. The emitter and detector (optodes) of a near infrared spectrophotometer were placed over the occipital region of the head. Changes in concentration of oxy- and deoxyhemoglobin (Hbo2 and Hb) were measured and compared during 10-s epochs of stimulus on and off. A control group of 10 infants aged 18 d to 13 wk were examined with the same setup, but with the optodes over the frontoparietal region. In the test group the total hemoglobin concentration (Hbo2 + Hb) increased while the stimulus was on by a mean (+/-SD) of 2.51 (+/-1.48) micromol x L(-1). Nine out of 10 infants showed an Hbo2 increase, and 9 out of 10 an Hb increase related to the stimulus. There was no significant change in any of these parameters in the control group. The results imply that there is increased cerebral blood flow due to stimulation that is specific to the visual cortex and that infants, unlike adults, show increased cerebral oxygen utilization during activation that outstrips this hemodynamic effect. The study demonstrates that near infrared spectroscopy can be used as a practical and noninvasive method of measuring visual functional activation and its hemodynamic correlates in the awake infant.

Adult↗

Hematological considerations in out-of-treatment drug users.

Complete blood counts (CBCs) were performed on 215 out-of-treatment injecting and noninjecting drug users participating in a federally sponsored human immunodeficiency virus (HIV) risk-reduction program in Houston, Texas. A substantial proportion of patients/clients were found to be suffering from varying degrees of anemia and other hematological conditions. Anemia is known to affect cognitive skills such as the ability to concentrate and process information. This impairment can limit the effectiveness of drug intervention and treatment, even among those users eager to participate in intervention or treatment programs. Consideration of substance users' physical condition as manifested by hematological measures can provide an important compliment to health behavioral models that stress cognitive functioning without consideration of the underlying physical processes involved.

Adolescent↗

[Aging of arterial extracellular matrix elastin: etiology and consequences].

This review discusses the hypothesis that the accumulation with advancing age of physical insults to the arterial wall (pressure, flow, diameter) may induce fragmentation of the medial elastic network, thereby leading to cardiovascular dysfunction. Physical factors have been shown to alter medial cell activity, inducing medial hypertrophy and other changes. Their potential contribution to changes in extracellular matrix proteins (perhaps mediated by integrins) has been less extensively studied. A metabolic factor may also be involved in age-related elastic fiber fragmentation. Oxidative stress in the arterial wall increases with age and leads to an increase in the production of cytokines, which stimulate the activity of elastases. Changes in elastic fiber composition may be associated with a greater propensity for calcification. Elastic fiber architecture can be modified by three reactions, namely elastolysis, elastocalcinosis, and production of new elastin fibers. These changes in the elastic network may have a number of consequences. Dilatation may shift strain to collagen, resulting in increases in the elastic modulus and impedance of the arterial wall. In turn, these changes may modify ventricle-artery coupling, leading to left ventricular hypertrophy (an independent risk factor for cardiovascular morbidity and mortality in elderly individuals). The increase in arterial wall elastic modulus associated with arteriosclerosis, together with arterial dilatation and flow profile changes, may also increase the susceptibility of the arterial wall to atheroma lesions.

Aging↗

A specific deficit of dorsal stream function in Williams' syndrome.

Williams' syndrome (WS) is a rare, genetically based disorder of cognitive development. Affected individuals show a severe deficit of spatial cognition but a relative sparing of language and face recognition. To examine the possible neural basis of the spatial deficit, we tested a group of WS children, aged 4-14 years, on two measures specific to dorsal cortical stream function: global motion coherence thresholds, in comparison with an analogous form-coherence test, and visuo-manual accuracy in posting a card through a slot, compared with matching the slot orientation. Deficits in these tasks provide the first evidence of specific involvement in WS of the dorsal stream, the cortical system believed to encode information about spatial relationships and the visual control of action.

Adolescent↗

Disruption of the rat mesenteric arterial bed endothelial function by air perfusion.

The impact of air perfusion on the endothelial function of the rat mesenteric arterial bed (MAB; perfused with Krebs' bicarbonate plus indomethacin) was compared to that of the NO synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME). Air shifted the dose-response curve for the alpha-adrenoceptor agonist, norepinephrine (NE) to the left (ED50%: 2.9+/-0.7 to 0.9+/-0.7 microg, P < 0.05); maximal vasoconstriction did not change. L-NAME produced a similar increase in midrange sensitivity (ED50% 1.4+/-0.7 microg, P < 0.05) and a 20% increase in maximum (152+/-6 to 183+/-7 mmHg, P < 0.05). Electromechanical stimulation with potassium chloride (KCl) was not modified by reserpine. Neither air nor L-NAME modified midrange sensitivity to KCl. L-NAME produced a 17% increase in maximum (91+/-4 to 107+/-5 mmHg, P < 0.05); reserpine abolished the latter effect. Air and L-NAME diminished endothelium-dependent vasodilation elicited by carbachol. Air did not modify endothelium-dependent vasodilation elicited by sodium nitroprusside; this response was potentiated by L-NAME. In summary, air and L-NAME produced similar effects on receptor-dependent activation of the endothelial L-arginine nitric oxide (NO) pathway. Potentiation by L-NAME of the maximal electromechanical response suggests the existence of a tone-dependent NO system. Abolition of the latter response by reserpine suggests that this system is of sympathetic origin.

Air↗

Primary sequence of baboon CR1 demonstrates concerted evolution within the CR1 gene.

Complement receptor type one (CR1) in primates has several remarkable structural features including a size polymorphism (Mr 190000, 220000, 250000 and 280000) in man, multiple size variants (Mr 55000-220000) among non-human primates, and a partial amino-terminal duplication (CR1-like gene) that appears to encode the short (55000-70000) forms expressed on primate erythrocytes. In general, these short CR1 forms, some of which are GPI anchored, are expressed on erythrocytes and the 220000 molecular weight CR1 form is expressed on PBMC, except in man, where only the 220000 molecular weight form has been detected. In addition, the Mr 220000 human CR1 sequence carries several long internal repeats of up to 99% homology. It has been suggested that the highest homology is maintained by gene conversion and/or unequal crossover. To address further the evolutionary and biologic implications of these multiple forms, a 6 kb cDNA encoding baboon CR1(220) was identified by RTPCR using human CR1 primers. Its sequence contains the expected 30 complement control protein repeats (CCP) and demonstrates an overall homology to human CR1 of 95.4% at the nucleotide level and 93.2% at the amino acid level. As in human CR1, the first 28 CCP maintain the characteristic "seven CCP-long homologous repeats (LHR)" organization. Analysis of baboon CR1(220) indicates that horizontal or concerted evolution has maintained a high degree (> 98%) of identity between corresponding CCP within the LHRs from CCP 4 to CCP 19, while this homology region extends from CCP 3 to CCP 18 in man. In contrast, substitutions occurring in other CCP are not propagated to the corresponding sites of other LHR. Sequence differences in CCP 1, 2 and 3 are likely to be related to the acquisition of enhanced C3b binding capability by this amino-terminal region of the protein. Thus, the sequence data strongly support the hypotheses that gene conversion and or unequal crossover events have driven the evolution of the protein in regions of high homology while selective forces, probably ligand binding requirements, have maintained the regions of divergence.

Amino Acid Sequence↗

Chiari I malformation in asymptomatic young children with Williams syndrome: clinical and MRI study.

We report clinical and magnetic resonance imaging findings in two young children, aged 2 years 4 months and 3 years, with Williams syndrome. Both showed a mild global delay, although their neurological examination was completely normal. Their magnetic resonance imaging, however, showed Chiari I malformation and some non-specific changes in the centrum semiovale and in the white matter posterior to the lateral ventricles. Cerebellar tonsils were displaced through the foramen magnum 8.5 and 7.5 mm respectively. Our results suggest that Chiari I malformation can also be a frequent feature in subjects with Williams syndrome even in the absence of overt neurological signs suggestive of it. Whether these children might develop acute signs later is not known at present. Further studies are needed not only to evaluate the incidence of these findings in the global population of subjects with Williams syndrome but also to identify the children who are at risk for developing acute neurological signs.

Arnold-Chiari Malformation↗

The antihypertensive effect of orally administered nifedipine-loaded nanoparticles in spontaneously hypertensive rats.

1. The therapeutic use of nifedipine is limited by the rapidity of the onset of its action and its short biological half-life. In order to produce a form devoid of these disadvantages we made nanoparticles of nifedipine from three different polymers, poly-epsilon-caprolactone (PCL), polylactic and glycolic acid (1:1) copolymers (PLAGA), and Eudragit RL/RS (Eudragit). Nifedipine in polyethylene glycol 400 (PEG) solution was used as a control. 2. The average diameters of the nanoparticles ranged from 0.12 to 0.21 micron; the encapsulation ratio was 82% to 88%. 3. In spontaneously hypertensive rats (SHR), the initial rapid fall in systolic arterial blood pressure following oral administration of nifedipine in PEG solution (from 193 +/- 3 to 102 +/- 2 mmHg) was not seen following administration of the same dose in Eudragit nanoparticles (from 189 +/- 2 to 156 +/- 2 mmHg); with PCL and PLAGA nanoparticles the initial fall in blood pressure was significantly reduced (nadirs PCL 124 +/- 2 and PLAGA 113 +/- 2 mmHg). Ten hours following administration, blood pressure in rats administered the nifedipine/PEG preparation had returned to normal (183 +/- 3 mmHg) whereas that of animals given nifedipine in nanoparticles (PCL 170 +/- 3, PLAGA 168 +/- 2, Eudragit 160 +/- 3 mmHg) was still significantly reduced. 4. All of the nanoparticle dosage forms decreased Cmax and increased Tmax and the mean residence time (MRT) values. Relative bioavailability was significantly increased with Eudragit nanoparticles compared to the nifedipine/PEG solution. 5. There was an inverse linear correlation between the fall in blood pressure and plasma nifedipine concentration with all preparations. 6. The nanoparticle nifedipine preparations represent sustained release forms with increased bioavailability, a less pronounced initial antihypertensive effect and a long-lasting action.

Acrylic Resins↗

Secondary structures and starvation-induced frameshifting.

We have examined the effect of a downstream secondary structure (the stem-loop sequence found downstream on the MMTV gag-pro frameshift site) on frameshifting at a bacterial shifty site (U UUC AUA) that responds strongly to a isoleucine-tRNA limitation. Our findings are as follows: (i) the downstream stem-loop has little effect on frameshifting in growing, unstarved cells; (ii) the stem-loop increases the frameshifting effect of isoleucine-tRNA limitation about fourfold, and this synergism is maximal with a distance of 5-9 nucleotides between the 'hungry' AUA codon and the stem-loop; and (iii) a stem-loop of different sequence at the same position has the same effect.

Escherichia coli↗