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Characterization of Iron Uptake from Ferrioxamine B by Chlorella vulgaris.

Iron uptake from two Fe(3+)-hydroxamate siderophores, ferrioxamine B and Fe(3+)-rhodotorulate, by iron-stressed Chlorella vulgaris (ATCC strain 11468) was evaluated with some comparison to iron uptake from synthetic and organic acid ferric chelates. Iron-stress induced iron uptake from ferrioxamine B. Dissipation of the electrochemical gradient, via uncouplers, inhibited iron uptake. Respiratory inhibitors gave variable results, an indication that a direct link to respiration was not apparent. Vanadate inhibition of iron uptake indicated that an ATPase or phosphate intermediate could be involved in the uptake mechanism. Divalent cations manifested variable effects dependent on the cation and chelator used. These data confirm that C. vulgaris has an inducible iron-uptake system for Fe(3+)-hydroxamic acid siderophores which may involve a different mechanism than that observed for other chelates.

Journal Article↗

Gender typing of game choices and qualities of boys' play behavior.

Relationships between gender choices and both movement patterns and social behavior were studied in first- and second-grade boys. Three-child, structured play groups were each composed of a boy whose mother saw him as high masculine in play preference on the Games Inventory, one seen as average, and one low masculine. Behaviors rated from videotapes included gender presentation variables, (e.g., leg separation), indicators of dominance and personal comfort (e.g., range of movements), and indicators of social skill and peer response (e.g., interaction initiations). The low masculine boys were found to be the most feminine in their gender presentation, least dominant and aggressive, and the lest socially successful of the boys. The greatest difference was between the low and the high masculine boys. The average masculine boys' scores were generally intermediate, but more similar to the low masculine boys on some variables and more similar to the high masculine boys on others. These conclusions apply to a grou interaction play task, but not to an initial noninteractive play task. A secondary study in which girls played with low and average masculine boys is also reported. Here it was found that low masculine boys were generally intermediate between average boys and girls on gender presentation and dominance variables, but lowest of the groups on social interaction variables.

Child Behavior↗

Polymorphisms of microsomal epoxide hydrolase in French vinyl chloride workers.

OBJECTIVES: The purpose of this study was to determine if polymorphisms in microsomal epoxide hydrolase, an enzyme involved in the metabolism of reactive intermediates of vinyl chloride (VC), contribute to the variable susceptibility to the mutagenic effects of vinyl chloride among exposed workers. MATERIALS AND METHODS: Polymorphisms at codons 113 and 139 were determined in DNA samples from 211 French vinyl chloride workers. Genotypes were stratified into low, medium and high activity groups and odds ratios and 95% confidence intervals were determined for the presence of one or both of two VC-induced mutant biomarkers (mutant ras-p21 and mutant p53) by logistic regression adjusting for age, smoking, drinking and cumulative VC exposure. RESULTS: Compared to the low-activity microsomal epoxide hydrolase genotype stratum, the odds ratio for the presence of the VC-induced mutant biomarkers increased to 1.16 (95% CI: 0.64-2.10) in the medium-activity genotype stratum and to 1.35 (95% CI: 0.66-2.77) in the high-activity genotype stratum. The test for trend was not statistically significant and was in the opposite direction from that expected based on increasing removal of reactive intermediates with increasing activity. CONCLUSIONS: The results suggest that polymorphisms in microsomal epoxide hydrolase do not play a significant role in susceptibility to the mutagenic effects of vinyl chloride.

Adult↗

Flt3 internal tandem duplication and P-glycoprotein functionality in 171 patients with acute myeloid leukemia.

PURPOSE: Patients with adult acute myeloid leukemia (AML) with intermediate cytogenetics remain a heterogeneous group with highly variable individual prognoses. New molecular markers could help to refine cytogenetic stratification. EXPERIMENTAL DESIGN: We assessed P-glycoprotein (Pgp) activity and Flt3 internal tandem duplication (ITD+) because of their known prognostic value and because they might lead to targeted therapy. We did a multivariate analysis on 171 patients with adult AML treated in the European Organization for Research and Treatment of Cancer protocols. RESULTS: ITD+ and high Pgp activity (Pgp+) were found in 26 of 171 (15%) and 55 of 171 (32%) of all patients, respectively. ITD and Pgp activities were negative in 94 of 171 (55%, Pgp-ITD- group), mutually exclusive in 73 of 171 (43%, Pgp-ITD+ and Pgp+ITD- groups), and only 4 of 171 (2%, Pgp+ITD+ group) patients were positive for both. In multivariate analyses, Pgp+ITD+ (P < 0.0001) and age (P = 0.0022) were independent prognostic factors for the achievement of complete remission (CR). Overall survival (OS), CR achievement (P < 0.0001), WHO performance status (P = 0.0007), and Pgp+ITD+ status (P = 0.0014) were also independent prognostic factors. In 95 patients with intermediate cytogenetics, the CR rates of ITD+ patients were 40% versus 62% for ITD- (P = 0.099) and 41% versus 67% (P = 0.014) for Pgp+ versus Pgp- patients. In the Pgp-ITD- group (41 of 95), CR rates were 70% versus 44% for others (P = 0.012), OS achieved 48% versus 16% (P < 0.0001) and disease-free survival was 56% versus 27% (P = 0.024), respectively. Furthermore, the OS curves of the intermediate cytogenetics-Pgp-ITD- group were not significantly different from the favorable cytogenetic group. CONCLUSION: Flt3/ITD and Pgp activity are independent and additive prognostic factors which provide a powerful risk classification that can be routinely used to stratify the treatment of patients with intermediate cytogenetic AML. ITD+ and Pgp+ patients should be considered for targeted therapy.

ATP Binding Cassette Transporter, Subfamily B↗

Relation between exercise-induced ventricular arrhythmias and myocardial perfusion abnormalities in patients with intermediate pretest probability of coronary artery disease.

The significance of exercise-induced ventricular arrhythmias (VAs) is largely dependent on the clinical characteristics of the studied population. The relation between exercise-induced VAs and myocardial perfusion abnormalities has not yet been evaluated in a homogeneous patient population with intermediate probability of coronary artery disease (CAD). We studied 302 patients (mean age 54+/-9 years, 152 men and 150 women) with intermediate pretest probability of CAD (range=0.25-0.80, mean=0.43+/-0.20) by upright bicycle exercise stress test in conjunction with technetium-99m single-photon emission tomography (SPET) imaging. Exercise-induced VAs (frequent or complex premature ventricular contractions or ventricular tachycardia) occurred in 65 patients (22%). No significant difference was found between patients with and patient without VAs regarding the pretest probability of CAD (0.45+/-0.21 vs 0.43+/-0.20). Patients with exercise-induced VAs had a higher prevalence of perfusion abnormalities (52% vs 26%, P=0.002) and ischaemic electrocardiographic changes (31% vs 16%, P<0.05) compared to patients without VAs. A higher prevalence of perfusion abnormalities in patients with VAs was observed in both men (67% vs 35%, P<0.01) and women (38% vs 16%, P<0.05). However, the positive predictive value of exercise-induced VAs for the presence of myocardial perfusion abnormalities was higher in men than in women (67% vs 38%, P<0.05). The presence of abnormal myocardial perfusion was the only independent predictor of exercise-induced VAs (OR 2.2; 95% CI, 1.2-4.2) by multivariate analysis of clinical and stress test variables. It is concluded that in patients with intermediate pretest probability of CAD, exercise-induced VAs are predictive of a higher prevalence of myocardial perfusion abnormalities in both men and women. However, the positive predictive value of exercise-induced VAs for perfusion abnormalities is higher in men. Because of the underestimation of ischaemia by electrocardiographic changes, exercise-induced VAs should be interpreted as a marker of a higher probability of CAD.

Coronary Angiography↗

Quantification of plasma lipids and apolipoproteins by use of proton NMR spectroscopy, multivariate and neural network analysis.

New approaches for quantification of human blood plasma lipids and apolipoproteins are presented. One method is based on multivariate analysis of proton nuclear magnetic resonance spectra of human blood plasma. Although similar approaches have been developed previously, this is the first time principal component analysis (PCA) and partial least squares regression (PLS) have been applied to this particular task. Further, a large proportion of the subjects in this study were cancer patients undergoing treatment, which introduced a new dimension to the quantification of lipoprotein distributions. Calibration models for prediction of lipids and apolipoproteins were constructed by use of PLS, and blind samples were used to test the predictive ability. Comparison of the predicted vs observed data obtained by standard clinical chemical procedures gave good agreement; the correlation coefficient for total plasma triglyceride was 0.99, for total plasma cholesterol 0.98, for LDL cholesterol 0. 97, and for HDL cholesterol 0.88. These results are comparable with those obtained with other methods. The quantitative analysis of 14 components (including total cholesterol and total triglyceride) of human blood plasma was also undertaken using various neural network (NN) analyses of selected portions of the spectra. Conventional fully connected backpropagation neural network topologies were capable of providing excellent predictions for the majority of the variables, confirming and reinforcing literature related to this approach. However HDL triglycerides were poorly predicted, while intermediate-quality results were obtained for the LDL cholesterol, plasma apoA1 and LDL apoB variables. In these instances, applying significantly different neural network algorithms involving either general regression or polynomial neural networks in combination with genetic adaptive components for parameter optimisation made improved predictions.

Adult↗

Recombinant human insulin-like growth factor-I abolishes changes in insulin requirements consequent upon growth hormone pulsatility in young adults with type I diabetes mellitus.

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.

Adolescent↗

Pharmacoeconomic evaluation of COPD.

STUDY OBJECTIVES: The clinical outcomes and health-care costs of a cohort of 413 patients with COPD are reported. DESIGN: This study was a retrospective pharmacoeconomic analysis. SETTING: University teaching hospital and affiliated clinics. PATIENTS: COPD patients with an FEV(1) < 65% of predicted and an FEV(1)/FVC ratio < 70% were eligible to be included in this analysis. INTERVENTIONS: Health-care resource utilization and costs were identified through chart review and were stratified according to the severity of COPD using the American Thoracic Society stages I, II, and III. The pharmacoeconomic analysis was a cost-of-illness evaluation that included the acquisition costs of initially prescribed pulmonary drugs, acquisition cost of pulmonary drugs added during the follow-up period, oxygen therapy, laboratory and diagnostic test costs, clinic visit costs, and emergency department and hospital costs. RESULTS: Total treatment cost was highly correlated with disease severity, with stage I COPD having the lowest cost ($1,681 per patient per year), stage III COPD having the highest cost ($10, 812 per patient per year), and stage II COPD having a cost intermediate to stage I and stage III ($5,037 per patient per year). With the exception of add-on drug acquisition cost, all cost variables were the highest in stage III COPD, the lowest in stage I COPD, and intermediate in stage II COPD. Hospitalization was the most important cost variable for all three stages of COPD severity. When stratified by both disease severity and initial bronchodilator drug selection, ipratropium alone in stage I COPD patients and the combination of ipratropium plus a ss-agonist (with or without steroid therapy) in stage II and stage III COPD patients had the lowest total costs. Reasons for the lower total cost of the ipratropium and ipratropium plus ss-agonist treatment groups included lower add-on drug costs, fewer diagnostic and laboratory tests, and a lower utilization rate for clinic visits, emergency department visits, and hospitalizations. CONCLUSIONS: Our study demonstrates a strong correlation between disease severity and total treatment cost in COPD. In addition, the type of bronchodilator therapy impacts total cost in COPD. In stage I COPD, ipratropium alone had the lowest total cost, while in stage II and stage III COPD, a combination of ipratropium plus a ss-agonist had the lowest total cost. These data support the concept that adherence to published treatment guidelines will result in lower health-care costs due to COPD.

Adult↗

Morphology of neurons in the thalamic reticular nucleus (TRN) of mammals as revealed by intracellular injections into fixed brain slices.

I have investigated the morphology of neurons in the thalamic reticular nucleus (TRN) by means of intracellular injections in fixed tissue in order to study whether neurons in visual (dorsocaudal part), somatosensory (intermediate part), or limbic/motor (rostral part) sectors in the rat, rabbit, and cat differ morphologically in relation to their different sensory cortical or thalamic inputs. In addition, I have compared the different mammalian species to ask whether there is a morphological difference of TRN neurons according to reported differences in the intrinsic thalamic organisation, for example, due to the presence of GABAergic local circuit neurons in the majority of thalamic nuclei in the cat and the lack of those neurons in most of the rat thalamic nuclei, and presynaptic dendrites in the cat but not in the rat. In all animals investigated so far, neurons in the caudal (visual) and intermediate (somatosensory) part of the TRN have an elongated dendritic morphology in all three species, but some neurons in the rostral part, in particular in dorsal sections, have a distinctive multipolar morphology. Neurons have round, ovoid, or elongated somata ranging in area between 150 and 860 microns 2. In general, 4-8 first order dendrites emerge directly from the two poles of the soma or from a thick stem segment. Most of the dendrites then run parallel to the borders of the nucleus extending for relatively long distances, up to 450 microns, but remain inside the border of the nucleus. Only a few (1-3) dendrites could be observed to run perpendicular to the border of the nucleus and generally only for a short distance (20-70 microns). Some of the smooth first order dendrites give rise to second order dendrites (up to 200 microns in length), which then branch into short (15-70 microns) third order dendrites. Dendritic spines and varicosities, spine-like protusions and/or hair-like processes are mainly found on second and third order dendrites. Surprisingly, the shape, arrangement, and the size of the dendritic field are not strictly related to the shape and size of the nucleus. In mammalian species with a comparatively narrow TRN (rat and cat) the dendritic field size was similar to that in the rabbit with a broad TRN. There was considerable variability in dendritic morphology in the caudal and intermediate parts of TRN. However, in contrast to two recent studies in the rat TRN I have found no obvious basis for classification of neurons in the mammalian TRN according to dendritic morphology.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Relationship of unrecognised myocardial infarction, diabetes mellitus and type of surgery to postoperative cardiac outcomes in vascular surgery.

OBJECTIVES: to evaluate preoperative clinical, surgical and instrumental variables as predictors of postoperative cardiac events in patients undergoing different types of elective major vascular surgery. MATERIAL AND METHODS: on the basis of an algorithm including clinical and test echocardiographic data, we prospectively stratified 604 consecutive patients into low, intermediate and high-risk groups. The value of the variables in predicting postoperative cardiac events was assessed by means of multivariate analysis. RESULTS: there were 16 major postoperative cardiac events and six of 16 postoperative deaths were cardiac related (1%). Significant predictors of cardiac complications were unrecognised myocardial infarction (odds ratio - (OR) 5.6), coronary artery disease (OR 2.5), severe hypertension (OR 2.1) and peripheral vascular surgery (OR 1.9). In the intermediate-risk group, the best correlates with cardiac complications were unrecognised myocardial infarction (OR 3.3) and diabetes (OR 2.5). CONCLUSIONS: our results suggest the importance of identifying patients with unrecognised ischaemic heart disease and of using aggressive perioperative protocols for managing diabetic patients undergoing peripheral vascular procedures.

Aged↗

Molecular genetic approaches to investigate individual variations in behavioral and neuroendocrine stress responses.

A large response range can be observed in both behavioral and neuroendocrine responses to environmental challenges. This variation can arise from central mechanisms such as those involved in the shaping of general response tendencies (temperaments) or involves only one or the other output system (behavioral vs. endocrine response). The participation of genetic factors in this variability is demonstrated by family and twin studies in humans, the comparison of inbred strains and selection experiments in animals. Those inbred strains diverging for specific traits of stress reactivity are invaluable tools for the study of the molecular bases of this genetic variability. Until recently, it was only possible to study biological differences between contrasting strains, such as neurotransmitter pathways in the brain or hormone receptor properties, in order to suggest structural differences in candidate genes. The increase of the power of molecular biology tools allows the systematic screening of significant genes for the search of molecular variants. More recently, it was possible to search for genes without any preliminary functional hypothesis (mRNA differential expression, nucleic acid arrays, QTL search). The approach known as quantitative trait loci (QTL) analysis is based on the association between polymorphic anonymous markers and the phenotypical value of the trait under study in a segregating population (such as F2 or backcross). It allows the location of chromosomal regions involved in trait variability and ultimately the identification of the mutated gene(s). Therefore, in a first step, those studies skip the 'black box' of intermediate mechanisms, but the knowledge of the gene(s) responsible for trait variability will point out to the pathway responsible for the phenotypical differences. Since variations in stress-related responses may be related to numerous pathological conditions such as behavioral and mood disorders, drug abuse, cardiovascular diseases or obesity, and production traits in farm animals, these studies can be expected to bring significant knowledge for new therapeutic approaches in humans and improved efficiency of selection in farm animals.

Animals↗

The impact of anomia as a factor in a demand resource model of health.

The particular aim of the present study was to explore the interrelations between the construct of anomia, conceptualized as internal health demand or resource, and self-reported ill-health in the framework of a demand resource model. The four main constructs of this model were considered as recursive causal levels: (1) socio-economic data, (2) external resources/demands, (3) internal resources/ demands, and (4) ill-health. Study statistics comprised graphical models to reveal the relations between variables using the statistical program DIGRAM designed for discrete graphical models. This method of data analysis permits a focus on the link between anomia and the other three levels. The function of anomia as an intermediate data level which might prove to be an intervening variable can be evaluated. A total of 440 subjects of a random community sample were included in the final analysis. In the framework of a demand resource model, it was possible to confirm that the construct of anomia plays a key role in health outcome. Graphical models showed that a low degree of anomia is related to high psychological quality of life and few psychosomatic symptoms on the one hand, and to good social integration and emotional support, a low amount of daily hassles and high educational level on the other hand. As an overall conclusion, it can be stated that the evaluation by the graphical modeling procedure permits a good fit of theory with methods.

Adaptation, Psychological↗

[7 years study of erythrocyte membrane transport of monoamine precursors. 395 patients (335 depressed, 60 schizophrenic patients)].

According to the monoaminergic hypothesis of affective and schizophrenic syndromes, a perturbation of influx of precursors of monoamines such as tyrosine (TYR) and tryptophan (TRYP) into the brain might be correlated with the clinical syndromes. The measure of blood cell membrane transports of TYR and TRYP is an interesting peripheral model for the study of these syndromes. This work concerns 395 patients (335 depressed and 60 schizophrenics); 215 of depressed patients were followed after the antidepressant therapy. The transport of TYR and TRYP into erythrocytes was measured as followed: erythrocytes were incubated in plasma for 10 min. at 0 degree and 37 degrees C with radiolabeled TYR and TRYP; facilitated diffusion was calculated by subtracting from the total amount of radioactivity taken up by the cells at 37 degrees C (total uptake) that accumulated at 0 degree C (passive diffusion). The results showed that: 1) The depressive syndromes were characterised by a decrease of facilitated diffusion of TYR, an increase of facilitated diffusion of TRYP and a decrease of the index diffusion of TYR/TRYP. 2) The means of variables were different according to the diagnostic sub-groups (DSM III). In the depressions with alcoholism, the facilitated diffusions were increased compared to depressive syndromes without others diagnosis. The depressions with dementia were in intermediate position. 3) After treatment with antidepressant drugs, the biological variables improved with the clinical improvement, without complete normalization compared to controls. The patients without clinical improvement showed no change in the biological measures. 4) Patients for whom the choice of antidepressant drug was done according to the facilitated diffusions showed a 87% rate of clinical improvement, while this rate was 60% in the other patients. 5) In schizophrenic patients, the biological variables were different than in depressed or normal controls and showed a little decrease of facilitated diffusion of TYR, a marked decrease of diffusion of TRYP and an increased index of diffusion TYR/TRYP.

Adolescent↗

Short-term intraindividual variability in lipoprotein measurements: the Atherosclerosis Risk in Communities (ARIC) Study.

Much epidemiologic research is based on estimation of an association between a putative risk factor and a health outcome--for example, plasma concentration of lipoproteins and ischemic heart disease. Since the repeatability of a risk factor measurement determines, in part, the ability to ascertain its association in populations, the Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability Study was conducted to estimate various components of variation in analyte data and to estimate the repeatability of these measurements. A total of 40 subjects (17 males and 23 females) from Forsyth County, North Carolina, Minneapolis, Minnesota, Jackson, Mississippi, and Washington County, Maryland, were studied in 1988. Fasting blood was collected three times from each subject, with a 1- to 2-week interval between each visit. The contributions of between-person variability, within-person variability, and processing and assay variability were estimated. From these components, the reliability coefficient, R, the correlation between measures made at repeat visits, was estimated. R was above 0.85 for total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and lipoprotein(a). Low repeatability was obtained for apolipoprotein A-I (R = 0.60). High density lipoprotein subfractions 2 and 3 were intermediate in repeatability. Reliability coefficients from the ARIC Intraindividual Variability Study are generally higher than those found in other studies, and this is related to relative variability in populations studied, to the time between measurements, and to differences in laboratory variability. Only for apolipoprotein A-I would the findings strongly suggest the need to adjust for measurement variability in estimation using one of these analytes as an independent variable.

Cardiovascular Diseases↗

Polyaxonal amacrine cells of rabbit retina: PA2, PA3, and PA4 cells. Light and electron microscopic studies with a functional interpretation.

Polyaxonal (PA) amacrine cells are a new class of amacrine cell bearing one to six branching, axon-like processes that emerge from the cell body or dendritic trees within 50 microns of the cell body. These slender processes of uniform caliber branch at right angles and in many respects closely resemble the axons of Golgi type II cells found elsewhere in the brain. Of the four types of polyaxonal amacrine cell that we have recognized in rabbit retina, two have been described previously in brief communications. One of these, the PA1 amacrine cell with its interstitially displaced cell body, located in the inner plexiform layer (IPL), has been analyzed extensively in two preceding reports. This paper concerns PA2, PA3, and PA4 amacrine cells. Type 2 polyaxonal (PA2) amacrine cells, identified in Golgi preparations of whole-mounted rabbit retinas, have smaller cell bodies (9-14 microns) than the other three types and these are always displaced to the ganglion cell layer (GCL) or the inner border of the inner plexiform layer (IPL). The dendritic fields of PA2 cells are also smaller than those of other PA amacrine cells, and most of their sparse dendritic branching is narrowly stratified at the border of strata (S) 4 and 5. Some members of this more heterogeneous amacrine cell "type" are bistratified, however, and more highly branched with terminal branches rising to end in S1. PA2 amacrine cells bear a scattering of small dendritic spines and may also exhibit complex dendritic appendages arising at the ends of terminal branches in proximal regions of the dendritic tree. PA2 cells emit one to three axons from the proximal dendritic tree, and about half of the cells bear a single axon. Type 3 polyaxonal (PA3) amacrine cells resemble PA1 cells in the large size of their cells bodies (11-16 microns) and dendritic fields, but differ from the latter in placement of cell bodies, which is in the GCL, and dendritic and axonal stratification, which is multistratified, ranging from S4 to S1, with a concentration in S3 or S4 and a variable contribution to S1. PA3 cells differ from PA1 cells in several other respects, including dendritic branching which occurs at higher frequency and is biased toward temporal retina, and in characteristic bristling dendritic spines, clustered in the intermediate regions of the dendritic tree, that are longer, more variable in appearance and more tightly clustered than the small, uniform spines of PA1 cells that are clustered on proximal dendrites.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Ocular↗

Genetic heterogeneity of beta-thalassemia in southeast Sicily.

In this study we have defined the spectrum of the beta-thalassemia mutations, the beta-thalassemia haplotypes, and the genotype-to-phenotype correlations in a large number of patients with different beta-thalassemia conditions. Seventeen different beta-thalassemia mutations were detected which included one chromosome each with Hb Dhonburi and Hb Lepore. Five alleles, namely, codon 39 (C-->T), IVS-I-110 (G-->A), IVS-I-6 (T-->C), IVS-II-745 (C-->G), and IVS-I-1 (G-->A), account for 90% of all beta-thalassemia mutations in 846 thalassemic chromosomes studied. Haplotyping for a large number of subjects showed that the five common mutations are linked to a few haplotypes. The presence of milder mutations, mainly IVS-I-6 (T C), in about 19% of our patients explains some of the clinical variables. Among the 37 patients with thalassemia of intermediate severity, only 6 were homozygous or compound heterozygous for two severe alleles. The type of beta-thalassemia is the main factor responsible for differences in the phenotypic expression of the disease in patients with Hb S-beta-thalassemia; patients with Hb S-beta(+)-thalassemia are less severely affected than those with Hb S-beta(0)-thalassemia. The five most frequent mutations have comparable distributions all over Sicily.

Fetal Hemoglobin↗

Can true papillary neoplasms of breast and their mimickers be accurately classified by cytology?

BACKGROUND: The cytologic accuracy in assessing malignancy in papillary breast neoplasms (PBNs) is controversial. This is further complicated by overlapping features observed in other breast lesions that produce papillary-like tissue fragments. METHODS: The authors reviewed 22 fine-needle aspirates (FNAs) from histologically proven papillary neoplasms: papillary carcinoma (PCA; 10 aspirates) and intraductal papilloma (IDP; 12 aspirates). They also reviewed 8 FNAs in which a papillary neoplasm was suggested by cytology but not confirmed by follow-up biopsy: fibroadenoma (6), mucinous carcinoma (1), and cribriform ductal carcinoma in situ (1). RESULTS: Papillary carcinoma can be distinguished from IDP by the higher cellularity, more complex papillae with thin disorganized fronds, mild to moderate nuclear atypia, and prominent dissociation with many single papillae. Fibrovascular cores (FVCs) were more common in PCA than IDP in which detached fibrous tissue fragments were frequently seen. Atypical IDP exhibited features intermediate between PCA and IDP. Apocrine metaplasia was variably present in IDP, atypical IDP, and fibroadenoma but absent in all carcinomas. Intraductal papilloma can be distinguished from fibroadenoma by their broad ruffled branches, scalloped borders, and tiny tongue-like projections. True papillae were commonly covered by tall columnar cells. Myoepithelial cells were few in IDP but were numerous in fibroadenoma. The epithelial fragments in nonpapillary lesions presented as cellular spheres and/or complex sheets with finger-like projections but lacked FVCs and columnar cells. CONCLUSIONS: Papillary breast neoplasms can be accurately classified by cytology. Closer evaluation of the tissue fragments architecture and the background can help in separating PBN from their mimics.

Adenocarcinoma, Mucinous↗

Thermodynamics and kinetics of protein folding: an evolutionary perspective.

This article appeals to an evolutionary model which postulates that primordial proteins were described by small polypeptide chains which (i) lack disulfide bridges, and (ii) display slow folding rates with multi-state kinetics, to determine relations between structural properties of proteins and their folding kinetics. We parameterize the energy landscape of proteins in terms of thermodynamic activation variables. The model studies evolutionary changes in these thermodynamic parameters, and we invoke relations between these activation variables and structural properties of the protein to predict the following correspondence between protein structure and folding kinetics. 1. Proteins with inter- and intra-chain disulfide bridges: large variability in both folding rates and stability of intermediates, multi-state kinetics. 2. Proteins which lack inter and intra-chain disulfide bridges. 2.1 Single-domain chains: fast folding rates; unstable intermediates; two-state kinetics. 2.2 Multi-domain monomers: intermediate rates; metastable intermediates; multi-state kinetics. 2.3 Multi-domain oligomers: slow rates; metastable intermediates; multi-state kinetics. The evolutionary model thus provides a kinetic characterization of one important subfamily of proteins which we describe by the following properties: Folding dynamics of single-domain proteins which lack disulfide bridges are described by two-state kinetics. Folding rate of this class of proteins is positively correlated with the thermodynamic stability of the folded state.

Disulfides↗