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PubMed2006

Mean length of utterance in children with specific language impairment and in younger control children shows concurrent validity and stable and parallel growth trajectories.

PURPOSE: Although mean length of utterance (MLU) is a useful benchmark in studies of children with specific language impairment (SLI), some empirical and interpretive issues are unresolved. The authors report on 2 studies examining, respectively, the concurrent validity and temporal stability of MLU equivalency between children with SLI and typically developing children. METHOD: Study 1 used 124 archival conversational samples consisting of 39 children with SLI (age 5;0 [years;months]), 40 MLU-equivalent typically developing children (age 3;0), and 45 age-equivalent controls. Concurrent validity of MLU matches was examined by considering the correspondence between MLU and developmental sentence scoring (DSS), index of productive syntax (IPSyn), and MLU in words. Study 2 used 205 archival conversational samples, representing 5 years of longitudinal data collected on 20 children with SLI (from age 5;0) and 18 MLU matches (from age 3;0). Evaluation of growth dimensions within and across groups was carried out via growth-curve modeling. RESULTS: In Study 1, high levels of correlation among the MLU, DSS, and IPSyn measures were observed. Differences between groups were not significant. In Study 2, temporal stability of MLU matches was robust over a 5 year period. CONCLUSIONS: MLU appears to be a reliable and valid index of general language development and an appropriate grouping variable from age 3 to 10. The developmental stability of MLU matches is indicative of shared underlying growth mechanisms.

Case-Control Studies↗

PubMed1999

The genetic element pSSVx of the extremely thermophilic crenarchaeon Sulfolobus is a hybrid between a plasmid and a virus.

A new Sulfolobus islandicus strain, REY15/4, harboured both a novel fusellovirus, SSV2, and a small plasmid, pSSVx. The plasmid spread in S. solfataricus P1 together with the virus after infection with either the supernatant of a culture of REY15/4 or purified virus. Spreading of the plasmid required co-transfection with either SSV2 or the related SSV1 as helpers. Virus purified from REY15/4 constituted a mixture of two sizes of particles, one with the dimensions of a normal fusellovirus and the other smaller. Cloned SSV2 produced only the larger particles and only SSV2 DNA, indicating that the smaller particles contained pSSVx packaged into capsids made up of SSV2 components. The 5.7 kb genome of pSSVx revealed regions of high sequence similarity to the cryptic Sulfolobales plasmids pRN1, pRN2 and pDL10. Thus, pSSVx belongs to the family of pRN plasmids that share a highly conserved region, which probably constitutes the minimal replicon. They also contain a variable region showing no sequence similarity. In pSSVx, this region contains three open reading frames (ORFs), two of which are juxtapositioned and show high sequence similarity to a tandem of ORFs in fusellovirus genomes. Neither pRN1 nor pRN2, which lack this tandem, spread in the presence of the fuselloviruses, which implies that the sequences of these ORFs enable pSSVx to use the packaging system of the viral helpers for spreading.

Amino Acid Sequence↗

PubMed1985

Initiator tRNA may recognize more than the initiation codon in mRNA: a model for translational initiation.

A special methionine tRNA (tRNAi) is universally required to initiate translation. Amongst species a tRNAi structural conservation is most apparent in the anticodon and T arms of the molecule but extends into the variable loop and the 3' strand of the D stem. This suggested that they could share a similar ancestral or current function in initiation of translation. We report that the sequence of bases neighboring the translational start codons of many eubacterial genes are complementary not only to the extended anticodon but also to the D and T loops of tRNAi. Study of the coding properties of tRNAi and of mutations that affect translation suggests that the translational start domain can be a mosaic of signals complementary to the loops of tRNAi. The hypothesis of multiple loop recognition suggests that unusual triplets can start prokaryotic and mitochondrial genes and predicts the occurrence of other reading frames. Furthermore, it suggests a unifying model for chain initiation based on RNA contacts and displacements.

Animals↗

PubMed1997

A novel pair of immunoglobulin-like receptors expressed by B cells and myeloid cells.

An Fcalpha receptor probe of human origin was used to identify novel members of the Ig gene superfamily in mice. Paired Ig-like receptors, named PIR-A and PIR-B, are predicted from sequence analysis of the cDNAs isolated from a mouse splenic library. Both type I transmembrane proteins possess similar ectodomains with six Ig-like loops, but have different transmembrane and cytoplasmic regions. The predicted PIR-A protein has a short cytoplasmic tail and a charged Arg residue in the transmembrane region that, by analogy with the FcalphaR relative, suggests the potential for association with an additional transmembrane protein to form a signal transducing unit. In contrast, the PIR-B protein has an uncharged transmembrane region and a long cytoplasmic tail containing four potential immunoreceptor tyrosine-based inhibitory motifs. These features are shared by the related killer inhibitory receptors. PIR-A proteins appear to be highly variable, in that predicted peptide sequences differ for seven randomly selected PIR-A clones, whereas PIR-B cDNA clones are invariant. Southern blot analysis with PIR-B and PIR-A-specific probes suggests only one PIR-B gene and multiple PIR-A genes. The PIR-A and PIR-B genes are expressed in B lymphocytes and myeloid lineage cells, wherein both are expressed simultaneously. The characteristics of the highly-conserved PIR-A and PIR-B genes and their coordinate cellular expression suggest a potential regulatory role in humoral, inflammatory, and allergic responses.

Amino Acid Sequence↗

PubMed2000

Variability of attitudes toward early initiation of HAART for HIV infection: a study of French prescribing physicians.

This study assessed prescribing physicians' attitudes toward early initiation of HAART, three months after the dissemination of the first French official treatment guideline. Telephone interviews have been made in a national random sample of physicians with full- or part-time practice in hospital departments delivering care for HIV-infected patients. Questionnaires included hypothetical clinical cases. Logistic regression compared characteristics of respondents according to attitudes toward HAART. Among the 483 respondents (response rate = 87.0%), agreement was high with official recommendations to systematically initiate HAART with protease inhibitors (PIs) for patients with CD4+ cell counts < or = 300/mm3, following a diagnosis of acute primary HIV infection, or for HIV sexual risk post-exposure prophylaxis. Confronted with a case of a naive asymptomatic patient with stable 450 CD4+/mm3, 34.6% would prescribe HAART with PIs in any case, and 29.8% only if the patient has plasma viral load < or = 10,000 HIV RNA copies/ml. The remaining 35.6% would not prescribe PIs and were older, had limited activity in HIV care and expressed more interest in alternative medicines. To avoid a confusing impact of variability of clinical attitudes toward uncertainties associated with antiretroviral treatments among HIV-infected patients, shared decision-making between patient and physician should be promoted for initiation of HAART.

Adult↗

PubMed1986

Stimulation and expansion of a human T-cell subpopulation by a monoclonal antibody to T-cell receptor molecule.

A murine monoclonal antibody (MAb) was obtained that showed unique specificity for the immunizing T-cell line HPB-ALL. This antibody, C37 (an IgG1,K) also reacted with a small (2-5%) population of normal peripheral blood T (PBL-T) cells. These C37-positive (C37+) cells were found in both the T4/Leu3+ and T8/Leu2+ subsets. Like OKT3 antibody, C37 induced T-cell mitogenesis with a peak proliferative response at day 3. In long-term cultures containing irradiated autologous feeder cells and IL-2, C37 antibody caused the selective expansion of C37+ T cells. On HPB-ALL cells C37 induced comodulation of the T3 molecule. C37 precipitated a disulfide-linked dimer characteristic of the T-cell antigen receptor consisting of an alpha-subunit (45-48 kD) and a beta-subunit (38-42 kD) from both C37+ T-cell blasts of a normal individual and HPB-ALL cells that were surface radioiodinated. However, the precipitated molecule isolated from C37 antibody-activated T-cell blasts exhibited a different pI from that isolated from HPB-ALL cells. Our studies indicate that C37 recognizes an epitope on the T-cell receptor molecule that is shared by a subpopulation of human T cells, which raises the possibility that multiple variable-region associated and/or framework-like determinants of the T-cell antigen receptor can be defined serologically and used in functional and molecular studies of T-cell subsets.

Antibodies, Monoclonal↗

PubMed1993

Monoclonal anti-lipid A IgM antibodies HA-1A and E-5 recognize distinct epitopes on lipopolysaccharide and lipid A.

Specific binding of two monoclonal IgM antibodies previously investigated as therapeutic agents for treating gram-negative septic shock, HA-1A and E5, was assessed with respect to lipid A and lipopolysaccharide (LPS). Both antibodies bound to lipid A; however, binding of HA-1A was significantly greater than that of E5 to LPS derived from rough strains of bacteria. Reciprocal competitive inhibition experiments supported the concept that HA-1A and E5 bind to distinct epitopes on lipid A. Further, competitive inhibition studies using a monoclonal anti-idiotype antibody with specificity for the variable region of HA-1A suggested that HA-1A and E5 do not share a common idiotype. Finally, studies using double-stranded DNA as antigen indicated that E5 but not HA-1A will bind to DNA. Collectively, these data indicate that HA-1A and E5 are different lipid A-specific antibodies that bind to distinct epitopes on lipid A.

Animals↗

PubMed1993

Differential expression of retinal proteins in a pineal parenchymal tumor.

The pineal gland and retina share histogenetic features that reflect a similar neurosensory/photosensory ontogeny. Pineal parenchymal tumors demonstrate a highly variable and incomplete photosensory differentiation evidenced by specific cytoarchitectural features and the expression of photosensory retinal S-Antigen (S-Ag). Despite these neuro-ontogenetic parallels, pineal parenchymal tumors have not been well studied for the neuroretinal phenotypes that accompany normal neuroretinal development. The investigation of photoreceptor gene expression may provide an important insight into the histogenesis of pineal parenchymal neoplasms. In this study, a pineal parenchymal tumor of the "mixed pineoblastoma/pineocytoma" type was examined for the expression of several photoreceptor, glial and neuronal proteins including: interphotoreceptor retinoid-binding protein (IRBP), rod opsin, cone opsin, S-Ag and cellular retinaldehyde-binding protein (CRA1BP). The detection of IRBP and its mRNA, the earliest photoreceptor-associated protein expressed during retinal development, corroborated the rudimentary photosensory differentiation of this tumor which had limited cytoarchitectural evidence for pineal differentiation. The analysis of IRBP expression may facilitate the diagnostic recognition of primitive pineal neoplasms and further define the neuroretinal differentiation which occurs in pineal parenchymal tumors.

Adolescent↗

PubMed2005

Missed expectations? Physicians' views of patients' participation in medical decision-making.

OBJECTIVE: Physicians are encouraged to actively involve patients in clinical decision-making, but this expectation has not been adequately examined from the physicians' perspective. Our objective was to identify and characterize physicians' attitudes toward patient participation in decision-making and to gain insight into how they consequently think about and structure the decision-making process. DESIGN: This was a qualitative cross-sectional study of physicians' reported attitudes and practices. SETTING: The study took place in private practice and academic physicians' practices. PARTICIPANTS: A total of 53 academic and private practice physicians from primary care and surgical specialties, ranging from first year residents to recently retired, participated in the study. MEASUREMENTS: We performed a qualitative analysis of semistructured individual interviews. RESULTS: The physicians in this study expressed consistently positive attitudes toward patient participation in medical decision-making. They identified patient autonomy as an essential justification for patient participation but often went beyond an autonomy-based rationale. Several were motivated by the fundamental principle of beneficence as well as their own self-interest in avoiding legal liability. Many physicians saw their role as an expert who educates the patient but retains control over the decision-making process; others took a more collaborative approach, encouraging patients to assume decisional priority. The decision-making process often was modified by patient, physician, and environmental factors. CONCLUSIONS: The physicians in this study demonstrated a positive, flexible approach toward including patients in decision-making. A one-dimensional model of shared decision-making based solely on the principle of autonomy fails to account for variability in how physicians allocate decisional priority and is therefore ethically inadequate.

Academic Medical Centers↗

PubMed2004

Rapid evolution in conformational space: a study of loop regions in a ubiquitous GTP binding domain.

The rapidly evolving subsets of a protein are often evident in multiple sequence alignments as poorly defined, gap-containing regions. We investigated the 3D context of these regions observed in 28 protein structures containing a GTP-binding domain assumed to be homologous to the transforming factor p21-RAS. The phylogenetic depth of this data set is such that it is possible to observe lineages sharing a common protein core that diverged early in the eukaryotic cell history. The sequence variability among these homolog proteins is directly linked to the structural variability of surface loops. We demonstrate that these regions are self-contained and thus mostly free of the evolutionary constraints imposed by the conserved core of the domain. These intraloop interactions have the property to create stem-like structures. Interestingly, these stem-like structures can be observed in loops of varying size, up to the size of small protein domains. We propose a model under which the diversity of protein topologies observed in these loops can be the product of a stochastic sampling of sequence and conformational space in a near-neutral fashion, while the proximity of the functional features of the domain core allows novel beneficial traits to be fixed. Our comparative observations, limited here to the proteins containing the RAS-like GTP-binding domain, suggest that a stochastic process of insertion/deletion analogous to "budding" of loops is a likely mechanism of structural innovation. Such a framework could be experimentally exploited to investigate the folding of increasingly complex model inserts.

Amino Acid Sequence↗

PubMed2005

Indeterminate cell histiocytosis: fact or fiction?

Indeterminate cell histiocytosis is a rare disorder, in which the predominant cells have the characteristics of both Langerhans cells and macrophages. We, in this study, describe 18 patients and compare them with those previously published. Most patients were adults with either solitary or multiple red-brown papules or nodules. While most lesions were confined to the skin, both conjunctival and bony involvement was seen. Histologically, the lesions showed patterns resembling those described for xanthogranulomas, with predominantly oncocytic (nine patients), spindled (five patients), scalloped (two patients) or vacuolated (two patients) macrophages. The accompanying infiltrate was mainly lymphocytic, although eosinophils and occasionally plasma cells were seen. All lesions were positive for macrophage markers, such as KP1 (CD68) and Ki-M1p, as well as for S-100 protein and showed variable reactivity for CD1a. No Birbeck granules were seen ultrastructurally in one patient. Some patients shared features with sinus histiocytosis with massive lymphadenopathy. It is unclear whether this disorder is a separate entity or represents various macrophage disorders identified at various time points in the inflammatory response. Ratzinger G, Burgdorf WHC, Metze D, Zelger BG, Zelger B. Indeterminate cell histiocytosis: fact or fiction? A clinicopathological series of 18 patients.

Adult↗

PubMed2004

alpha-crystallin: a review of its structure and function.

alpha-crystallin, the major protein of the mammalian lens in most species, is an aggregate assembled from two polypeptides, each with a molecular weight around 20,000 Da. It is polydisperse and can be isolated in a variety of forms, including spherical particles with molecular weights ranging upwards from about 200 kDa. Sequence comparisons reveal that it is a member of the small heat shock protein (shsp) family. These proteins are aggregates assembled from polypeptides of 10 to 25 kDa that share a common central domain of about 90 residues (the 'alpha-crystallin domain') with variable N- and C-terminal extensions. alpha-crystallin has been intensively studied for more than 50 years but its three-dimensional structure remains unknown because it has not been possible to obtain crystals for X-ray studies and it is too large for NMR measurements. Structural information has been derived from a variety of solution studies. Because of the protein's polydispersity, interpretation of data has been difficult. This led to different viewpoints and vigorous debate on its structure and properties. Recently, the crystal structures of two closely-related small heat shock proteins have been determined. These have provided some insight into the structure of a-crystallin and explanations of previous observations. Like many other heat shock proteins, alpha-crystallin exhibits chaperone-like properties, including the ability to prevent the precipitation of denatured proteins and to increase cellular tolerance to stress. It has been suggested that these functions are important for the maintenance of lens transparency and the prevention of cataract.

Amino Acid Sequence↗

PubMed1984

Environmental and personality similarities in case histories of suicide and self-poisoning by children under ten.

Research on suicide in latency age children is reviewed and case histories of two 9-year-old children who suicided by shooting themselves and one 7-year-old who died by self-poisoning are presented. Similarities in environmental and family histories, and in personality variables among these three cases have suggested underlying mechanisms in development and maintenance of symbiotically shared self-concept between parent and child which may be useful in helping to identify similar cases and in assessing potential for suicidal and self-destructive behavior in latency age children.

Achievement↗

PubMed2005

Clonal association between Streptococcus pneumoniae serotype 23A, circulating within the United States, and an internationally dispersed clone of serotype 23F.

Streptococcus pneumoniae is an important pathogen in the United States and is associated with significant morbidity and mortality. Since the introduction of the seven-valent conjugate vaccine, a significant decline in pneumococcal disease has been reported. However, surveillance for pneumococcal disease remains essential, as the extent of cross protection against vaccine-related serotypes is still unclear. Further, any increase in non-vaccine-related serotypes also needs monitoring. We report on a new clonal association between a vaccine-related serotype, serotype 23A, obtained as part of the Active Bacterial Core surveillance, with an established internationally dispersed Pneumococcal Molecular Epidemiology Network (PMEN) clone, clone Colombia(23F)-26. Sixty-two isolates of serotype 23A collected from sterile sites during a 2-year period (2002 and 2003) were characterized. Twenty-one (34%) isolates were penicillin nonsusceptible, although none were fully resistant. Pulsed-field gel electrophoresis and multilocus sequence typing analysis showed that 24 (39%) of the serotype 23A isolates shared either genetic identity or high genetic relatedness with PMEN clone Colombia(23F)-26. Extensive variability was noted within the sequenced region of pbp2b in two penicillin-nonsusceptible isolates as well as in PMEN clone Colombia(23F)-26, suggesting that these isolates probably acquired penicillin resistance independently. The emergence of such new serotype and genotype associations highlights the dynamic nature of the pneumococcal population, necessitating continuous monitoring in the post-vaccine era.

Adolescent↗

PubMed2005

A comparison between microsatellite and single-nucleotide polymorphism markers with respect to two measures of information content.

Using the Genetic Analysis Workshop 14 (GAW14) simulated dataset, we compare microsatellite and single-nucleotide polymorphism (SNP) markers in terms of two measures of information content, the traditional entropy-based information content measure, and a new "relative information" measure. Both attempt to measure the amount of information contained in the markers about the identity-by-descent (IBD) sharing among relatives. The performance of the two information measures are compared based on their variability and ability to predict change in the LOD score (Delta LOD) as map density increases for SNP markers. Although in a linked region, LOD scores are correlated with measures of information, we observe that none of the measures predict the LOD score itself very well. In an unlinked region, the LOD score is not related to either measures of information. The information content of microsatellite markers with 7.5-cM spacing is slightly higher than that of SNP markers with 3-cM spacing. At these map densities, microsatellites are found to be uniformly more informative than SNPs irrespective of their level of heterozygosity. For SNPs, we found that as the level of heterozygosity increases, the information content increases. As reported in all other previous studies, we also found that high-density SNPs have higher information content compared to low-density microsatellites. Performance of both the two information measures considered here are similar, but the relative information measure predicts Delta LOD as marker density increases better than the traditional entropy-based information measure.

Genetic Markers↗

PubMed1984

Disorders with overvalued ideas.

The overvalued idea, first described by Wernicke, refers to a solitary, abnormal belief that is neither delusional nor obsessional in nature, but which is preoccupying to the extent of dominating the sufferer's life. Disorders conforming to his definition are well documented, though their recognition as such has been variable, and they may not be as rare as is often thought. As well as sharing a distinctive phenomenology, the conditions develop in similar settings and carry a uniformly poor prognosis. Their pathogenesis is obscure and difficult to account for in conventional terms.

Anorexia Nervosa↗

PubMed1990

All-payer rate-setting and the provision of hospital care to the uninsured: the New Jersey experience.

The New Jersey all-payer prospective payment system compensates hospitals for charity care and bad debts. This study examines its impact on the provision of care to self-pay patients. Self-pay patients include two types of uninsured individuals: (1) patients who cannot afford to pay their bill and (2) more affluent patients who can afford to pay but who evade collection. Using data for the period 1979-85, the study employed a sample of seventy-nine New Jersey hospitals that entered the all-payer system during the years 1980-82. A regression equation, which included independent variables to control for the community's pool of uninsured residents and the hospital's share of this pool, was estimated for the number of self-pay discharges. The results indicate that the volume of care provided to self-pay patients increased when the New Jersey all-payer system was introduced. The results also show that teaching hospitals and facilities in urban areas discharge a disproportionately large number of self-pay patients. Analysis of the operating margin ratio suggests that the all-payer system helped to restore the financial viability of hospitals that tend to provide larger amounts of services to the uninsured.

Economics, Hospital↗

PubMed2002

Muscarinic toxin-like proteins from Taiwan banded krait (Bungarus multicinctus) venom: purification, characterization and gene organization.

Two novel proteins, BM8 and BM14, were isolated from Bungarus multicinctus (Taiwan banded krait) venom using the combination of chromatography on a SP-Sephadex C-25 column and a reverse-phase HPLC column. Both proteins contained 82 amino acid residues including 10 cysteine residues, but there were two amino acid substitutions at positions 37 and 38 (Glu37-Ala38 in BM8; Lys37-Lys38 in BM14). CD spectra and acrylamide quenching studies revealed that the gross conformation of BM8 and BM14 differed. In contrast to BM8, BM14 inhibited the binding of [3H]quinuclidinyl benzilate to the M2 muscarinic acetylcholine (mAchR) receptor subtype. Trinitrophenylation of Lys residues abolished the mAchR-binding activity of BM14, indicating that the Lys substitutions at positions 37 and 38 played a crucial role in the activity of BM14. The genomic DNA encoding the precursor of BM14 was amplified by PCR. The gene shared virtually identical structural organization with alpha-neurotoxin and cardiotoxin genes. The intron sequences of these genes shared a sequence identity up to 84%, but the protein-coding regions were highly variable. These results suggest that BM8, BM14, neurotoxins and cardiotoxins may have originated from a common ancestor, and the evolution of snake venom proteins shows a tendency to diversify their functions.

Amino Acid Sequence↗