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PubMed2002

The role of sperm-mediated gene transfer in genome mutation and evolution.

Contradictory evidence surrounds the claim that sperm cells are able to introduce exogenous DNA into the oocyte at the time of fertilisation. Although strong natural barriers exist against sperm-mediated gene transfer, such barriers are unlikely to be absolutely inviolable. If sperm cells can act as vectors for exogenous DNA, it follows that the genome of sexually reproducing animals may be subject to alteration by exogenous DNA sequences carried by sperm cells. At present there are insufficient data to permit quantification of the rate of sperm-mediated gene transfer. The implications of sperm-mediated gene transfer are significant and include evolutionary effects on the mammalian genome and pathologies in humans from de novo mutations. Despite the absence of firm data, geneticists would be wise to be vigilant to the potential consequences of sperm-mediated gene transfer.

Animals↗

PubMed2003

Recommendations for the bioanalytical method validation of ligand-binding assays to support pharmacokinetic assessments of macromolecules.

PURPOSE: With this publication a subcommittee of the AAPS Ligand Binding Assay Bioanalytical Focus Group (LBABFG) makes recommendations for the development, validation, and implementation of ligand binding assays (LBAs) that are intended to support pharmacokinetic and toxicokinetic assessments of macromolecules. METHODS: This subcommittee was comprised of 10 members representing Pharmaceutical, Biotechnology, and the contract research organization industries from the United States, Canada, and Europe. Each section of this consensus document addresses a specific analytical performance characteristic or aspect for validation of a LBA. Within each section the topics are organized by an assay's life cycle, the development phase, pre-study validation, and in-study validation. Because unique issues often accompany bioanalytical assays for macromolecules, this document should be viewed as a guide for designing and conducting the validation of ligand binding assays. RESULTS: Values of +/- 20% (25% at the lower limit of quantification [LLOQ]) are recommended as default acceptance criteria for accuracy (% relative error [RE], mean bias) and interbatch precision (%coefficient of variation [CV]). In addition, we propose as secondary criteria for method acceptance that the sum of the interbatch precision (%CV) and the absolute value of the mean bias (%RE) be less than or equal to 30%. This added criterion is recommended to help ensure that in-study runs of test samples will meet the proposed run acceptance criteria of 4-6-30. Exceptions to the proposed process and acceptance criteria are appropriate when accompanied by a sound scientific rationale. CONCLUSIONS: In this consensus document, we attempt to make recommendations that are based on bioanalytical best practices and statistical thinking for development and validation of LBAs.

Carrier Proteins↗

PubMed2005

Genome-wide identification and testing of superior reference genes for transcript normalization in Arabidopsis.

Gene transcripts with invariant abundance during development and in the face of environmental stimuli are essential reference points for accurate gene expression analyses, such as RNA gel-blot analysis or quantitative reverse transcription-polymerase chain reaction (PCR). An exceptionally large set of data from Affymetrix ATH1 whole-genome GeneChip studies provided the means to identify a new generation of reference genes with very stable expression levels in the model plant species Arabidopsis (Arabidopsis thaliana). Hundreds of Arabidopsis genes were found that outperform traditional reference genes in terms of expression stability throughout development and under a range of environmental conditions. Most of these were expressed at much lower levels than traditional reference genes, making them very suitable for normalization of gene expression over a wide range of transcript levels. Specific and efficient primers were developed for 22 genes and tested on a diverse set of 20 cDNA samples. Quantitative reverse transcription-PCR confirmed superior expression stability and lower absolute expression levels for many of these genes, including genes encoding a protein phosphatase 2A subunit, a coatomer subunit, and an ubiquitin-conjugating enzyme. The developed PCR primers or hybridization probes for the novel reference genes will enable better normalization and quantification of transcript levels in Arabidopsis in the future.

Arabidopsis↗

PubMed2006

Determination of SMN1/SMN2 gene dosage by a quantitative genotyping platform combining capillary electrophoresis and MALDI-TOF mass spectrometry.

BACKGROUND: Spinal muscular atrophy (SMA) is a common inherited and fatal neuromuscular disease caused by deletions and/or mutations that lead to altered concentrations of proteins encoded by the survival motor neuron genes SMN1 and SMN2. Because of the high incidence (at least 1 in 10,000 live births and a carrier frequency of 1 in 35 to 1 in 50) and severity of the disease, precise quantification of SMN1 and SMN2 gene copy numbers is essential for diagnosis and genetic counseling. METHODS: We developed a genotyping platform combining capillary electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantify absolute gene dosage. The absolute gene dosage can be determined by a multiplexed competitive PCR protocol followed by capillary electrophoresis analysis. The relative SMN1/SMN2 ratio can be analyzed by PinPoint assay followed by MALDI-TOF MS analysis. RESULTS: The complementary assays were evaluated in confirmed cases including 9 affected patients, 33 carriers, and 478 healthy individuals from the general population. We were able to determine all genotypes with different SMN1/SMN2 gene copy number ratios, which unambiguously diagnosed carrier status and the severity of SMA with 100% specificity. CONCLUSIONS: This quantitative genotyping platform is suitable for detection of SMA. The described approach may serve as a general quantitative genotyping method for molecular diagnosis of other inheritable diseases.

Cyclic AMP Response Element-Binding Protein↗

PubMed1995

Male reproductive toxicity of ethinylestradiol associated with 4 weeks daily dosing prior to mating in rats.

Parameters of male reproductive toxicity of ethinylestradiol were assessed by conducting a mating test, sperm assay, organ weight determination and histopathological examination. Male Sprague Dawley rats were orally administered 0.1, 0.3, 3 or 10 mg/kg/day ethinylestradiol for 4 weeks prior to mating. Body weight gain and food consumption were suppressed in all treated groups. Reproductive ability of the 3 and 10 mg/kg/day males disappeared. Slightly low copulation indices were observed in the 0.1 and 0.3 mg/kg/day groups, although fertility indices were not affected. Sperm could hardly be found in the epididymis of 3 and 10 mg/kg/day males. Sperm counts were also decreased in the other treated groups, but sperm motility was not affected. Decreased absolute and/or relative weights of testes, epididymides, prostate and seminal vesicles were observed in all treated groups along with testis, epididymis, seminal vesicle and prostate atrophy, and degenerative changes of spermatocytes, spermatids, Sertoli cells and Leydig cells. These results suggest that sperm quantification and histopathological assessment are more appropriate for assessing male reproductive toxicity of ethinylestradiol than performance of copulation and fertility tests.

Animals↗

PubMedDate not supplied

Quantification of metabolites from single-voxel in vivo 1H NMR data of normal human brain by means of time-domain data analysis.

We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.

Aspartic Acid↗

PubMed1997

Effects of ageing and X-irradiation on the diurnal rhythm of mouse urinary bladder capacity.

The effect of single-dose irradiation (19 Gy) or sham treatment on circadian variations in urinary bladder storage capacity was assessed during a 250-day period following treatment using transurethral cystometry under anesthesia. Changes in bladder function were quantified as the deviation from individual pretreatment values of bladder volume at defined intravesical pressures. A marked diurnal rhythm with a peak at 19.00 h and an extended nadir between 1.00 h and 12.00 h was found in 11- to 12-week-old untreated mice. No systematic changes in bladder function with age could be observed in repeated cystometries after sham treatment. X-Irradiation resulted in a triphasic response. After an early reversible decrease in bladder capacity (acute phase) complete recovery was observed within 30 days after irradiation. Following a symptom-free latent period of about 15 weeks, chronic progressive impairment of bladder storage function developed (chronic phase). During the acute and latent period, no changes in the diurnal pattern were observed. In the late phase, not only a decrease in the absolute capacity values but also in the amplitude of diurnal fluctuations was seen. The daily minimum values, however, were still found between 1.00 and 12.00 h. The data indicate that cystometry values obtained between 8.00 and 12.00 h provide suitable parameters for the quantification of radiation effects in the urinary bladder in longitudinal studies.

Aging↗

PubMed1998

Descriptive information of topographic parameters computed at the optic nerve head with the Heidelberg retina tomograph.

PURPOSE: To analyze the frequency distribution and descriptive information of topometric data obtained with the Heidelberg Retina Tomograph (HRT) in a normal population. METHODS: Topographic measurements of the optic disc were acquired and evaluated using the HRT in 225 subjects between 12 and 90 years of age. After randomly selecting one eye per subject, the frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles were evaluated for topographic parameters computed by the HRT. The influence of age, intraocular pressure (IOP), disc size, and disc shape on optic disc topometric data was analyzed. A principal component analysis of the topometric parameters was performed. The frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles of the interocular difference in topographic parameters were evaluated. RESULTS: All topographic parameters showed a unimodal but not necessarily normal distribution. None of the parameters showed a relevant correlation with age, IOP (in the normal range), and overall shape of the anterior optic nerve, but a few parameters showed a clinically significant correlation with disc size. A principal component analysis identified four relevant factors (optic nerve cup, retinal nerve fiber layer, optic disc size, and optic nerve cup shape) in the entire data set of optic nerve topometric data. The absolute value of all interocular differences in topographic parameters showed an asymmetric but unimodal distribution. CONCLUSION: The mathematical description of the optic nerve cup shape provides information on optic nerve head topography independently from cupping, nerve fiber layer thickness, and disc size. Potentially, quantification of further aspects in optic nerve head topography might improve the discriminatory power of computerized quantitative optic nerve head analysis.

Adolescent↗

PubMed1999

Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography.

Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D2 receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using 123I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90 degrees), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21-0.46 GBq of 123I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to 123I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a 123I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC + AT) and (SC + CBC + AT) corrected images were compared. PET acquisitions using 0.11-0.44 GBq of 11C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (% ID/100 ml) obtained after (SC + CBC + AT) in SPET are in good agreement with those obtained with PET and 11C-epidepride. A method for the in vivo absolute quantitation of 123I-epidepride uptake using SPET has been developed which can be directly applied to other 123I-labelled molecules used in the study of the dopamine system. Further work will consist in using PET to model the radioligand-receptor interactions and to derive a simplified model applicable in SPET.

Animals↗

PubMed2003

Proton high-resolution magic angle spinning NMR analysis of fresh and previously frozen tissue of human prostate.

The previously observed improvement in spectral resolution of tissue proton NMR with high-resolution magic angle spinning (HRMAS) was speculated to be due largely to freeze-thawing artifacts resulting from tissue storage. In this study, 12 human prostate samples were analyzed on a 14.1T spectrometer at 3 degrees C, with HRMAS rates of 600 and 700 Hz. These samples were measured fresh and after they were frozen for 12-16 hr prior to thawing. The spectral linewidths measured from fresh and previously frozen samples were identical for all metabolites except citrate and acetate. The metabolite intensities of fresh and freeze-thawed samples depend on the quantification procedures used; however, in this experiment the differences of means were <30%. As expected, it was found that tissue storage impacts tissue quality for pathological analysis, and HRMAS conditions alone are not sufficiently destructive to impair pathological evaluation. Furthermore, although storage conditions affect absolute metabolite concentrations in NMR analysis, relative metabolite concentrations are less affected.

Cryopreservation↗

PubMed1993

Consideration of measurements of myocardial blood flow with positron-emission tomography.

The available data suggest that the different approaches permit the noninvasive quantification of regional myocardial blood flow in humans with comparable degrees of accuracy. Much of this accuracy depends on how carefully such measurements are performed and on the attention paid to detail when quantitative information is derived from the serially acquired PET images. Although absolute values for estimated flow may differ among laboratories and among techniques, consistency in analysis of data is of utmost importance. Yet, the choice of a specific measurement approach is often determined by practical considerations specific to a given laboratory. Factors are availability of a given tracer, ease of synthesis, proximity of the cyclotron to the scanner, instrument performance, as well as the type of studies performed in the same laboratory in other organs and associated needs for a given tracer. On the other hand, it is clear that the technology for quantifying blood flow in human myocardium has reached a point at which it can be applied routinely and reliably for the study of coronary circulatory physiology and pathophysiology of the human heart. What remains less certain at present is to what extent such quantitative approaches will augment the accuracy with which coronary artery disease can be diagnosed and characterized, and the effects of therapy monitored. However, it is clear that these novel approaches are likely to offer new insights into the pathophysiology of other than apparent coronary artery disease, as exemplified by the initial observations in patients with syndrome-X or hypertrophic cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2004

Increased percentage of CD4+CD25+ regulatory T cells during septic shock is due to the decrease of CD4+CD25- lymphocytes.

OBJECTIVE: The elevation of the percentage of regulatory CD4+CD25+ T lymphocytes (Treg) has been recently described during septic shock. The objective of the present study was to investigate whether this increased percentage was due to Treg proliferation. DESIGN: Observational study. SETTING: Adult intensive care units in a university hospital. SUBJECTS: Patients with septic shock (n = 54) and healthy individuals (n = 30). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In patients, we first confirmed the increased percentage of Treg among CD4+ lymphocytes in comparison with healthy individuals. Surprisingly, regarding absolute counting, we demonstrated that both T CD4+ lineages (CD25+ and CD25-) were diminished immediately after the onset of shock. Then, whereas Treg returned rapidly to healthy donors values, CD4+CD25- T lymphocytes remained dramatically reduced. Finally, Foxp3 (Treg-related gene) messenger RNA quantification enabled us to definitively rule out a lack of proliferation since it was not increased during shock. CONCLUSION: The increased percentage of Treg after shock is due not to their proliferation but to a decrease in CD4+CD25- T lymphocyte number. We hypothesize that it might be due to a resistance of Treg to apoptosis processes occurring during septic shock.

APACHE↗

PubMed1993

Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy.

Cerebral metabolite concentrations and water content were measured by means of localized proton magnetic resonance spectroscopy in 50 children, while metabolite peak ratios in short echo time spectra were evaluated in 173 examinations. Normative curves for normal development were established for two cerebral locations. The current report presents the first study of absolute metabolite concentrations and T1- and T2- relaxation as a function of age. Myo-inositol was found dominating the spectra at birth (12 mmoles/kg), while choline is responsible for the strongest peak in older infants (2.5 mmoles/kg). Creatine and N-acetyl groups are at significantly lower concentrations in the neonate than in the adult (Cr: 6, NA: 5 mmoles/kg). NA and Cr are determined by gestational age, whereas the concentration of ml correlates best with postnatal age. Quantitative 1H MRS is expected to be of particular value in diagnosis and monitoring of pathology in infants, since metabolite ratios are often misleading.

Brain↗

PubMed2006

Progressive high-intensity resistance training and bone mineral density changes among premenopausal women: evidence of discordant site-specific skeletal effects.

Regular weight-bearing physical activity has been widely recommended for adult women and may be beneficial in preserving bone mineral density (BMD). However, there is conflicting evidence regarding the effects of resistance training on BMD in premenopausal women. Novel systematic review and meta-analysis evidence is presented on the effects of progressive high-intensity resistance training on BMD in premenopausal women. Structured computer searches of MEDLINE, EMBASE, PubMed, Web of Science, SportDiscus and Evidence Based Medicine Reviews Multifile were undertaken along with hand-searching of key journals and reference lists to locate relevant studies published up to September 2004. Criteria for included studies were published controlled studies and randomised controlled trials (RCTs) evaluating the effects of progressive, high-intensity resistance training studies on BMD in premenopausal women. Two authors reached consensus on all included and excluded studies. Study outcomes for analysis were radiographic BMD assessment from first follow-up at lumbar spine and femoral neck. Primary outcomes for analysis were absolute changes in BMD g/cm(2) at lumbar spine and femoral neck. Relative changes (percentage change) in BMD at lumbar spine were also assessed. Data were extracted from studies including study design, participant characteristics and treatment mode, intensity and duration, using electronic data extraction forms. Where necessary, relevant information was obtained by contacting study authors. Methodological quality of studies was assessed using a well recognised three-question instrument designed to assess bias. Informal assessment for small sample study effects and potential bias was undertaken through visual inspection of funnel plots. The weighted mean difference method (inverse of the variances) was used for combining study group estimates. Quantification of the effect of heterogeneity among study outcomes was assessed using the I(2) statistic. Random effects and fixed-effect models were applied according to observed study heterogeneity. Comparisons resulting in I(2) > 50.0% were considered heterogeneous. Where heterogeneity was observed, a random effects model was applied. Pooled estimates of effect were calculated using the Cochrane Collaboration's Review Manager (RevMan) 4.2.1 software.High-intensity progressive resistance training was shown to be efficacious in increasing absolute BMD at the lumbar spine (p < 0.00001) but not the femoral neck (p = 0.78) in premenopausal women. The weighted mean difference (WMD) using a fixed-effect model for six controlled trials investigating the lumbar spine BMD change was 0.014 g/cm(2) (95% CI 0.009, 0.019; p < 0.00001). The relative BMD change for this site was 0.98% (WMD [random effects], 95% CI 0.49, 3.91%; p = 0.04). In contrast, studies evaluating femoral neck BMD changes showed no significant BMD change (WMD [fixed effect], 0.001 g/cm(2) 95% CI -0.006, 0.008; p = 0.78). Funnel plot inspection of lumbar spine effects indicated that smaller studies demonstrated larger treatment effects. An asymmetry towards studies with positive BMD outcomes was also noted. The methodological quality score of all included studies was low and no study presented a valid intention-to-treat accounting for participant drop-out (attrition). As such, the modest overall treatment effects for resistance training on BMD among premenopausal women observed in this review may be biased and should be interpreted with caution. It is concluded that further RCTs of resistance training of sufficiently long duration and providing optimum type, intensity and volume of loading, with intention-to-treat analysis are now required.

Bone Density↗

PubMed2006

Comparative quantification of umbilical cord blood CD34+ and CD34+ bright cells using the ProCount-BD and ISHAGE protocols.

The total number of CD34+ cells is the most relevant clinical parameter when selecting human umbilical cord blood (HUCB) for transplantation. The objective of the present study was to compare the two most commonly used CD34+ cell quantification methods (ISHAGE protocol and ProCount - BD) and analyze the CD34+ bright cells whose 7-amino actinomycin D (7AAD) analysis suggests are apoptotic or dead cells. Twenty-six HUCB samples obtained at the Placental Blood Program of New York Blood Center were evaluated. The absolute numbers of CD34+ cells evaluated by the ISHAGE (with exclusion of 7AAD+ cells) and ProCount (with exclusion of CD34+ bright cells) were determined. Using the ISHAGE protocol we found 35.6 +/- 19.4 CD34+ cells/microL and with the ProCount method we found 36.6 +/- 23.2 CD34+ cells/microL. With the ProCount method, CD34+ bright cell counts were 9.3 +/- 8.2 cells/microL. CD34+ bright and regular cells were individually analyzed by the ISHAGE protocol. Only about 1.8% of the bright CD34+ cells are alive, whereas a small part (19.0%) is undergoing apoptosis and most of them (79.2%) are dead cells. Our study showed that the two methods produced similar results and that 7AAD is important to exclude CD34 bright cells. These results will be of value to assist in the correct counting of CD34+ cells and to choose the best HUCB unit for transplantation, i.e., the unit with the greatest number of potentially viable stem cells for the reconstitution of bone marrow. This increases the likelihood of success of the transplant and, therefore, the survival of the patient.

Antigens, CD34↗

PubMed2006

Smaller cerebellar volumes in very preterm infants at term-equivalent age are associated with the presence of supratentorial lesions.

BACKGROUND AND PURPOSE: Traditionally cerebellar functions are thought to be related to control of tone, posture, gait, and coordination of skilled motor activity. However, there is an increasing body of evidence implicating the cerebellum in cognition, language, memory, and motor learning. Preterm infants are at increased risk of neurodevelopmental delay, cognitive dysfunction, and behavioral and emotional disturbances. The role of the cerebellum in these adverse outcomes is unclear. OBJECTIVE: The objective of this study was to determine whether absolute cerebellar volumes differ between term-equivalent preterm infants and term-born control infants and to assess whether cerebellar volume is influenced by any possible antenatal, perinatal, and postnatal factors. METHODS: The study compared the MR imaging cerebellar volume by using a manual quantification program of 113 preterm infants at term-equivalent age and 15 term-born control infants. RESULTS: The median cerebellar volume of preterm at term-equivalent age was 25.4 cm3 and that of term-born control infants was 26.9 cm3. On initial analysis, there was a significant median difference of 2.0 cm3 (95% CI, 1.2 cm3 to 2.7 cm3) (2-sided P < .0001). However multiple regression analysis of perinatal variables showed that only infants with supratentorial lesions (P = .003) were significantly associated with the reduction in cerebellar volumes. The median cerebellar volumes were the following: supratentorial lesions, 18.9 cm3; no supratentorial lesions, 26.1 cm3; and term infants, 26.9 cm3 (analysis of variance, P < .0001). Hence, there was no significant difference in cerebellar volumes of preterm infants at term-equivalent age in the absence of supratentorial lesions. The median vermal volumes were 0.7 cm3 and were significantly related to cerebellar volumes both in preterm infants with and without lesions and in term-control infants. CONCLUSION: Premature infants at term-equivalent age have similar total cerebellar and vermal volumes compared with term infants in the presence of normal brain imaging. Reduced cerebellar volume in preterm infants at term-equivalent age is seen in association with supratentorial pathology such as hemorrhagic parenchymal infarction, intraventricular hemorrhage with dilation, and periventricular leukomalacia.

Cerebellum↗

PubMed1991

Comparison of thallium-201 SPECT and planar imaging methods for quantification of experimental myocardial infarct size.

To compare single photon emission computed tomography (SPECT) and planar thallium-201 (TI-201) myocardial perfusion imaging methods for quantification of left ventricular infarct size, 12 dogs with 6 to 8 hours of closed-chest coronary occlusion and 5 normal dogs were studied. After intravenous administration of TI-201, SPECT and three-view planar images were obtained. After the animals were put to death, hearts were sliced and stained with triphenyltetrazolium chloride (TTC) for planimetric determination of left ventricular infarct size. Infarct size on each SPECT slice and planar image was defined as the percentage of circumferential count profiles falling below the limits derived from normal dogs. Infarct size as a percentage of left ventricular mass was determined from SPECT and planar images before and after correcting for differences in myocardial slice mass from apex to base. The correlation coefficients, the concordance correlation coefficients (reflecting closeness to the line of identity), and the mean absolute deviations of the four methods versus TTC staining were 0.83, 0.77, and 5.1% (SPECT, no correction); 0.85, 0.84, and 3.7% (SPECT with correction); 0.81, 0.42, and 12.9% (planar, no correction); and 0.75, 0.49, and 10.4% (planar with correction). The regression lines did not differ from the line of identity for SPECT, whereas they differed significantly for planar imaging. Thus both SPECT and planar imaging are well suited for quantification of left ventricular infarct size. SPECT, however, appears to be superior to planar imaging, since its regression line more closely approximates the line of identity.

Animals↗

PubMed2002

The in vivo regulation of pulsatile insulin secretion.

The presence of oscillations in peripheral insulin concentrations has sparked a number of studies evaluating the impact of the insulin release pattern on the action of insulin on target organs. These have convincingly shown that equal amounts of insulin presented to target organs have improved action when delivered in a pulsatile manner. In addition, impaired (not absent) pulsatility of insulin secretion has been demonstrated in Type II (non-insulin-dependent) diabetes mellitus, suggesting a possible mechanism to explain impaired insulin action in Type II diabetes. Whereas the regulation of overall insulin secretion has been described in detail, the mechanisms by which this regulation affects the pulsatile insulin secretory pattern, and the relative and absolute contribution of changes in the characteristics of pulsatile insulin release have not been reviewed previously. This review will focus on the importance of the secretory bursts to overall insulin release, and on how insulin secretion is adjusted by changes in these secretory bursts. Detection and quantification of secretory bursts depend on methods, and the methodology involved in studies dealing with pulsatile insulin secretion is described. Finally, data suggest that impaired pulsatile insulin secretion is an early marker for beta-cell dysfunction in Type II diabetes, and the role of early detection of impaired pulsatility to predict diabetes or to examine mechanisms to cause beta-cell dysfunction is mentioned.

Animals↗