Biomedical subjects

J L Jones

Publications and source records attributed to J L Jones.

At least 19 recordsLinked to original sources

PubMed2006

EGFR expression: associations with outcome and clinicopathological variables in malignant pleural mesothelioma.

Malignant mesothelioma (MM) is a fatal tumour of increasing incidence which is related to asbestos exposure. This work evaluated expression in MM of Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry in 168 tumour sections and its correlations with clinicopathological and biological factors. The microvessel density (MVD) was derived from CD34 immunostained sections. Hematoxylin and eosin stained sections were examined for intratumoural necrosis. COX-2 protein expression was evaluated with semi-quantitative Western blotting of homogenised tumour supernatants (n=45). EGFR expression was correlated with survival by Kaplan-Meier and log rank analysis. Univariate and multivariate Cox proportional hazards models were used to compare the effects of EGFR with clinicopathological and biological prognostic factors and prognostic scoring systems. EGFR expression was identified in 74 cases (44%) and correlated with epithelioid cell type (p<0.0001), good performance status (p<0.0001), the absence of chest pain (p<0.0001) and the presence of TN (p=0.004), but not MVD or COX-2. EGFR expression was a good prognostic factor in univariate analysis (p=0.01). Independent indicators of poor prognosis in multivariate analysis were non-epithelioid cell type (p=0.0001), weight loss, performance status and WBC>8.3x10(9)L(-1). EGFR status was not an independent prognostic factor. EGFR expression in MM correlates with epithelioid histology and TN. EGFR may be a target for selective therapies in MM.

Biomarkers, Tumor↗

PubMed2006

Factors associated with ELISA scores for paratuberculosis in an Angus-Brahman multibreed herd of beef cattle.

Cow and calf genetic and environmental factors were evaluated for their association with ELISA scores for paratuberculosis in a multibreed population of beef cattle. The ELISA scores are a measure of the presence or absence of antibodies against Mycobacterium avium subsp. paratuberculosis in bovine serum. The linear mixed-model analysis used 352 ELISA scores from 238 cows: 51 Angus (A); 34 Brahman (B); 41 (3/4 A 1/4 B); 45 (1/2 A 1/2 B); 34 (1/4 A 3/4 B); and 33 Brangus (5/8 A 3/8 B). Cows were assumed to be unrelated. Year affected (P < 0.001) ELISA scores, but age of cow did not, which was expected to be significant because of the chronic progressive nature of this disease. Important regressions on fixed effects associated with cows were 1) a positive estimate of cow B breed effect (0.59 +/- 0.24; P < 0.017), indicating an upward trend of ELISA scores toward 100% B cows; 2) a negative estimate for weight change from before calving (late November) to the date of the blood sample in May (-0.0062 +/- 0.0019 score/kg; P < 0.002), indicating that poorer maintenance of cow weights was associated with higher ELISA scores; and 3) a positive estimate for days in lactation of cow on the date of the blood sample (0.0086 +/- 0.0034 score/d; P < 0.021), indicating the production of larger amounts of antibodies against Mycobacterium avium subsp. paratuberculosis as lactation progressed. Relevant regressions on fixed effects associated with calves were 1) calf birth weight (-0.022 +/- 0.010 score/kg; P < 0.035), and 2) calf gain from birth to the date of the cow blood sample (-0.0092 +/- 0.0027 score/kg; P < 0.001). These estimates indicate that cows that produced lighter calves at birth and/or calves with slower preweaning growth tended to have greater ELISA scores. Although the sensitivity (percentage of infected animals detected) of ELISA was only 50%, these results suggest that subclinical paratuberculosis may be negatively affecting cows and their offspring. Factors identified as associated with ELISA scores could help producers with culling decisions related to paratuberculosis control and eradication in beef cattle.

Animals↗

PubMed2005

Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm.

BACKGROUND: Loss of elastin is the initiating event in abdominal aortic aneurysm (AAA) formation, whereas loss of collagen is required for continued expansion. The elastolytic matrix metalloproteinases (MMPs) 2 and 9 are well described, but the source of excessive collagenolysis remains undefined. The aim of this study was to determine the expression of MMP-8, a potent type I collagenase, in normal aorta and AAA. METHODS: Infrarenal aortic biopsies were taken from 40 AAA and ten age-matched normal aortas. The concentrations of MMP-8 protein and its inhibitors, tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-2, were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was used to localize MMP-8 expression. RESULTS: MMP-8 concentrations were significantly raised in AAA compared with normal aorta (active MMP-8: 4.5 versus 0.5 ng per mg protein, P < 0.001; total MMP-8: 16.6 versus 2.8 ng per mg protein, P < 0.001). Levels of TIMP-1 and TIMP-2 were significantly lower in AAA than in normal aortic samples (TIMP-1: 142.2 versus 302.8 ng per mg protein; P = 0.010; TIMP-2: 9.2 versus 33.1 ng per mg protein, P < 0.001). Immunohistochemistry localized MMP-8 to mesenchymal cells within the adventitia of the aortic wall. CONCLUSION: The high concentration of MMP-8 in aortic aneurysms represents a potent pathway for collagen degradation, and hence aneurysm formation and expansion.

Aged↗

PubMed2005

Prevalence of viable Toxoplasma gondii in beef, chicken, and pork from retail meat stores in the United States: risk assessment to consumers.

The prevalence of viable Toxoplasma gondii was determined in 6,282 samples (2,094 each of beef, chicken, and pork) obtained from 698 retail meat stores from 28 major geographic areas of the United States. Each sample consisted of a minimum of 1 kg of meat purchased from the retail meat case. To detect viable T. gondii, meat samples were fed to T. gondii-free cats and feces of cats were examined for oocyst shedding. Initially, 100 g of meat from 6 individual samples of a given species were pooled (total, 600 g), fed to a cat over a period of 3 days, and feces were examined for oocysts for 14 days; the remaining meat samples were stored at 4 C for 14 days (until results of the initial cat fecal examination were known). When a cat fed pooled samples had shed oocysts, 6 individual meat samples from each pool were bioassayed for T. gondii in cats and mice. Toxoplasma gondii isolates were then genetically characterized using the SAG2 locus and 5 hypervariable microsatellite loci. In all, 7 cats fed pooled pork samples shed oocysts. Toxoplasma gondii oocysts were detected microscopically in the feces of 2 of the cats; 1 isolate was Type II and the second was Type III. Analyzed individually, T. gondii was detected by bioassay in 3 of the 12 associated samples with genetic data indicating T. gondii isolates present in 2. The remaining 5 pooled pork samples had so few oocysts that they were not initially detected by microscopic examination, but rather by mouse bioassay of cat feces. Two were Type I, 1 was Type II, and 2 were Type III. None of the cats fed chicken or beef samples shed oocysts. Overall, the prevalence of viable T. gondii in retail meat was very low. Nevertheless, consumers, especially pregnant women, should be aware that they can acquire T. gondii infection from ingestion of undercooked meat, and in particular, pork. Cooking meat to an internal temperature of 66 C kills T. gondii.

Animals↗

PubMed2004

Unstable carotid plaques exhibit raised matrix metalloproteinase-8 activity.

BACKGROUND: The fibrous cap of atherosclerotic plaques is composed predominantly of type I and III collagen. Unstable carotid plaques are characterized by rupture of their cap, leading to thromboembolism and stroke. The proteolytic mechanisms causing plaque disruption are undefined, but the collagenolytic matrix metalloproteinase (MMP) -1, -8, and -13 may be implicated. The aim of this study was to quantify the concentrations of these collagenases in carotid plaques and to determine their relationship to markers of plaque instability. METHODS AND RESULTS: Atherosclerotic plaques were collected from 159 patients undergoing carotid endarterectomy. The presence and timing of carotid territory symptoms were ascertained. Preoperative embolization was recorded by transcranial Doppler. Each plaque was assessed for histological features of instability. Plaque MMP concentrations were quantified with ELISA. Significantly higher concentrations of active MMP-8 were observed in the plaques of symptomatic patients (20.5 versus 11.4 ng/g; P=0.0002), in plaques of emboli-positive patients (22.7 versus 13.5 ng/g; P=0.0037), and in those plaques showing histological evidence of rupture (20.8 versus 14.7 ng/g; P=0.0036). No differences were seen in the levels of MMP-1 and MMP-13. Immunohistochemistry, in situ hybridization, and colocalization studies confirmed the presence of MMP-8 protein and mRNA within the plaque, which colocalized with macrophages. CONCLUSIONS: These data suggest that the active form of MMP-8 may be partly responsible for degradation of the collagen cap of atherosclerotic plaques. This enzyme represents an attractive target for drug therapy aimed at stabilizing vulnerable plaques.

Aged↗

PubMed2003

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura.

Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n=35), inflamed pleura (IP, n=12) and uninflammed pleura (UP, n=14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan-Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P=0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P=0.03, total MMP-2 P=0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM.

Adult↗

PubMed2003

Primary breast myoepithelial cells exert an invasion-suppressor effect on breast cancer cells via paracrine down-regulation of MMP expression in fibroblasts and tumour cells.

In normal breast and ductal carcinoma in situ, myoepithelial cells form an incomplete layer separating the epithelial compartment from the stromal environment. Transition to invasive disease is marked by penetration of the myoepithelial-basement membrane (BM) interface. One mechanism involved in tumour invasion is breakdown of extracellular matrices by matrix metalloproteinases (MMPs). It was hypothesized that myoepithelial cells may modulate tumour invasion by controlling MMP gene expression, both in tumour cells and in peri-ductal fibroblasts. To investigate this, myoepithelial cells from normal breast were purified and characterized and their effect on tumour cell invasive potential was assessed. The effect on MMP gene expression of breast cancer cells cultured alone or in combination with primary normal breast fibroblasts was also analysed using RT-PCR with ELISA quantitation, with zymographic analysis to measure enzyme activity. Normal breast myoepithelial cells significantly reduced invasion by the breast cancer cell lines MCF-7, T47D, MDA-MB 231, and MDA-MB 468 when they were cultured alone or in the presence of a fibroblast population. Reduced invasion was associated with changes in MMP gene expression. In those tumour cells expressing MMP, there was a significant down-regulation of MMP-2 (MDA-MB 468, p<0.001), MMP-9 (MDA-MB 231, p=0.05; MDA-MB 468, p<0.001), and MT1-MMP (p<0.001 for both MDA-MB 231 and MDA-MB 468). Myoepithelial cells also caused a significant decrease in MMP gene expression in co-cultured fibroblasts. Furthermore, this was associated with reduced gelatinolytic activity as identified by zymography. This study demonstrates for the first time that primary myoepithelial cells from normal breast reduce breast cancer cell invasion and that this is mediated via modulation of both tumour cell and fibroblast function. This emphasizes the importance of the myoepithelial cell in controlling the breast microenvironment and focuses on the potential significance of the loss of this population with disease progression.

Antineoplastic Agents↗

PubMed2003

There is more than one kind of myofibroblast: analysis of CD34 expression in benign, in situ, and invasive breast lesions.

AIMS: Smooth muscle actin (SMA) positive myofibroblasts have been implicated in tumour invasion; however, acquisition of SMA is not limited to peritumorous fibroblasts and other changes in fibroblasts may be more specifically related to the malignant environment. CD34 is a sialomucin expressed by normal breast fibroblasts but lost in invasive carcinomas. The aim of this study was to establish the relation between CD34 and SMA expression in breast fibroblasts and to analyse whether loss of CD34 is specific for invasive disease. METHODS: Immunohistochemistry for CD34 and SMA was performed on 135 cases including 10 normal, 10 fibroadenomas, 40 infiltrating ductal carcinomas, 55 cases of ductal carcinoma in situ (DCIS), and 20 radial scar/complex sclerosing lesions. The relation between staining pattern and histopathological features was recorded as positive, negative, or reduced. RESULTS: Fibroblasts around all normal duct-lobule units and those showing epithelial hyperplasia were CD34 positive and mainly SMA negative. In fibroadenomas, fibroblasts retained CD34 but acquired SMA expression. In contrast, fibroblasts around invasive carcinoma were CD34 positive and SMA negative. In DCIS, loss of CD34 was significantly more frequent in high grade tumours than in low or intermediate grade ones (p < 0.001). The acquisition of SMA was seen more frequently than the loss of CD34, particularly in non-high grade DCIS. In all radial scars, fibroblasts were SMA positive but CD34 negative, and a similar pattern was seen in stromal cells in areas of fibrosis following core biopsy. CONCLUSIONS: These results show that SMA positive myofibroblasts exhibit variable expression of CD34, indicating that these markers are not coordinately controlled. Loss of CD34 is strongly related to the malignant phenotype, in both invasive and preinvasive disease, but is not entirely specific because radial scar fibroblasts and fibroblasts in reactive fibrosis exhibit a similar phenotype. The functional relevance of altered CD34 expression is unclear but the very focal changes implicate local signalling mechanisms probably of epithelial origin.

Actins↗

PubMed2002

Low prevalence of antiretroviral resistance among persons recently infected with human immunodeficiency virus in two US cities.

Resistance testing for treatment-naïve, recently HIV-infected persons is not currently recommended; its clinical value will depend on the prevalence of resistance-associated mutations among recently infected persons. To estimate this prevalence, specimens were collected during 1997-1999 in Seattle and Los Angeles from drug-naïve, recently HIV-infected persons. HIV-1 protease and reverse transcriptase (RT) RNA sequences were amplified from plasma by RT-polymerase chain reaction (RT-PCR), sequenced, and analysed. Of 69 patients, five (7%) had resistance-associated mutations: three (4%) had primary mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI) or non-nucleoside-RTIs, and three patients (4%) had secondary NRTI mutations. No primary mutation associated with resistance to protease inhibitors was observed. Mean age of the five persons with resistance-associated mutations (38 years) was higher than that of the 64 persons without resistance-associated mutations (31 years, P=0.04). The findings suggest that the prevalence of resistance-associated mutations among persons recently infected with HIV in these cities is low.

Adolescent↗

PubMed2001

Viral load as an independent risk factor for opportunistic infections in HIV-infected adults and adolescents.

OBJECTIVE: We investigated whether HIV plasma RNA (viral load; VL) predicts risk for opportunistic infections (OI) in HIV-infected persons, independent of CD4 lymphocyte count and other factors that might affect disease outcome. METHODS: Among persons who had initiated antiretroviral therapy (ART), we studied the risk for OI following a VL measurement in the Centers for Disease Control and Prevention Adult and Adolescent Spectrum of HIV Disease (ASD) Project, a medical record review study of HIV-infected persons in 11 US cities. Analysis was limited to persons who had initiated ART and who had VL data, primarily from the period 1996-1999. Persons were considered at risk for OI for 1 to 6 months after a given VL; risk for OI was assessed using a Poisson multiple regression model controlling for CD4 lymphocyte count, ART, and other variables potentially associated with development of OI: history of AIDS OI, age, sex, race, HIV risk category, OI prophylaxis, and calendar year. RESULTS: Although decreasing CD4 count was the strongest predictor of risk for OI [relative risk (RR), 13.3 for persons with CD4 lymphocyte count < 50 x 10(6)/l compared with persons with CD4 lymphocyte count > or = 500 x 10(6)/l], increasing VL was independently associated with increased risk [RR, 1.6, 1.9, 2.7, and 3.5 for VL of 7000-19 999, 20 000-54 999, 55 000-149 999, and > or = 150 000 copies/ml (by reverse transcription-PCR), respectively, compared with VL < 400]. Similar results were obtained when the risk period was reduced to 5, 4, 3, and 2 months after VL measurement. CONCLUSIONS: VL is an independent risk factor for OI and should be considered in special situations, such as in decisions to discontinue primary or secondary OI prophylaxis after CD4 lymphocyte counts have increased in response to ART.

AIDS-Related Opportunistic Infections↗

PubMed2001

Angiogenesis is an independent prognostic factor in malignant mesothelioma.

Angiogenesis is essential for tumour growth beyond 1 to 2 mm in diameter. The clinical relevance of angiogenesis, as assessed by microvessel density (MVD), is unclear in malignant mesothelioma (MM). Immunohistochemistry was performed on 104 archival, paraffin-embedded, surgically resected MM samples with an anti-CD34 monoclonal antibody, using the Streptavidin-biotin complex immunoperoxidase technique. 93 cases were suitable for microvessel quantification. MVD was obtained from 3 intratumoural hotspots, using a Chalkley eyepiece graticule at x 250 power. MVD was correlated with survival by Kaplan-Meier and log-rank analysis. A stepwise, multivariate Cox model was used to compare MVD with known prognostic factors and the EORTC and CALGB prognostic scoring systems. Overall median survival from the date of diagnosis was 5.0 months. Increasing MVD was a poor prognostic factor in univariate analysis (P = 0.02). Independent indicators of poor prognosis in multivariate analysis were non-epithelial cell type (P = 0.002), performance status > 0 (P = 0.003) and increasing MVD (P = 0.01). In multivariate Cox analysis, MVD contributed independently to the EORTC (P = 0.006), but not to the CALGB (P = 0.1), prognostic groups. Angiogenesis, as assessed by MVD, is a poor prognostic factor in MM, independent of other clinicopathological variables and the EORTC prognostic scoring system. Further work is required to assess the prognostic importance of angiogenic regulatory factors in this disease.

Age Factors↗

PubMed2001

Toxoplasma gondii infection in the United States: seroprevalence and risk factors.

Infection with Toxoplasma gondii can cause severe illness when the organism is contracted congenitally or when it is reactivated in immune-suppressed persons. To determine the prevalence of T. gondii infection in a representative sample of the US population, the authors tested sera from participants in the Third National Health and Nutrition Examination Survey (1988-1994) for immunoglobulin G antibodies to T. gondii. Of 27,145 persons aged > or =12 years, 17,658 (65%) had sera tested. The overall age-adjusted seroprevalence was 22.5% (95% confidence interval (CI): 21.1, 23.9); among women aged 15-44 years, seroprevalence was 15.0% (95% CI: 13.2, 17.0). Age-adjusted seroprevalence was higher in the Northeast (29.2%) than in the South (22.8%), Midwest (20.5%), or West (17.5%) (p < 0.05). In multivariate analysis, risk for T. gondii infection increased with age and was higher among persons who were foreign-born, persons with a lower educational level, those who lived in crowded conditions, and those who worked in soil-related occupations, although in subset analyses risk categories varied by race/ethnicity. Nearly one quarter of adults and adolescents in the United States have been infected with T. gondii. Most women of childbearing age in the United States are susceptible to acute infection and should be educated about ways to minimize exposure to T. gondii.

Adolescent↗

PubMed2001

PCDD/F deposition time trend to Esthwaite Water, U.K., and its relevance to sources.

PCDD/Fs were measured in 16 sections of a sediment core from a freshwater lake in rural England. Each section represented 10 yr of deposition. Concentrations greater than the limit of detection were observed for most homologues in all samples. Three eras of PCDD/F input were identified by their distinct homologue and isomer profiles. sigma(4-8)CDD/F levels in core sections deposited before 1900 were in the order of 100 pg/g dry weight (dw) as compared to 1500 pg/g dw in the most recently deposited sediment. Local industries such as mining, quarrying, charcoal burning, and iron smelting appear to have had a minor impact on the PCDD/F deposition in the lake. Since 1900, two major peaks in PCDD/F input to the lake were evident. The first, reaching a maximum in the 1930s, had an unusual homologue pattern dominated by high molecular weight PCDFs, and the source of this input is unknown. The second, with a maximum in the 1970s, is in keeping with previously reported time trends for Europe and North America. Pre-1900, the TCDD/F isomer pattern was dominated by dimerization products of 2,4-dichlorophenol. Concentrations of P(1-3)CDFs appeared to be connected with the input that peaked in the 1930s, while highest concentrations of P(1-3)CDDs were found in the deepest sediment sections. Concentrations of diCDDs were observed to have increased again over the most recent decades to levels similar to pre-1900 sections. Despite detailed knowledge of the catchment and of industry in the surrounding area, the identity of some sources and the contribution of other known sources remain unclear for each era. This indicates that there remain significant gaps in our understanding of PCDD/F sources and undermines our ability to predict future trends in PCDD/F emissions.

Benzofurans↗

PubMed2001

Prophylaxis with trimethoprim-sulfamethoxazole for human immunodeficiency virus-infected patients: impact on risk for infectious diseases.

Trimethoprim-sulfamethoxazole (TMP-SMZ) is widely prescribed as prophylaxis for Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected persons. Its efficacy against other infections has not been thoroughly evaluated. To compare the risk for infectious diseases for persons who were prescribed TMP-SMZ with that for patients who were not prescribed TMP-SMZ, we examined data collected from the medical records of HIV-infected patients (January 1990 through September 1999) who were enrolled in the Adult and Adolescent Spectrum of HIV Disease Project. During intervals when patients had CD4(+) T lymphocyte counts of <200 cells/microL (19,081 persons; 22,801 person-years), prescription of TMP-SMZ was associated with significant protection from toxoplasmosis, salmonellosis, infection with Haemophilus species, invasive or any staphylococcal infection, and PCP, but not from Shigella, pneumococcal or nonpneumococcal Streptococcus, Klebsiella, or Pseudomonas species. We demonstrate that prescription of TMP-SMZ for PCP prophylaxis in persons with HIV infection is associated with significantly decreased risk for several infectious diseases. These findings may be of interest to HIV prevention programs in resource-poor countries.

AIDS-Related Opportunistic Infections↗

PubMed2001

Risk factors for and trends in gonorrhea incidence among persons infected with HIV in the United States.

OBJECTIVE: To determine the risk factors for and trends in gonorrhea infections among HIV-infected persons. DESIGN: Longitudinal review of medical records of HIV-infected patients. METHODS: We analyzed data about HIV-infected patients obtained from 1991 to 1998 in over 100 facilities participating in the Adult/Adolescent Spectrum of HIV Disease Project. RESULTS: The overall incidence of gonorrhea was 9.5 cases per 1000 person--years. Factors associated with higher gonorrhea incidence (P < 0.01) included younger age, male--male sex, black race, HIV infection without AIDS (namely AIDS-defining opportunistic illness or CD4 cell count < 200 x 10(6) cells/l), and recent recreational use of injection or non-injection drugs. There was an increase in the trend among men who have sex with men (P < 0.01) and a decrease in the trend among patients with heterosexual contact as their HIV exposure risk (P < 0.01). Among injection drug users there was no significant trend from 1991 to 1996, but there was an increase in gonorrhea incidence from 6.6 cases/1000 person-years in 1997 to 16.3 cases/1000 person--years in 1998. CONCLUSIONS: Following HIV diagnosis, some individuals continue to practice risky sexual behaviors which result in gonorrhea and may transmit HIV. The increase in the trend in gonorrhea incidence among HIV-infected men who have sex with men is of particular concern because it suggests an increase in risky sexual behaviors. These findings indicate a need for effective HIV prevention strategies that involve reducing risky sexual behaviors in HIV-infected persons.

AIDS-Related Opportunistic Infections↗

PubMed2001

Further evidence for the existence of PCDD/Fs in the environment prior to 1900.

PCDD/Fs and PCBs have been analyzed in a series of archived soil samples collected from various depths during the 1800s and early 1900s. PCBs were not found in soil samples collected before 1900, whereas PCDD/Fs were present in concentrations between 43 and 110 pg/g in surface soils, and between 9 and 150 pg/g in soils collected from below the surface. The PCDD/F homologue patterns of all surface soils were consistent with each other. The homologue pattern of deeper soils altered with depth to one that was dominated by highly chlorinated PCDDs. The highest sigma(4-8)PCDD/F concentration (150 pg/g) was found in the deepest soil analyzed (230-250 cm below the surface). The cork from one of the storage bottles contained considerable quantities of both PCBs and PCDD/Fs. However, contamination of the soils, either by diffusion through the cork or by cork particles, was discounted on the basis that no PCBs were evident in the soil, and that the PCDD/F homologue pattern in the cork was very different to that found in the soil. Similar arguments were used to discount contamination of the soil by dust. A sample of ashed vegetation from the archive, that had no cork stopper, contained high concentrations of PCBs (78 ng/g), concentrations of mono- to tri-CDFs that were higher than in any of the soils (190 pg/g), but very low concentrations of sigma(4-8)PCDD/F (12 pg/g). This pattern of analytes was considered to be representative of contamination from store room air and was completely different from the pattern observed in the soils. Taken together these observations indicate that contamination during storage, or subsequent handling, is unlikely to have occurred in archived soil samples that were stored with cork and wax seal intact. The results imply surface soil sigma(4-8)PCDD/F concentrations of around 60 pg/g at Rothamsted (southeast England) in the late 1800s, compared with approximately 300 pg/g reported for rural UK soils in the 1990s.

Benzofurans↗

PubMed2001

Decreased glutamate + glutamine in Alzheimer's disease detected in vivo with (1)H-MRS at 0.5 T.

OBJECTIVE: To determine whether glutamate + glutamine (GLX) levels in the brain as measured in vivo with proton MRS at 0.5 tesla (T) distinguish between probable Alzheimer's disease and normal aging. BACKGROUND: Glutamatergic markers had been measured previously in postmortem brain tissue. Conventional proton MRS at 1.5 T cannot reliably detect the GLX resonance in vivo. The authors developed a technique at 0.5 T that is sensitive to the GLX resonance. METHODS: Metabolite ratios using creatine and phosphocreatine resonance as an internal standard were acquired from the cingulate region of 18 patients with AD and 12 healthy controls. The major resonances in the spectrum were examined: N-acetylaspartate (NAA), choline-containing compounds, myo-inositol, and GLX. The Mini-Mental State Examination (MMSE) was used to assess cognitive status. The Instrumental Activities of Daily Living Scale (Instrumental ADL) was used to assess functional status. RESULTS: Reduced ratios of GLX (-10%, p = 0.001) and NAA (-12%, p = 0.000) were found in patients with AD. Increased ratios of myo-inositol in patients with AD approached significance (+14%). GLX ratios of patients with AD were correlated with MMSE (r = 0.61, p = 0.007) and Instrumental ADL (r = 0.59, p = 0.01) scores. The combined sensitivity of NAA and myo-inositol in correctly diagnosing AD was 78%. The addition of GLX to NAA and myo-inositol increased the sensitivity to 89%. Overall diagnostic accuracy improved from 80 to 83% with the addition of GLX. CONCLUSIONS: Glutamate + glutamine reduction may be a biologic marker for AD and may be a potential aid in the early clinical diagnosis of AD.

Activities of Daily Living↗

PubMed2001

Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination.

To determine the factors associated with pneumococcal disease (pneumococcal pneumonia or invasive disease) and the impact of pneumococcal vaccine in HIV-infected persons, we analyzed patient data collected by the Adult and Adolescent Spectrum of HIV Disease Project for person-time between January 1990 and December 1998. Among 39,086 persons with 71,116 person-years (py) of observation, 585 episodes of pneumococcal disease were diagnosed (incidence, 8.2 episodes per 1000 py). Factors associated with an increased risk for pneumococcal disease (P < .05) included injection drug use (adjusted relative risk [RR], 1.5) and blood transfusion (RR, 2.0) as the mode of HIV transmission (referent, male-male sex); black race/ethnicity (RR, 1.5; referent, white race); history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic illness (RR, 2.1); a CD4(+) cell count of 200-499 cells/microL (RR, 2.5) or < 200 cells/microL (RR, 3.7; referent, CD4(+) cell count of > or = 500 cells/microL); and alcoholism (RR, 2.0). Factors associated with a decreased risk included prescription of antiretroviral therapy (RR for monotherapy, 0.6; for dual therapy, 0.7; for triple therapy, 0.5) and pneumococcal vaccination (RR for persons vaccinated at a CD4(+) cell count of > or = 500 cells/microL, 0.5). We recommend that pneumococcal vaccine be given to HIV-infected persons before profound immunosuppression has occurred.

AIDS-Related Opportunistic Infections↗