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Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p

Background: The clinical diagnosis of the postural tachycardia syndrome (POTS) includes the demonstration of an upright heart rate (HR) of at least 30 beats per minute (bpm) above supine HR. The dynamic behavior of HR during the course of standing has not yet been studied systematically in POTS. Methods: HR and arterial blood pressure (ABP) were continuously monitored in 17 POTS patients and in 24 age-matched controls at rest and during an 11-minute phase of 80° tilt. Results: ABP values at different time intervals of the protocol did not differ between the subgroups with the exception of higher diastolic pressures in POTS after 5 and 10 minutes of tilt. POTS patients showed a higher resting HR (80.6 ± 17.0 bpm vs 67.8 ± 10.9 bpm in controls, P < 0.05) and there was a continuous HR acceleration in the course of the 11-minute tilt phase. In control subjects, the tilt-induced HR increase was nearly completed after 1 minute with only a minimal further rise between minute 1 and minute 10 (from 83.7 ± 11.5 to 85.3 ± 11.9 bpm vs from 106.1 ± 15.6 to 120.1 ± 13.8 bpm in POTS). Conclusions: Continuously progressing orthostatic tachycardia can serve as an additional criterion in the diagnosis of POTS. It may be related to the recently observed increased orthostatic capillary filtration rate in POTS.

An artificial polypeptide scaffold composed of surface anchor and protein capture domains was designed and expressed in vivo. By using a mutant E. coli phenylalanyl−tRNA synthetase, the photoreactive amino acid para-azidophenylalanine was incorporated into the surface anchor domain. Octyltrichlorosilane-treated surfaces were functionalized with this polypeptide by spin coating and photocrosslinking. The resulting protein films were shown to immobilize recombinant proteins through association of coiled coil heterodimer.

Genetic polymorphisms resulting in variation in metabolism of tobacco carcinogens may influence oral cancer risk. In a population-based case-control study in Puerto Rico, genotypes of CYP1A1, GSTM1, and GSTT1 were determined by a PCR-based method for 132 oral cancer patients and 143 control subjects. Genotype-associated risks were estimated by logistic regression. The null variant of GSTM1 was associated with a marginally significant decrease in oral cancer risk [odds ratio (OR) = 0.6, 95% confidence interval (CI) = 0.3-1.0, and P for trend = 0.09]. Risks increased with increasing cigarette use among subjects with the GSTM1-present genotype (P for trend

BACKGROUND AND PURPOSE: Doppler sonography has been used to assess global cerebral circulation time (CCT) in healthy volunteers and a small number of patients with cerebral arteriovenous malformations. We evaluated the effect of arteriovenous shunts on global CCT in patients with dural arteriovenous fistulas (DAVFs) by using this Doppler echo contrast-bolus tracking test. METHODS: We measured CCT as the time delay in a contrast bolus to the internal carotid artery (ICA) and internal jugular vein (IJV) in 13 patients with DAVF and 30 age-matched control subjects. Mean CCT and mean arterial and venous rise times (Δt = 80% of total signal-intensity increase) were compared. Posttreatment follow-up measurements were performed in five patients. RESULTS: Mean CCT and venous Δt were significantly different between patients and controls (CCT, 1.1 ± 0.9 vs 6.9 ± 1.2 seconds, P < .0001; venous Δt, 5.2 ± 2.0 vs 7.0 ± 2.6 seconds, P = .024), but arterial Δt values were not (4.4 ± 1.8 vs 4.7 ± 2.0 seconds). Posttreatment follow-up of two occluded fistulas showed CCT normalization. One near-occlusion showed a two-step increase in signal intensity, and incomplete occlusion in two patients left the CCT unchanged. One patient with an extracranial, highly vascularized glomus tumor draining into the IJV had a CCT of 1.8 seconds. CONCLUSION: In DAVF patients, sonographic CCT is significantly shortened. Our test is highly sensitive for arteriovenous shunts but not specific for DAVF alone. Follow-up measurements in DAVF patients are well correlated with results of angiographic treatment. CCT assessment might become an additional tool for evaluating these patients and monitoring their treatment.

Our previous genome-wide Quantitative Trait Locus (QTL) mapping study using mouse A/J by C57BL/6J recombinant inbred (RI) lines suggested several chromosomal regions contain genes influencing susceptibility to phenytoin (PT)-induced cleft lip with or without cleft palate [CL(P)] and 6-aminonicotinamide (6-AN)-induced isolated cleft palate (CP). Importantly, the same chromosomal regions but different RI parental strain alleles were sometimes implicated in susceptibility to these different kinds of orofacial clefting. Here we report the susceptibility to hydrocortisone (HC)-induced CP in these RI lines. We treated pregnant females with HC and studied the incidence of CP in day 17 fetuses. RI lines showed highly correlated responses to HC and 6-AN. The A/J parental line and five RI lines showed very high levels of clefting in response to both of these teratogens. The C57BL/6J parental line and five other RI lines exhibited low incidence of CP for these teratogens. In contrast, there was no significant correlation between incidence of PT-induced CL(P) and HC-induced CP.

Carotid artery disease (CAD) is able to critically impair cerebral autoregulation which increases the risk for stroke. As therapeutic strategy largely depends on the degree of CAD, we investigated whether this gradation is also related to significant changes in autoregulatory capacity. We applied cross-spectral analysis (CSA) of spontaneous Mayer-wave (M-wave) oscillations and passive tilting (PT) to test cerebral autoregulation.Cerebral autoregulation was tested in 102 patients with carotid stenosis (or =70%) or occlusion and 14 controls by comparison of continuous transcranial Doppler sonography of the middle cerebral artery and beat-to-beat arterial blood pressure (ABP) during PT to 80 degrees head-up position as well as by CSA of M-waves (3-9 cpm).The orthostatic decrease of cerebral blood flow velocity (CBFV) was not correlated with the degree of CAD and showed a lower sensitivity and specificity than phase angle shifts between M-waves in ABP and CBFV (sensitivity: 75-80%, specificity: 86%). Phase angles were gradually lowered in carotid stenoses70%, but apparently, they were only moderately correlated with the degree of CAD (r = -0.35, P0.01). An additional influencing factor seemed to be the sufficiency of collateralization.The results show that CSA of M-waves is more appropriate for testing autoregulation than PT. CSA suggests that the capacity to autoregulate depends to a certain extent on the degree of CAD but is also influenced by the sufficiency of collateral pathways and pre-existing strokes.

Four exons of porcine platelet-activating factor receptor (PAFr) gene expressing transcript 1 and transcript 2 were determined previously. In this study, we cloned and sequenced a new exon, which also initiates transcript 2, and determined the order of 5 exons in the PAFr gene. In addition, two other variants of transcript 2 were found, but no additional variants of transcript 1 were found. Transcript 2 has three variants that were detected in porcine tissues other than in white blood cells.

Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B* 2 and ADH1C* 1, and the null allele for aldehyde dehydrogenase (ALDH), ALDH2± 2, results in increased acetylaldehyde levels and is hypothesized to increase the risk of head and neck cancer. To examine this association, the authors undertook a Human Genome Epidemiology review on these three genes and a pooled analysis of published studies on ADH1C. The majority of Asians had the fast ADH1B* 2 and ADH1C* 1 alleles, while the majority of Caucasians had the slow ADH1B* 1/1 and ADH1C* 1/2 genotypes. The ALDH2* 2 null allele was frequently observed among Asians, though it was rarely observed in other populations. In a pooled analysis of data from seven case-control studies with a total of 1,325 cases and 1,760 controls, an increased risk of head and neck cancer was not observed for the ADH1C* 1/2 genotype (odds ratio = 1.00, 95% confidence interval: 0.81, 1.23) or the ADH1C* 1/1 genotype (odds ratio = 1.14, 95% confidence interval: 0.92, 1.41). Increased relative risks of head and neck cancer were reported for the ADH1B* 1/1 and ALDH2* 1/2 genotypes in several studies. Recommendations for future studies include larger sample sizes and incorporation of relevant ADH and ALDH genes simultaneously, as well as other genes. These considerations suggest the potential for the organization of a consortium of investigators conducting studies in this field.

Background and Purpose— Cross-spectral analysis (CSA) of spontaneous oscillations in cerebral blood flow velocity (CBFV) and arterial blood pressure is considered a sensitive and convenient method for dynamic autoregulation testing. So far, it has been unclear whether CSA can be used to assess stenoses of the intracranial arteries. Methods— This study for the first time applies CSA to 26 patients with low-, moderate-, and high-degree M1 stenoses and 14 normal control subjects. Using CSA, we studied spontaneous oscillations (M waves, 3 to 9 cpm; B waves, 0.5 to 3 cpm) in continuous recordings of transcranial Doppler of the middle cerebral artery and simultaneously recorded beat-to-beat blood pressure. Results— A gradual decrease in pulsatility indexes confirmed the increasing hemodynamic relevance of the stenoses. Compared with control subjects, M-wave phase shifts between CBFV and blood pressure were gradually reduced with increasing degree of M1 stenosis (control subjects, 44.6±21.1°; high-degree stenosis, 16.7±19.5°). The phase relation between B waves in blood pressure and CBFV was shifted to positive values (low-degree stenosis, −9.7±108.4°; high-degree stenosis, 50.9±43.8°). Conclusions— Because B- and M-wave phase shifts seem to characterize the degree of autonomy of CBFV modulation, this study suggests that with increasing degree of M1 stenosis, the arteriolar function is impaired. It shows that CSA is of indicative use for the assessment of intracranial artery stenosis.

Alcohol consumption is a major risk factor for cancers of the mouth and pharynx (oral cancer), but the differential risks by beverage type are unclear. In this 1992-1995 study, the authors examined oral cancer risk in Puerto Rico, comparing alcohol intake among 286 male cases aged 21-79 years and 417 population-based male controls, frequency matched by age. Heavy consumers of liquor (>/=43 drinks per week) had strongly increased risks of oral cancer (odds ratio = 6.4, 95% confidence interval: 2.4, 16.8); beer/wine showed only modest effects. Among liquor drinkers, risks were consistently greater for those who drank straight (undiluted) liquor than for those who usually drank mixed (diluted) liquor (odds ratio = 4.0, 95% confidence interval: 2.4, 6.7). Risks associated with combined exposure to tobacco were also more pronounced when subjects drank liquor straight. The elevated risks associated with drinking homemade rum were similar to those for other types of liquor. These results suggest that alcohol concentration is a risk factor for oral cancer independent of the total quantity of alcohol consumed.

The data of 825 consecutive patients with ischemic stroke or TIA were retrospectively reviewed for ultrasound findings of stenoses or occlusions of the middle cerebral artery (MCA). Using survival statistics,we studied the influence of various factors on the prognosis of MCA findings. We identified 90 subjects with MCA stenosis or occlusion. Microembolic signals were demonstrated in 33% and spontaneous flow variations in 7%. Symptomatic MCA findings normalized more quickly than asymptomatic findings. Microembolic signals occurred only in symptomatic stenoses. Spontaneous flow variations strongly predicted the disappearance of a stenosis. Atherogenic risk factors were associated with stable ultrasound findings. These data suggest that different types of MCA findings exist: (1) dynamic, emboligenic stenoses or occlusions with early normalization and a high risk for ischemic events and (2) static, nonemboligenic stenoses with rare normalization and a low risk of ischemic events. A high percentage of the former may be of embolic origin, and the latter may be atherosclerotic plaques.

Objective Our objective was to determine the possible underlying etiologies and outcome in isolated fetal pericardial effusion. Methods Doppler fetal echocardiography allowed the diagnosis of pericardial effusion in three patients and revealed the etiology in two. Results We present the findings in three cases of isolated pericardial effusion. In the first, the pericardial effusion was a manifestation of trisomy 21 associated with a myeloproliferative disorder. In the second, the pericardial fluid collection was the first sign of an autosomal recessive disease, idiopathic infantile arterial calcification.The third case was remarkable because of the spontaneous resolution of a large pericardial fluid collection. Conclusion Isolated fetal pericardial effusion covers a wide spectrum of etiologies from severe genetic and chromosomal diseases to transient forms. Copyright © 2003 John Wiley & Sons, Ltd.

Our purpose was to evaluate inherited short tandem repeat polymorphisms of the insulin-like growth factor II receptor gene (IGF2R) in oral cancer risk. The 197 individuals that consented to participate in a hospital-based, case-control study were interviewed with a structured questionnaire and provided blood and saliva. DNA was extracted for genotyping using a PCR-based method. Odds ratios were calculated using multivariate logistic regression. Subjects carrying the heterozygous 167-bp IGF2R genotype had a 2.7-fold higher risk of oral cancer compared with subjects with other genotypes (odds ratio = 2.7, 95% confidence interval: 1.16-6.48), controlling for major confounders. Our results suggest that genetic variation of IGF2R may influence significantly the risk of oral cancer.

We present the analysis of the first observations of the Cygnus region by the SPI spectrometer onboard the Integral Gamma Ray Observatory, encompassing ~600 ks of data. Three sources namely Cyg X-1, Cyg X-3 and EXO 2030+375 were clearly detected. Our data illustrate the temporal variability of Cyg X-1 in the energy range from 20 keV to 300 keV. The spectral analysis shows a remarkable stability of the Cyg X-1 spectra when averaged over one day timescale. The other goal of these observations is SPI inflight calibration and performance verification. The latest objective has been achieved as demonstrated by the results presented in this paper.

In its space environment the INTEGRAL observatory is subject to an intense irradiation by energetic cosmic-ray particles that leads, via nuclear interactions with the telescope and spacecraft materials, to an important background of false events. In this paper we present the characteristics of the instrumental background that is observed in the spectrometer SPI (SPectrometer of INTEGRAL). We explain the tuning that has been performed on the parameters of the anticoincidence system in order to optimise the telescope sensitivity over the full energy range. Temporal variations of the instrumental background are discussed and methods are proposed that allow for their modelling in first order. Based on observations with INTEGRAL, an ESA project with instruments and science data centre funded by ESA member states (especially the PI countries: Denmark, France, Germany, Italy, Switzerland, Spain), Czech Republic and Poland, and with the participation of Russia and the USA.

The SPI instrument has been launched on-board the INTEGRAL observatory on October 17, 2002. SPI is a spectrometer devoted to the sky observation in the 20 keV-8 MeV energy range using 19 germanium detectors. The performance of the cryogenic system is nominal and allows to cool the 19 kg of germanium down to 85 K with a comfortable margin. The energy resolution of the whole camera is 2.5 keV at 1.1 MeV. This resolution degrades with time due to particle irradiation in space. We show that the annealing process allows the recovery of the initial performance. The anticoincidence shield works as expected, with a low threshold at 75 keV, reducing the GeD background by a factor of 20. The digital front-end electronics system allows the perfect alignement in time of all the signals as well as the optimisation of the dead time (12%). We demonstrate that SPI is able to map regions as complex as the galactic plane. The obtained spectrum of the Crab nebula validates the present version of our response matrix. The 3sigma sensitivity of the instrument at 1 MeV is 8*E-7 ph cm-2 s-1 keV-1 for the continuum and 3*E-5 ph cm-2 s-1 for narrow lines.

The activated transport of organelles, vesicles, and many other subcellular commodities along cytoskeletal filaments is central to mechanisms that regulate the internal organization of eukaryotic cells ( 1 ). The motions of these cargos are driven by several classes of ATP–dependent enzymes called motor proteins that are capable of converting chemical energy into mechanical work. A variety of bulk biochemical and single-molecule techniques have been developed over the past decade to characterize the principles that allow these enzymes to function effectively as molecular machines ( 2 , 3 ). Yet most cargos are transported by multicomponent motor systems containing multiple copies of the same motor, or even by mixtures of different classes of motors that move with different velocities, in opposite directions, and along different types of cytoskeletal filaments ( 4 , 5 ). Understanding how motors cooperate productively and compete antagonistically has therefore become increasingly important for dissecting mechanisms that regulate intracellular transport as well as the impact of motor mutations in diseases. On page 662 of this issue, Derr et al. ( 6 ) demonstrate a new materials approach to these problems that allows the characterization of key relationships among the structural organization of multiple motor systems, the properties of motors within these complexes, and their collective dynamic behaviors.

Despite the efficiencies of many microtubule motors, sub-cellular cargos are often transported by motor teams composed of multiple processive molecular motors. Furthermore, mutant motors associated with diseases can be coupled to cargos that are also outfitted with copies of wild-type motors. Together, these observations raise important questions regarding the role of motor cooperation in intracellular transport. Although abilities to characterize the transport behaviors of multiple motor systems have improved substantially, many aspects of multiple-motor dynamics remain poorly understood. Here, I will describe our efforts to create structurally-defined complexes composed of multiple kinesin motors and examine their dynamics at the ‘single-motor’ level. I will also describe a transition rate model that predicts the load-dependent transport behaviors of these complexes from detailed measurements of a single motor's elastic and mechanochemical properties. The model reproduces key signatures found in optical trapping studies two-kinesin complexes including observations of non-monotonic dependencies of cargo velocities and motor-microtubule unbinding rates on the applied load, and predicts that multiple kinesins have generic difficulties cooperating productively. While such behavior is influenced significantly by extrinsic factors including the spatio-temporal dependence of the applied load, the net-negative cooperative behaviors exhibited by multiple kinesins appear to be directly linked to the efficiency of kinesin's stepping mechanism, and other types of less efficient and ‘weaker’ processive motors are predicted to cooperate more productively. Thus, mechanochemical efficiencies of different motor types may distinguish how effectively they function as a team, and hence, how motor copy number contributes to the regulation of cargo motion. Finally, the extension of our experimental and computational approaches to studies of multiple motor dynamics inside of living cells will be discussed.

During the past 15 years several paradigms to study dynamic cerebral autoregulation (CA) were developed by measuring cerebral blood flow (CBF) velocity with transcranial Doppler (TCD) in response to blood pressure changes. As a more indirect approach to measure autoregulation, vasomotor reactivity (VMR) can be determined by the use of vasodilatory stimuli. CA or VMR are often severely disturbed in occlusive carotid artery disease. Several prospective studies have shown that reduced VMR is an important risk factor for stroke or TIA in patients with symptomatic and asymptomatic carotid artery stenosis or occlusion. Future randomized intervention studies will show whether asymptomatic patients with carotid artery stenosis and pathological autoregulation or VMR will benefit from revascularization therapy.

Although platelet-activating factor receptor (PAFr) gene was well characterized in the human, little was known about it in domestic animals. Porcine PAFr gene was mapped using fluorescence in situ hybridization (FISH). The structure of this gene was investigated using a 5′ rapid amplification of cDNA ends (RACE) technique. Temporal expression of PAFr and estrogen receptor α genes (ER), and distribution of the PAFr transcripts in porcine endometrial and embryonic tissues on days 0, 10, 12, 14, 16, and 18 were analyzed using DNA competitors and reverse transcription and polymerase chain reaction (RT-PCR). The porcine PAFr gene was mapped to SSC6q26-27. Alternative splicing of primary transcripts of the PAFr gene produced two different transcripts. Transcript 1 was expressed in all tissues and cells, and transcript 2 was detected in all tissues but white blood cells. The temporal expression of the PAFr gene in endometrial (P > 0.05) and embryonic (P

BACKGROUND Carcinoma of the oral cavity is one of the most common cancers worldwide. Tobacco smoking and the consumption of alcoholic beverages are significant risk factors but to the authors' knowledge the role of nutrition is not adequately understood. The authors undertook an epidemiologic study of oral carcinoma occurring in Greece, where tobacco smoking and alcohol consumption are common but the incidence of the disease is among the lowest reported in Europe. METHODS One hundred six patients with histologically confirmed incident oral carcinoma and an equal number of control subjects matched for age and gender were studied. Dietary information was assessed through a validated extensive food frequency questionnaire and the data were analyzed using conditional logistic regression. RESULTS After adjustment for energy intake, tobacco smoking, and alcohol consumption, there was evidence that the consumption of cereals, fruits, dairy products, and added lipids (which in Greece are represented mostly by olive oil) was found to be associated inversely with the risk of oral carcinoma. Only with respect to meat and meat products was there adequate evidence of a positive association with the risk of oral carcinoma. Among the micronutrients studied, riboflavin, magnesium, and iron appeared to be correlated inversely with the disease. CONCLUSIONS Fruits, cereals, dairy products, and olive oil appear to convey protection against oral carcinoma and their effects may be mediated through higher intakes of riboflavin, iron, and magnesium. The low incidence of oral carcinoma reported in Greece may be explained in part by the higher consumption of the food groups and micronutrients that appear to protect against the disease. Cancer 2002;94:2981–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10560

The significance of serum concentrations of various antibodies and cytokines in the pathogenesis of early-onset periodontitis (EOP) is not well understood. Recent reports suggest differences between young blacks and whites in certain humoral responses, regardless of periodontal status. This study was undertaken to compare the serum concentrations of IgG, IgA, IgM, and IL-1beta in EOP subjects with that of healthy controls, and to study the effect of race on these levels.This case-control study included 228 individuals, 19-25 years old who were selected from a larger population examined in the National Survey of Oral Health of United States Children in 1986/1987. The subjects were classified by their EOP status and they included 166 subjects with EOP and 62 healthy controls. Blood samples were used to assess the serum concentrations of IgG, IgM, IgA, IgG subclass, and IL-1beta.The serum concentrations of IgG, IgG subclasses, IgA, and IgM in blacks were not significantly different in the generalized, localized and incidental EOP groups as compared to the healthy controls. The serum IL-1beta concentration was slightly and uniformly lower in the EOP groups than in the control group, although not statistically significant. Blacks had significantly higher serum concentrations of total IgG, and of IgG1, IgG2 and IgG3 than whites and Hispanics. Hispanics had significantly higher serum concentrations of IgM and IgG4 than whites and blacks. Hispanics also had a significantly higher serum concentration of IL-1beta than blacks.Total antibody response in blacks is not associated with EOP classification. Race has a significant effect on serum antibody concentrations irrespective of disease classification, with blacks having significantly higher serum concentrations of IgG1, IgG2 and IgG3 than whites and Hispanics.

A Mars relay network is being built using relay radios carried by nearly every Mars orbiter. Mars relay network performance has been limited because Mars orbiters are usually designed to support science missions from low, near-polar orbits; their relay functions are of secondary importance in spacecraft and mission design. The ASI/NASA G. Marconi Orbiter (GMO) will be the first Mars orbiter designed primarily for relay support; science experiments on GMO are secondary. Combining a high performance relay payload with a custom relay orbit, GMO can increase the data returned from in-situ missions by an order of magnitude or more. GMO can increase connectivity to in-situ missions from a few minutes (typical of other orbiters) to hours at a time, offering much greater operational flexibility and resilience and enabling new relay services.

Hypothalamic corticotropin releasing hormone (CRH) stimulates pituitary ACTH secretion through interaction with type 1 CRH receptors (CRH-R1), the number of which varies during alterations of the hypothalamic-pituitary-adrenal (HPA) axis. CRH-R1 are essential for ACTH responses to stress but CRH receptor content in the pituitary does not correlate with corticotroph responsiveness. This indicates that a small number of receptors is sufficient for full ACTH responses probably through post-receptor interaction with vasopressin (VP) signaling. CRH binding and hybridization studies in adrenalectomized, glucocorticoid-treated or stressed rats revealed divergent levels of CRH receptors and CRH-R1 mRNA in the pituitary, with binding reductions but normal or elevated CRH-R1 mRNA levels during alterations of the HPA axis. Western blot analysis of CRH-R1 protein in pituitary membranes from adrenalectomized rats show unchanged CRH-R1 mRNA levels, but reduced CRH binding associated with significant increases in CRH-R1 protein, suggesting that the decrease in binding is due to homologous desensitization and not to reduced receptor synthesis. In contrast, decreased CRH binding following glucocorticoid administration is associated with reduction in CRH-R1 protein suggesting inhibition of CRH-R1 mRNA translation. Regulation of CRH-R1 translation may involve binding of cytosolic proteins, and a minicistron in the 5'UTR of the CRH-R1 mRNA. Post-transcriptional regulatory mechanisms allowing rapid changes in CRH receptor activity are important for adaptation of corticotroph responsiveness to continuous change in physiological demand.

We examined the relationships between folate and methionine intake, serum homocysteine levels (as a biomarker for folate metabolism), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype and risk of oral cancer in a population-based, case-control study in Puerto Rico. Structured questionnaires were used to collect information on demographic factors, usual adult diet, and tobacco and alcohol use. Oral epithelial cells and blood samples were collected from a subset of subjects. Analyses were conducted by logistic regression, adjusting for age, sex, lifetime smoking and lifetime alcohol intake, with the following numbers of cases/controls, respectively: dietary data (341/521); MTHFR genotype (148/149); and homocysteine (60/90). Although increased folate intake was associated with decreased oral cancer risk [adjusted odds ratio (OR) in highest vs. lowest quartile = 0.6, 95% confidence interval (CI): 0.4, 1.0, P(trend) = 0.05)], this finding was due almost entirely to folate intake from fruit (adjusted OR = 0.4, 95% CI: 0.2, 0.6; P(trend) = 0.0001), whereas other dietary folate sources showed no clear association. Methionine intake and serum homocysteine levels were not associated with oral cancer risk. Subjects with the MTHFR C677T homozygous variant (TT) genotype had a nonsignificantly lower risk, and risk patterns tended to differ by level of folate, methionine, alcohol intake and smoking, although the power to detect significant associations in subgroups of these variables was low. Risks for oral cancer are not folate specific; preventive recommendations for this disease should emphasize the importance of a healthy diet, including substantial intake of fruits.

The actions of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) are mediated through the PAF receptor (PAFr), which is a member of G-protein coupled superfamily of receptors. Our laboratory has data showing PAF has a role(s) in reproduction in domestic animals. Porcine, bovine and caprine PAFr genes cloned in BAC vectors were sequenced. Each PAFr coding sequence (cds) in these three species is 1029 nucleotides long and contains no intervening sequences. The deduced amino acid sequences (AAS) appear to contain seven putative transmembrane domains with an extracellular N-terminus in each species. There is a common glycosylation site at the fourth asparagine residue of N-terminus. In the tail of each deduced amino acid sequence, five to six serines and five threonine residues could act as phosphorylation sites, which play an important role in rapid receptor desensitization. The degree of homology of the three species is from 89 to 96% in nucleotide sequences (NtS), and 87-96% in identities (I) and 94-97% in positives (P) in amino acid sequences (AAS). The degree of homology with human, guinea pig, mouse and rat is 84-87, 82-88 and 83-88% in NtS, 77-84 (I) or 85-90 (P), 77-84 (I) or 85-90 (P) and 75-83 (I) or 87-90% (P) in AAS for caprine, bovine and pig, respectively. Southern blotting results suggested that the PAFr gene exists as a single copy in the genome of pig.

The GMO design team is developing standard processes and interfaces in cooperation with the designers of other Mars orbiters to enable relay users to easily access multiple relay orbiters.

Early detection and treatment improve the prognosis for oral cancer. Delays from the onset of symptoms to clinical diagnosis are common. Our aim is to identify factors associated with this delay. Between 1995 and 1998, we interviewed 105 consecutive patients with histologically confirmed oral cancer in Greece. If 21 or more days elapsed from the time the patient noticed major symptoms to a definitive diagnosis, we called it a delay (52% of cases). We used logistic and linear regression to estimate odds ratios of delayed diagnosis and to identify correlates of length of delay, respectively. Former smokers had a 4.3 times greater risk of delayed diagnosis compared with current smokers (95% confidence interval: 1.1-17.1). The length of delay was greater among single patients, non-smokers, or those with stage IV tumors. Clinicians should be advised that delay in the diagnosis of oral cancer occurs frequently, even in individuals who do not smoke heavily.

Extracranial Doppler sonography and transcranial Doppler sonography (TCD) allow the assessment and monitoring of hemodynamic and embolic events in cerebrovascular diseases. We describe an unusual hemodynamic phenomenon in a patient with intracranial carotid siphon stenosis and no clinical symptoms of stenosis. TCD examination suggested and angiography confirmed stenosis of the left internal carotid artery siphon. TCD examination revealed a sudden, intermittent drop in blood flow velocity in both the prestenotic and poststenotic segments of the internal carotid artery, whereas cardiac hemodynamic parameters were unaffected. Embolic signals were detected in the poststenotic vessels only. We speculate that such sonographic findings may be caused by intermittent vessel occlusions due to the reversible displacement of an intraluminal thrombus in relation to the cardiac cycle.

The role of antibodies to periodontal microorganisms in the development of periodontal tissue destruction is still unclear. The aim of this study was to investigate the association between serum levels of IgG, IgA, and IgM antibodies to 6 periodontal microorganisms and clinical subtypes of varying severity of early-onset periodontitis (EOP) in young African American adults.The study group consisted of 159 African Americans aged 19 to 25 years (mean 22 years) and included 97 cases with EOP and 62 controls with no clinical signs of EOP. These subjects were selected from a nationally representative sample of adolescents who received an oral examination as part of the National Survey of Oral Health of United States Children in 1986-1987. The group was examined clinically a second time 6 years later and blood samples were collected. Serum levels of IgG, IgA, and IgM reactive to Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, Eikenella corrodens, and Fusobacterium nucleatum were assessed.Serum levels of IgG and IgA antibody reactive to P. gingivalis and A. actinomycetemcomitans and IgA antibody to P. intermedia were significantly higher in generalized EOP cases compared to healthy controls. IgM antibody levels did not show any significant associations with EOP for any of the 6 bacterial species tested. There were no significant differences in antibody levels between controls and the 13 subjects in our study who were classified with localized EOP.The findings suggest that antibodies to P. gingivalis, P. intermedia, and A. actinomycetemcomitans may play a significant role in the pathogenesis of EOP. Substantial longitudinal studies that monitor antibody levels and avidity prior to disease onset, during progression, and following clinical intervention will be necessary to fully understand the role of this component of the immune response in protection versus tissue destruction and the potential use in EOP risk assessment and disease management.

Der Gesetzgeber verpflichtet die Krankenhauser zu internem Qualitatsmanagement und externer Qualitatssicherung, so im Sozialgesetzbuch V und im Infektionsschutzgesetz. Hierzu stehen Verfahren der Zertifizierung von technischen und medizinischen Standards (ISO 9000:2000, EFQM, KTQ) sowie der Erfassung und Meldung unerwunschter Ereignisse (z.B. Qualitatssicherung bei Fallpauschalen und Sonderentgelten) zur Verfugung. Zunehmend gewinnt bei diesen Verfahren die Entwicklung und Anwendung von Indikatoren an Bedeutung, wie sie als leistungsbezogene Methode des Qualitatsmanagements im medizinischen Umfeld durch die Joint Commission on Accreditation of Healthcare Organizations (JCAHO) beschrieben worden sind. Zielsetzung: Ziel dieses Vorhabens war die Entwicklung eines indikatorgestutzten Qualitatsmanagements postoperativer und postinterventioneller Komplikationen, bei welchem als wesentliche Anforderung die Integration in ein vorhandenes Klinisches Arbeitsplatzsystem (KAS) sowie eine krankenhausweite Umsetzung im Rahmen einer Basisdokumentation vorgegeben war. Bei der Auswahl von Indikatoren mussten daher neben medizinischen Aspekten auch informationstechnische Aspekte berucksichtigt werden. Methoden: Ein aus Sicht der Fachabteilungen erarbeiteter Katalog von Indikatoren wurde mit einer Analyse des vorhandenen KAS in Beziehung gesetzt. Hierzu wurden die Indikatoren in einer Entscheidungsmatrix nach ihrer Bedeutung, der zu erwartenden Pravalenz, der Erfassbarkeit der Daten, der Kopplung mit bestehenden Dokumentationsablaufen, den Moglichkeiten des Dokumentationscontrollings sowie einer Einschatzung von Interventionsmechanismen bewertet und eine Teilmenge fur eine erste Umsetzungsphase ausgewahlt. Fur diese Indikatoren wurde dann sowohl ein informationstechnisches als auch ein Organisationskonzept entworfen, in denen die zu erfassenden Merkmale, Verantwortlichkeiten fur Dokumentation und Intervention, die durchzufuhrenden Berechnungen sowie die fur den jeweiligen Indikator festgelegten Interventionsgrunde und -mechanismen definiert sind. Ergebnisse: Mit diesem Ansatz sind gute Voraussetzungen fur eine vollstandige und valide Erfassung von Komplikationen durch die Integration in die Routineverfahren der Dokumentation gegeben. Hieraus ergeben sich gleichzeitig synergistische Effekte fur die Umsetzung der German Diagnosis Related Groups (G-DRGs) ab dem 1.1.2003, da hier Komplikationen und Begleiterkrankungen als Merkmal fur den Ressourcenverbrauch auch okonomisch von hoher Bedeutung sind.

Im Normalfall werden der frontale Kortex und das oberflachliche Marklager durch folgende Aste gespeist: A. cerebri media (ACM; dorsolaterale Konvexitat) und A. cerebri anterior (ACA; ventrale und mediale Flache bis 2–3 cm uber die Mantelkante nach dorsal reichend).

Exakte sonomorphologische Kriterien zur Beurteilung der Risiken von Carotisstenosen liegen bislang nur unzureichend vor. Als potentiell mit hoherem Embolierisiko versehen gelten weiche ulcerierende und thrombosierte Plaques. In den letzten Jahren hat sich die transkranielle Emboliedetektion als Methode der Wahl zur Beurteilung der Emboligenitat einer Carotisstenose durchgesetzt. In der vorliegenden Studie werden die praoperativen sonomorphologischen Befunde den pathomorphologischen Ergebnissen und den intraoperativen Embolieraten gegenubergestellt, um unter anderem Auswirkungen auf therapeutische Konsequenzen zu uberprufen. Material und Methoden: 167 hochgradige (> 70%) Stenosen der A. carotis interna wurden prospektiv praoperativ duplexsonographisch eingeteilt (echoarm, echoreich, ulcerierend, thrombosiert) und mit dem pathomorphologischen Befund verglichen. Alle Patienten wurden pra- und postoperativ neurologisch untersucht. Intraopertiv wurde ein kontinuierliches transkranielles bitemporales Dopplermonitoring mit Emboliedetektion durchgefuhrt. Resultate: Von den 167 operierten Carotisstenosen waren 46 (27,3%) asymptomatisch, 101 (65,5%) wiesen eine TIA, Amaurosis fugax oder PRIND auf. Bei 20 (12,2%) lag ein bleibendes neurologisches Defizit vor. Sonomorphologisch waren 104 (62,3%) Stenosen echoreich, 63 (37,7%) echoarm. In 34 (20,4%) Fallen fanden sich Thromben, in 57 (34,1%) Fallen Ulceration. Die Ubereinstimmung mit dem intraoperativen pathomorphologischen Befund lag bei 96,2%. Echoarme Plaques waren in 51 (81%) Fallen symptomatisch, echoreiche in 70 (67,3%) Fallen. Eine intraopertive Emboliedetektion war bei 152 (91%) Operationen moglich. Bei 69 (41,3%) Eingriffen traten intraoperitv Embolien auf, die in 19 (6,6%) Fallen die Praparationsphase betrafen. Hiervon waren 12 (63,1%) praoperativ symptomatisch. Morphologisch wiesen 17 von den 19 embolisierenden Plaques entweder Ulcerationen mit oder ohne Thromben oder die Kriterien von weichen Plaques auf. Postoperativ kam es bei 6 (3,6%) Patienten zu neurologischen Defiziten (2 permanent, 4 temporar), 4 von diesen 6 Patienten wiesen Embolien in der Praparationsphase auf. Zusammenfassungg: In der vorliegenden Studie konnte eine hohe Ubereinstimmung zwischen sonomorphologischem und pathomorphologischem Befund festgestellt werden. Als besonders emboligen erwiesen sich die echoarmen und ulcerierenden Plaques. Neurologische Komplikationen traten vorwiegend in der Gruppe auf, bei der es in der Praparationsphase zu Embolien kam. Diese Daten bestatigen die Gefahrlichkeit der symptomatischen echoarmen oder ulcerierenden Plaques und den Wert der praoperativen duplexsonographischen Beurteilung in der Detektion von Risikopatienten.

Transcranial Doppler monitoring enables the detection of emboli passing through intracranial arteries. Comparison of the different intracranial vessels with respect to emboli detection can be of use in identifying the source of embolism. We report the case of a patient with an acute posterior cerebral artery (PCA) infarct on the right side, with evidence for high-degree ipsilateral PCA narrowing on admission. During transcranial Doppler monitoring 3 days later, we found frequent emboli-like signals in the power spectrum of the right PCA distal to the stenosis but not in any other intracranial vessels. Four days later, angiography and transcranial Doppler failed to show PCA narrowing, and transcranial Doppler monitoring of the right PCA showed no further emboli-like signals. A stenosis of the right vertebral artery was regarded as the possible source of thromboembolic narrowing of the PCA. We assume that in our patient a thrombotic clot in the PCA was resolved autolytically through detachment of small emboli into the distal part of the PCA. We speculate that in the early course of autolysis a larger fragment of the clot had occluded one of the distal branches, thus leading to the small PCA territory infarct.

Characterizing the collective dynamics of cytoskeletal motors has become increasingly important to resolving transport regulatory mechanisms and the impact of mutated motor molecules in disease. Yet, many analyses multiple motor behaviors, especially those in living cells, have been limited by inabilities to control and / or characterize the number of motors responsible for cargo motion, their organization on cargos, as well as the mechanical barriers motors face during intracellular transport. Here, we describe an approach to engineer COS7 cells that provides genetic-level control over the densities and ratios of different motors on vesicular cargos (peroxisomes), as well as the loads imposed experienced by motors via the regulation of cargo size. Such control is facilitated by the construction of multi-component gene regulatory constructs and opens new opportunities to evaluate the collective responses of different types of motor molecules systematically in living cells. Assays comparing the collective behaviors of kinesin-1 and myosinVa motors - via analyses of the responses of peroxisome velocities, run lengths, and position noise to motor density and cargo size - indicate that multiple myosinVa motors can cooperate more productively that groups of kinesins. Overall, these results support predictions from in vitro experiments and theoretical analyses suggesting that the susceptibilities of motor velocity and filament detachment rates to forces are primary determinants of how effectively teams of motors can cooperate under the applied load imposed by the COS7 cell cytoplasm. The role of such behaviors in mechanisms regulating cargo motion will be discussed.

Discovery of causal genes and awareness of risk factors for dental caries may assist development of personalised prevention and early detection of dental caries. A computational approach to identify and prioritise candidate genes and single nucleotide polymorphisms (SNPs) was developed and applied to dental caries susceptibility. Information on normal biological functions from gene ontology (GO) and on clinical relevance from the genetic association studies reported in literature identified good candidate genes. Although no significant agreement was found between the selected genes/SNPs from our study to those obtained from the first genome wide association study (GWAS) for caries susceptibility, it should be noted that the GWAS showed only moderate to weak associations. The genes that were prioritised in our study may still serve as high priority targets for searches of rare variants by whole exome/genome sequencing in future.

Local thrombolysis may reduce mortality after acute vertebrobasilar artery occlusion. We focused on variables affecting recanalization, outcome and long-term prognosis. Thirty-six patients with vertebrobasilar artery occlusion were treated with local intraarterial thrombolytic therapy. Four of the survivors were among the 16 patients without recanalization. Recanalization was associated with a higher survival rate. Top-of-the-basilar-type occlusions have the highest recanalization rate. The thrombolytic medication used did not influence the recanalization frequency. One patient died due to an intracerebral bleed after thrombolysis. There was no association between the time interval (greater or less than 6 h) between the onset of symptoms and therapy initiation and survival. Relapses during follow-up (mean follow-up 3.7 years) did not occur. MRI/MRA and ultrasound studies during follow-up showed unchanged results in these patients. All survivors at the time of follow-up lived at home.

Use of alcohol and tobacco are the major risk factors for cancers of the oral cavity and pharynx in most of the world. A heritable component to oral carcinoma risk also has been suggested, although only limited data are available on familial aggregation of this disease.A population-based case-control study of 342 subjects with carcinomas of the oral cavity and pharynx (oral carcinoma) and 521 controls was conducted in Puerto Rico. The relation between family history of carcinomas of the oral cavity, the upper aerodigestive tract (UADT), and other selected sites with risk of oral carcinoma was explored using logistic regression modeling techniques.Risk of oral carcinoma was elevated for subjects reporting a first-degree relative with carcinoma of the oral cavity (odds ratio [OR], 2.5; 95% confidence interval [CI], 0.8-8.0) or any UADT carcinoma (OR, 2.6; 95% CI, 1.4-4.8). The increased risk associated with family history of UADT carcinoma tended to be greatest for subjects with known risk factors (i.e., heavy consumption of alcohol and/or tobacco and infrequent intake of raw fruits and vegetables) and with oral carcinoma diagnoses at ages younger than 65 years.These findings are consistent with a heritable component to oral carcinoma, although shared lifestyle risk factors may be partially involved.

To determine if the risk of cancers of the mouth and pharynx is associated with mouthwash use in Puerto Rico, an area of relatively high risk.Interviews were conducted with 342 cases of oral and pharyngeal cancer registered in Puerto Rico and diagnosed between 1992 and 1995 and with 521 population-based controls regarding mouthwash use and other factors. Mouthwash-related risks were estimated using unconditional logistic regression controlling for potential confounders.The adjusted odds ratio associated with using mouthwash with an alcohol content of 25% or greater was 1.0. Risks were not higher with greater frequency, years of use, or lifetime mouthwash exposure. Among tobacco and alcohol abstainers the odds ratio associated with mouthwash use was 2.8 (CI = 0.8-9.9), in contrast to 0.8 (CI = 0.4-1.7) and 0.9 (CI = 0.6-1.3) among those with light and heavy cigarette smoking/alcohol drinking behaviors, respectively.There was no overall increased risk of oral cancer associated with mouthwash use. An elevated, but not statistically significant, risk was observed among the small number of subjects who neither smoked cigarettes nor drank alcohol, among whom an effect of alcohol-containing mouthwash would be most likely evident. Our findings indicate the need to clarify the mechanisms of oral carcinogenesis, including the possible role of alcohol-containing mouthwash.

We undertook this study to assess the effect of urine and fecal contamination in the cages of male mice on embryo production in females placed in these cages for breeding. Each superovulated female was placed with a stud male in a cage that was cleaned at 1, 24, or 168 h prior to breeding. Approximately 41 h after mating, embryos were flushed from the oviducts, and we determined the number of embryos and their developmental stages for each treatment group. The number of two-cell embryos collected did not differ significantly when cages were cleaned 1 or 24 h prior to mating the mice. However, significantly (p0.05) fewer embryos were recovered when cages were changed 168 h before the animals were mated.

Our objectives were to determine if: (1) patients with migraine have B wave abnormalities in comparison to normal controls and patients with chronic tension headache and (2) patients with chronic tension headache have an imbalance in autonomic activity that is reflected in differences in Mayer wave activity in comparison to normal controls.B waves and Mayer waves are spontaneous oscillations in cerebral blood flow velocity with a frequency of 0.5 to 3 or 4 to 7 cycles per minute, respectively, and can be measured by transcranial Doppler sonography. There is experimental evidence that B waves are generated by certain brain stem nuclei which modulate the lumen of the small intracerebral vessels via monoaminergic nerve endings. In contrast, Mayer waves in cerebral blood flow velocity have no central generator but mirror the Mayer waves in arterial blood pressure which represent peripheral autonomic activity. Migraine may be attributed to a neurotransmitter imbalance in brain stem nuclei. Dysfunctions of the peripheral autonomic nervous system are known in patients with chronic tension headache.Using bilateral transcranial Doppler monitoring of the middle cerebral artery B waves and Mayer waves were studied in 30 patients with migraine without aura, 28 subjects with tension-type headache, and 30 normal controls. Coefficient of variation as a quantitative parameter for amplitude of waves and the mean frequency were calculated from the envelope curves of the Doppler spectra.The coefficient of variation of B waves was higher in migrainous patients compared with patients with tension-type headache and normal controls (P.05), indicating an increase in activity of brain stem nuclei in migraine only. Patients with chronic tension headaches had lower values for Mayer wave activity in comparison with normal controls (P.05), a sign of an impairment of sympathetic activity.Our data support the dysfunction of the brain stem monoaminergic/serotonergic system in migraine. In contrast, patients with chronic tension headache have an autonomic dysfunction of peripheral origin presenting as a decrease of sympathetic activity.

The observation of the interstellar 1.809 MeV decay-line of radioactive 26 Al by the imaging gamma-ray telescope COMPTEL have let to the conclusion, that massive stars and their subsequent core-collapse su­ pernovae are the dominant sources of the interstellar 26 Al abundance. Massive stars are known to affect the surrounding interstellar medium by their energetic stellar winds and by the emission of ionising radia­ tion. We present a population synthesis model allowing the correlated investigation of the gamma-ray emission characteristics with integrated matter, kinetic energy and extreme ultra-violet radiation emission of as­ sociations of massive stars. We study the time evolution of the various observables. In addition, we discuss systematic as well as statistical un­ certainties affecting the model. Beside uncertainties in the input stellar physics such as stellar rotation, mass loss rates or internal mixing mod­ ifications due to a unknown binary component may lead to significant uncertainties.