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Biomedical subjects

A W Lo

Publications and source records attributed to A W Lo.

12 recordsLinked to original sources
PubMed2001

A 330 kb CENP-A binding domain and altered replication timing at a human neocentromere.

Centromere protein A (CENP-A) is an essential centromere-specific histone H3 homologue. Using combined chromatin immunoprecipitation and DNA array analysis, we have defined a 330 kb CENP-A binding domain of a 10q25.3 neocentromere found on the human marker chromosome mardel(10). This domain is situated adjacent to the 80 kb region identified previously as the neocentromere site through lower-resolution immunofluorescence/FISH analysis of metaphase chromosomes. The 330 kb CENP-A binding domain shows a depletion of histone H3, providing evidence for the replacement of histone H3 by CENP-A within centromere-specific nucleosomes. The DNA within this domain has a high AT-content comparable to that of alpha-satellite, a high prevalence of LINEs and tandem repeats, and fewer SINEs and potential genes than the surrounding region. FISH analysis indicates that the normal 10q25.3 genomic region replicates around mid-S phase. Neocentromere formation is accompanied by a replication time lag around but not within the CENP-A binding region, with this lag being significantly more prominent to one side. The availability of fully sequenced genomic markers makes human neocentromeres a powerful model for dissecting the functional domains of complex higher eukaryotic centromeres.

Autoantigens↗
PubMed2001

A novel chromatin immunoprecipitation and array (CIA) analysis identifies a 460-kb CENP-A-binding neocentromere DNA.

Centromere protein A (CENP-A) is an essential histone H3-related protein that constitutes the specialized chromatin of an active centromere. It has been suggested that this protein plays a key role in the epigenetic marking and transformation of noncentromeric genomic DNA into functional neocentromeres. Neocentromeres have been identified on more than two-thirds of the human chromosomes, presumably involving different noncentromeric DNA sequences, but it is unclear whether some generalized sequence properties account for these neocentromeric sites. Using a novel method combining chromatin immunoprecipitation and genomic array hybridization, we have identified a 460-kb CENP-A-binding DNA domain of a neocentromere derived from the 20p12 region of an invdup (20p) human marker chromosome. Detailed sequence analysis indicates that this domain contains no centromeric alpha-satellite, classical satellites, or other known pericentric repetitive sequence motifs. Putative gene loci are detected, suggesting that their presence does not preclude neocentromere formation. The sequence is not significantly different from surrounding non-CENP-A-binding DNA in terms of the prevalence of various interspersed repeats and binding sites for DNA-interacting proteins (Topoisomerase II and High-Mobility-Group protein I). Notable variations include a higher AT content similar to that seen in human alpha-satellite DNA and a reduced prevalence of long terminal repeats (LTRs), short interspersed repeats (SINEs), and Alus. The significance of these features in neocentromerization is discussed.

Alu Elements↗
PubMed1999

Plasma cell-rich acute renal allograft rejection.

BACKGROUND: Acute renal allograft rejection is usually seen within the first 3 months posttransplant, and is characterized by an intense infiltrate of T cells. Some acute rejections, however, contain many plasma cells and/or appear late posttransplant. METHODS: We have investigated 27 cases of intensely plasma cell-rich acute rejections (PCAR) from 1987 to 1997 and have compared them to 21 control cases (CAR) of typical acute rejection. Each group was divided into early (<6 months) and late (>6 months) subgroups. PCAR and CAR cases were matched for histological features of chronic allograft nephropathy. In all four groups, most cases had Banff '97 type IB and IIA acute rejection. RESULTS: A significantly greater number of PCAR cases experienced graft failure due to chronic allograft nephropathy or complications of acute rejection (P<0.05). There was no significant difference between PCAR and CAR in HLA matching, occurrence of posttransplant acute tubular necrosis, presence versus absence of previous allografts, number of previous or subsequent acute rejection episodes, Banff '97 sum scores for acute rejection, cyclosporine A or FK506 levels, or percent change from baseline creatinine at time of biopsy. Plasma cells in PCAR cases showed IgG predominance whereas those in CAR had comparable staining for IgG and IgA. Kappa and lambda light chain immunostaining of all PCAR cases revealed polyclonality. Three of 18 PCAR cases studied for the presence of Epstein-Barr virus RNA showed scattered positivity in 2-7% of lymphoid cells, although the remainder was negative. None of the PCAR cases developed post-transpland lymphoproliferative disorder. CONCLUSIONS: We conclude that PCAR can occur from 1 month to many years posttransplant, is associated with poor graft survival, and is not a manifestation of concomitant chronic allograft nephropathy or viral infection, including posttransplant lymphoproliferative disorder.

Acute Disease↗
PubMed1999

Frontiers of finance: evolution and efficient markets.

In this review article, we explore several recent advances in the quantitative modeling of financial markets. We begin with the Efficient Markets Hypothesis and describe how this controversial idea has stimulated a number of new directions of research, some focusing on more elaborate mathematical models that are capable of rationalizing the empirical facts, others taking a completely different tack in rejecting rationality altogether. One of the most promising directions is to view financial markets from a biological perspective and, specifically, within an evolutionary framework in which markets, instruments, institutions, and investors interact and evolve dynamically according to the "law" of economic selection. Under this view, financial agents compete and adapt, but they do not necessarily do so in an optimal fashion. Evolutionary and ecological models of financial markets is truly a new frontier whose exploration has just begun.

Economics↗
PubMed1999

Extreme reduction of chromosome-specific alpha-satellite array is unusually common in human chromosome 21.

Human centromeres contain large arrays of alpha-satellite DNA that are thought to provide centromere function. The arrays show size and sequence variation, but the extent to which extremely low levels of this DNA can occur on normal centromeres is unclear. Using a set of chromosome-specific alpha-satellite probes for each of the human chromosomes, we performed interphase fluorescence in situ hybridization (FISH) in a population-screening study. Our results demonstrate that extreme reduction of chromosome-specific alpha satellite is unusually common in chromosome 21 (screened with the alphaRI probe), with a prevalence of 3.70%, compared to < or =0.12% for each of chromosomes 13 and 17, and 0% for the other chromosomes. No analphoid centromere was identified in >17,000 morphologically normal chromosomes studied. All of the low-alphoid centromeres are fully functional as indicated by their mitotic stability and binding to centromere proteins CENP-B, CENP-C, and CENP-E. Sensitive metaphase FISH analysis of the low-alphoid chromosome 21 centromeres established the presence of residual alphaRI as well as other non-alphaRI alpha-satellite DNA suggesting that centromere function may be provided by (1) the residual alphaRI DNA, (2) other non-alphaRI alpha-satellite sequences, (3) a combination of 1 and 2, or (4) an activated neocentromere DNA. The low-alphoid centromeres, in particular those of chromosome 21, should provide unique opportunities for the study of the evolution and the minimal DNA requirement of the human centromere.

Autoantigens↗
PubMed1999

Neocentromere formation in a stable ring 1p32-p36.1 chromosome.

Neocentromeres are functional centromeres formed in chromosome regions outside the normal centromere domains and are found in an increasing number of mitotically stable human marker chromosomes in both neoplastic and non-neoplastic cells. We describe here the formation of a neocentromere in a previously undescribed chromosomal region at 1p32-->p36.1 in an oligospermic patient. Cytogenetic GTL banding analysis and the absence of detectable fluorescence in situ hybridisation (FISH) signals using telomeric probes indicate the marker to be a ring chromosome. The chromosome is negative for CBG banding and is devoid of detectable centromeric alpha satellite and its associated centromere protein CENP-B, suggesting activation of a neocentromere within the 1p32-36.1 region. Functional activity of the neocentromere is shown by the retention of the ring chromosome in 97% of the patient's lymphocytes and 100% of his cultured fibroblasts, as well as by the presence of key centromere binding proteins CENP-E, CENP-F, and INCENP. These results indicate that in addition to CENP-A, CENP-C, and CENP-E described in earlier studies, neocentromere activity can further be defined by CENP-F and INCENP binding. Our evidence suggests that neocentromere formation constitutes a viable mechanism for the mitotic stabilisation of acentric ring chromosomes.

Adult↗
PubMed1981

Voluntary and visual control of the vestibuloocular reflex after cerebral hemidecortication.

Horizontal vestibuloocular reflex (VOR) function was studied in five patients after cerebral hemidecortication. In darkness, VOR gain contralateral to the decorticate hemisphere was slightly higher than ipsilateral gain. Voluntary modulation of the reflex by attempted fixation of imaginary targets in darkness increased this VOR asymmetry. Voluntary cancellation of the ipsilateral VOR was better than cancellation of the contralateral VOR. Voluntary enhancement of the contralateral VOR was better than enhancement of the ipsilateral VOR. Visual control of the reflex while viewing foveal targets further increased the VOR asymmetry. Defective visual modulation corresponded to paresis of ipsilateral smooth pursuit. Abnormal voluntary responses in darkness indicate that cerebral control of the reflex can be independent of the pursuit system. The hemispheres may use a corollary discharge of eye position in the orbit and a head velocity signal to direct smooth eye movements toward the perceived location of objects. One hemisphere regulates ipsilateral smooth eye movements that achieve voluntary and visual control of the VOR.

Adolescent↗
PubMed1981

Visual-vestibular interaction in multiple sclerosis.

Visual modulation of the vestibuloocular reflex (VOR) was analyzed in 20 patients with multiple sclerosis who had no vestibular or ocular motor symptoms. Visual suppression of the VOR was impaired in 75% of patients. VOR gains in darkness were elevated in 35% of patients. Elevated VOR gain in darkness is attributed to vestibular adaptation to defective smooth pursuit. This vestibular plasticity achieved retinal image stability by matching eye velocity to head velocity when stationary targets were viewed. The high incidence of impaired visual suppression of the VOR rivals the sensitivity of other physiologic tests used to identify multiple sclerosis.

Adult↗
PubMed1979

Control of the saccadic and smooth pursuit systems after cerebral hemidecortication.

Saccadic and smooth pursuit eye movements were analysed in 5 patients eight to twelve years after cerebral hemidecortication. Saccadic peak velocities were mildly reduced and saccadic durations were prolonged in both horizontal directions. Slowing of saccades may signify a loss of cerebral modulation of the discharge frequency and duration of brain-stem burst units or a less specific susceptibility of the hemidecorticate brain to fatigue. Symmetrical latencies of saccades to 20- and 40-degree target steps into the hemianopic and intact visual fields provided evidence for brain-stem processing of retinal signals from the hemianopic field. Latencies of saccades to 5-degree target steps into the blind hemifield were significantly longer than to 5-degree steps into the intact field. Disparity between saccadic latencies to parafoveal (5 degrees) and peripheral (20- and 40-degrees) targets indicated that such visual capacity in the hemianopic field is dependent upon target eccentricity.

Adult↗