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Biomedical subjects

J Shi

Publications and source records attributed to J Shi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Clinical-grade myeloma Ag pre-loaded DC vaccines retain potency after cryopreservation.

BACKGROUND: The use of myeloma Ag-loaded mature DC vaccines, cryopreserved in single-use aliquots, is an attractive immunotherapeutic strategy. In this study we investigated the retention of phenotype, viability and potency of DC vaccines after freezing and thawing. METHODS: Plastic-adherent monocytes, derived from a steady-state leukapheresis, were cultured in serum-free media containing GM-CSF and IL-4. DC were loaded on day 6 with myeloma lysate (ML) or idiotype (Id) Ag and keyhole limpet hemocyanin (KLH), induced to mature on day 7 with CD40-ligand and cryopreserved on day 9. Seventeen clinical-scale cultures were evaluated for DC yield, recovery and immunophenotype after potency was validated with allogeneic mixed lymphocyte culture and Ag presentation assays. RESULTS: We produced 88 individual vaccines from 17 clinical-scale cultures. Median DC yield at harvest was 131 x 10(6) (range 37-375 x 10(6)) and median recovery of viable DC after thawing was 69% (range 11-100%). We confirmed viability (7AAD-), phenotype (CD14-, CD83+/CD40+, CD83+/CD80+, CD83+/CD86+, CD83+/CD54+, HLA-DR++) and the ability of the DC to present Ag and stimulate allogeneic T cells post-thawing. DISCUSSION: We have validated a serum-free culture system for the production of DC. Cryopreservation did not interfere with DC activity, allowed time for rigorous quality control (QC) and flexible scheduling of intranodal vaccination, and reduced the time to prepare multiple vaccines.

Antigens, Neoplasm↗
PubMed2005

Stability of lycopene during food processing and storage.

With an increasing understanding of the health benefit of lycopene, how to preserve lycopene during food processing and storage has caused much attention. Lycopene belongs to the carotenoid family and mostly exists in nature as the all-trans form. Heat, light, oxygen, and different food matrices are factors that have an effect on lycopene isomerization and autooxidation. Lycopene may isomerize to mono- or poly-cis forms with the presence of heat or oil or during dehydration. Reisomerization takes place during storage. After oxidation, the lycopene molecule split, which causes loss of color and off-flavor. The effects of heat, oxygen, light, and the presence of oil on the stability of lycopene are uniform in much of the literature; however, controversy still exists on some details, such as the conditions causing the occurrence of isomerization, the optimal moisture, and temperature for storage.

Carotenoids↗
PubMed2005

Polymorphisms in the 5-lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population.

BACKGROUND: The cysteinyl-leukotrienes (cys-LTs) are important pro-inflammatory mediators in asthma, and have been shown to have a role in specific disease subtypes, including asthma severity. Few studies have investigated the role of polymorphisms in the ALOX5AP gene, encoding 5-lipoxygenase activating protein (FLAP), and asthma. We hypothesized that polymorphisms in this gene are associated with asthma and in particular, with asthma severity, in an Australian population. OBJECTIVE: To screen the coding region of the ALOX5AP gene for polymorphisms and to determine the association between previously described polymorphisms and asthma and asthma severity in an Australian population. METHODS: We used PCR-SSCP and PCR-RFLP analysis to examine a previously described promoter polyA variable repeat polymorphism and two intronic polymorphisms (IVS2+12C>A, IVS2+105T>C), and to screen all five exons of the gene for new polymorphisms, in a large Australian population of randomly selected, non-asthmatic controls (n=457), mild asthmatics (n=274), moderate asthmatics (n=231) and severe asthmatics (n=79). RESULTS: We confirmed the presence of two polymorphisms in intron 2 and found no association between these polymorphisms and asthma or asthma severity, nor between a promoter polymorphism in the ALOX5AP gene and asthma or asthma severity. Gene fragment analysis of the promoter polymorphism revealed novel, conserved repeat numbers in our population, and no new polymorphisms were found in the coding region of the gene. CONCLUSION: These findings in a large, well characterized asthma population, reveal that, while FLAP is an important enzyme in cys-LTs biosynthesis, polymorphisms in the ALOX5AP gene are not likely to be functionally associated with the asthma phenotype.

5-Lipoxygenase-Activating Proteins↗
PubMed2005

Is there a relation between APOE expression and brain amyloid load in Alzheimer's disease?

BACKGROUND: It has been proposed that, independent of the epsilon4 allele, APOE promoter polymorphisms (-491 A/T and -219 G/T) may be risks factor for Alzheimer's disease by modulating APOE expression. OBJECTIVE: To measure the level of APOE expression in Alzheimer's disease. METHODS: Brains were obtained at necropsy from 114 patients with early and late onset sporadic Alzheimer's disease in Greater Manchester (UK) during years 1986 to 2001. Total RNA was extracted from 84 brains. Purified lymphocytes were obtained from fresh blood from 16 probable Alzheimer cases from Lille (France). APOE and beta-actin gene expression was determined by reverse transcriptase polymerase chain reaction in brain and lymphocytes. RESULTS: An inverse correlation between APOE expression level and A beta loads was observed. As previously described and extended to 114 cases here, an association between the -219 TT genotype and a higher level of parenchymal A beta deposition was found, irrespective of APOE epsilon4 allele status. This effect was more pronounced in older individuals, whereas higher A beta load appeared more closely related to epsilon4 in the younger age group (cut off point at the median age at death (72.5 years)). The -219 TT genotype was associated with a decrease in APOE expression. There was a 60% decrease in APOE expression in lymphocytes from probable Alzheimer cases v controls (p = 0.01). CONCLUSIONS: In the oldest individuals, reduced APOE expression, modulated in part by -219 G/T polymorphism, may influence risk and constitute a determinant A beta load in Alzheimer's disease.

Actins↗
PubMed2005

Cyclooxygenase-1 gene polymorphisms in patients with different asthma phenotypes and atopy.

Cyclooxygenase-1 (COX-1) regulates the biosynthesis of prostaglandins, which are important mediators in asthma. The possible association of COX-1 gene polymorphisms with asthma has not been investigated. The allele frequencies of 20 COX-1 polymorphisms were determined in a random Australian Caucasian population using MassARRAY technology. Informative and potentially functional promoter (c.8592C > T, c.1676C > T) and coding region (c.22C > T, c.50C > T) polymorphisms were investigated in carefully phenotyped patients with mild (n = 316), moderate (n = 241), severe (n = 86) or aspirin-intolerant asthma (AIA) (n = 58), and in nonasthmatic subjects (n = 477). There were no allelic, genotypic or haplotypic associations between these four polymorphisms and asthma or asthma severity. Over-representation of the c.50TT genotype among AIA patients (3.4%) compared with aspirin-tolerant patients (0.8%), and a global haplotype association with AIA did not reach statistical significance. The c.22TT genotype was less frequent among atopic (0.1%) rather than nonatopic individuals (1.2%; odds ratio = 9.05, 95% confidence interval 1.01-81.29). In conclusion, the present investigation of cyclooxygenase-1 polymorphisms in asthma indicates that they do not appear to play a substantial role in genetic pre-disposition for asthma or asthma severity. However, the c.22TT genotype confers a small protective effect against atopy. Potential associations with aspirin-intolerant asthma were identified and warrant further investigation in a larger population of aspirin-intolerant asthma patients.

Adult↗
PubMed2005

Effect of ketoconazole on the pharmacokinetics and safety of telithromycin and clarithromycin in older subjects with renal impairment.

OBJECTIVE: The objective of this study was to determine the effect of multiple impairments in drug elimination on the pharmacokinetics and pharmacodynamics (effect on QTc interval), using clarithromycin as a comparator. METHODS: Thirty-two subjects aged > or = 60 years with renal impairment who were otherwise medically stable were recruited into this parallel-group study. Following stratification according to creatinine clearance (CL(CR)), subjects were randomized to a five-day treatment with ketoconazole (400 mg once daily) alone, or a five-day treatment with ketoconazole (400 mg once daily) and telithromycin (800 mg once daily) given concomitantly or a five-day treatment with ketoconazole (400 mg once daily) and clarithromycin (500 mg twice daily) given concomitantly. Steady-state pharmacokinetics and safety, including serial electrocardiograms, were assessed. RESULTS: In subjects with CL(CR) 30 - 80 ml/min, the mean maximal telithromycin concentration at steady state (C(max),ss) was 3.6 mg/l and the steady state area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24 h) ss) was 33.4 mg x h/l. The mean C(max), ss and AUC(0-12 h)ss for clarithromycin were 6.2 mg/l and 56.1 mg x h/l, respectively. The increases in telithromycin C(max) ss and AUC(0-24 h) ss compared to corresponding data for healthy young subjects were 1.6- and 2.7-fold, respectively, whereas corresponding increases for clarithromycin were 2.2- and 3.3-fold, respectively. In the telithromycin plus ketoconazole group deltaQTc values were equal or < 60 ms. All QTc values were equal or < 450 ms in males and equal or < 470 ms in females. CONCLUSIONS: The increase in telithromycin plasma concentrations during ketoconazole-mediated inhibition of CYP3A4 in subjects aged 60 years or older with renal impairment was similar to that for clarithromycin under the same conditions. Telithromycin was well tolerated and produced no clinically significant prolongations in the QTc interval.

Aged↗
PubMed2004

High resolution ultrasound elastomicroscopy imaging of soft tissues: system development and feasibility.

Research in elasticity imaging typically relies on 1-10 MHz ultrasound. Elasticity imaging at these frequencies can provide strain maps with a resolution in the order of millimetres, but this is not sufficient for applications to skin, articular cartilage or other fine structures. We developed a prototype high resolution elastomicroscopy system consisting of a 50 MHz ultrasound backscatter microscope system and a calibrated compression device using a load cell to measure the pressure applied to the specimen, which was installed between a rigidly fixed face-plate and a specimen platform. Radiofrequency data were acquired in a B-scan format (10 mm wide x 3 mm deep) in specimens of mouse skin and bovine patellar cartilage. The scanning resolution along the B-scan plane direction was 50 microm, and the ultrasound signals were digitized at 500 MHz to achieve a sensitivity better than 1 microm for the axial displacement measurement. Because of elevated attenuation of ultrasound at high frequencies, special consideration was necessary to design a face-plate permitting efficient ultrasound transmission into the specimen and relative uniformity of the compression. Best results were obtained using a thin plastic film to cover a specially shaped slit in the face-plate. Local tissue strain maps were constructed by applying a cross-correlation tracking method to signals obtained at the same site at different compression levels. The speed of sound in the tissue specimen (1589.8+/-7.8 m s(-1) for cartilage and 1532.4+/-4.4 m s(-1) for skin) was simultaneously measured during the compression test. Preliminary results demonstrated that this ultrasound elastomicroscopy technique was able to map deformations of the skin and articular cartilage specimens to high resolution, in the order of 50 microm. This system can also be potentially used for the assessment of other biological tissues, bioengineered tissues or biomaterials with fine structures.

Animals↗
PubMed2004

The differential effects of IL-1 and TNF-alpha on proinflammatory cytokine and matrix metalloproteinase expression in human chondrosarcoma cells.

OBJECTIVE AND DESIGN: Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and matrix metalloproteinases (MMPs) play important roles in the pathogenesis of osteoarthritis (OA). In the present study, using Affymetrix oligonucleotide array technology and real-time quantitative RT-PCR we have investigated the molecular mechanisms underlying the differential effect of IL-1 and TNF-alpha on gene expression in the human chondrosarcoma cell line, SW1353. MATERIALS AND METHODS: SW1353 cells were stimulated singularly with IL-1alpha, TNF-alpha, Phorbol 12-myristate 13-acetate (PMA), or treated with the combination of cytokine and PMA. Total RNA was collected at multiple time points over a 24-h period followed by biotinylated cRNA target preparation and hybridization onto the Affymetrix HG-U95Av2 array. The differential expression patterns of several cytokine and MMP genes were further confirmed by real time quantitative RT-PCR, Western blot, and ELISA. RESULTS: Our microarray experiments have broadly confirmed previously published data on chondrocyte gene expression regulated by IL-1 and TNF-alpha. The expression pattern of proIL-1beta, MMP-1, and MMP-13 in chondrocytes is differentially regulated when stimulated with proinflammatory cytokines. IL-1, but not TNF-alpha, can induce IL-6, bone morphogenic protein 2 (BMP-2), and cyclooxygenase (COX-2) expression in SW1353 cells. Additionally, our Western blot results provide the first evidence that IL-1beta is produced in the proform in IL-1alpha-activated chondrosarcoma cells and that additional signals are required for its posttranslational processing/activation. CONCLUSIONS: IL-1 and TNF-alpha each activate a distinct set of genes in chondrosarcoma cells, and gene expression in these cells is regulated by groups of genes related in part by their function. Chondrocyte IL-1alpha appears to serve an important role in the pathogenesis OA contributing to joint inflammation and cartilage destruction.

Cell Line, Tumor↗
PubMed2004

A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease.

The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD). The possible influence of APO E epsilon4 allele acting in concert with ACE D allele was assessed. The extent of ML did not differ between D/D, I/D and I/I genotype groups when data from all four brain regions were combined. However, separate analysis showed that the frontal and temporal cortex tended to be affected more severely by ML in patients with D/D genotype compared to those with I/D and I/I genotypes. Stratification according to APO E epsilon4 allele revealed a greater overall ML in patients bearing at least one copy of ACE D allele and one APO E epsilon4 allele, especially in individuals homozygous for both. The APO E epsilon4 allele may therefore act synergistically in patients with AD (and other subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through transient ischaemic episodes consequent upon poor cardiac output associated with coronary atherosclerosis in patients with the APO E epsilon4 allele.

Adult↗
PubMed2004

Flavonoids in food and their health benefits.

There has been increasing interest in the research of flavonoids from dietary sources, due to growing evidence of the versatile health benefits of flavonoids through epidemiological studies. As occurrence of flavonoids is directly associated with human daily dietary intake of antioxidants, it is important to evaluate flavonoid sources in food. Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine. However, there is still difficulty in accurately measuring the daily intake of flavonoids because of the complexity of existence of flavonoids from various food sources, the diversity of dietary culture, and the occurrence of a large amount of flavonoids itself in nature. Nevertheless, research on the health aspects of flavonoids for humans is expanding rapidly. Many flavonoids are shown to have antioxidative activity, free-radical scavenging capacity, coronary heart disease prevention, and anticancer activity, while some flavonoids exhibit potential for anti-human immunodeficiency virus functions. As such research progresses. further achievements will undoubtedly lead to a new era of flavonoids in either foods or pharmaceutical supplements. Accordingly, an appropriate model for a precise assessment of intake of flavonoids needs to be developed. Most recent research has focused on the health aspects of flavonoids from food sources for humans. This paper reviews the current advances in flavonoids in food, with emphasis on health aspects on the basis of the published literature, which may provide some guidance for researchers in further investigations and for industries in developing practical health agents.

Antioxidants↗
PubMed2004

Differential gene expression after complete spinal cord transection in adult rats: an analysis focused on a subchronic post-injury stage.

In an attempt to characterize changes in transcription after a sub-chronic spinal cord injury (SCI), we investigated gene expression profiles using cDNA microarray. Among 7523 genes and expressed sequence tags (ESTs) examined, 444 transcripts, including 218 genes and 226 ESTs, were identified to be either up-regulated (373 of 444) or down-regulated (71 of 444) greater than 2.0-fold in the spinal cord at 14 days after a complete spinal transection at the 11th thoracic level in adult rats. Based on their potential function, these differentially expressed genes were categorized into seven classes which include cell division-related protein, channels and receptors, cytoskeletal elements, extracellular matrix proteins, metalloproteinases and inhibitors, growth-associated molecules, metabolism, intracellular transducers and transcription factors, as well as others. Strong expressional changes were found in all classes revealing the complexity and diversity of gene expression profiles following SCI. We verified array results with RT-PCR for eight genes, Northern blotting for nine genes, and in situ hybridization for one gene and immunohistochemistry for four genes. These analyses confirmed, to a large extent, that the array results have accurately reflected the molecular changes occurring at 14 days post-SCI. Importantly, the current study has identified a number of genes, including annexins, heparin-binding growth-associated protein (HB-GAM), P9ka (S100A4), matrix metalloproteinases, and lysozyme, that may shed new light on SCI-related inflammation, neuroprotection, neurite-outgrowth, synaptogenesis, and astrogliosis. In conclusion, the identification of molecular changes using the large-scale microarray analysis may lead to a better understanding of underlying mechanisms, thus, the development of new repair strategies for SCI.

Animals↗
PubMed2004

Dynamic depth-dependent osmotic swelling and solute diffusion in articular cartilage monitored using real-time ultrasound.

The objective of this study was to investigate the feasibility of ultrasonic monitoring for the transient depth-dependent osmotic swelling and solute diffusion in normal and degenerated articular cartilage (artC) tissues. Full-thickness artC specimens were collected from fresh bovine patellae. The artC specimens were continuously monitored using a focused beam of 50 MHz ultrasound (US) during sequential changes of the bathing solution from 0.15 mol/L to 2 mol/L saline, 0.15 mol/L saline, 1 mg/mL trypsin solution, 0.15 mol/L saline, 2 mol/L saline and back to 0.15 mol/L saline. The transient displacements of US echoes from the artC tissues at different depths were used to represent the tissue deformation and the NaCl diffusion. The trypsin solution was used selectively to digest the proteoglycans in artC. It was demonstrated that high-frequency US was feasible for monitoring the transient osmotic swelling, solute transport and progressive degeneration of artC in real-time. Preliminary results showed that the normal bovine patellar artC shrank during the first several minutes and then recovered to its original state in approximately 1 h when the solution was changed from 0.15 mol/L to 2 mol/L saline. Degenerated artC showed neither shrinkage nor recovery during the same process. In addition, a dehydrated-hydrated artC specimen showed much stronger shrinkage and it resumed the original state when the solution was changed from 2 mol/L back to 0.15 mol/L saline. The diffusion of NaCl and the digestion process of proteoglycans induced by trypsin were also successfully monitored in real-time.

Animals↗
PubMed2004

Measurement of depth-dependence and anisotropy of ultrasound speed of bovine articular cartilage in vitro.

The inhomogeneous and anisotropic mechanical properties and structural components of articular cartilage (artC) may cause complex acoustic properties in this important tissue. In this study, we used 50-MHz ultrasound (US) to measure in vitro the depth-dependence and anisotropy of the US speed of artC collected from the bovine patellae. The US speeds of 18 disk artC specimens sampled from 18 different patellae were measured in two orthogonal directions. One full-thickness layer (n=18) and three horizontal slices (n=18 x 3) with approximately equal thickness were prepared from each artC disk and measured with the US beam perpendicular to the artC surface. One full-thickness vertical slice (n=10) was measured at different depths with the US beam parallel to the artC surface. The measured US speeds of artC in the two orthogonal directions were significantly different (p < 0.001). The US speeds also significantly increased with the increase of tissue depth for both measurement directions (p < 0.001). The US speeds of artC from the superficial to deep regions were 1518 +/- 17 (mean + SD), 1532 +/- 26 and 1554 +/- 42 m/s for the US beam parallel to the artC surface, and 1574 +/- 29, 1621 +/- 34 and 1701 +/- 36 m/s for the beam perpendicular to the artC surface. The sound speed of the full-thickness layer was 1636 +/- 25 m/s. The results suggested that the depth-dependence and anisotropy of the US speed in artC should be taken into account when US is used for the artC measurement. It was also demonstrated in this study, using additional specimens (5 x 2), that the swelling of artC after detaching from its subchondral bone could cause the change of its sound speed.

Animals↗
PubMed2004

Association between apolipoprotein CI HpaI polymorphism and sporadic Alzheimer's disease in Chinese.

OBJECTIVE: To investigate into the relationship of apolipoprotein CI (ApoCI) polymorphism with sporadic Alzheimer's disease (AD) in Chinese. SUBJECTS AND METHODS: A total of 257 AD patients and 242 age-matched elderly individuals were genotyped for the ApoCI HpaI and apolipoprotein E (ApoE) HhaI polymorphisms. RESULTS: The ApoCI A allele was associated with AD of moderate to severe dementia when patients were divided into two subgroups according to Clinical Dementia Rating scale, and the AA genotype was strongly associated with moderate to severe AD in ApoE epsilon4 allele carriers [odds ratio (OR) = 8.19, 95% confidential interval: 1.28-52.30, after adjusting for age and gender by logistic regression analysis], although in total no significant differences of allele or genotype frequency between patients and controls were found. CONCLUSION: The present study partially confirmed the previous findings, suggesting that the ApoCI A allele might contribute to the susceptibility to moderate to severe sporadic AD in Chinese.

Aged↗
PubMed2004

Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer.

BACKGROUND: The type IV collagenases/gelatinases matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play an important role in cancer invasion and metastasis. In the present study, we measured the expression of mRNAs and enzymatic activities of MMP-9 and -2 in prostate tissues and serum samples from men with or without prostate cancer. METHODS: A total of 44 tissue samples (three from healthy volunteers, 21 from patients with benign prostate hyperplasia, 10 from patients with localized prostate cancer and 10 from patients with metastatic disease) and 71 serum samples were collected (20 from healthy volunteers, 26 from patients with benign prostatic hyperplasia, 10 from patients with localized cancer, 15 from patients with metastatic cancer). The level of mRNA for MMP-2 and -9 was determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The enzymatic activity of MMPs was determined by zymography. RESULTS: Expression of MMP-9 mRNA was significantly higher in malignant than in nonmalignant prostate tissues (P < 0.001), while no significant difference of MMP-2 expression was detected in different prostate tissues. Results of zymography showed that there was significant difference in the enzymatic activity of MMP-9, but not MMP-2, among normal prostate, BPH, localized and metastatic prostate cancer tissues, serum samples (P < 0.05). The active form of MMP-2, with a molecular mass of 62 kDa, was detected in normal prostate, BPH and prostate cancer tissues, but not in the serum samples. Moreover, there was a significant difference in the ratio of the active form (62 kDa) and proform (72 kDa) of MMP-2 among normal, BPH and prostate cancer tissues. This ratio was further increased in metastatic prostate cancer tissues. CONCLUSION: The activity of MMP-9 and the ratio of active form/proform of MMP-2 are associated with the progression and metastasis of prostate cancer.

Adult↗
PubMed2004

Relationships between arteriosclerosis, cerebral amyloid angiopathy and myelin loss from cerebral cortical white matter in Alzheimer's disease.

Pathological relationships between damage to the deep white matter of the cerebral cortex [as evidenced by myelin loss (ML)], cerebral amyloid angiopathy (CAA) and arteriosclerosis (ART) were investigated in the brains of 137 patients with autopsy-confirmed Alzheimer's disease (AD), in order to better understand the causes of white matter damage in AD, and the contribution of this to the pathogenesis of the disorder. All 137 patients had some degree of CAA in one or more brain regions although the occipital cortex was severely affected by CAA more frequently, and consequently mean CAA severity score was significantly greater, than other cortical regions. Eighty-seven patients (63.5%) were affected by ML, with more patients showing ML from occipital cortex than from other cortical regions leading to a significantly higher mean ML severity score in this region. One hundred and twenty-six patients (92%) were affected by ART, although the occipital cortex was not more frequently affected by ART than other cortical areas, the mean ART severity score in occipital cortex was nonetheless significantly greater than that of frontal and temporal cortex. Eighty-seven patients showed both CAA and ML, although there was only a weak correlation between degree of CAA and extent of ML (P = 0.035). Forty-seven patients showed ML and significant ART, 16 patients showed significant ART but no ML, 40 patients showed ML in the absence of significant ART and 34 patients showed neither significant ART nor ML. Overall, and for each of the four brain regions, the extent of ML correlated significantly (P < 0.001) with degree of ART. However, when only those 47 patients with ML and significant ART were considered, much stronger correlations between the extent of ML and the degree of ART were achieved both overall and within each of the four brain regions. The overall ART severity score (and overall scores for each pathological marker of ART) significantly correlated with that of CAA (P < 0.001). Pathological processes leading to white matter damage, in terms of ML at least, in AD are thus likely to be heterogeneous. Many patients suffer ML in association with ART, but in others ML cannot be explained by presence of ART or CAA. In such patients, autoregulatory changes in blood vessels might be responsible for ML. The association between the extent of CAA and ART suggests shared risk factors for each pathological change.

Age of Onset↗
PubMed2004

A functional polymorphism in the promoter region of the cyclooxygenase-2 gene is not associated with asthma and atopy in an Australian population.

BACKGROUND: Cyclooxygenase (COX)-2 is a key inducible enzyme that regulates the production of anti-inflammatory prostaglandin E(2). A single-nucleotide polymorphism, -765G>C, located within a stimulatory protein-1 binding site in the COX-2 promoter region, has been shown to have significantly lower promoter activity in vitro compared with the wild-type and was associated with decreased plasma levels of C-reactive protein after coronary artery bypass surgery. We hypothesized that this polymorphism, which may result in decreased COX-2 transcription, could be associated with more severe asthma, and/or aspirin-intolerant asthma (AIA). OBJECTIVE: To determine the association between the -765G>C COX-2 polymorphism and asthma, disease severity and AIA in a large, well-phenotyped Australian population. METHODS: PCR and restriction fragment length polymorphism analysis was used to characterize the polymorphism in an Australian Caucasian population of patients with mild (n=322), moderate (n=254) or severe (n=88) asthma and in non-asthmatic control subjects (n=512), as well as in patients with AIA (n=58). Genotype and allele association analyses were performed using chi(2) tests. RESULTS: The polymorphic -765C allele was present in approximately 30% of asthmatic patients and non-asthmatic controls. There was no association between the -765G>C polymorphism and asthma (P=0.920), disease severity (P=0.840), atopy (P=0.655) or AIA (P=0.841) in this population. CONCLUSION: Although the -765G>C polymorphism may have lower promoter activity and result in decreased COX-2 expression, it is not associated with asthma, disease severity, AIA or atopy in this Australian population.

Adult↗