Biomedical subjects

P Vig

Publications and source records attributed to P Vig.

14 recordsLinked to original sources

PubMed2004

Hepatic stem cells: from inside and outside the liver?

The liver is normally proliferatively quiescent, but hepatocyte loss through partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response from all cell types in the liver to perfectly restore liver mass. Moreover, hepatocyte transplants in animals have shown that a certain proportion of hepatocytes in foetal and adult liver can clonally expand, suggesting that hepatoblasts/hepatocytes are themselves the functional stem cells of the liver. More severe liver injury can activate a potential stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of bipotential transit amplifying cells (oval cells), that can ultimately differentiate into hepatocytes and biliary epithelial cells. A third population of stem cells with hepatic potential resides in the bone marrow; these haematopoietic stem cells may contribute to the albeit low renewal rate of hepatocytes, but can make a more significant contribution to regeneration under a very strong positive selection pressure. In such instances, cell fusion rather than transdifferentiation appears to be the underlying mechanism by which the haematopoietic genome becomes reprogrammed.

Animals↗

PubMed2004

Recipes for adult stem cell plasticity: fusion cuisine or readymade?

A large body of evidence supports the idea that certain adult stem cells, particularly those of bone marrow origin, can engraft at alternative locations, particularly when the recipient organ is damaged. Under strong and positive selection pressure these cells will clonally expand/differentiate, making an important contribution to tissue replacement. Similarly, bone marrow derived cells can be amplified in vitro and differentiated into many types of tissue. Despite seemingly irrefutable evidence for stem cell plasticity, a veritable chorus of detractors has emerged, some doubting its very existence, motivated perhaps by more than a little self interest. The issues that have led to this situation include the inability to reproduce certain quite startling observations, and extrapolation from the behaviour of embryonic stem cells to suggest that adult bone marrow cells simply fuse with other cells and adopt their phenotype. Although these issues need resolving and, accepting that cell fusion does appear to allow reprogramming of haemopoietic cells in special circumstances, criticising this whole new field because some areas remain unclear is not good science.

Adult↗

PubMed2001

Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study.

BACKGROUND: Lamivudine-resistant hepatitis B virus (HBV) is found in about 15-32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV. We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an open-label trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients. METHODS: 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy. FINDINGS: Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44-48). Mean decreases in serum HBV DNA concentrations from baseline (log 8.64 copies/mL [SE log 0.08]) were 2log 3.40 copies/mL [log 0.12] at week 24 (n=31) and 2log 4.01 copies/mL [log 0.17] at week 48 (n=29; p<0.0001). Two patients underwent hepatitis B e antigen seroconversion-one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count. INTERPRETATION: These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.

Adenine↗

PubMed2000

Pooled analysis of 3 randomized, controlled trials of interleukin-2 therapy in adult human immunodeficiency virus type 1 disease.

We collected human immunodeficiency virus (HIV) disease progression, survival, most recent CD4 cell count, and plasma HIV RNA levels from patients (n=157) who participated in randomized clinical trials of interleukin (IL)-2 that commenced before 1995. Data were available for 155 (99%) patients. Statistical analyses were based on the intention-to-treat principle. Median follow-up was 28 months and 30 months for control and IL-2 patients, respectively. Twenty-five (16%) patients developed AIDS or died during follow-up (16 control patients vs. 9 IL-2 patients; R2=0.57; P=.22). Mean change from baseline CD4 cell count was significantly higher in patients randomized to receive IL-2 (368 vs. 153 cells/microL; P=.003). Mean change from baseline plasma HIV RNA was significantly lower in patients randomized to receive IL-2 (-0.98 vs. -0.63 log copies/mL; P=.004). Significant improvements in CD4 cell count and plasma HIV RNA in recipients of IL-2 relative to control patients were associated with a nonsignificant trend toward improved clinical outcome.

Adult↗

PubMed1997

Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3.

The mechanism of neurodegeneration in CAG/polyglutamine repeat expansion diseases is unknown but is thought to occur at the protein level. Here, in studies of spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), we show that the disease protein ataxin-3 accumulates in ubiquitinated intranuclear inclusions selectively in neurons of affected brain regions. We further provide evidence in vitro for a model of disease in which an expanded polyglutamine-containing fragment recruits full-length protein into insoluble aggregates. Together with recent findings from transgenic models, our results suggest that intranuclear aggregation of the expanded protein is a unifying feature of CAG/polyglutamine diseases and may be initiated or catalyzed by a glutamine-containing fragment of the disease protein.

Glutamine↗

PubMed1996

Consistency of orthodontic extraction decisions.

Ten orthodontists having completed specialist training, examined on two occasions 1 month apart, the complete pre-treatment records of 60 Class II division 1 patients representing the full range of dental malocclusion severity. At each session the orthodontist recorded whether their proposed treatment involved extractions. The level of agreement both between and within the orthodontists was evaluated with the Kappa statistic. Data analysis revealed that the level of agreement within the examiners was good, however the between examiner agreement was poor. It appeared that the orthodontists were applying different criteria in terms of the extraction decision and this has implications for orthodontic patients.

Adolescent↗

PubMed1993

Changes in the nasal and labial soft tissues after surgical repositioning of the maxilla.

Accurate prediction of postsurgical function and esthetics of the nose and upper lip requires an understanding of the relationship between maxillary surgical movement and soft tissue change. Thirty-two patients underwent Le Fort I osteotomies, some with concomitant mandibular procedures. Preoperative, postoperative, and 1-year postsurgical data derived from cephalometric and nasolabial cast analysis were compared to assess skeletodental changes, soft tissue changes, and stability. A multiple stepwise regression (including age, gender, alar cinch suture, V-Y closure, and contouring of the anterior nasal spine as variables) indicated that accurate prediction equations could be formulated, particularly if the patients were grouped by vector-specific maxillary movements. In general, the base of the nose widened in all patients regardless of the vector of surgical maxillary movement. An associated shortening of the nose was found. The nasolabial angle decreased or remained constant in most patients. The upper lip widened and lengthened at the philtral columns. Narrow noses widened more than did broad noses and alar cinch suturing widened the alar base even more. Results indicated that soft tissue changes associated with maxillary surgery may be more affected by the position of the soft tissue incision and methods used in closure than by the surgically induced hard tissue change.

Adolescent↗

PubMed1984

Photocephalometry: errors of projection and landmark location.

A method called photocephalometry was recently described for the possible soft-tissue evaluation of orthognathic surgery patients by the superimposition of coordinated cephalographs and photographs. A grid analysis was performed to determine the accuracy of the superimposition method. In addition, the reliability of landmark identification was analyzed by the method error of Baumrind and Frantz, using three replicates of twelve patients' photographs. Comparison of twenty-one grid intervals showed that the magnification of the photographic image for any given grid plane is not correlated to that of the radiographic image. Accurate comparisons between soft- and hard-tissue anatomy by simply superimposing the images are not feasible because of the difference in the enlargement factors between the photographs and x-ray films. As was noted by Baumrind and Frantz, a wide range exists in the variability of estimating the location of landmarks. Sixty-six percent of the lateral photographic landmarks and 57% of the frontal landmarks had absolute mean errors for all twelve patients that were less than or equal to 2.0 mm. In general, the envelope of error for most landmarks was not circular. Although the photocephalometric apparatus as described by Hohl and colleagues does not yield the desired quantitative correlation between hard and soft tissues, valuable quantitative information on soft tissue can be easily obtained with the standardization and replication possible with the camera setup and enlarged photographs.

Adult↗

PubMed1975