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PubMed2001

Risk factors for intermediate-term survival after coronary artery bypass grafting.

BACKGROUND: Risk factors for short-term mortality after coronary artery bypass grafting are well established, but little is known about risk factors for intermediate-term mortality. METHODS: We analyzed the outcomes of 11,815 patients undergoing coronary artery bypass grafting in one of the 43 cardiac surgery programs of the Department of Veteran Affairs. Risk factors for intermediate- and short-term mortality were determined using Cox proportional hazards regression models. Effects of risk factors during these two periods were explicitly compared. RESULTS: We found important differences in mortality risk-factor sets between the intermediate- and short-term periods after coronary artery bypass grafting. The majority of predictors of intermediate-term mortality were noncardiac-related variables, whereas the majority of predictors of short-term mortality were cardiac-related variables. Impaired functional status, chronic obstructive pulmonary disease, and renal dysfunction had greater effects in the intermediate-term period. Previous heart operation, angina class III or IV, previous myocardial infarction, and preoperative use of an intraaortic balloon pump had greater effects in the short-term period. CONCLUSIONS: The risk factors for intermediate-term mortality identified in this study can augment preoperative risk assessment and counseling of patients. Clinicians should be aware of the importance of noncardiac-related variables as predictors of mortality in the intermediate-term period after coronary artery bypass grafting.

Aged↗
PubMedDate not supplied

Type A behavior pattern and hypertension among inner-city black women.

Inner-city Black women were administered Rosenman and Friedman's A-B interview and invited to discuss stress experiences and traditional coronary heart disease risk factors while their blood pressure was monitored at two-minute intervals. Results revealed the essential reliability of the A-B classification for the sample and demonstrated a general congruence with type A behaviors reported in previous (mostly white male) samples. While type A Black women were not significantly more likely to be hypertensive than type B women, analyses of the intrasubject blood pressure variability revealed an interaction between A-B and hypertensive-normotensive status. Consistent with earlier findings, hypertensives were more variable than normotensives, but this was true only for type Bs; type As were intermediate and not differentiated in their variability. This finding calls attention to the possible adaptive function of type A behavior among stress inner-city Black females and raises the question of whether Rosenman and Friedman's personality theory might be objectionably simplistic.

Adult↗
PubMed2000

Modeling approach to diameter breakpoint determination.

In determining zone diameter breakpoints, the error-rate bounded method focuses directly on the observed discrepancy percentages (very major, major, and minor). These percentages, however, are quite variable due to the number of isolates investigated, the drug-specific relationship between MIC and zone diameter, the location of the isolates relative to the MIC intermediate zone, and the inherent variability of each test. To overcome potential sampling problems, a hierarchical model is proposed which explicitly accounts for each of these factors and probabilities from this model are used to determine diameter breakpoints. A simulation study is performed to demonstrate the improved consistency of this model-based procedure. Application to three published scatterplots demonstrate its interpretability advantages.

Bayes Theorem↗
PubMed1998

The accuracy of methods for coding and sampling higher-level taxa for phylogenetic analysis: a simulation study.

Many phylogenetic analyses, particularly morphological studies, use higher taxa (e.g., genera, families) rather than species as terminal taxa. This general approach requires dealing with interspecific variation among the species that make up the higher taxon. In this paper, I review different parsimony methods for coding and sampling higher taxa and compare their relative accuracies using computer simulations. Despite their widespread use, methods that involve coding higher taxa as terminals perform poorly in simulations, relative to splitting up the higher taxa and using species as terminals. Among the methods that use higher taxa as terminals, coding a taxon based on the most common condition among the included species (majority or modal coding) is generally more accurate than other coding methods, such as coding taxa as missing or polymorphic. The success of the majority method, and results of further simulations, suggest that in many cases "common equals primitive" within variable taxa, at least for low and intermediate rates of character change. The fixed-only method (excluding variable characters) performs very poorly, a result that is indirectly supported by analyses of published data for squamate reptiles. Sampling only a single species per higher taxon also yields low accuracy under many conditions. Along with recent studies of intraspecific polymorphism, the results of this study show the general importance of (1) including characters despite variation within taxa and (2) using methods that incorporate detailed information on the distribution of states within variable taxa.

Computer Simulation↗
PubMed1993

Generation of processed pseudogenes in murine cells.

Using as a reporter gene a non-coding proviral structure marked with an intron-containing indicator, we demonstrate the de novo formation, via a retrotransposition pathway, of canonical processed pseudogenes in cultured mammalian cells. Their structural features include endings corresponding to the start and termination of the RNA intermediate, intron loss, acquisition of a 3' poly(A) tail, and target site duplications of variable length. The absence of extracellular intermediates for these processes, and the elimination during retrotransposition of sequences in the reporter gene essential in cis for a retroviral cycle, further suggest that endogenous retroviruses or related elements are not involved. Pseudogene formation frequency is markedly increased (up to 10-fold) by several treatments including treatment with 5-azacytidine or tetradecanoyl phorbol acetate, or serum starvation, which do not act at the reporter gene transcription level, but rather on endogenous genes--including the LINE elements--necessarily involved in trans-complementation for retrotransposition.

3T3 Cells↗
PubMed1987

Analysis of individual, intraspecific and interspecific variability in quantitative parameters of caprine tooth enamel structure.

Qualitative and quantitative features of mammalian tooth enamel structure are increasingly being used in taxonomic and phylogenetic analyses, although the variability shown by these traits has not received adequate consideration. This study evaluates the variability displayed by nine quantitative parameters in deep, intermediate, and superficial molar enamel in the closely related bovids Ovis aries and Capra hircus. These parameters are assessed in terms of the absolute and/or relative variability evinced at a given depth within a single individual, among conspecific individuals, and between species samples. The degrees of relative variability expressed at a given depth are comparable among conspecific individuals and between taxonomic samples. Nevertheless, in many instances, there are significant differences in absolute variability amongst individuals. Also, in four parameters for which individual specimen averages could be calculated, the equality of these means among conspecifics can be rejected. Variability is not equivalent at different enamel depths. The null hypothesis of equality of individual, conspecific variances can be rejected most commonly for parameters measured in deep and superficial enamel, and coefficients of variation also tend to be higher for deep and superficial enamel than for enamel of intermediate depth. The greater variability displayed by deep and especially superficial enamel may be related to the initial onset and the terminal phase of ameloblastic secretory activity. Taxonomic and phylogenetic analyses that utilize quantitative data on enamel structure are valid only if comparisons have been made at equivalent enamel depths.

Ameloblasts↗
PubMed2001

A new model for intermediate molecular weight recombinant bispecific and trispecific antibodies by efficient heterodimerization of single chain variable domains through fusion to a Fab-chain.

Due to their specificity and versatility in use, bispecific antibodies (BsAbs) are promising therapeutic tools in tomorrow's medicine, provided sufficient BsAb can be produced. Expression systems favoring efficient heterodimerization of intermediate-sized bispecific antibodies will significantly improve existing production methods. Recombinant BsAb can be made by fusing single chain variable fragments (scFv) to a heterodimerization domain. We compare the efficiency of the isolated CL and CH1 constant domains with complete Fab chains to drive heterodimerization of BsAbs in mammalian cells. We found that the isolated CL:CH1 domain interaction was inefficient for secretion of heterodimers. However, when the complete Fab chains were used, secretion of a heterodimerized bispecific antibody was successful. Since the Fab chain encodes a binding specificity on its own, bispecific (BsAb) or trispecific (TsAb) antibodies can be made by C-terminal fusion of scFv molecules to the L or Fd Fab chains. This gave rise to disulphide stabilized Fab-scFv BsAb (Bibody)or Fab-(scFv)2 TsAb (Tribody) of intermediate molecular size. Heterodimerization of the L and Fd-containing fusion proteins was very efficient, and up to 90% of all secreted antibody fragments was in the desired heterodimerized format. All building blocks remained functional in the fusion product, and the bispecific character of the molecules as well as the immunological functionality was demonstrated.

Alkaline Phosphatase↗
PubMedDate not supplied

Neuroendocrine neoplasms in unusual primary sites.

Primary neoplasms arising in the liver (3 cases), skin (3 cases) and larynx (2 cases) were studied with a combination of light microscopy, immunohistochemical and electron microscopic techniques. Clinically, only one case exhibited a hormonal syndrome (Zollinger-Ellison) while another had elevated levels of calcitonin in the serum. By light microscopy only one tumour appeared characteristically neuroendocrine ('carcinoid'). The other cases showed variable patterns of small to intermediate size cell carcinomas at times admixed with exocrine appearing areas. Immunoperoxidase studies showed reactivity for various peptides including gastrin, calcitonin, somatostatin and ACTH. Several tumours were positive for more than one peptide. Electron microscopy revealed variable populations of neurosecretory type granules either in the main cytoplasmic mass or in cytoplasmic processes. We conclude that some 'undifferentiated' neoplasms from the aforementioned sites may prove to have neuroendocrine differentiation if the proper techniques are applied to their study. Clinical hormonal syndromes appear to be rare in these tumours;s however, determination of various amine and/or peptide materials, or possibly their metabolites, may be valid aids for their recognition and monitoring. The structural patterns of these tumours are very variable and may include cells with squamous features as well as exocrine differentiation with occasionally prominent production of mucosubstances.

Adult↗
PubMed2006

Identification of a novel, highly variable amino-terminal amino acid sequence element in the nuclear intermediate filament protein lamin B(2) from higher vertebrates.

By comparing newly available cDNA sequences of the human intermediate filament protein lamin B(2) with published sequences, we have identified an additional translation initiation codon 60 nucleotides upstream of the previously assumed translation start. In addition, corresponding sequences were identified in the chimpanzee, mouse, rat and bovine genes and cDNAs, respectively. Therefore, we generated antibodies against these potential 20 new amino acids of the human sequence. By immunoblot analysis and immunofluorescence microscopy we show that human lamin B(2) is indeed synthesized as a longer version than previously reported, because it contains these additional 20 amino acids. Notably, the sequence homology to mouse, rat and bovine lamin B(2) is significantly lower in this segment than in that between the second methionine codon and the start of the alpha-helical rod indicating that the tip of the "head" is engaged in more species-specific functions. Forced expression of the GFP-tagged authentic "long" and the 20 amino acid shorter version of lamin B(2) in human cultured SW-13 cells demonstrated that both the longer and the shorter version are properly integrated into the nuclear lamina, although the shorter version exhibited a tendency to disturb envelope architecture at higher expression levels.

Amino Acid Sequence↗
PubMed1999

Ontogeny and regional variability of keratin 2e (K2e) in developing human fetal skin: a unique spatial and temporal pattern of keratin expression in development.

Keratin 2e (K2e) is expressed in the upper spinous and granular cells of adult epidermis. A highly specific polyclonal antibody was made against a C-terminal peptide of K2e and used to observe K2e expression at different developmental stages. At 12.5 weeks estimated gestational age (EGA) K2e was detected in trunk skin in scattered cells in the intermediate layer. At 13.5 weeks EGA, greater numbers of intermediate cells were stained with variable intensity, and staining in this pattern increased with age. Epidermal sheets from 14 weeks EGA showed that K2e + cells were excluded from developing hair follicles. At 135 days EGA, the following regional patterns were observed: in cheek, trunk, dorsal and ventral knee, elbow and dorsal hand there was moderate to intense staining of upper intermediate keratinocytes excluding cells of the hair canals and sweat ducts. The periumbilical region distinctly lacked K2e staining, while more distal areas showed increasing numbers of K2e + cells. The earliest expression of K2e was at 10 weeks EGA in the presumptive nail bed of developing digits. By 13.5 weeks EGA this pattern had shifted to the proximal nail fold, and K2e was absent in the nail bed. K2e was excluded from developing sweat glands and ducts and from developing hair follicles at the hair germ and early peg stages. By 15 weeks EGA in the fetal hair follicle small groups of cells were K2e + and by 19 weeks K2e + cells were seen at the level of the matrix. Some overlap in staining was detected for K2e with K10, and in palmar skin with K9; however, mostly the filamentous staining patterns for these keratins were distinctive. This study shows that the complex patterns of temporal and regional expression of K2e differ from known patterns for other epidermal keratins and suggest different regulation and function for this epidermal keratin.

Embryonic and Fetal Development↗
PubMed1991

Vascular transformation of sinuses in lymph nodes. A study of its morphological spectrum and distinction from Kaposi's sarcoma.

Vascular transformation of lymph node sinuses (VTS) is characterized by conversion of nodal sinuses into capillary-like channels, often accompanied by fibrosis. A detailed study of this entity, based on 76 cases, showed that the morphologic spectrum was much broader than that originally described. The vasoproliferative process caused variable expansion of the subcapsular, intermediate, and medullary sinuses of the lymph nodes and involved single or multiple lymph nodes in a diffuse or segmental fashion. The proliferated vessels formed anastomosing narrow clefts, rounded spaces of different sizes, plexiform channels, or solid spindled to plump cellular foci and often were associated with variable degrees of sclerosis. The vascular spaces were empty, filled with lymph-like fluid, congested with blood, or occasionally thrombosed; extravasation of red cells was common. Several patterns were commonly observed in an individual case. Less common features included perivascular fibrin deposition and the presence of eosinophilic globules. Vascular thrombosis was identified only rarely in extranodal vessels available for histologic assessment. The more cellular forms of this vascular transformation may be mistaken for Kaposi's sarcoma, but can be distinguished from it by the pure sinusoidal distribution, a lack of well-formed spindle cell fascicles, the associated fibrosis, the maturation of the spindle cells into well-formed vascular channels toward the capsular aspect, and the failure of this process to involve the capsule itself, which is frequently affected by Kaposi's sarcoma.

Adolescent↗
PubMedDate not supplied

Low-field magnetic resonance imaging of bone marrow in the lumbar spine, pelvis, and femur in the adult dog.

The purpose of this study was to describe the appearance of normal bone marrow in seven adult dogs using low-field (0.3T) magnetic resonance (MR) imaging. The areas imaged included the lumbar spine, pelvis, and femur. T1-weighted, fast spin-echo T2-weighted, and short tau (T1) inversion recovery (STIR) sequences were obtained at all locations. Histopathology was performed on sections from the sixth lumbar vertebral body, the wing of the ilium, and the femur (head and neck, mid-diaphysis, and condyle) for evaluation of cellularity and fat content. The lumbar spine and pelvic marrow MR images were similar in all dogs. The lumbar vertebral bone marrow was uniform, intermediate signal intensity, and isointense to muscle on all sequences. There was variation between dogs in the bone marrow distribution with MR imaging of the femur. In the proximal and mid-diaphysis of the femur there was patchy high-signal intensity on T1- and T2-weighted images, and hypointense foci on the STIR images. The distal femoral metaphysis had a variable pattern ranging from intermediate-to-high signal on T1- and T2-weighted images and intermediate-to-low signal on STIR images. The femoral condyles were uniformly high signal on T1- and T2-weighted images and hypointense on STIR images. Histopathologically there was a normal variation in the bone marrow cellularity. The marrow was normocellular (25-75% cellularity) for all sites examined except the femoral condyles, which were hypocellular (<25% cellularity).

Adipose Tissue↗
PubMed2004

Echinococcus granulosus strain typing in Bulgaria: the G1 genotype is predominant in intermediate and definitive wild hosts.

Addressing the genetic variability in Echinococcus granulosus is epidemiologically important, as strain characteristics may influence the local transmission patterns of zoonotic cystic echinococcosis. To classify the genotype(s) present in intermediate (pig, cattle and sheep) and definitive (jackal and wolf) hosts in Bulgaria, a DNA-based approach was used to assess parasite protoscoleces or strobiles. Genes corresponding to coding and non-coding regions of the nuclear and mitochondrial genome ( ND-1, HBX, Act II, AgB-1) were amplified by PCR and subsequently sequenced. The sequences resolved were all found to be identical to those published for the common sheep strain of E. granulosus, indicating that the G1 genotype is predominant in Bulgaria. One microvariant for ND-1 was found in the pig isolates; however no epidemiological significance was attributed to this finding.

Animals↗
PubMed1980

Effects of reserpine on fast, intermediate and slow axonal transport of proteins in rat locus coeruleus neurons.

The effects of a single injection of reserpine (5 mg/kg, i.p.) on protein turnover and axonal transport (AT) in locus coeruleus (LC) noradrenergic neurons was investigated in the rat. Reserpine pretreatment, at intervals of 1--21 days prior to [3H]-fucose or leucine injection into the LC, resulted in marked alterations in the turnover of [3H]glycoproteins and proteins in the LC and hypothalamus which were present for up to 14 days and varied according to the time after reserpine pretreatment. Reserpine produced an intermittent blockade, of variable degree, in rapidly and intermediately transported proteins for up to 2 weeks following injection. Slow AT was uniformly decreased over the first 10 post-treatment days to 2--42% of controls. Blockade and not a change in the rate or time of onset of transport appeared to be responsible for the observed changes. The suggested mechanism for these alterations is a re-ordering of metabolic priorities in the synthesis and transport of proteins in these noradrenergic cells secondary to a reserpine-induced depletion of norepinephrine in the nerve terminals.

Animals↗
PubMed2002

The antisaccade task in a sample of 2,006 young men. I. Normal population characteristics.

A population of 2,075 young men aged 18-25 years selected from the conscripts of the Greek Air Force performed an antisaccade task as part of a prospective study for the identification of risk factors in the development of psychoses. The aim of this study, which is ongoing, is to follow this population and investigate the possible predictive value of oculomotor, cognitive, and psychometric factors for the development of psychosis and other psychiatric conditions. In this report we present data concerning the antisaccade task in this population. We measured performance indices, including the percentage of errors (PE), the latencies of different eye movement responses (latency for correct antisaccades, errors, corrections), and performance in perseveration-prone trials. These indices were also evaluated with respect to IQ (measured by the Raven progressive matrices test) and educational level. Mean PE was 23%, with 17% variance. This large variance is of particular importance whenever the detection of a putative deviant behavior is explored. As mean latency of the first eye movement decreased, the PE increased, as did the latency variance. While the negative correlation between percentage of error and mean latency is well established, the relationship of the latency variability of the first response to error production has not been studied before. Thus, optimal performance appears to require both an intermediate mean latency and a small variability. Furthermore, performance seems to be affected by IQ (the higher the IQ score, the lower the percentage of errors). This report offers an analysis of the interindividual variation in the performance of the antisaccade task and discusses some of the sources of this variation.

Adolescent↗
PubMed2006

[Neurofeedback for children with ADHD: a comparison of SCP- and theta/beta-protocols].

Research groups have consistently reported on behavioral and cognitive improvements of children with ADHD after neurofeedback. However, neurofeedback has not been commonly accepted as a treatment for ADHD. This is due, in part, to several methodological limitations. The neurofeedback literature is further complicated by having several different training protocols. Differences between the clinical efficacy of such protocols have not been examined. This study addresses previous methodological shortcomings while comparing the training of theta-beta-frequencies (theta-beta-group) with the training of slow cortical potentials (SCP-group). Each group comprised of 19 children with ADHD that were blind to group assignment. The training procedure consisted of 30 sessions and a six months follow-up training. Pre-/post measures at pretest, the end of the training and the follow-up included tests of attention, intelligence and behavioral variables. After having already reported intermediate data (Strehl et al. 2004), this paper gives account on final results: Both groups are able to voluntarily regulate cortical activity, with the extent of learned self-regulation depending on task and condition. Both groups improve in attention and IQ. Parents and teachers report significant behavioral and cognitive improvements. Clinical effects for both groups remain stable six months after training. Groups do not differ in behavioral or cognitive outcome variables.

Adolescent↗
PubMedDate not supplied

The effect of collagen removal and the use of a low-viscosity resin liner on marginal adaptation of resin composite restorations with margins in dentin.

This study evaluated the influence of collagen removal and the use of a low-viscosity liner on the marginal quality of composite restorations for the total-etch system, Prime & Bond 2.1 (PB) and the self-etching primer system, Clearfil SE Bond (CSEB), in high C-factor cavities with margins in dentin. High C-factor cavities were made on dentin exposed from ground labial surfaces of 100 bovine lower incisors, randomly assigned to 10 treatment groups and restored with composite Z 250, placed in bulk. In Group 1 (PB), control group, PB was applied according to the manufacturer's directions; in Group 2 (PB/PLF), an intermediate layer of low-viscosity composite Protect Liner F (PLF) was applied on the bonding resin surface; in Group 3 (PB/SH) following acid-etching, the surfaces were treated with 10% sodium hypochlorite (SH) for one minute and in Group 4 (PB/SH/PLF), the same procedure was conducted as for Group 3, plus an intermediate layer of PLF was applied as for Group 2. In Group 5 (CSEB), the control group, CSEB was applied according to the manufacturer's directions; in Group 6 (CSEB/PLF), an intermediate layer of PLF was applied; in Group 7 (SH/CSEB), the cavity surface was pre-treated with SH; in Group 8 (SH/CSEB/PLF), SH pre-treatment was conducted as for Group 7, then an intermediate layer of PLF was applied; in Group 9 (CSEB/SH), after CSEB-primer application, the surface was treated with SH, followed by CSEB-adhesive application and in Group 10 (CSEB/SH/PLF), the same was conducted as for Group 9, then an intermediate layer of PLF was applied. The specimens were stored at 37 degrees C for 24 hours, polished, molded and replicas were obtained in epoxy resin. The replicas were gold-sputter coated and observed by SEM (300x) for marginal quality classification. The Kruskal-Wallis non-parametrical multi-comparison Test (p<0.05) was used to obtain statistical analysis of the data. Results demonstrated that both adhesive systems in the control groups presented low marginal quality and a high variability. The use of an intermediate layer of PLF significantly improved the marginal quality with the CSEB system but had no effect with the PB system. Collagen depletion with SH enhanced marginal quality for the PB system and did not influence the CSEB system results.

Acetone↗
PubMed1995

Housing and house-dust mites.

Because the mite-allergen content in homes is highly variable even in the same geographic area, we tried to determine which variables influence mite infestation. We evaluated mite-allergen content in bedding relative to housing conditions and living habits. This cross-sectional study included 108 homes. Housing conditions were assessed by an architect and living habits by a researcher specialized in social and family economics. Group I allergen level was measured on the mattress dust with monoclonal antibodies, and relative humidity (RH) was monitored in the bedroom during a 2-week period. Homes with low RH did have low mite-allergen content. In contrast, homes with intermediate RH levels had very variable mite-allergen content. Using analysis of variance and a logistic regression analysis, we were unable to identify any variable predictive of mite-allergen content. Thus, factors other than relative humidity seem to influence mite infestation. Moreover, the absence of association between mite infestation and ventilation rate might be accounted for by the gentle climate in our area with notable outdoor RH.

Allergens↗