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PubMed2002

Assessment of acetazolamide reactivity in cerebral blood flow using spectral analysis and technetium-99m hexamethylpropylene amine oxime.

Cerebral blood flow (CBF) can be quantified noninvasively using the brain perfusion index (BPI), determined from radionuclide angiographic data generated with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). Previously, the BPI has been calculated using graphical analysis (GA); however, the GA method is greatly affected by the first-pass extraction fraction and retention fraction, which are not only variable, but lower in cases with an increased CBF, such as after the administration of acetazolamide. Thus, GA-calculated BPI values (BPIG) may not reflect the absolute CBF. The objective of this study was to use the spectral analysis of radionuclide angiographic data collected using 99mTc-HMPAO to examine changes in the BPI after the administration of acetazolamide. We studied the CBF of both cerebral hemispheres in six healthy male volunteers; the BPI was measured at rest and after the intravenous administration of 1 g of acetazolamide. In all participants, an H215O positron emission tomography (PET) examination was also performed, and the spectral analysis-calculated BPI values (BPIS) and BPIG values were compared with the actual CBF measured using H215O PET (mCBFPET). The BPIS was 1.070 +/- 0.051 (mean +/- SD) at rest and 1.497 +/- 0.098 after acetazolamide; the corresponding BPIG values were 0.646 +/- 0.073 and 0.721 +/- 0.107. The BPIS values were significantly correlated with the mCBFPET values, whereas the BPIG values were not. According to the BPIS values, the increase in BPI after the intravenous administration of acetazolamide was 40.1 +/- 8.4%, as opposed to an increase of only 11.3 +/- 6.5% according to the BPIG values. These results suggest that the spectral analysis of 99mTc-HMPAO-generated data yields a more reliable BPI than GA for the quantification of CBF after acetazolamide administration.

Acetazolamide↗

PubMed2001

Electrocardiographically gated blood-pool SPECT and left ventricular function: comparative value of 3 methods for ejection fraction and volume estimation.

UNLABELLED: The current major limitation to development of electrocardiographically (ECG) gated blood-pool SPECT (GBPS) for measurement of the left ventricular (LV) ejection fraction (LVEF) and volumes is the lack of availability of clinically validated automatic processing software. Recently, 2 processing software methods for quantification of the LV function have been described. Their LVEFs have been validated separately, but no validation of the LV volume measurement has been reported. METHODS: We compared 3 processing methods for evaluation of the LVEF (n = 29) and volumes (n = 58) in 29 patients: automatic geometric method (GBPS(G)), semiautomatic activity method (GBPS(M)), and 35% maximal activity manual method (GBPS(35%)). The LVEF provided by the ECG gated equilibrium planar left anterior oblique view (planar(LAO)) and the LV volumes provided by LV digital angiography (Rx) were used as gold standards. RESULTS: Whereas the GBPS(G) and GBPS(M) methods present similar low percentage variabilities, the GBPS(35%) method provided the lowest percentage variabilities for the LVEF and volume measurements (P < 0.04 and P < 0.02, respectively). The LVEF and volume provided by the 3 methods were highly correlated with the gold standard methods (r > 0.98 and r > 0.83, respectively). The LVEFs provided by the GBPS(35%) and GBPS(M) methods are similar and higher than those of the GBPS(G) method and planar(LAO) method, respectively (P < 0.0001). For the LVEF, there is no correlation between the average and paired absolute difference for the 3 GBPS methods against the planar(LAO) method, and the limits of agreement are relatively large. LV volumes are lower when calculated with the GBPS(M), GBPS(G), and Rx methods (P < 0.0001). However, the GBPS(35%) and Rx methods provide LV volumes that are similar. There is no linear correlation between the average and the paired absolute difference of volumes calculated with the GBPS(G) and GBPS(35%) methods against Rx LV volumes. However, a moderate linear correlation was found with the GBPS(M) method (r = 0.6; P = 0.0001). The 95% limits of agreement between the Rx LV volumes and the 3 GBPS methods are relatively large. CONCLUSION: GBPS is a simple, highly reproducible, and accurate technique for the LVEF and volume measurement. The reported findings should be considered when comparing results of different methods (GBPS vs. planar(LAO) LVEF; GBPS vs. Rx volume) and results of different GBPS processing methods.

Electrocardiography↗

PubMed1996

Ultrastructure and quantification of synapses in the insect nervous system.

Standard EM methods can be successfully used to reveal the various organelles of synaptic junctions in different insect species. The individual junctions of a synaptic class exhibit a high level of morphological stereotypy, but the study of serial sections is generally necessary to understand the different appearances of a junction's profiles when it is cut in different planes. Most synaptic profiles seen in single sections may then be attributed to one or a few morphological classes, not to many. Probably most central synapses are of the multiple-contact type, containing a number of postsynaptic elements, with the diversity of the combinations of these providing the major difference between particular synaptic junctions. The different profiles of a synapse when cut serially in oblique, non-canonical section planes provide the investigator with search images, prior knowledge of which is needed for a comprehensive identification of synaptic sites in single sections. The latter can be used to describe the synaptic organization of an unknown neuropile from the variety of synaptic contacts that form between different neurons. This requires that continuity be established between a postsynaptic dendrite and its parent axon, and that the position of the axon can then be used to identify the neuron of origin. Tracing between dendrite and axon can be undertaken either systematically in serial sections of a restricted region or by protracted searches of single sections. The number of synaptic profiles in a single section can be used to estimate the number of synaptic contacts, either in relative terms, as the number of profiles per section in different cells, or as the absolute number of synapses per cell. The latter requires use of correction formulae, taking into account the influence of section thickness and of the mean size of the synaptic junction on the number of synaptic profiles recorded in a particular section.

Animals↗

PubMed1995

Use of polymerase chain reaction and quantitative antibody tests in children born to human immunodeficiency virus-1-infected mothers.

The diagnosis of human immunodeficiency virus (HIV) infection in children born to HIV-infected mothers is complicated by the presence of passively acquired maternal antibodies, and exclusion of infection in these infants remains problematic. The use of genome detection by polymerase chain reaction (PCR) amplification and the quantification of anti-HIV-1 antibodies were examined as methods for early diagnosis. Blood samples were taken from 84 non-breast-fed infants of HIV-infected mothers in five Italian and Spanish centres, a subgroup of children enrolled in the European Collaborative Study (ECS) for whom clinical and immunological information has been documented from birth. Whole blood was added to glycigel cryopreservative, stored, and tested in the United Kingdom by a nested PCR method. Antibody to HIV-1 was detected and quantified by titration using a gelatin particle agglutination test. PCR sensitivity and specificity were assessed. Twenty-one of the 84 children tested were infected. The estimated PCR sensitivity ranged from 0% (95% CI 0-26%) on day 1, 57% (19-85) on day 7, to 63% (33-92) on day 30. The negative predictive value of PCR ranged from 85% (83-88) on day 0 to 98% (94-100) at 3 months of age. On average, the level of maternal antibody halved every 33 days (31-36.5) in uninfected children. Between 6 and 9 months of age, increases in antibody titres in infected children were not more informative than absolute levels. These findings suggest that antibody measurement may supplement genomic diagnosis and that this collection method provides an alternative to the use of dried blood spots.

Age Factors↗

PubMed2002

The ratio of polymorphonuclear leucocytes (PMN) to non-PMN cells--a novel method of assessing acute lung inflammation.

Polymorphonuclear leucocyte (PMN) numbers are an indicator of the degree of acute lung inflammation. However, there is no standardized system for accurately quantifying their numbers in tissue sections. Also, the effect of lung inflation on the quantification of PMN's is usually overlooked. Lung specimens obtained from clinical biopsies are usually deflated, while inflated lung tissue is commonly used in experimental studies. We report a method, which is independent of the degree of inflation, for measuring the degree of PMN infiltration in the both inflated and non-inflated lungs. Using light microscopy, we counted the numbers of PMN and non-PMN cells in 240 fields from each of five inflated and five non-inflated lung sections and calculated a ratio of PMN: non-PMN cells (the PMN ratio). The effect on accuracy and precision of number of fields counted was investigated by randomly selecting 200, 160, 80 or 40 readings from the original 240 fields. The mean PMN ratio, its 95% confidence interval (CI) and the coefficient of variation (CV) were calculated for each of the four levels of sampling. Both CI and CV increased as the number of readings decreased. Inflated lung tissue had consistently higher values for CV compared to non-inflated lung. In practice, we recommend that for both inflated and non-inflated lungs, 80-160 fields (approximate 0.23-0.45 mm2 of absolute area evaluated) need to be counted to yield a PMN ratio with acceptable accuracy and precision. The PMN ratio provides a simple and objective way of quantifying the degree of acute inflammation in clinical histopathology and experimental toxicology studies involving lungs. It is suitable for use in research of lung inflammation, and as an accessory diagnostic tool and an objective descriptor for clinical histopathology.

Animals↗

PubMed1996

Triple primer polymerase chain reaction. A new way to quantify truncated mRNA expression.

The most practical method to quantify mRNA expression within small tumor samples is reverse transcription (RT) followed by quantitative polymerase chain reaction (PCR). One approach, known as "competitive RT-PCR" allows absolute quantitation by reference to synthetic RNA standards but is time-consuming and requires multiple manipulations that limit its usefulness as a screening assay. We describe here a new approach to quantify truncated type mRNAs relative to the wild-type transcripts in small amounts of tissue. This technique, called RT-triple primer-PCR, consists of coamplification of wild-type and truncated cDNAs using three primers in the PCR. To validate this approach, a truncated estrogen receptor variant (clone 4) was quantified relative to the wild-type estrogen receptor using plasmid preparations. The ratio of triple primer-PCR products obtained was directly related to the initial ratio of input cDNAs. RT-triple primer-PCR was then used to compare the relative expression of clone 4 mRNA in frozen sections of normal human breast tissue and human breast tumors with characteristics of good prognosis. The statistically significant difference (P = 0.03) observed between normal and tumor tissues suggests that elevated expression of the clone 4 variant may be associated with early steps of tumorigenesis. This technique provides a useful alternative to already described quantitative RT-PCR techniques for the quantification of truncated mRNA within small amounts of biological material.

Base Sequence↗

PubMed1995

Quantification of coronary artery calcium by electron beam computed tomography for determination of severity of angiographic coronary artery disease in younger patients.

OBJECTIVES: This study attempted to 1) evaluate five quantitative measures of coronary artery calcium and determine which best agreed with coronary artery disease severity at angiography; and 2) determine optimal quantity cutpoints to distinguish among no, mild and significant disease. BACKGROUND: Coronary artery calcium identified noninvasively by electron beam computed tomography is a sensitive marker for atherosclerosis. Quantitative assessments of calcium could distinguish among patients with no, mild and significant disease in clinical, screening and research settings. METHODS: One hundred sixty patients, 23 to 59 years old, underwent coronary angiography and electron beam computed tomography. Coronary artery calcium was defined as dense (> 130 Hounsfield units) foci > or = 2 mm2 on the tomogram. Regression and receiver operating characteristic analyses were used to evaluate five quantitative measures of calcium as predictors of the largest stenosis in the coronary arteries and to identify optimal cutpoints for distinguishing among disease categories. No disease was defined as no stenosis, mild disease as 10% to 49% diameter stenosis in one or more major branches and significant disease as > or = 50% diameter stenosis in one or more major branches. RESULTS: All measures evaluated performed well. With calcific area as the quantitative measure, the best cutpoint for discriminating between patients with and without disease was the presence of calcium: sensitivity 81%, specificity 86% and overall accuracy 83%. The best cutpoint for discriminating between patients with and without significant disease was 18 mm2: sensitivity 86%, specificity 81% and accuracy 83%. CONCLUSIONS: Because the ranges of calcium quantity overlapped across disease categories, no cutpoints would distinguish among categories with absolute certainty. However, selected cutpoints could rule out disease in most healthy subjects and identify most patients with significant disease.

Adult↗

PubMed2003

Quantitative analysis of immobilized proteins and protein mixtures by amino acid analysis.

Biomolecular surface engineering of materials often requires precise, versatile and efficient quantification of immobilized proteins at solid surfaces. Acidic hydrolysis of surface-bound proteins and subsequent HPLC analysis of fluorescence-derivatized amino acids were adapted and critically evaluated for that purpose. Contaminations and concentration-dependent amino acid retrieval during HPLC were found to influence the accuracy of the method. In addition to the choice of adequate conditions for hydrolysis, derivatization and chromatographic separation extensions of the data evaluation were suggested to improve the accuracy of the approach when applied to single protein systems: comparing the experimentally obtained amino acid ratio to the protein constitution enabled to identify the properly separated and detected amino acids. Those amino acids were selected for a more precise calculation of the amount of immobilized protein. To further increase the accuracy of the method, the retrieval of amino acids corresponding to protein amounts in the range between 0.5 and 4.0 microg was analyzed for a variety of proteins of interest to derive protein-specific correction factors. The evaluation of amino acid data was furthermore applied to quantify binary protein mixtures at similar settings. This method was proven useful to detect the composition of protein mixtures throughout a wide range of absolute and relative concentrations.

Amino Acids↗

PubMed1984

Apoprotein B quantification in rhesus and cynomolgus monkey atherosclerotic lesions.

The concept that much of the cholesterol deposition in atherosclerotic plaque development is provided by ingress of blood-derived apo B-rich lipoproteins into the arterial intima is given support by the study of arterial apo B accumulation. To compare the arterial wall level of immunoreactive apo B during the progression of diet-induced atherosclerosis in two widely used animal models of atherosclerosis, rhesus and cynomolgus monkeys were fed an atherogenic diet for 4, 8, and 12 months and their abdominal aortas quantitated for apo B. Apo B was extracted from aortic intima-media homogenates in two forms: Tris-buffer extractable or 'loosely bounds' and detergent (Triton X-100) extractable or 'tightly bound'. The aortic extracts were quantitated for apo B by radial immunodiffusion, using goat anti-rhesus apo B along with serum LDL standards of the appropriate species diluted in the two extract solutions. The control monkeys' aortas contained only buffer-extractable apo B. The atherosclerotic aortas of both species of monkeys progressively increased their levels of loosely bound and tightly bound apo B through 4, 8, and 12 months of atherogenic diet feeding, with the 8- and 12-month cynomolgus aortas containing much larger amounts of apo B than the rhesus aortas. These differences in aortic apo B content could be accounted for by the greater rate at which the cynomolgus atherosclerotic lesions developed at the later time points. When the total lesion apo B levels were correlated with representative morphometrically-quantitated histopathologic sections of the homogenized aortas, a highly significant correlation was seen between the total aortic apo B values and both the absolute area of the intimal lesions and the total area of oil red O stainable lipid in the lesions (P less than 0.001). These data indicate that as atherosclerotic lesions become larger and richer in lipid with progression of the disease, the amount of apo B-associated lipoproteins which are deposited unmetabolized in the lesions increases. These lipoproteins are increased in both the tightly bound and loosely bound forms.

Animals↗

PubMed1998

Quantification of insulin-like growth factor-1 (IGF-1) mRNA: modulation of growth intensity by feeding results in inter- and intra-tissue-specific differences of IGF-1 mRNA expression in steers.

The effect of constant and compensating body growth velocities on IGF-1 mRNA expression was studied in various tissues of growing steers. Twenty-six steers were allocated to three groups in which the average daily gains were kept either constantly high on intensive feeding, low on pasture feeding or were accelerated to compensatory growth after feed restriction. All animals were slaughtered at 570+/-2.6 kg and samples were collected from liver, heart, kidney and from 4 different muscles (m. splenius, m. soleus, m. cutaneus truncii and m. semispinalis capitis), which were selected in order to include maximal differences in fibre composition as well as in growth impetus. IGF-1 mRNA was quantified by a validated internally standardised RT-PCR method. The amount of RNA extracted from the various tissues investigated was constant within each type of tissue and showed no differences between treatment groups. As indicated by a constant ratio between the amount of RNA extracted and the DNA concentrations, there was no effect of the feeding on total transcriptional activity. The order of IGF-1 mRNA abundance per g tissue was liver > > kidney > heart > skeletal muscle. The different feeding regimen resulted in significant differences of IGF-1 mRNA expression rates in all organs showing different patterns between organs. IGF-1 mRNA concentrations showed muscle specific differences and also divergent reactions in response to the differing growth rates. These results support that the liver is the main IGF-1 producing tissue; above that they indicate that skeletal muscle, in particular when taking its absolute mass into account, might considerably contribute to the IGF-1 levels in blood. Our findings demonstrate that IGF-1 mRNA expression is regulated tissue specifically not only between different organs but also within musculature.

Animals↗

PubMed2006

The role of TGF-beta1 as a determinant of foreign body reaction to alloplastic materials in rat fibroblast cultures: comparison of different commercially available polypropylene meshes for hernia repair.

BACKGROUND: Animal experiments on hernia repair demonstrated better biocompatibility of light-weight polypropylene meshes. However, implanted medical devices trigger a variety of adverse tissue responses, such as inflammation, fibrosis, infection and thrombosis, but the mechanisms involved in such responses remain largely unknown. This study aimed to determine the effect of transforming growth factor beta1 (TGF-beta1) on host tolerance by quantification of foreign body reaction in cultured fibroblasts depending on the amount and composition of implanted material used for hernia repair. MATERIALS AND METHODS: An NRK-49F fibroblast culture was incubated in the presence of 4 commercially available meshes approved for hernia repair. A mesh-free cell suspension served as a control group, in which the influence of TGF-beta1 on fibroblasts was evaluated. Levels of TGF-beta1 in the supernatant were dynamically measured in a time interval of 6 to 96 h and cell proliferation rates were assessed colorimetrically using MTT test. RESULTS: A dose-dependent suppression of fibroblasts proliferation by TGF-beta1 was observed. All meshes suppressed the secretion of TGF-beta1 and conversely increased significantly cell proliferation in comparison to the control group (p<0.01) in the first 24 to 48 h of incubation. That effect was more pronounced in meshes partially containing absorbable material when compared to samples of pure polypropylene meshes (p<0.05) and to the control group (p<0.001). CONCLUSION: Our experiment revealed that early biological reaction of connective tissue cells towards polypropylene meshes and their variants depended much more on the composition and type of the material than on its absolute amount. The assumption that material weight reduction alone might affect the foreign body reaction of mesh implants could not be confirmed by our in vitro study.

Animals↗

PubMed2026

Ultra-high-frequency ECG quantifies residual electrical dyssynchrony during left bundle branch area pacing in patients with wide QRS: a paired within-patient study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may restore a more physiological pattern of ventricular activation in patients with conduction delay; however, QRS narrowing alone may incompletely characterize electrical resynchronization. Ultra-high-frequency ECG (UHF-ECG) provides quantitative markers of ventricular activation timing and dyssynchrony. OBJECTIVE: To quantify paired OFF-to-ON changes in conventional ECG and UHF-ECG metrics during LBBAP in patients with baseline wide QRS and to assess the relationship between paced R-wave peak time (RWPT) and residual UHF-ECG dyssynchrony. METHODS: In this prospective single-center paired study, 21 patients with bradycardia and baseline wide QRS underwent standard ECG and UHF-ECG assessment during intrinsic rhythm (pacing OFF) and during LBBAP (pacing ON). Endpoints included QRS duration, signed VED16, absolute VED16 (|VED16|), mean ventricular delay (meanVD), and a clinically interpretable distance-to-normal metric defined as dist = max(|VED16|-20, 0). Paired changes were summarized as medians with bootstrap 95% confidence intervals and tested using the Wilcoxon signed-rank test. Associations between paced RWPT and residual dyssynchrony during pacing were evaluated using Pearson and Spearman correlation coefficients. RESULTS: LBBAP significantly narrowed QRS duration from 136.8 [130.2-153.6] ms during intrinsic rhythm to 116.0 [107.8-125.6] ms during pacing (median Δ -21.0 ms; 95% CI -33.9 to -18.6; p < 0.001). Signed VED16 did not change significantly (median Δ 0.4 ms; p = 1.000), consistent with the mixed conduction-phenotype composition of the cohort. In contrast, severity-oriented UHF-ECG endpoints improved: |VED16| decreased numerically (median Δ -5.2 ms; p = 0.070), whereas dist decreased significantly (median Δ -0.7 ms; 95% CI -14.4 to 0.0; p = 0.015). The proportion of patients within the normal dyssynchrony band (|VED16| ≤ 20 ms) increased from 7/21 (33.3%) to 12/21 (57.1%). Median paced RWPT was 66.6 [58.6-74.6] ms, and shorter RWPT correlated with lower residual |VED16| during pacing (Pearson r = -0.45, p = 0.038). CONCLUSIONS: In patients with baseline wide QRS, LBBAP produces marked QRS narrowing, whereas UHF-ECG provides complementary quantification of residual electrical dyssynchrony. Severity-oriented UHF-ECG endpoints, particularly a distance-to-normal metric, may offer an interpretable mechanistic framework beyond conventional ECG alone. Shorter paced RWPT was associated with lower residual dyssynchrony during pacing, supporting physiological coherence between procedural and high-resolution electrocardiographic markers.

Humans↗

PubMed2005

A sensitive and selective HPLC/ESI-MS/MS assay for the simultaneous quantification of 16-dehydropregnenolone and its major metabolites in rabbit plasma.

A sensitive, selective and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric assay was developed and validated for the simultaneous quantification of 16-dehydropregnenolone (DHP) and its five metabolites 4,16-pregnadien-3, 20-dione (M(1)), 5-pregnene-3beta-ol-20-one (M(2)), 5-pregnene-3beta, 20-diol (M(3)), 5-pregnene-3beta-ol-16, 17-epoxi-20-one (M(4)) and 5,16-pregnadien-3beta, 11-diol-20-one (M(5)) in rabbit plasma using dexamethasone as internal standard (IS). The analytes were chromatographed on Spheri-5 RP-18 column (5 microm, 100 mm x 4.6 mm i.d.) coupled with guard column using acetonitrile:ammonium acetate buffer (90:10, v/v) as mobile phase at a flow rate of 0.65 ml/min. The quantitation of the analytes was carried out using API 4000 LC-MS-MS system in the multiple reaction monitoring (MRM) mode. The method was validated in terms of linearity, specificity, sensitivity, recovery, accuracy, precision (intra- and inter-assay variation), freeze-thaw, long-term, auto injector and dry residue stability. Linearity in plasma was observed over a concentration range of 1.56-400 ng/ml with a limit of detection (LOD) of 0.78 ng/ml for all analytes except M(3) and M(5) where linearity was over the 3.13-400 ng/ml with LOD of 1.56 ng/ml. The absolute recoveries from plasma were consistent and reproducible over the linearity range for all analytes. The intra- and inter-day accuracy and precision method were within the acceptable limits and the analytes were stable after three freeze-thaw cycles and their dry residues were stable at -60 degrees C for 15 days. The method was successfully applied to determine concentrations of DHP and its putative metabolites in plasma during a pilot pharmacokinetic study in rabbits.

Animals↗

PubMed1990

Effect of blood collection and processing on radioimmunoassay results for apolipoprotein B in plasma.

We studied the effects of different blood collection and processing procedures on quantification of apolipoprotein (apo) B by radioimmunoassay. High-density lipoprotein subfractions HDL3 and HDL2 and isolated apoA-I did not cross-react in the assay. Analytical recovery of apoB at different doses of very-low- and low-density lipoproteins were complete. Inter- and intra-assay coefficients of variation (CVs) averaged 7.4% and 6.0%, respectively. Blood from 20 subjects was collected into tubes containing EDTA alone or EDTA with antiproteolytic and antioxidant agents; one half of each plasma was separated immediately, half after 3 h at 4 degrees C. Regardless of the addition of protective agents or the time difference in separating plasma from other blood elements, freezing plasma at -70 degrees C decreased apoB content a similar amount, an average of 6.8%. This loss of apoB immunoreactivity was not related to apoB content in fresh plasma. Analysis of variance showed no differential effect on apoB content by the various additions to whole blood or plasma. No additional apoB content was lost in once-frozen aliquots of three human plasma pools during storage at -70 degrees C for up to 18 months. We conclude that concentrations of apoB in human plasma can be measured reliably after long-term storage, although the absolute value may decrease slightly as a result of freezing.

Analysis of Variance↗

PubMed2003

Effects of cis-nonachlor, trans-nonachlor and chlordane on the immune system of Sprague-Dawley rats following a 28-day oral (gavage) treatment.

The immunotoxicity of cis- and trans-nonachlor and chlordane were investigated in adult male and female Sprague-Dawley rats following a 28-day oral (gavage) treatment. Rats were randomly assigned to six experimental groups: cis-nonachlor, females; trans-nonachlor, females; technical chlordane females; cis-nonachlor, males; trans-nonachlor, males; technical chlordane, males. The immunologic endpoints included: quantification of the total serum immunoglobulin (Ig) levels and subclasses and flow cytometric analysis of peripheral blood leukocytes and T-lymphocyte subsets, evaluation of the lymphoproliferative activity of splenocytes in response to concanavalin A (Con A) and Salmonella typhimurium (STM) mitogens, and natural killer (NK) cell activity of splenocytes. Satellite experiments to examine the delayed-type hypersensitivity (DTH) response to oxazolone, and resistance to Listeria monocytogenes were set up for female rats treated with cis- or trans-nonachlor. Statistically significant (P<0.05) effects included: increased serum immunoglobulin M (IgM) levels in the chlordane-treated females at the 25 mg/kg dose (pairwise comparison); increased serum IgG(1) and IgG(2c) in the cis-nonachlor-treated males at the 2.5 and 25 mg/kg doses and increased serum IgG(2a) levels at all doses; increased serum IgG(2b) at the 25 mg/kg dose and decreased (dose-related) serum IgM levels in the cis-nonachlor-treated male rats; increased (linear trend) IgG(1) and IgG(2a) in the cis-nonachlor-treated females with effects on IgG(2a) significant at the 25 mg/kg dose compared with control; increased serum IgG(2a) in the trans-nonachlor-treated male and female rats at the 2.5 mg/kg dose; increased absolute numbers (linear trend) of peripheral white blood cells, B lymphocytes, natural killer (NK) cells, T-suppressor/cytotoxic lymphocytes, and the double positive (T-helper/inducer, T-suppressor/cytotoxic) cells in the trans-nonachlor-treated females; increased (non-linear trend) lymphoproliferative activity in the Con A-stimulated splenocytes and decreased (linear trend) activity in the S. typhimurium mitogen-stimulated splenocytes of the cis-nonachlor-treated females; reduced resistance to L. monocytogenes in the cis-nonachlor (day 3, P=0.034)- and trans-nonachlor (day 2, P=0.0001)-treated females, and reduced (linear trend) NK cell activity in the cis-nonachlor-treated males. The present data indicated that the chlordane compounds tested in this study had significant effects on a number of immunologic endpoints. In comparison to technical chlordane, cis- and trans-nonachlors were more immunotoxic. Therefore, an evaluation of the risk these chlorinated compounds may pose to human health should consider the potential effects different chlordane compounds may have on the immune system.

Administration, Oral↗

PubMed2001

Plasma levels of viro-immunological markers in HIV-infected and non-infected Ethiopians: correlation with cell surface activation markers.

Cross-sectional studies were conducted to measure soluble viral and immunological markers in plasma in order to determine the prognostic value of these markers for HIV disease progression in Ethiopians and to see their association with cell surface markers in HIV-1-infected and noninfected Ethiopians. Whole blood samples were collected from 52 HIV-1-negative Ethiopians, 32 HIV-1-positive Ethiopians with absolute CD4(+) T-cell count >200/microl whole blood and no AIDS defining conditions, and 39 HIV-positive Ethiopians with CD4(+) T-cell count <200/microl and/or AIDS defining conditions. Plasma levels of b(2)-microglobulin (b(2)m), soluble CD27 (sCD27), soluble tumor necrosis factor alpha receptor type II (sTNFR-II), IgG, IgA, IGE, and IL12 were elevated in HIV-1-infected individuals. The plasma levels of sTNFR-II, sCD27, b(2)m, IL12, and IgG were inversely correlated with numbers of CD4(+) T-cells, the proportion of naïve (CD45RA(+)CD27(+)) CD8(+) T-cells, and the proportion of CD8(+) T-cells expressing CD28 (CD8(+)CD28(+)) were positively correlated with the proportions of activated (HLA-DR(+)CD38(+)) CD4(+) T-cells, as well as activated (HLA-DR(+)CD38(+)) CD8(+) T-cells. A strong positive correlation was also observed when soluble immune markers were compared to each other. Multivariate regression analyses of soluble markers with numbers of CD4(+) T-cells showed that sCD27 is the best independent marker for CD4(+) T-cell decline in the HIV-1-infected Ethiopians. Our results indicate that measurement of soluble immune markers, which is relatively easy to perform, could be a good alternative to the quantification of T-cell subsets for monitoring HIV-1 disease progression in places where there is no facility for flow cytometric measurements.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Ecological toxicology and human health effects of heptachlor.

The chlorinated cyclodiene heptachlor was registered in 1952 as an agricultural and domestic insecticide. By early 1984, registration for all purposes, except subterranean termite control and for limited use in the control of fire ants, had been cancelled. This restriction of use arose primarily from concerns over the environmental persistance and bioaccumulation potential of the organochlorine pesticides. Currently, sale of heptachlor has been voluntarily suspended over questions about its carcinogenic potential, and the absence of safe and effective application methods. As a persistent organochlorine pesticide, heptachlor residues are detected in all components of the environment. In historical use, heptachlor was directly applied to terrestrial systems, while air and water were secondarily contaminated via volatilization and land run-off, respectively. Within each environmental compartment, heptachlor undergoes a variety of metabolic and abiotic transformations. In vivo studies indicate that heptachlor epoxide is the predominant metabolite, formed as a product of the mixed-function oxidase system, while 1-hydroxychlordene is the major soil metabolite. For quantification, heptachlor and its metabolites are extracted from air, soil and sediment, water, or biological materials using various organic solvents and analyzed by gas chromatography or thin-layer chromatography. Residue reports comprise most of the literature concerning the effects of heptachlor on the biota. In many such reports, toxic effects cannot be conclusively attributed to heptachlor exposure. Toxicity to organisms seems more dependent on acute exposure, while the chronic effects of low level exposure to heptachlor are poorly defined. Maximal terrestrial residues coincide with temporal and spatial proximity to application; peak residues in aquatic systems on the other hand, correlate to periods of maximum run-off. The lipophilic nature of both heptachlor and heptachlor epoxide results in the potential for significant bioaccumulation in all lipid-type compartments in the environment. The toxic effects of heptachlor are not specific for any one organ system. The liver and the central nervous system are most significantly affected by heptachlor, although effects can also be seen in the reproductive, hematopoietic, immune, and renal systems. An important consideration is the relation of relevant environmental exposure levels to toxicity. The concentrations necessary to elicit results in laboratory experiments do not translate directly to the same results upon environmental exposure, nor do experimental laboratory animal models absolutely equate with native-state organisms or with humans.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

ELISA quantification of CCI-103F binding in canine tumors prior to and during irradiation.

PURPOSE: The purpose of this work was to evaluate multiple injections of CCI-103F, a marker of hypoxia, as a method to quantify alterations in tumor hypoxia during irradiation. METHODS AND MATERIALS: Twelve dogs with spontaneous solid tumors were given intravenous CCI-103F, and tumor biopsies were taken at various times after injection. Two tumor samples were taken at each biopsy procedure. CCI-103F antigen concentration was quantified by ELISA. Four of the dogs were given one injection of CCI-103F, and the other eight received two injections. In dogs receiving two injections, CCI-103F was administered before irradiation and 7 days later, following a total dose of 15.0 Gy. Plasma CCI-103F pharmacokinetics were assessed in dogs receiving two injections. RESULTS: CCI-103F antigen was detectable in the initial biopsy in each of the four dogs receiving one injection, and the amount of detectable antigen decreased in subsequent biopsies with an initial half life of approximately 19 h. This suggests that multiple injections of CCI-103F could be used in the same subject to monitor tumor hypoxia as a function of time or during a course of treatment. In the eight dogs receiving two injections of CCI-103F, the CCI-103F antigen concentration in the 24 h samples ranged from 4.66-151.9 mumol CCI-103F antigen/kg tumor, a difference of a factor of approximately 33. The ratio of maximum to minimum concentration of CCI-103F antigen in 51 paired biopsy samples ranged from 1.01-4.07, with a mean (+/- s.d.) of 1.67 +/- 0.67. Seventy-five percent of the ratios were < or = 2.02. There was no apparent relationship between the magnitude of the ratio, i.e., intratumoral variation, and tumor volume or the absolute tumor concentration of CCI-103F antigen. Absolute radiobiologic hypoxic fraction was not known but the pattern of change in amount of intratumoral CCI-103F antigen in dogs given two injections of CCI-103F was consistent with little change in pretreatment oxygen status in six dogs, and an increase in tumor oxygenation in two dogs. CONCLUSION: It appears possible to obtain an estimate of the change in tumor hypoxia in an individual tumor over time by assaying biopsy samples for CCI-103F antigen concentration.

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