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At least 721 records · Page 40Linked to original sources
PubMed2004

New CCR5 variants associated with reduced HIV coreceptor function in southeast Asia.

BACKGROUND: Despite multiple exposure to HIV-1, some individuals remain uninfected. This resistance has been associated with homozygosity for a 32 base pair deletion in the gene for the CCR5 receptor. This variant occurs frequently in Caucasians but is extremely rare in Asians or Africans. OBJECTIVE: To identify variations in CCR5 receptor gene that affect susceptibility to HIV infection in non-Caucasians. METHODS: CCR5 coding region polymorphisms were screened in three groups of Vietnamese subjects: 47 HIV-1 infected intravascular drug users, 50 highly HIV-1-exposed but seronegative intravascular drug users and 37 HIV-1-unexposed seronegative individuals. DNA was analysed by denaturing high performance liquid chromatography; this was followed by examination of the biochemical and HIV coreceptor properties of the coding regions. RESULTS: Five CCR5 coding region variants were identified in this Vietnamese population. The S185R, I254T and C269F mutations have not been previously described; G106R and R223Q have already been found in other Asian populations, but the functional properties of G106R is not known. These variants differed in biochemical and HIV coreceptor properties. S185R and I254T variants had receptor and coreceptor activities comparable to that of the wild type, whereas C269F and G106R behaved differently. This latter pair are poorly expressed at the cell surface, weakly bind macrophage inflammatory protein 1beta (CCL4) and RANTES (CCL5), and display reduced HIV-1 coreceptor efficiency. CONCLUSIONS: Among the five CCR5 variants found in this Vietnamese population, G106R and C269F displayed significant modifications of their receptor and coreceptor properties, which may contribute to susceptibility to HIV-1 infection and/or disease progression within this population.

Cambodia↗
PubMed1999

Accuracy of intramucosal pH calculated from arterial bicarbonate and the Henderson-Hasselbalch equation: assessment using simulated ischemia.

OBJECTIVES: To determine the accuracy of intramucosal pH (pHi) calculated using arterial bicarbonate instead of mucosal capillary bicarbonate in the Henderson-Hasselbalch equation. DESIGN: Simulation of progressive ischemia in mucosal capillary blood. SETTING: University research laboratory. SUBJECTS: Normal human blood diluted with plasma. INTERVENTIONS: Three venous blood specimens were heparinized and diluted to a mean hemoglobin concentration of 5.0 (+/-0.9) g/dL by addition of plasma (2:1, vol:vol). Mucosal capillary aerobic flow stagnation was simulated by multiple exposures of each cooled specimen to a gas mixture containing 90% nitrogen and 10% CO2. When PCO2 measured at 37 degrees C (98.6 degrees F) was approximately 120 torr (16 kPa), the assigned anaerobic threshold, subsequent anaerobic flow stagnation was simulated by mixing the hypercapnic specimens in sealed syringes with five to six successive small aliquots (<100 microL) of lactic acid (10 g/L). MEASUREMENTS AND MAIN RESULTS: The relationship between Pco2 and pH in the specimens was compared with the relationship between the same PCO2 values and pHi calculated by substituting bicarbonate concentrations of 22 and 26 mmol/L in the Henderson-Hasselbalch equation. As PCO2 rose from 50 torr (8 kPa), conventionally calculated pHi increasingly underestimated simulated mucosal capillary pH, with bias >0.1 pH unit at the simulated anaerobic threshold of 120 torr (16 kPa). As PCO2 rose further the values converged, becoming equivalent at PCO2 approximately 150 torr (20 kPa). From PCO2 > or =200 torr (26.7 kPa), conventional pHi progressively overestimated simulated mucosal pH. The difference was >0.3 pH units at PCO2 = 250 torr (33.3 kPa). CONCLUSIONS: In the mucosal PCO2 range usually encountered clinically, the arterial bicarbonate substitution causes underestimation of mucosal capillary pH. With moderate mucosal capillary lactic acidosis the error becomes small, and in severe regional ischemia there is significant overestimation of mucosal capillary pH.

Anaerobic Threshold↗
PubMed2001

New therapeutic targets revealed through investigations of innate immunity.

OBJECTIVE: This review describes efforts to define new therapeutic targets by utilizing information derived from studies of the innate immune response to infection. These targets will provide new means to design novel therapeutics for the treatment of human disease caused by dysregulation of the innate immune response. DATA SOURCES AND ANALYSIS: The results were derived from model systems that reflect the cellular changes accompanying activation of the innate immune system. These model systems include the use of a rabbit model of endotoxin shock that requires multiple exposures to lipopolysaccharide to induce severe pathophysiological changes that result in death. The cellular systems range from primary explants of myeloid lineage cells to stably transfected lines bearing key receptors of the innate immune system, the latter of which includes the Toll-like receptors and CD14. Studies in animal models include blocking monoclonal antibodies to rabbit CD14 and rabbit tumor necrosis factor-alpha. Cellular studies use measurements of cell activation as defined by activation of nuclear factor-kappaB, MAP kinase, and gene expression. In some studies, direct measurements of secreted cytokine levels were performed. Standard approaches to data analysis have been used. CONCLUSIONS: Evidence demonstrates the utility of anti-CD14 monoclonal antibody therapy in septic shock and the potential value of targeting intracellular kinases to modulate harmful cellular responses during sepsis. The key element to each of these approaches is to blunt, but not eliminate, the dysregulated inflammatory response that may occur in sepsis.

Animals↗
PubMed1990

An improved passive activated C collector for measuring environmental 222Rn in indoor air.

A modified version of an activated C monitor has been developed for the time-weighted average measurement of 222Rn for periods ranging from 1-7 d. The new collector consists of a metal can containing 50 g of activated C with a sintered metal filter covering the 3.2-cm diameter sample port in its lid. The new configuration reduces the adsorption and desorption rate of both 222Rn and water vapor by a factor of 4-5, as compared to an open-faced canister. The device measures the average 222Rn concentration accurately, even if the 222Rn concentration varies by more than a factor of 10. For practical situations encountered indoors, the modified collector yields results that are accurate to within +/- 10%. The integration time constant of the collector, tested at relative humidities ranging from 23-75%, is 9-11 d, which is more than three times longer than that of existing diffusion barrier collectors. It is simple to use, inexpensive (total cost of materials is +3.50), maintenance-free, easily sent and returned in the mail (total weight = 100 g), and is reusable for multiple exposures after simple regeneration by heating. The lower limit of detection for a 10-min counting interval is 7 Bq m-3 (0.2 pCi L-1) when counted within 3 d after the end of exposure.

Adsorption↗
PubMed1998

Report of a national neurosurgical emergency teleconsulting system.

OBJECTIVE: The goal was to develop a low-cost, national, neurosurgical emergency teleconsulting system that is independent of vendor computed tomographic (CT) or magnetic resonance imaging (MRI) scanner type. METHODS: Charge-coupled device scanners are used to digitize hard copies of CT and MRI scans. An enhanced optical density range is achieved by using an algorithm to fuse data from multiple exposures at different integration periods. The system is based on personal computers using Microsoft Windows 3.11. Data are transmitted on a wide-area network at 128 kilobits/s, over Integrated Systems Digital Network lines. The network connects both neurosurgical departments in Ireland to all major hospitals with CT/MRI scanners. RESULTS: The scanner optical density is 0.05 to 3.0, with 2.24 to 2.5 line pairs/mm. Five-megabyte images are transmitted uncompressed in 6 minutes. To date, more than 750 CT and MRI scans have been transmitted. The system is completely automated, and operator acceptance has been very high. Images are automatically stored and displayed at the receiving workstation, where the images can be viewed and manipulated on-screen. This system has significantly enhanced acute neurosurgical patient care. CONCLUSION: The system is cost effective and simple to use, has gained widespread physician acceptance, and delivers an image quality superior to that of many commercially available systems.

Angiography↗
PubMedDate not supplied

Declining prevalence of cervicovaginal human papillomavirus infection with age is independent of other risk factors.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) infection of the female genital tract is the most common sexually transmitted disease. Although the prevalence of HPV in women without detectable cervical disease has been shown to decline with increasing age, the relationship to sexual behavior has not been investigated. GOAL: To identify risk factors for, and associated with the age-dependent decline in, genital HPV infection in women. STUDY DESIGN: The prevalence of HPV was determined in a cohort of 439 sexually active inner-city women between the ages of 18 and 50 years recruited in Brooklyn, New York. Cervicovaginal cells were collected by lavage, and HPV was detected by low-stringent Southern blot hybridization. RESULTS: The prevalence of HPV infection ranged from 36% in women younger than 25 years of age to 2.8% in women 45 years or older. Logistic regression analysis identified an increased risk for cervical HPV infection to be independently associated with number of sex partners in the past year (odds ratio [OR], 1.04 per yearly increase in age; 95% confidence interval [CI], 1.00 to 1.08), younger age (OR, 0.92 per year increase in age; 95% CI, 0.88 to 0.95), and not living with partner (OR, 2.28; 95% CI, 1.40 to 4.22). CONCLUSIONS: The lower prevalence of HPV infection in older women compared to younger women was found to be independent of sexual behavior. These results suggest that a biologic effect, such as HPV immunity acquired over time and with multiple exposures, may mediate the inverse relationship between age and HPV prevalence.

Adolescent↗
PubMed1996

Endotoxin tolerance is induced in Chinese hamster ovary cell lines expressing human CD14.

Changes in patterns of gene induction by myeloid lineage cells following multiple exposures to endotoxin (lipopolysaccharide; LPS) is a feature of LPS tolerance. To further understand the mechanism of this phenomenon we describe studies using stably transfected Chinese hamster ovary cell lines that express human CD14 (CHO-hCD14). Using NF-kappa B activation as a measure of LPS-induced cell activation we show that a single treatment with LPS renders CHO-hCD14 cells tolerant to subsequent challenge with LPS, but not with other stimuli such as tumor necrosis factor. Tolerance may result from the induction of gene(s) that control LPS-induced signaling pathways and here we suggest that such genes may be found in the group of immediate, early response genes characterized by the protein phosphatase 3CH134. The CHO-hCD14 cell lines provide a novel model system to further explore the mechanism of endotoxin tolerance.

Animals↗
PubMed2000

Risk-based selection of respirators against infectious aerosols: application to anthrax spores.

This article presents two methods for estimating infection risk among individuals wearing air-purifying respirators against airborne pathogens, with the overall aim of selecting appropriate respiratory protection. Necessary data inputs are the parameters for the ambient pathogen concentration distribution, the respirator penetration distribution, and the infectious dose distribution, along with the breathing rate, duration of a respirator use period, and the number of use periods. The first method assumes that the pathogen does not exhibit a cumulative dose effect, whereas the second accounts for a cumulative dose effect. The methods are illustrated with hypothetical scenarios involving Bacillus anthracis (anthrax) spores. Available data suggest that anthrax spores would exhibit a cumulative dose effect for multiple exposures occurring close in time, as would likely affect personnel responding to a bioterrorist release. The analysis shows that failure to account for a cumulative dose effect when present leads to underestimating infection risk. Three types of air-purifying respirators are compared for their predicted efficacy in reducing the risk of inhalation anthrax. Although uncertainty analyses are not performed, a general conclusion is that a full-facepiece powered air-purifying respirator would be the best air-purifying device for responding to an anthrax spore release. Because such respirators would not prevent all personnel from inhaling an infectious dose, it would be advisable for users not previously vaccinated against anthrax to receive post-exposure prophylactic therapy.

Adult↗
PubMed2005

A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of colorectal cancer.

OBJECTIVES: Sporadic colorectal cancer (CRC) is considered a multifactorial disease where multiple exposures interact with the individual genetic background resulting in risk modulation. We performed an association study aimed to investigate the role of single nucleotide polymorphisms (SNPs) within genes of phase I (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2D6, CYP2E1, CYP2C9, CYP2C19, CYP3A4, ADH2, EPHX1) and phase II of the xenobiotic metabolism (ALDH2, COMT, GSTA2, GSTA4, GSTM1, GSTM3, GSTP1, GSTT2, MTHFR, NAT1, NAT2, NQO1, MnSOD2, SULT1A1, TPMT). METHODS: We genotyped 377 cases and 326 controls, by use of an oligonucleotide micro-array and the arrayed primer extension technique (APEX). RESULTS: N-acetyl-transferase 1 'rapid' phenotype and CYP1A2 -164C>A carriers were associated with increased risk of CRC, confirming data reported in previous studies. Interestingly, homozygotes for allele 48G within CYP1B1, a variant with an increased activity towards several substrates including sex hormones, were at increased risk (OR=2.81, 95% CI 1.32-5.99). Moreover, CYP1A1 SNPs T461N and -1738A>C were associated with a reduced risk of cancer (OR=0.52; 95% CI 0.31-0.88 and OR=0.69, 95% CI 0.50-0.94 for carriers, respectively). CONCLUSIONS: The present data suggest a role for CYP1B1 and CYP1A1 as new candidate genes in the etiology of CRC and confirm the carcinogenic role of aromatic amines metabolism for colorectum.

Case-Control Studies↗
PubMed2005

Biochemical and HIV-1 coreceptor properties of K26R, a new CCR5 Variant in China's Sichuan population.

Despite multiple exposures to HIV-1, some individuals remain uninfected. This resistance to HIV infection has been associated with homozygosity for a 32-basepair deletion in the CCR5 receptor gene. This variant is frequent in caucasians but extremely rare in Asians and Africans. Identifying variations in the CCR5 gene that affect susceptibility to HIV infection in non-caucasians is therefore of great interest. In this report, we identify 5 CCR5 coding region variants in a Chinese population. The K26R mutation is an undescribed gene variant, whereas 228delK was already found in caucasians and G106R, C178R, and R223Q were previously described in Asian populations and functionally analyzed. As the function of K26R was still unknown, we focused our work on studying its chemokine receptor activity and HIV coreceptor properties compared with wild-type CCR5 and G106R, an already analyzed mutant taken as another control. We observed that K26R displayed alteration in MIP1-beta/CCL4 and RANTES/CCL5 ligand binding and exhibited a slightly decrease for HIV coreceptor properties.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Use of fluorescence ratio imaging for intracellular pH determination of individual bacterial cells in mixed cultures.

The development of a rapid method for measuring intracellular pH (pHi) in single bacterial cells is described. Lactobacillus delbrueckii subsp. bulgaricus and Listeria innocua were used as test organisms. The method is based upon fluorescence microscopy and ratio imaging of cells stained with carboxyfluorescein succinimidyl ester. After staining, the bacteria were immobilized on a membrane filter and transferred to a closed perfusion chamber, allowing control of the cell environment during analysis. The set-up was optimized with regard to the use of neutral-density filters and background subtraction, for determining the excitation ratio 490 nm/435 nm (R490/435) independent of the excitation light intensity, and to reduce photobleaching. This allowed for time-lapse studies with multiple exposures. To study the pHi of Lb. delbrueckii subsp. bulgaricus and L. innocua in response to different extracellular pH (pHex) values, an in vivo calibration curve was constructed in the pHi range 5.0-8.5. Distinct differences between the two cultures were observed. L. innocua maintained a near-neutral pHi almost independently of pHex (5.0-8.0), whereas the pHi of Lb. delbrueckii subsp. bulgaricus decreased with decreasing pHex. In pure and mixed cultures at pHex 5.0, the pHi values of Lb. delbrueckii subsp. bulgaricus and L. innocua were 6.1 +/- 0.2 and 7.5 +/- 0.2, respectively. This difference in pHi may explain how Lb. delbrueckii subsp. bulgaricus obtains a competitive advantage over L. innocua at low pHex.

Culture Media↗
PubMed2003

Distortion of a spherical gaseous interface accelerated by a plane shock wave.

The evolution of a spherical gaseous interface accelerated by a plane weak shock wave has been investigated in a square cross section shock tube via a multiple exposure shadowgraph diagnostic. Different gaseous bubbles, i.e., helium, nitrogen, and krypton, were introduced in air at atmospheric pressure in order to study the Richtmyer-Meshkov instability in the spherical geometry for negative, close to zero, and positive initial density jumps across the interface. We show that the bubble distortion is strongly different for the three cases and we present the experimental velocity and volume of the developed vortical structures. We prove that at late times the bubble velocities reach constant values which are in good agreement with previous calculations. Finally, we point out that, in our flow conditions, the gaseous bubble motion and shape are mainly influenced by vorticity and aerodynamic forces.

Journal Article↗
PubMed1994

Differential vascular response to laser photothermolysis.

Individual blood vessels in the chick choriallantoic membrane were selectively coagulated through photothermolysis, using pulsed laser irradiation at 585 nm. Pulse durations were chosen to be 0.45 ms and 10 ms, which correspond to the thermal relaxation times in blood vessels of 30 microns and 150 microns diameter, respectively. The short pulses, at a light fluence F = 3 Jcm-2, caused permanent occlusion of vessels of 40 microns diameter or less, whereas larger caliber vessels (60-120 microns) required F = 4-5 Jcm-2. The long-duration pulses, at F = 7 Jcm-2, caused coagulation of the larger diameter vessels; the small-caliber vessels and capillaries showed resistance to photothermolysis and required multiple exposures to achieve coagulation. The fluence versus diameter (F versus d) relationship for coagulation was calculated for the two pulse durations. The energy deposited in a cylindrical absorber of diameter d by an optical field, incident perpendicular to the vessel, was expressed analytically and compared with the energy required to coagulate a blood vessel of the same lumen dimeter. When thermal diffusion is incorporated into the model, our findings can be accounted for quantitatively. This information will be of use for improving the laser treatment of port wine stains and other vasculopathies. A surprising observation was that arterioles were damaged at lower incident energy densities than venules having the same lumen diameter, despite the fact that absorbance in oxygen-rich and oxygen-poor blood is the same at 585 nm.

Allantois↗
PubMed1992

Molecular bases for hereditary cancer-prone diseases.

Constitutional loss or inactivation of one copy of a tumor-suppressor gene, as exemplified by hereditary retinoblastoma, increases the propensity for malignancies by reducing the number of events necessary for the complete loss of the negative regulatory function. We developed a selectable mutation assay employing a human lymphoblastoid cell line (LCL) derived from a heterozygous carrier of 2,8-dihydroxyadenine urolithiasis, adenine phosphoribosyltransferase (APRT) deficiency, for dissecting the second step in loss-of-function mutations and for determining the potential of physical and chemical agents for producing such mutations. The mode of mutational events arising in the wild-type allele of the functionally heterozygous APRT gene resembled that reported for tumor-suppressor genes in malignancies in that mitotic non-disjunctions or recombinations as well as deletions prevailed. Ultraviolet light (UV) was much less efficient in inducing these types of mutations than ionizing radiation. A group of autosomal recessive cancer-prone diseases, including xeroderma pigmentosum (XP), has been characterized as being more susceptible to genomic insults, owing to some defects in DNA processing, such as replication, repair, or recombination. This increased genomic instability may accelerate the gain-of-function mutation at a proto-oncogene and/or the loss-of-function mutation at a tumor-suppressor gene. XP complementation group A (XP-A) LCLs were extremely sensitive to UV-mutagenesis at the hypoxanthine phosphoribosyltransferase (HPRT) locus even at equicytotoxic doses. Some unique mechanism may operate in UV-mutagenesis in XP-A. We have succeeded for the first time in rendering XP-A cells tumorigenic in athymic mice by applying multiple exposures to UV and subsequent treatment with TPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Halothane hepatitis in an 11-month-old child.

Halothane hepatitis is extremely rare in childhood. However, this occurred in an 11-month-old infant, following multiple exposure to halothane. The diagnosis was confirmed by detection of specific antibodies to halothane-sensitised rabbit hepatocytes. The anaesthetic technique for a subsequent procedure with a halothane-free breathing system is also outlined.

Anesthesia, Inhalation↗
PubMed1980

Distribution of normal and abnormal forms among motile, non-motile, live and dead human spermatozoa.

The distribution of normal and abnormal forms among motile, non-motile live, and dead spermatozoa was investigated . For this purpose samples from each specimen of 100 fertile and infertile patients was photographed twice: once with the aid of the multiple exposure photography (MEP) technique and again by an ordinary high-speed phase-contrast photomicrography. From enlarged projected photographed images, percentage of abnormal forms in both, non motile fraction and in the while sperm population were determined. By using a simple formula the percentage of abnormal forms among motile spermatozoa has been easily calculated. An average of 42% abnormal forms among all 100 analyzed specimens was found. However, this rate was not distributed equally among the two sperm populations: only 22% abnormal forms were among motile spermatozoa, contrary to 59% among non-motile spermatozoa. In 30 specimens that have been further analyzed by the combined supravital staining and the MEP method, percentage of abnormal forms among non-motile-live spermatozoa was found to be 32, and 67 among the fraction of dead spermatozoa. The importance of studying the distribution of normal forms among motile spermatozoa, and the question of any relationship of this parameter to the fertilization capacity of the semen, is discussed.

Humans↗
PubMed1981

Factors affecting sperm motility. VIII. Velocity and survival of human spermatozoa as related to temperatures above zero.

The effect of temperature on motility and survival of ejaculated human spermatozoa was investigated with the aid of the multiple exposure photography (MEP) method for objective sperm motility determination. Fresh specimens from healthy donors were analyzed while being heated or cooled gradually, or during their storage at various temperatures from 0 to 48 degrees C. Sperm velocity increased steadily from zero to 50.4 nm/sec between freezing point and body temperature. Thereafter, their activity dropped dramatically and total immobilization occurred at 45 degrees C. The induced immobilization was reversible providing exposure to those extreme temperatures was short enough to prevent permanent damage. Sperm survived up to 24-48 h when stored at 23 degrees C, while at body temperature, their survival in vitro was much shorter and rarely extended beyond 12 h. Their longevity was still shorter at higher or lower temperatures, especially when approaching 48 degrees C. With the aid of the combined supravital staining and MEP methods it was found that temperatures of extreme levels induced mainly immobilization rather than a spermicidic effect. The possible mechanism of thermal effect on sperm motility and some of its practical implications are discussed.

Cell Survival↗
PubMed1982

Fertilization of hamster ova by human spermatozoa in relation to other semen parameters.

Different indices of the zona-free hamster ovum test system were interrelated. High correlations were found between the fertilization percentage and the average number of penetrated spermatozoa/ovum (r = 0.99) and between the fertilization percentage and the number of spermatozoa attached to the ova surfaces (r = 0.72). Fertilization percentages from 63 subfertile patients were correlated with different semen factors assessed by multiple exposure photography (MEP). Low correlations were found between sperm concentration and fertilization percentage (r = 0.29) and between fertilization percentage and motile sperm count (r = 0.33). Spermatozoa progressing with high average velocity had low fertilization rates compared to specimen with moderate average velocity. Effects of sperm washing on the in vitro fertilizing capacity were studied in a group of 40 subfertile men. The fertilization percentages of 8 specimens--with visual seminal plasma abnormalities--increased significantly when immediate dilution of semen was applied.

Animals↗