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PubMed1999

Postnatal transient renal insufficiency in the feto-fetal transfusion syndrome.

Twinning and higher-order multiple-gestation pregnancies have become relatively frequent in the current era of assisted reproductive techniques. Vascular interconnections are present in nearly all monochorionic twin placentae, yet hemodynamically significant arteriovenous anastomoses resulting in the feto-fetal transfusion syndrome occur in only 5%-18% of these. When arteriovenous connections through a shared placental cotyledon are present, variable amounts of blood may be transfused from one fetus to the other, and feto-fetal transfusion syndrome may result. While reports of renal failure due to a small non-functioning kidney in the donor infant pre- or postnatally have been published, recoverable renal insufficiency has not been previously delineated in feto-fetal transfusion syndrome. This article describes a case of postnatal transient renal insufficiency in a donor infant from a pair of monozygotic twins.

Acute Kidney Injury↗

PubMed1985

The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes.

The T cell surface glycoproteins T4 and T8 are thought to mediate efficient cell-cell interactions in the immune system and in this way may be responsible for the appropriate targeting of subpopulations of T cells. We have used gene transfer combined with subtractive hybridization to isolate both cDNA and functional genomic clones encoding the T8 protein. The sequence of the cDNA reveals that T8 is a transmembrane protein with an N-terminal domain which shares significant homology to immunoglobulin variable region light chains. This immunoglobulin-like structure is likely to be important in the function of T8 during differentiation and in the course of the immune response.

Amino Acid Sequence↗

PubMed1988

Senescence in Podospora anserina: a possible role for nucleic acid interacting proteins suggested by the sequence analysis of a mitochondrial DNA region specifically amplified in senescent cultures.

In Podospora anserina, the phenomenon of senescence was previously shown to be correlated with the presence of a senescence-specific DNA (sen-DNA) resulting from the amplification of some regions (alpha, beta, gamma, epsilon) of the mitochondrial chromosome. The beta region gives rise to sen-DNAs with variable sizes and junctions which share a 1,100-bp common sequence. Here we report the complete nucleotide sequence of one 4-kb beta sen-DNA. Included in the sequence are a large part of the first intron open reading frame (ORF) of the gene ND4L and three short unidentified ORFs more precisely located in the common beta region. The primary structure of the polypeptide possibly encoded by one of them is very similar to the glycine-rich domains present in various single-stranded DNA-binding proteins. The comparison of the information content of this beta sen-DNA with that of other previously sequenced sen-DNAs suggests that the role in the senescence process attributed to the sen-DNAs could be related to the overproduction of a variety of proteins which interact with nucleic acids.

Amino Acid Sequence↗

PubMed2004

CDR3 spectratyping identifies clonal expansion within T-cell subpopulations that demonstrate therapeutic antitumor activity.

BACKGROUND: Antigen-specific T cells undergoing clonal expansion share common rearrangements of the variable complementary determining region 3 (CDR3) of the T-cell receptor (TCR), which can be identified using polymerase chain reaction-based V beta (VB) spectratyping. The purpose of this study was to determine whether CDR3 spectratyping identifies clonal expansion within tumor-draining lymph node (TDLN) subpopulations with antitumor therapeutic activity. METHODS: Recently sensitized T cells from 4T1 murine mammary carcinoma TDLN were fractionated based on CD62L (L-selectin) surface expression before RNA isolation and culture. L-selectinlow and L-selectinhigh TDLN were analyzed for T-cell receptor usage by immunophenotyping and CDR3 spectratyping, and then culture activated with anti-CD3/IL-2 to assess therapeutic efficacy after adoptive transfer. RESULTS: Adoptive transfer experiments confirmed that mice treated with culture-activated L-selectinlow TDLN cells exhibited delayed subcutaneous tumor growth and prolonged survival as compared to control or L-selectinhigh-treated mice (P < .01). CDR3 spectratyping demonstrated oligoclonal skewing of the CDR3 regions within several VB families including VB3, VB5.2, and VB17 in L-selectinlow but not in L-selectinhigh TDLN. Although fluorescence-activated cell sorter analysis demonstrated the highest percentage of cells expressing VB13 usage in both populations, CDR3 spectratyping did not identify the presence of clonal expansion. CONCLUSIONS: These data suggest that CDR3 spectratyping may be useful in identifying T cells undergoing clonal expansion that demonstrate antitumor therapeutic activity.

Animals↗

PubMed2003

Use of denaturing gradient gel electrophoresis for analysis of the stool microbiota of hospitalized patients.

Denaturing gradient gel electrophoresis (DGGE) of PCR-amplified ribosomal RNA gene amplicons was used to study the stool microbiota of hospitalized patients and to examine the effect of antibiotic therapy. For one patient, 16 anaerobic species identified by random cloning and sequencing of PCR-amplified rRNA genes from stool were represented by bands on the DGGE gel. DGGE analysis and similarity index comparisons demonstrated that the anaerobic microbiota of this individual remained stable in the absence of antibiotic therapy, was minimally affected by ciprofloxacin but markedly reduced by clindamycin therapy, and recovery of some organisms was evident within days after discontinuation of clindamycin. DGGE analysis of additional patients demonstrated similar disruptions of the intestinal microbiota associated with antibiotic therapy. The DGGE banding patterns of nine patients showed considerable variability, but several bands were shared among patients. Thus, our findings are consistent with previous studies that utilized culture techniques, and suggest that DGGE is a useful technique for analysis of the stool microbiota of hospitalized patients.

Actinobacteria↗

PubMed2003

Induced oscillations and the distributed cortical sources during the Wisconsin card sorting test performance in schizophrenic patients: new clues to neural connectivity.

Prefrontal dysfunction has been associated with schizophrenia. Activation during Wisconsin card sorting test (WCST) is a common approach used in functional neuroimaging to address this failure. Equally, current knowledge states that oscillations are basic forms of cells-assembly communications during mental activity. Promising results were revealed in a previous study assessing healthy subjects, WCST and oscillations. However, those previous studies failed to meet the functional integration of the network during the WCST in schizophrenics, based on the induced oscillations and their distributed cortical sources. In this research, we utilized the brain electrical tomography (variable-resolution brain electromagnetic tomography) technique to accomplish this goal. Task specific delta, theta, alpha and beta-2 oscillations were induced and simultaneously synchronized over large extensions of cortex, encompassing prefrontal, temporal and posterior regions as in healthy subjects. Every frequency had a well-defined network involving a variable number of areas and sharing some of them. Oscillations at 11.5, 5.0 and 30 Hz seem to reflect an abnormal increase or decrease, being located at supplementary motor area (SMA), left occipitotemporal region (OT), and right frontotemporal subregions (RFT), respectively. Three cortical areas appeared to be critical, that may lead to difficulties either in coordinating/sequencing the input/output of the prefrontal networks-SMA, and retention of information in memory-RFT, both preceded or paralleled by a deficient visual information processing-OT.

Adult↗

PubMed1998

T-cell receptor peptide vaccination in the treatment of rheumatoid arthritis.

In several human T-cell-mediated autoimmune diseases and animal models of such illnesses, T-cell receptors (TCR) specific for antigens that initiate or perpetuate the disease share a limited number of variable region determinants. Vaccinations with peptides derived from over-represented TCRs are effective treatment for some of these disorders. RA is a chronic inflammatory disease in which there is prominent T-cell infiltration in the synovial lining layer. TCR V beta 3, V beta 14, and V beta 17 have been found to be over-represented among IL-2 receptor-positive T-cells from patients with RA. A phase II clinical trial in RA, using a combination of three peptides derived from V beta 3, V beta 14, and V beta 17, has yielded promising results. Larger clinical efficacy and safety studies must be performed to determine if TCR peptide vaccination will become a viable treatment alternative for patients with RA.

Antibody Formation↗

PubMed2001

The NART as an index of prior intellectual functioning: a retrospective validity study covering a 66-year interval.

BACKGROUND: The National Adult Reading Test (NART) is widely used in research and clinical practice as an estimate of pre-morbid or prior ability. However, most of the evidence on the NART's validity as a measure of prior intellectual ability is based on concurrent administration of the NART and an IQ measure. METHOD: We followed up 179 individuals who had taken an IQ test (the Moray House Test) at age 11 and administered the NART and the Mini-Mental State Examination (MMSE) at age 77. A subset (N = 97) were also re-administered the original IQ test. RESULTS: The correlation between NART performance at age 77 and IQ age 11 was high and statistically significant (r = 0.73; P < 0001). This correlation was comparable to the correlation between NART and current IQ, and childhood IQ and current IQ, despite the shared influences on the latter variable pairings. The NART had a significant correlation with the MMSE but this correlation fell to near zero (r = 0.02) after partialling out the influence of childhood IQ. DISCUSSION: The pattern of results provides strong support for the claim that the NART primarily indexes prior (rather than current) intellectual ability.

Aged↗

PubMed1998

Sib mating designs for mapping quantitative trait loci.

The power to separate the variance of a quantitative trait locus (QTL) from the polygenic variance is determined by the variability of genes identical by descent (IBD) at the QTL. This variability may increase with inbreeding. Selfing, the most extreme form of inbreeding, increases the variability of the IBD value shared by siblings, and thus has a higher efficiency for QTL mapping than random mating. In self-incompatible organisms, sib mating is the closest form of inbreeding. Similar to selfing, sib mating may also increase the power of QTL detection relative to random mating. In this study, we develop an IBD-based method under sib mating designs for QTL mapping. The efficiency of sib mating is then compared with random mating. Monte Carlo simulations show that sib mating designs notably increase the power for QTL detection. When power is intermediate, the power to detect a QTL using full-sib mating is, on average, 7% higher than under random mating. In addition, the IBD-based method proposed in this paper can be used to combine data from multiple families. As a result, the estimated QTL parameters can be applied to a wide statistical inference space relating to the entire reference population.

Animals↗

PubMed1989

Ratings of social support by adolescents and adult informants: degree of correspondence and prediction of depressive symptoms.

It has been suggested that the personality of the individual influences appraisal processes that determine ratings of both social support and mental health, thus leading to an association between these variables that reflects only their shared self-report bias. To test whether ratings of social support made by someone other than the target individual would significantly predict outcomes, 115 pregnant adolescent girls and 115 adults who knew the adolescents well both completed ratings of the adolescent's social support. Results showed a moderate level of agreement between adolescent and informant support ratings. Both self-report and informant total social support ratings predicted pregnancy depression scores. Only informant social support ratings were significant predictors of postpartum depression scores. The ability of informants' ratings of social support to predict the adjustment of the adolescents to a major life stress was viewed as evidence that the commonly found link between social support and mental health reflects more than self-report biases.

Adolescent↗

PubMed2006

Quantitative proteomic analysis of distinct mammalian Mediator complexes using normalized spectral abundance factors.

Components of multiprotein complexes are routinely determined by using proteomic approaches. However, this information lacks functional content except when new complex members are identified. To analyze quantitatively the abundance of proteins in human Mediator we used normalized spectral abundance factors generated from shotgun proteomics data sets. With this approach we define a common core of mammalian Mediator subunits shared by alternative forms that variably associate with the kinase module and RNA polymerase (pol) II. Although each version of affinity-purified Mediator contained some kinase module and RNA pol II, Mediator purified through F-Med26 contained the most RNA pol II and the least kinase module as demonstrated by the normalized spectral abundance factor approach. The distinct forms of Mediator were functionally characterized by using a transcriptional activity assay, where F-Med26 Mediator/RNA pol II was the most active. This method of protein complex visualization has important implications for the analysis of multiprotein complexes and assembly of protein interaction networks.

HeLa Cells↗

PubMed2003

Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity.

Vascular endothelial growth factor (VEGF) and its receptors have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. We previously identified several fully human neutralizing anti-VEGF receptor 2 (or kinase inserting domain-containing receptor (KDR)) antibodies from a large antibody phage display library. These antibodies bind specifically to KDR, block VEGF/KDR interaction, and inhibit VEGF-induced proliferation of human endothelial cells and migration of KDR+ leukemia cells. Three of these antibodies, interestingly, share an identical heavy chain variable (VH) sequence. In this report, we constructed a new library comprising the single VH paired with the variable light chain (VL) repertoire obtained from the original naïve human library. Initial in vitro selection revealed that the single VH could pair with a number of different VL while retaining its specificity for KDR. However, a consensus VH/VL pair, clone 1121, was identified after three or four rounds of selection by tailoring the stringency of the panning conditions. Clone 1121 showed a >30-fold higher binding affinity to KDR (Kd, 100 pm) because of improvement on both association and dissociation constants and blocked VEGF/KDR interaction with an IC50 of approximately 1 nm, compared with that of 3-4 nm for the parent Fab fragments. Further, clone 1121 was more potent in inhibiting VEGF-stimulated KDR phosphorylation in endothelial cells. A binding epitope mapping study on clone 1121 and one of the parent clones, 2C6, demonstrated that both antibodies interacted with the third immunoglobulin domain within the extracellular region of KDR. Several peptide phage display libraries were utilized to further examine the fine binding specificities of the two antibodies. All of the 2C6-binding peptides are cysteine-constrained, whereas clone 1121 binds to both cysteine-constrained and linear peptides. It is noteworthy that most of the 2C6-binding peptides also cross-react with clone 1121, but none of the clone 1121-specific peptides binds to 2C6, indicating that clone 1121 retained part of the original binding epitope(s) of 2C6 while gaining new binding specificity. Taken together, our observation suggests that clone 1121 may have great clinical potential in anti-angiogenesis therapy. It further underscores the efforts to identify antibodies of high affinity for enhanced biological activities.

Amino Acid Sequence↗

PubMed2000

Morphometric analysis of CC10-hASH1 transgenic mouse lung: a model for bronchiolization of alveoli and neuroendocrine carcinoma.

Constitutive expression of human achaete-scute homolog-1 (hASH1) alone or in combination with Simian virus 40 (SV40) large T antigen (TAg) under the Clara cell 10-kDa secretory protein (CC10) promoter results in bronchiolization of alveoli and enhanced tumorigenesis, respectively. A novel morphometric system composed of series of fixed distance concentric rings originating at the bronchioloalveolar junction was used to determine spatial growth patterns. hASH1 mice exhibited progressive airway epithelial hyperplasia near this junction, and minimal changes further away in the alveolar compartment. TAg animals shared this increase, but exhibited variable distance-dependent growth. By 2 months TAg/hASH1 animals showed highly increased growth at all points measured. Remarkably, TAg/hASH1 animals expressed both CC10 and extensive neuroendocrine differentiation in airways and tumors. The results suggest that these transgenic mice provide a useful model with many similarities to human lung carcinogenesis, which originates in airway epithelium, and often reveals neuroendocrine differentiation.

Animals↗

PubMed1990

Factors associated with risk behaviour among injecting drug users.

A project which investigated the injecting and sexual behaviour of drug users in the North West of England revealed several social and behavioural factors strongly associated with HIV-related risk behaviour. For example, homelessness, crime, ignorance of drug-related health problems and drug use by a regular partner were associated with the sharing of injecting equipment. Other variables predicted casual sexual intercourse and intercourse without condoms. Some factors were identified that were common to both injecting and sexual risk behaviour.

Adolescent↗

PubMed2006

Utility of nuclear allele networks for the analysis of closely related species in the genus Carabus, subgenus Ohomopterus.

Nuclear DNA sequence data for diploid organisms are potentially a rich source of phylogenetic information for disentangling the evolutionary relationships of closely related organisms, but present special phylogenetic problems owing to difficulties arising from heterozygosity and recombination. We analyzed allelic relationships for two nuclear gene regions (phosphoenolpyruvate carboxykinase and elongation factor-1a), along with a mitochondrial gene region (NADH dehydrogenase subunit 5), for an assemblage of closely related species of carabid beetles (Carabus subgenus Ohomopterus). We used a network approach to examine whether the nuclear gene sequences provide substantial phylogenetic information on species relationships and evolutionary history. The mitochondrial gene genealogy strongly contradicted the morphological species boundary as a result of introgression of heterospecific mitochondria. Two nuclear gene regions showed high allelic diversity within species, and this diversity was partially attributable to recombination between various alleles and high variability in the intron region. Shared nuclear alleles among species were rare and were considered to represent shared ancestral polymorphism. Despite the presence of recombination, nuclear allelic networks recovered species monophyly more often and presented genetic differentiation patterns (low to high) among species more clearly. Overall, nuclear gene networks provide clear evidence for separate biological species and information on the phylogenetic relationships among closely related carabid beetles.

Alleles↗

PubMed2003

Why are you telling me that? A conceptual model of the social function of autobiographical memory.

In an effort to stimulate and guide empirical work within a functional framework, this paper provides a conceptual model of the social functions of autobiographical memory (AM) across the lifespan. The model delineates the processes and variables involved when AMs are shared to serve social functions. Components of the model include: lifespan contextual influences, the qualitative characteristics of memory (emotionality and level of detail recalled), the speaker's characteristics (age, gender, and personality), the familiarity and similarity of the listener to the speaker, the level of responsiveness during the memory-sharing process, and the nature of the social relationship in which the memory sharing occurs (valence and length of the relationship). These components are shown to influence the type of social function served and/or, the extent to which social functions are served. Directions for future empirical work to substantiate the model and hypotheses derived from the model are provided.

Age Factors↗

PubMed1984

Invertebrate recognition protein cross-reacts with an immunoglobulin idiotype.

To estimate the minimal structural requirements for cross-reaction of idiotypic determinants, we determined the capacity of monoclonal antibodies specific for the idiotype of the phosphorylcholine (PC)-binding myeloma protein TEPC-15 for cross-reactivities with the PC-binding, acute-phase protein C-reactive protein (CRP) and the hemagglutinin from the horseshoe crab Limulus polyphemus (limulin), which binds sialic acid and PC. Certain monoclonal antibodies (MAb) to the TEPC-15 idiotype showed strong cross-reactions with CRP and limulin when tested by enzyme-linked immunoadsorbent assays. The specificity of the cross-reactivities was confirmed by testing the binding of the reactive anti-TEPC-15 MAb to both CRP and limulin in the presence of p-nitrophenylphosphorylcholine (pNPPC), N-acetylneuraminic acid, and bovine submaxillary mucin. The binding of the MAb to both CRP and limulin was strongly decreased by pNPPC, partially decreased by free PC, and not affected by N-acetylneuraminic acid or bovine submaxillary mucin. Neither CRP nor limulin showed significant overall sequence homology to vertebrate immunoglobulins. However, CRP, limulin, and TEPC-15 variable region heavy chain (VH) shared short stretches of homology (8-10 amino acids) that mapped to a stretch comprised of the second complementarity determining region and third framework region of the TEPC-15 VH. These results might reflect either evolutionary convergence forced upon molecules of diverse evolutionary histories because of steric requirements of binding the same ligand, or a conservation of primitive combining site gene segments in evolution.

Animals↗

PubMed1986

Genomic variability of selected LAV-related AIDS retroviruses.

All AIDS retroviruses isolated from different patients have shown degrees of heterogeneity as defined by restriction fragment polymorphisms. Despite this variability, all these virus isolates share a number of structural features, including immunological cross-reactivity of virally encoded proteins. In this paper, we compare restriction patterns of integrated proviral DNA from viral isolates of patients belonging to different geographical groups, at risk or not for the disease. We confirm the existence of different clones in the same isolate of the Lymphadenopathy-associated virus (LAV) and of Human T lymphotropic virus (HTLV-III), which are identical. One of these forms is very similar to a Haitian isolate, as well as to an isolate from an early recognized New York case, suggesting a common origin for these viruses. More variation is apparent with Zairian viral isolates, and one of two clones found in a virus from a child who received an allogeneic bone marrow transplant. Greater disparity was also found in the restriction pattern of an isolate from an individual belonging to none of the so-called high-risk groups. We also show that this variation occurs mainly but not only in the env region of the genome, as previously described.

Adult↗