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PubMed2005

MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia.

PURPOSE: P-Glycoprotein (Pgp) is associated with poor outcome in acute myeloid leukemia (AML). We have investigated other ATP-binding cassette proteins such as BCRP, MRP1, MRP2, MRP3, and MRP5 for their potential implication in chemoresistance. EXPERIMENTAL DESIGN AND RESULTS: Eighty five AML patient samples were analyzed in this study. First, MRP3 function was higher in patients which had a high level of leukocytes (P = 0.01), a M5 FAB subtype (P = 0.04), and an intermediate or poor cytogenesis (P = 0.05). BCRP activity was not correlated with clinical or biological variables, but high Pgp activity was correlated with the following variables: CD34 expression (P = 0.002), FAB subtype (P = 0.002), intermediate or poor cytogenesis (P = 0.02), and elderly patients (P = 0.03). Second, Pgp, MRP3, and BCRP activities were correlated with complete remission (P = 0.02, P = 0.04, and P = 0.04, respectively), disease-free survival (P = 0.02, P = 0.03, and P = 0.25, respectively), and overall survival (P = 0.04, P = 0.04, and P = 0.05, respectively) in multivariate analysis. The patient samples expressing one or none of these Pgp, MRP3, or BCRP functional proteins have a better prognosis than the patients expressing two or three of these functional proteins (complete remission, P = 0.02; disease-free survival, P = 0.01; overall survival, P < 0.001). CONCLUSIONS: BCRP and MRP3 may also be involved in chemoresistance in AML, especially MRP3 in patients with M5 FAB. Additional modulation of BCRP or MRP3 to Pgp modulation may be necessary in some patients in order to improve the treatment outcome.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Histopathologic diagnosis and classification of prostate adenocarcinoma: biologic significance.

Early diagnosis and accurate, biologically meaningful classification of prostate neoplasia remain important goals. The relation of evolving clinicopathologic concepts of histologic appearances to potential tumor progression is a major advance in classification of prostatic neoplasia. The criteria for recognizing incidental or "occult" stage A-l adenocarcinomas remain problematic in diagnosis, and focal neoplasms with little or no propensity to progression must be differentiated from cancers with a high likelihood of aggressive behavior. Current histologic grading systems in classifying prostate adenocarcinoma accurately identify two cancer subsets: 1) focal well differentiated tumors which rarely progress, and 2) diffuse poorly differentiated tumors which invariably develop metastatic disease. Unfortunately, the majority of prostatic cancers are classified in the intermediate group in which the prognosis is variable and difficult to differentiate purely by histology. Our laboratory recently adapted image analysis of cellular DNA quantitation--a major improvement in accurately predicting tumor behavior, especially in the intermediate histologic grades. We and others have found that tumors with abnormal (aneuploid) DNA content are more likely to progress than neoplasms with normal (diploid) DNA content.

Adenocarcinoma↗
PubMed1981

Reproducibility of echocardiography. A study evaluating the variability of serial echocardiographic measurements.

In this study, serial reproducibility was determined on standard M-mode (M-mode) and two dimensional guided M-mode (2-D M-mode) records for ten normal volunteers and 20 patients. Overall intraobserver variability in the normal group was 518 +/- 1.8 percent (M-mode) and 3.1 +/- 0.8 percent (2-D M-mode), and in the patient group 3.1 +/- 0.6 percent (M-mode) and 4.7 +/- 0.7 percent (2-D M-mode) (P = NS). Variability on serial examination, however, was twofold to threefold greater. In the normal group, reproducibility varied by 10.8 +/- 1.6 percent (M-mode) and 9.4 +/- 1.2 percent (2-D M-mode), while in the patient group, it was 8.7 +/- 0.9 percent (M-mode) and 9.4 +/- 0.7 percent (2-D M-mode). The lowest serial variability achieved was for the diastolic LV dimension on serial M-mode examination (4 percent); the largest variability pertained to measurement of the interventricular septum (14 percent). Other structures had intermediate variation in reproducibility. This study emphasizes that establishing performance variability for an echocardiographic laboratory is an important part of the interpretation of serial records.

Echocardiography↗
PubMed2001

Role of variability in microvascular resistance on fractional flow reserve and coronary blood flow velocity reserve in intermediate coronary lesions.

BACKGROUND: Fractional flow reserve (FFR) and coronary blood flow velocity reserve (CFR) represent physiological quantities used to evaluate coronary lesion severity and to make clinical decisions. A comparison between the outcomes of both diagnostic techniques has not been performed in a large cohort of patients with intermediate coronary lesions. METHODS AND RESULTS: FFR and CFR were assessed in 126 consecutive patients with 150 intermediate coronary lesions (between 40% and 70% diameter stenosis by visual assessment). Agreement between outcomes of FFR and CFR, categorized at cut-off values of 0.75 and 2.0, respectively, was observed in 109 coronary lesions (73%), whereas discordant outcomes were present in 41 lesions (27%). In 26 of these 41 lesions, FFR was <0.75 and CFR>or=2.0 (group A); in the remaining 15 lesions, FFR was >or=0.75 and CFR<2.0 (group B). Minimum microvascular resistance, defined as the ratio of mean distal pressure to average peak blood flow velocity during maximum hyperemia, showed a large variability (overall range, 0.65 to 4.64 mm Hg x cm(-1) x s(-1)) and was significantly higher in group B than in group A (2.42+/-0.77 versus 1.91+/-0.70 mm Hg x cm(-1) x s(-1); P:=0.034). CONCLUSIONS: Our findings demonstrate the prominent role of microvascular resistance in modulating the relationship between FFR and CFR and emphasize the importance of combined pressure and flow velocity measurements to evaluate coronary lesion severity and microvascular involvement.

Angina Pectoris↗
PubMed1987

Hemodynamic pharmacology of p-chloroamphetamine, a serotonin agonist, in conscious rats.

The hemodynamic effects of p-chloroamphetamine (PCA), an indirect serotonin (5-HT) agonist, were studied in conscious, unrestrained rats. PCA caused an immediate hypotension and bradycardia followed by a dose-dependent increase in mean arterial pressure (MAP), which lasted for 15 to 60 min, associated with variable effects on heart rate. An intermediate dose increased MAP and resistance in hindquarter and mesenteric, but not renal, vascular beds. The pressor effect of PCA was blocked by prazosin and by 6-hydroxydopamine plus adrenal demedullation, but not by 6-hydroxydopamine or adrenal demedullation separately. Ganglionic blockade with chlorisondamine or beta adrenoceptor blockade with propranolol potentiated the pressor response to PCA, whereas several manipulations of central 5-HT systems (fluoxetine, methysergide and 5,7-dihydroxytryptamine) reduced but did not eliminate the hypertension observed after PCA. The initial bradycardia and hypotension were abolished by chlorisondamine or atropine but not reduced by any other pretreatment, whereas the variable heart rate response was converted to a marked, sustained tachycardia by ganglionic blockade or atropine and to a consistent bradycardia by propranolol and peripheral sympathectomy. The data suggest that PCA causes an immediate central or reflex vagal activation to decrease heart rate and MAP, followed by a central 5-HT-mediated increase in sympathetic activity that increases MAP. Most of the pressor effect observed between 5 and 30 min after PCA appears to be mediated by a direct effect on release of norepinephrine and epinephrine from sympathetic nerve terminals and the adrenal medulla, respectively. Only a minor part of the hemodynamic response to PCA appears to be attributable to its effect on release of 5-HT in the brain.

Adrenal Medulla↗
PubMed1977

Identification of a major locus contributing to erythrocyte 2,3-diphosphoglycerate variability in hooded (Long-Evans) rats.

The erythrocyte glycolytic intermediate 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) play an important role in oxygen transport and delivery by binding to hemoglobin (Hb) and reducing its affinity for oxygen. Considerable quantitative variability in the levels of DPG and ATP exists in human populations and in a population of hooded (Long-Evans) rats we have studied. This paper presents the results of studies on the genetic component of DPG-level variation in an outbred population of hooded rats. Beginning with about 100 rats, a two-way selection experiment was initiated. Pairs of rats with the highest DPG levels were mated to produce a High-DPG rat strain and animals with the lowest DPG levels were mated to produce a Low-DPG strain. Mean DPG levels responded rapidly to selection and, from generation 3 on, the differences between strain means were highly significant. Ten High-DPG strain rats were intercrossed with 10 Low-DPG strain rats of generation 10 to produce an F1 generation in which the DPG levels were almost as high as those of High-DPG animals. This indicates partial dominance of High-DPG alleles. The F2 DPG-level distribution showed two distinct subpopulations. The high DPG subpopulation contained three times as many animals as the low DPG subpopulation. From these results and the statistical analyses performed, it was concluded that the DPG differences between strains were due to an allelic difference at one major locus, the allele carried by the High-DPG strain showing partial dominance over the allele carried by the Low-DPG strain. It appears that this locus may also effect ATP levels to a large extent and is polymorphic in hooded rat populations. Identification of this locus gives us a useful tool for studies of the physiological effects of DPG variability, as well as providing an example of a major gene effect in a quantitatively varying trait.

Adenosine Triphosphate↗
PubMed2006

Semantics prevalence over syntax during sentence processing: a brain potential study of noun-adjective agreement in Spanish.

A review of the literature about the interplay of syntax and semantics, using event-related brain potentials (ERPs), revealed that the results are highly heterogeneous, owing to several possible variables. An experiment was conducted with Spanish sentences that factorially combined syntactic and semantic violations in the same sentence-intermediate adjective and controlled for working memory demands, variables that in previous studies have rarely been taken into consideration. Violations consisted in noun-adjective number or gender disagreements (syntactic violation), noun-adjective semantic incompatibility (semantic violation), or both (combined violation). The N400 to semantic violations was unaffected by additional syntactic violations. The P600/SPS component, considered to reflect syntactic processes, was elicited by both single syntactic and semantic violations but seemed to be diminished in combined violations relative to single syntactic violations. These results suggest that under the conditions of the present experiment semantic information may have a prevailing role over syntactic information.

Adolescent↗
PubMed1991

Comprehensive predictions of outcome in closed head-injured patients. The development of prognostic equations.

A comprehensive diagnostic evaluation was administered to 162 closed head-injured patients within 1 to 21 days (mean, 7.5 days) after injury. Each evaluation consisted of (1) power spectral analyses of electroencephalogram (EEG) recorded from 19 scalp locations referenced to age-matched norms, (2) brainstem auditory evoked potentials, (3) computed tomography (CT)-scan, and (4) Glasgow Coma Score (GCS) at time of admission (GCS-A) and at time of EEG test (GCS-T). Functional outcome at one year following injury was assessed using the Rappaport Disability Rating Scale (DRS), which measures the level of disability in the six diagnostic categories of (1) eye opening, (2) best verbal response, (3) best motor response, (4) self-care ability for feeding, grooming, and toileting, (5) level of cognitive functioning, and (6) employability. The ability of the different diagnostic measures to predict outcome at one year following injury was assessed using stepwise discriminant analyses to identify patients in the extreme outcome categories of complete recovery versus death and multivariate regression analyses to predict patients with intermediate outcome scores. The best combination of predictor variables was EEG and GCS-T, which accounted for 74.6% of the variance in the multivariate regression analysis of intermediate outcome scores and 95.8% discriminant accuracy between good outcome and death. The best single predictors of outcome in both the discriminant analyses and the regression analyses were EEG coherence and phase. A gradient of prognostic strength of diagnostic measures was EEG phase greater than EEG coherence greater than GCS-T greater than CT-scan greater than EEG relative power. The value of EEG coherence and phase in the assessment of diffuse axonal injury was discussed.

Activities of Daily Living↗
PubMed1998

Factors associated with maternal cell contamination in amniocentesis samples as evaluated by fluorescent in situ hybridization.

OBJECTIVE: To determine which patient- and procedure-related factors contribute to maternal cell contamination in uncultured amniocentesis fluid. METHODS: One hundred thirty amniotic fluid (AF) samples were obtained by three operator groups: maternal-fetal medicine faculty (n=50), general obstetrician gynecologists (n=50), and obstetrics and gynecology residents supervised by maternal-fetal medicine faculty (n=30). These groups were designated "most," "intermediate," and "least experience," respectively. Study variables were recorded at the time of the procedure. Amniotic fluid cells from male fetuses underwent fluorescent in situ hybridization. Maternal cell contamination was calculated by analyzing 100 cells and determining the number of XX and XY cells. A control system was created to validate the methods used for AF processing and cell counting. RESULTS: Median maternal cell contamination was 2.0%. Maternal cell contamination did not vary with body mass index (r=-.13, P=.14), gestational age (r=.08, P=.35), or placental location (P=.55). Maternal cell contamination was significantly elevated with placental penetration (6.0% compared with 1.0%, P < .001), two passes (27.5% compared with 2.0%, P=.002), blood-tinged fluid color (14.0% compared with 2.0%, P < .001), and operator inexperience ("intermediate experience" compared with "most experience," 4.5% compared with 1.0%, P=.026). Maternal cell contamination did not differ between the "most experience" and "least experience" groups (1.0% compared with 2.0%, not significant). Concordance between detected and actual maternal cell contamination in the control system was extremely high (concordance coefficient=0.98, P=.008), confirming the validity of the techniques used. CONCLUSION: Our techniques of cell counting and maternal cell contamination calculation are accurate. Maternal cell contamination is increased with placental penetration, two passes, and operator inexperience. However, with expert supervision, inexperienced physicians can perform amniocentesis without an increase in maternal cell contamination.

Amniocentesis↗
PubMed1975

Correlation between brain levels and biochemical effects of the optical isomers of p-chloroamphetamine.

The biochemical effects of d- and l-p-chloroamphetamine (PCA) were compared with the brain levels of the unchanged drug at various times after a single injection. Initially both isomers produced rapid and pronounced decreases in the whole brain levels of serotonin and 5-hydroxyindoleacetic acid, tryptophan hydroxylase activity and the synaptosomal uptake of 3-H-serotonin. At later times (e.g., 2 weeks), the effects of the d-isomer were much more pronounced than were those of the l-isomer. At intermediate times (2-4 days), a variable and dose-dependent recovery of synaptsomal uptake activity and tryptophan hydroxylase activity occurred after d-PCA. In both whole brain and forebrain, long-term reductions in these activities were found. However, in the midbrain, an area containing the cell bodies of serotonergic neurons, only a slight initial decrease in tryptophan hydroxylase activity occurred. The whole brain levels of the two isomers were equal from 4 to 96 hours after injection and declined exponentially in a single monophasic manner monophasic decine of the levels of PCA was found in forebrain and midbrain samples. Thus, the initial and long-term effects of PCA are apparently mediated by different mechanisms. The former is correlated with the brain levels of the unchanged drug; the latter is not. The lack of any indication of a biphasic decay curve after 10 half-lives and the intermediate recovery of serotonergic function do not support a reserpine-like mechanism for the long-term effects of PCA. Instead, a mechanism related to neurotoxicity is proposed.

Amphetamines↗
PubMed1991

Exon recognition and nucleocytoplasmic partitioning determine AMPD1 alternative transcript production.

Two mature transcripts are produced from the rat AMP deaminase 1 (AMPD1) gene, one that retains exon 2 and one from which exon 2 has been removed. The ratio of these two transcripts is controlled by stage-specific and tissue-specific signals (I. Mineo, P. R. H. Clarke, R. L. Sabina, and E. W. Holmes, Mol. Cell. Biol. 10:5271-5278, 1990; R. L. Sabina, N. Ogasawara, and E. W. Holmes, Mol. Cell. Biol. 9:2244-2246, 1989). By using transfection studies with native, mutant, and chimeric minigene constructs, two steps in RNA processing that determine the ratio of these two transcripts have been identified. The first step is recognition of this exon in the primary transcript. The primary transcript is subject to alternative splicing in which exon 2 is either recognized and thereby included in the mature mRNA or is ignored and retained in a composite intron containing intron 1-exon 2-intron 2. The following properties of the primary transcript influence exon recognition. (i) Exon 2 is intrinsically difficult to recognize, possibly because of its small size (only 12 bases) and/or a suboptimal 5' donor site at the exon 2-intron 2 boundary. (ii) Intron 2 plays a permissive role in recognition of exon 2 because it is removed at a relatively slow rate, presumably because of the suboptimal polypyrimidine tract in the putative 3' branch site. The second step in RNA processing that influences the ratio of mature transcripts produced from the AMPD1 gene occurs subsequent to the ligation of exon 2 to exon 1. An RNA intermediate, composed of exon 1-exon 2-intron 2-exon 3, is produced in the first processing step, but it is variably retained in the nucleus. Retention of this intermediate in the nucleus is associated with accumulation of the mature mRNA containing exon 2, while cytoplasmic escape of this intermediate is reactions, exon recognition and nucleocytoplasmic partitioning, determine the relative abundance of alternative mRNAs derived from the AMPD1 gene.

AMP Deaminase↗
PubMed1999

137Caesium distribution in the eastern Mediterranean Sea: recent changes and future trends.

A series of sampling campaigns were carried out in the eastern Mediterranean in the period 1995-1997, to examine the relationship between the distribution of 137Cs in the water column and water mass circulation. 137Cs concentration in the surface water ranges between 3.3 and 4.0 mBq/l all over the area, indicating that the input due to the Chernobyl accident has been transferred to deep water layers by convection processes. In fact, in the vertical profiles, relative maxima are observed in the intermediate (4 mBq/l) and deep waters (approximately 2.5 mBq/l) formed after the Chernobyl accident. A clear Chernobyl signal also traces the new deep waters formed in the Aegean Sea that, exiting from the Cretan Arc Straits, since 1991 are spreading in the bottom layer of the eastern Mediterranean. The changes in 137Cs vertical profiles related to the new thermohaline circulation of the intermediate and deep waters of the eastern Mediterranean are being monitored at a deep station in the western Ionian Sea. The 1997 profile shows a decrease in 137Cs concentration both in the Levantine intermediate water and in the eastern Mediterranean deep water with respect to 1996. The decrease in Levantine intermediate water is likely due to seasonal/interannual variability, while the changes in the deep layer are related to the spreading westward into the Ionian of the new Aegean dense water. Along the path towards the western Mediterranean, 137Cs content in the Levantine intermediate water decreases from approximately 4 mBq/l in the W-Ionian Sea to approximately 2 mBq/l at the western sill of the Sicily Straits, due to mixing with underlying water, with lower caesium content, near the Malta Sill. Time-series measurements at the western sill of the Sicily Straits show that, while 137Cs concentration in the surface water entering the eastern Mediterranean remained constant (approximately 3.5 mBq/l) in the period 1993-1997, its level in the Levantine intermediate water leaving the basin decreased from 3.5 to 2.0 mBq/l.

Cesium Radioisotopes↗
PubMed1995

Comparison of locus of control among nursing home residents with visual impairment and normal sight.

BACKGROUND: Despite well-documented effects of psychosocial factors on patients with visual impairment, eye care professionals often fail to incorporate these important concepts into management plans for this population. METHODS: This study reports findings using the Levenson Locus of Control (LoC) Scale and its two modifications by Shewchuk et al. The study compares nursing home residents with visual impairment to individuals having normal sight to determine the status of LoC as a factor in visual rehabilitation. RESULTS: T values vary significantly in LoC scores of nursing home residents sampled when compared with variables of gender and type of residence (i.e., independent living, congregate living, assisted living, intermediate care). T values do not vary significantly, however, across variables of visual impairment and normal sight. CONCLUSIONS: LoC does not appear to be a psychosocial factor that varies significantly among elderly nursing home residents sampled across the characteristics of normal sight and visual impairment. However, the population sampled may possess qualities that prevent generalization to the elderly population as a whole. A need for research with a larger, more diverse sample using locus of control scales as well as research using other psychosocial tests to evaluate patients with visual impairment is indicated.

Aged↗
PubMed1983

Methotrexate cerebrospinal fluid and serum concentrations after intermediate-dose methotrexate infusion.

Twenty-nine children with acute lymphocytic leukemia were given 24-hr infusions of intermediate-dose methotrexate (MTX, 1000 mg/m2) with and without intrathecal (IT) MTX (12 mg/m2), followed by leucovorin rescue. There was substantial interpatient variability in MTX systemic clearance (98.3 +/- 51 ml/min/m2), inducing total steady-state serum MTX concentrations ranging from 5.4 to 33.7 microM. The cerebrospinal fluid (CSF) concentration at the end of the infusion was 0.27 (+/- 0.1) microM when no IT-MTX was given and correlated with total steady-state (24-hr) serum concentration of MTX. By stepwise regression, the CSF MTX concentration correlated better with the nonprotein bound (free) steady-state serum MTX concentration (r = 0.66, P less than 0.01) than with total steady-state serum MTX concentration. Mean CSF: serum MTX concentration ratio was 0.023 (+/- 0.04) when no IT MTX was given. When an IT MTX dose (12 mg/m2) was given at the start of the MTX infusion, the steady-state CSF MTX concentration was 1.1 (+/- 0.4) microM, leading to a mean CSF: serum ratio of 0.073 (+/- 0.05). Despite 7-hydroxy-MTX serum concentrations exceeding MTX concentrations immediately after infusion, 7-hydroxy-MTX was not detectable in CSF of most patients (21 of 29), and was less than 50% of the concurrent MTX concentration when detectable. These data establish the substantial interpatient variability in CSF distribution of MTX after intermediate-dose MTX infusions and establish a significant correlation between steady-state free concentration of MTX in serum and CSF MTX concentration.

Child↗
PubMed2006

An investigation of FRAXA intermediate allele phenotype in a longitudinal sample.

The FRAXA trinucleotide repeat at Xq27.3 gives rise to fragile X syndrome when fully expanded, and both premature ovarian failure (POF) and fragile X tremor and ataxia syndrome (FXTAS) when in the premutation range. Reports of phenotypic effects extending into the intermediate repeat range are inconsistent but some studies suggest that these smaller expansions predispose to special educational needs (SEN). This study utilises the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort to investigate cognitive and behavioural variables that might be associated with FRAXA intermediate alleles. The current study failed to find any strong evidence of association of FRAXA intermediate alleles with SEN, behavioural problems or cognitive difficulties. However, our findings illustrate some of the difficulties encountered in identifying individuals with SEN. The power to identify specific components of cognitive and behavioural difficulties was reduced due to elective drop-out, which is characteristic of longitudinal studies. Our findings demonstrate the non-random loss of participants from this cohort and highlight problems that may arise when such data are used in genetic association studies.

Alleles↗
PubMed1997

Test-retest reliability and influence of practice effects on performance in a multi-user computerized psychometric test system for use in clinical pharmacological studies.

Fifty naive drug-free healthy young male or female volunteers performed psychometric tests on 6 sessions with 3- to 4-days intervals, using a new multi-user computerized test system for use in clinical pharmacology. Tests of simple reaction time, complex reaction time, concentration, motor coordination, and short-term memory (word pairs or figures) were performed. Clear practice effects were shown for almost every psychometric variable recorded. The magnitude differed considerably between tests. The magnitude of practice effects was most evident (46.5-55.0%) for the concentration test, the coordination test, and the Vienna reaction test. Intermediate practice effects (20.8-31.0%) were observed with the complex reaction test (percent correct reactions) and both short-term memory tests (test duration). Only small practice effects (5.1-14.3%) were observed with the reaction times of the simple and the complex reaction test, and the percent correct responses in the short-term memory tests. After 3 test sessions, significant further improvements could not be shown for most tests, but for the reaction times in the simple and the complex reaction test this was true from the first or the second test session, respectively. For the concentration test and the coordination test, significant practice effects could be shown even after 5 training sessions. It is recommended to perform at least one training session before the start of clinical pharmacological studies with psychometric testing. Test-retest-reliability, as determined from session 5 to session 6 by Spearman's rank correlation coefficient (R8), was very good (> or = 0.95) for the concentration test (percent correct responses) and the coordination test (mean steering time). Most other variables showed intermediate (0.44-0.68) reliability (reaction times in the simple and complex reaction test, percent correct reactions in the complex reaction test, percent errors in the concentration test, test duration of the short-term memory tests). The percent correct answers, which is the primary variable in both short-term memory tests, had a relatively poor reliability (0.14-0.18).

Adult↗
PubMed1976

Echocardiographic assessment of the level of cardiac compensation in valvular heart disease.

The level of cardiac compensation in valvular disease was studied by relating echocardiographic and cardiac catheterization measurements. Three groups -- compensated, intermediately compensated, and decompensated -- were defined according to the left ventricular angiographic pattern and cardiac output. The echocardiographic ejection indices, percent left ventricular minor diameter shortening, ejection fraction, and fiber shortening rate were significantly higher than normal in compensated mitral regurgitation, lower then normal in compensated aortic stenosis, and within normal limits in compensated aortic insufficiency. In the decomposed state these indices were depressed. Intermediate compensation was best recognized by combining several echocardiographic variables into an echocardiographic score based on multivariate discriminant function analysis. Thus, the compensated volume overload states (aortic and mitral regurgitation) and pressure overload state (aortic stenosis) have separate sets of "normal" echocardiographic values; low ejection indices characterize the decompensated group, while recognition of intermediate compensation requires analysis of multiple echocardiographic variables.

Adult↗
PubMed1990

On the relation between distinct components of the cytoskeleton: an epitope shared by intermediate filaments, microfilaments and cytoplasmic foci.

Monoclonal antibodies were generated against detergent-insoluble cytoskeletal proteins isolated from low-density membrane fractions of rat liver. By immunofluorescence, one of the antibodies stains three distinct structures in cultured rat fibroblast and hepatocyte lines as well as the PtK2 rat-kangaroo kidney epithelial line. These structures are: i) many tangled filaments similar to intermediate filaments (IFs), ii) fewer and variable numbers of straight filaments, and iii) punctate cytoplasmic foci, often most intense around the nucleus. All three of these structures are resistant to extraction by non-ionic detergent. Close examination reveals that the tangled and straight filaments are not stained uniformly, but as a series of bright patches. In cells treated with nocodazole, the antibody reacts strongly with a perinuclear filamentous cage. Very few tangled filaments are detected in these cells, however, the straight filaments and punctate cytoplasmic staining are resistant to nocodazole treatment. Double-label immunofluorescence shows that, even though tangled filament distribution and nocodazole sensitivity are similar to the behavior of vimentin IFs, there is only partial coincidence of staining with either vimentin or cytokeratin IFs. The straight filaments coincide with some actin stress fibers, but the punctate cytoplasmic staining is not related to IFs, actin, or tubulin. Thus, this monoclonal antibody stains a novel group of three seemingly unrelated cytoskeletal structures, including a previously undescribed insoluble nonfilamentous pool. Taken as a whole, two hypotheses are consistent with these data. i) The antigen recognized may be a protein which has a large insoluble cytoplasmic pool and binds both IFs and actin, but only binds to a subset of each class of filaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗