PubMed Health⌕ Search

Biomedical subjects

M Wong

Publications and source records attributed to M Wong.

At least 19 recordsLinked to original sources
PubMed2006

Feedback inhibition of high TGF-beta1 concentrations on myofibroblast induction and contraction by Dupuytren's fibroblasts.

Myofibroblasts and TGF-beta1 are implicated in Dupuytren's contracture. Transforming growth fact- or beta1(TGF-beta1) (1-10ng/ml) increases myofibroblast induction in Dupuytren's fibroblasts and contraction in a collagen model. However, higher doses (20-30ng/ml) inhibit contraction in dermal fibroblasts. We hypothesized higher doses of TGF-beta1 would inhibit induction of myofibroblasts and contraction by Dupuytren's fibroblasts. Increasing doses of TGF-beta1 (0-30ng/ml) were tested on Dupuytren's fibroblasts using immunofluorescence to determine myofibroblast upregulation and a 3D collagen model used to determine contractile forces. Flexor retinaculum fibroblasts were used as controls. TGF-beta1 induced myofibroblasts in Dupuytren's fibroblasts (n=3) from 12% (0ng/ml) to 23% (12.5ng/ml) at 24 hours but dropped to 13% at 30ng/ml (P<0.05). This response was mirrored in the contraction profiles. These trends were similar for flexor retinaculum fibroblasts (n=3), but contractile forces and myofibroblast induction were significantly less (P<0.001). This is the first report of negative feedback inhibition of TGF-beta1 at higher concentrations in Dupuytren's fibroblasts.

Cells, Cultured↗
PubMed2006

Antiretroviral therapy improves cognitive impairment in HIV+ individuals in sub-Saharan Africa.

BACKGROUND: Highly active antiretroviral therapy (HAART) can improve cognitive performance in some patients with HIV-associated cognitive impairment in the United States. The effect of HAART on HIV dementia in sub-Saharan Africa is largely unknown. OBJECTIVE: To evaluate neuropsychological test and functional performance in HIV+ individuals after 3 and 6 months of HAART in Uganda. METHODS: Twenty-three HIV+ individuals receiving HAART also received a detailed clinical history, neuropsychological testing, and a functional assessment. Follow-up evaluations were performed at 3 and 6 months after baseline. Longitudinal changes in the HIV dementia stage, the mean Z score for each neuropsychological test, and the Karnofsky Functional Performance Scale were evaluated at 3 and 6 months. RESULTS: The mean (SD) CD4 cell count improved from 71 (15) at baseline to 161 (30) at 3 months (p = 0.005) and 222 (46) at 6 months (p < 0.001). Improvements were found in the Memorial Sloan Kettering HIV dementia stage and in tests of verbal memory, psychomotor speed, and executive functioning after 3 and 6 months of HAART (p < 0.001 at 6 months for each neuropsychological test). There was also improvement in the Karnofsky Functional Performance Scale at both 3 and 6 months after the initiation of HAART (p < 0.001). CONCLUSION: Highly active antiretroviral therapy (HAART) can be associated with improvement in neurocognitive and functional performance in HIV+ individuals in sub-Saharan Africa. These results suggest that HAART, if available in areas with limited resources in sub-Saharan Africa, should be provided for patients with HIV-associated cognitive impairment.

Adult↗
PubMed2006

A prospective study of the immediate and delayed adverse events following intravenous immunoglobulin infusions.

AIM: To document the incidence of immediate and delayed adverse events (AE) following intravenous immunoglobulin (IVIG) infusion in children. METHODS: Immediate and delayed adverse events were prospectively recorded for 345 infusions in 58 children receiving IVIG for immunodeficiency (n = 33) or immunomodulation (n = 25). For each infusion adverse events were documented during the infusion and by follow up interview 4-7 days later. RESULTS: Immediate adverse events occurred in 10.3% and delayed adverse events in 41.4% of children treated during the study period. Three and a half per cent of the infusions were associated with immediate AE and 20.9% with delayed adverse events. Headache was the most common delayed AE, occurring in 24.1% of patients and 12.8% of infusions. CONCLUSIONS: Delayed adverse events to IVIG infusions are common in children. They occur more frequently than immediate adverse events and are the cause of significant morbidity. Recognition of the high frequency of delayed adverse events is important in the care of children receiving IVIG therapy.

Adolescent↗
PubMed2006

Rosai-Dorfman disease of the testis: an unusual entity that mimics testicular malignancy.

A 47 year old Chinese man with diabetes mellitus and previously treated pulmonary tuberculosis presented with painless right testicular enlargement of 1 month's duration. He underwent an orchidectomy for presumed testicular neoplasm corroborated clinicoradiologically. Histological examination of the testicular mass revealed an inflammatory lesion comprising lymphocytes, plasma cells and sheets of pale staining histiocytes, some containing lymphocytes within their ample cytoplasm, suggestive of emperipolesis. S100 immunohistochemistry stained the histiocytes, while ultrastructural examination confirmed emperipolesis. A diagnosis of Rosai-Dorfman disease was made, an exceedingly rare testicular lesion. Clinicoradiological findings mimicked a neoplasm, while the inflammatory histological appearances with occasionally discerned multinucleated cells raised the possibility of xanthogranulomatous orchitis. Tuberculous orchitis was excluded through negative Ziehl-Neelsen stains and PCR for mycobacterium, while seminoma, which sometimes features a predominant inflammatory component obscuring neoplastic cells, was excluded by absent immunostaining for placental alkaline phosphatase and CD117.

Diabetes Complications↗
PubMed2005

The management of compound leg injuries in the West Midlands (UK): are we meeting current guidelines?

The joint British Association of Plastic Surgeons and British Orthopaedic Association (BAPS/BOA) guidelines for the management of patients with open tibia fractures were published in 1991 and 1997 and provided a synopsis of injury epidemiology and best care. We present a retrospective review of 66 patients treated over a 2-year period (January 2001-February 2003) at a regional plastic surgery unit. There were 33 direct admissions and 33 transfers from other hospitals in which the average delay in transfer was 7.8 days (1-28) and in whom 26 (79%) patients had already undergone surgery. Plastic surgeons were involved in 46 (62%) of the 66 patient cohort and 27 (82%) transferred patients. The delay after admission until soft tissue cover was 3.8 days (0-15). Twenty-nine (44%) complications were recorded, 20 (69%) of these were in the transferred group and additional orthopaedic intervention was needed in 11 (42%) of patients who had been operated on in other hospitals. Despite widespread dissemination and teaching of the BAPS/BOA guidelines, complex extremity trauma is often not managed well in our region. There are unacceptable delays in admission, late communication, poor note keeping and follow up. The initial surgery/fixation is often sub-optimal and soft tissue reconstruction has to be considered at the least advantageous time period for the patient, leading to an increased hospital stay and complications.

Adult↗
PubMed2005

Human immunodeficiency virus neurological complications: an overview of the Ugandan experience.

Sub-Saharan Africa, which has about 12% of the global population, is home to almost 70% of individuals infected with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). A recent survey by the Ugandan Ministry of Health has found the HIV prevalence rate to be approximately 7% in sexually active adults. The predominant HIV subtypes present in Uganda are A and D. Health care resources are well planned but often lack human and fiscal resources. Uganda has adopted the World Health Organization (WHO) "3 by 5" global strategy for the introduction of antiretroviral therapy and has surpassed the target. Neurological complications of the HIV virus are common and often have devastating consequences. A recent study in Kampala found the rate of HIV dementia and peripheral neuropathy at 31% and 47%, respectively. Further studies are urgently required to determine the natural history and treatment outcomes of both these common HIV complications.

AIDS-Related Opportunistic Infections↗
PubMed2004

Validation of thoracic quantitative computed tomography as a method to measure bone mineral density.

The purpose of this study was to measure precision of thoracic quantitative computed tomography (QCT) bone mineral density (BMD) and correlation to lumbar spine QCT bone density. We measured the reproducibility of thoracic QCT; two consecutive thoracic QCT scans of the T9, T10, and T11 vertebrae were performed on 95 subjects (49 females, 46 males; mean age, 62.5 years) undergoing coronary scanning. In order to correlate the thoracic to standard lumbar measurement, the subjects also underwent a lumbar QCT scan of the L1, L2, and L3 vertebrae as part of an abdominal aortic scanning study. The variation of thoracic BMD was assessed in different ethnic subgroups. Consecutive thoracic QCT measurements showed good agreement (r=0.98; RMS CV=5.78%). Thoracic bone density was significantly higher than lumbar bone density results (paired t-test, P=0.003), but the two methods correlated well (r=0.86). The regression equation for the relationship between lumbar (X) and thoracic (Y) QCT was Y=0.87X + 22.97. The standard error of estimate was 19.0 mg/cm3. Thoracic QCT from coronary calcium thoracic scans is able to measure BMD with rescan precision and regression errors that are small compared to the biologic variability in the population. Given the relatively small precision error and the reasonable correlation to lumbar BMD, an ancillary assessment of thoracic BMD in a cardiac scan is likely to be a useful assessment of bone mineral status in the general population.

Bone Density↗
PubMed2004

Critical period for a teratogenic VLA-4 antagonist: Developmental effects and comparison of embryo drug concentrations of teratogenic and non-teratogenic VLA-4 antagonists.

BACKGROUND: Integrins such as VLA-4 (Very late antigen 4, integrin alpha4beta1) play key roles in cell-cell interactions that are critical for development. Homozygous null knockouts of the VLA-4 alpha4-subunit or VCAM-1 (VLA-4 cell surface ligand) in mice result in failure of the allantois and chorion to fuse leading to interrupted placentation and cardiac development and embryo lethality. Embryo-fetal studies of three VLA-4 antagonists, IVL745, IVL984, and HMR1031 [Crofts et al., Birth Defects Res B 71:55-68 (this issue), 2004] with exposure on gestation days (GD) 6-17 (rat), 6-18 (rabbit) or 6-15 (mouse) showed that only IVL984 treatment resulted in embryo lethality and cardiac defects. Objectives of the current study were to determine the critical period for inducing IVL984-related embryo-fetal effects, and to test the hypothesis that these effects were due to higher embryo drug concentrations. METHODS: IVL984 was administered at 40 mg/kg/day to pregnant rats on GD 4 and 5, GD 6 and 7, GD 8 and 9, GD 10 and 11, or GD 12 and 13. Animals were euthanized on GD 21 and uteri and fetuses were examined. A treatment period of GD 10-12 was selected for subsequent toxicokinetic (TK) studies in which IVL984, HMR1031, or IVL745 was administered to pregnant rats and rabbits. On GD 12, maternal plasma, extra-embryonic tissue (placenta and amniotic fluid), and embryonic tissue were collected and analyzed for drug concentrations. RESULTS: In the IVL984 critical period study in pregnant rats, treatment on GD 10 and 11 resulted in increased post-implantation loss, skeletal variations, and spiral septal defects similar to those observed in standard embryo-fetal development studies with treatment throughout organogenesis. There were no embryo-fetal effects after treatment on GD 4 and 5, GD 6 and 7, or GD 8 and 9. There was a single aorta malformation after treatment on GD 12 and 13. In the TK studies, IVL745, HMR1031, and IVL984 were all detectable in embryonic tissue and there was no evidence for accumulation. Rat and rabbit embryo exposures (AUC or dose-adjusted AUC) on GD 12 could not explain the observed teratology (IVL984<HMR1031<IVL745). Further analyses incorporating pharmacological activity, clearance, and protein binding data provided a positive correlation between embryonic exposure and teratogenic potency. CONCLUSIONS: The critical period for IVL984 in the rat, GD 10 to 11, corresponds to the expression of alpha-4 integrin on the chorion and VCAM-1 on the allantois and myocardium as well as chorioallantoic fusion and formation of the spiral septum. Embryo drug levels adjusted for pharmacological activity, clearance, and protein binding provide a possible explanation for the differing teratogenic potency of IVL984, HMR1031, and IVL745.

Abnormalities, Drug-Induced↗
PubMed2004

Clusterin as a possible predictor for biochemical recurrence of prostate cancer following radical prostatectomy with intermediate Gleason scores: a preliminary report.

Disease recurrence following radical prostatectomy is a major concern in prostate cancer patients. Gleason scores are useful in predicting recurrence. Low Gleason scores are usually associated with long disease-free intervals, while high Gleason scores are suggestive of early recurrence. However, prediction of recurrence has been difficult with intermediate Gleason scores. Clusterin is a ubiquitous secretory sulfated glycoprotein. It is also an antiapoptotic mediator in prostate cancer. The objective of the present study is to determine if clusterin can serve as a predictive biomarker for recurrence of prostate cancer with intermediate Gleason scores in patients following radical prostatectomy. Prostatic specimens with Gleason score of 6 (3+3) or 7 (3+4) were obtained from the archival bank. Three groups of specimens were investigated. The first group was from nine patients who developed recurrent disease according to a persistent rise of serum PSA within 3 years following radical prostatectomy. Those in the second group and the third group were from patients who showed no evidence of disease recurrence for at least 5 y (11 patients) and 10 y (eight patients), respectively following the surgery. Histological sections were subjected to immunohistochemical staining using a monoclonal antibody specific for clusterin. The staining intensity was scored as 0, 1, 2, and 3, with 0 being no staining, 1 showing less than 25% positive staining, 2 being 25-50% positive, and 3 showing greater than 75% positive staining. One-way ANOVA with Bonferroni correction was used for statistical analysis. Evaluation of the scores of clusterin staining was carried out according to four specific areas in each specimen. They were (a) benign epithelial cells, (b) malignant epithelial cells (cancer epithelia), (c) stromal cells surrounding benign cells, and (d) stromal cells surrounding malignant cells (cancer stroma). Staining score in prostatic epithelial cells, benign as well as malignant, showed no significant relationship among the three patient groups. However, when staining scores in stromal cells were compared, there was a significant difference between patients with recurrent disease and those showed no evidence of disease recurrence for at least 10 y. Results of this preliminary study support the important role of clusterin in the stromal component for prostate cancer progression. Clusterin immunostaining may be useful to aid the prediction of chance of disease recurrence in patients with Gleason score 6 or 7 prostate cancer following radical prostatectomy. Further studies with a large number of cases are warranted to verify this preliminary finding.

Biomarkers, Tumor↗
PubMed2004

Prognostic scoring systems in patients with follicular thyroid cancer: a comparison of different staging systems in predicting the patient outcome.

BACKGROUND: The use of prognostic scoring systems is important for predicting the survival of individuals with thyroid carcinoma. Relatively few studies have addressed this issue for patients with follicular thyroid cancer. The goal of this retrospective study was to establish the best and most pertinent prognostic scoring system to predict survival in patients with follicular thyroid cancer. METHODS: We selected 86 patients with follicular thyroid cancer treated at University of California, San Francisco (UCSF) hospitals from January 1954 to April 1998. The mean follow-up time was 11.5 years. There were 60 women (70%) and 26 men (30%), with a mean age if 48.6 years. Prognostic scoring systems included tumor, node, metastases (TNM), European Organization for Research and Treatment of Cancer (EORTC), Age, Grade, Extent, Size (AGES), Age, Metastases, Extent, Size (AMES), and the Metastases, Age, Completeness of resection, Invasion, Size (MACIS). Survival time was calculated using the Kaplan-Meier method. Using Cox proportional hazards analysis, the relative importance of each scoring method was determined by calculating the proportion of variation in survival time explained (PVE). RESULTS: Kaplan-Meier analysis indicated that all scoring systems were significant predictors of survival time (p < 0.0001). The PVE associated with each system was (from highest to lowest) 0.48 for MACIS, 0.46 for AGES, 0.44 for EORTC, 0.40 for AMES, and 0.33 for TNM. These results indicate that the MACIS scoring system accounted for a great proportion of explained variance in survival and is a more precise predictor of survival compared to the other scoring systems. CONCLUSIONS: TNM, EORTC, AGES, AMES, and MACIS, all provided useful prognostic information about the survival in our 86 patients with follicular thyroid cancers. The MACIS classification, however, was the most accurate predictor using PVE as a method of evaluation. Future scoring systems considering additional prognostic factors, may obtain a higher PVE.

Adenocarcinoma, Follicular↗
PubMed2003

The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase.

The breast cancer-associated T2A10 clone was originally isolated from a cDNA library enriched for tumour messenger ribonucleic acids. Our survey of 125 microarrayed primary tumour tissues using affinity purified polyclonal antibodies has revealed that corresponding protein is overexpressed in invasive breast cancer and is weakly expressed in kidney and prostate tumours. Now known as RNF11, the gene encodes a RING-H2 domain and a PY motif, both of which mediate protein-protein interactions. In particular, the PPPPY sequence of RNF11 PY motif is identical to that of Smad7, which has been shown to bind to WW domains of Smurf2, an E3 ubiquitin ligase that mediates the ubiquitination and degradation of the TGFbeta receptor complex. Using various mutants of RNF11 in GST pulldown and immunoprecipitation assays, we found that RNF11 interacts with Smurf2 through the PY motif, leading to ubiquitination of both proteins. Smurf2 plays an active role in the repression of TGFbeta signalling, and our data indicate that overexpression of RNF11, through its interaction with Smurf2, can restore TGFbeta responsiveness in transfected cells.

Breast Neoplasms↗
PubMed2003

Oxyphilic and non-oxyphilic thyroid carcinoma cell lines differ in expressing apoptosis-related genes.

Oxyphilic tumors of the thyroid are characterized by mitochondrion-rich cells and extensive DNA fragmentation. In order to clarify if a different expression of apoptosis-related genes could be responsible for DNA fragmentation in oxyphilic cell tumors, two thyroid follicular carcinoma-derived cell lines, having oxyphilic (XTC.UC1) and non-oxyphilic (WRO) features, were compared applying a gene array technique. Under basal culture conditions, several pro-apoptotic genes [caspases 3 and 10, Fas and the tumor necrosis factor-related apoptosis-inducing ligand (trail) genes] were switched on in oxyphilic, but not in non-oxyphilic cells. No difference in the mitochondrial apoptosis-related genes (bax, bad, bcl family etc.) was observed. Using the ISEL technique, the extent of DNA fragmentation did not differ under basal conditions in the two cell lines. Conversely, following an oxidative pro-apoptotic stress (6-h methylene blue treatment and light exposure), XTC.UC1 cells showed an extensive DNA fragmentation (up to 70% of cells), dramatically exceeding that observed in WRO cells (up to 20% of cells). In contrast, the oxidative stimulus induced a remarkable apoptosis gene activation in non-oxyphilic WRO cells only. These results suggest that oxyphilic cells may have a unique silent activation of a pro-apoptotic phenotype, which could be responsible for DNA instability and lead to cell death as the consequence of an increased sensitivity to ischemic stresses, as frequently observed in vivo.

Adenocarcinoma↗
PubMed2003

Articular cartilage functional histomorphology and mechanobiology: a research perspective.

The histomorphogenesis of articular cartilage is regulated during skeletal development by the intermittent forces and motions imposed at diarthrodial joints. A key feature in this development is the formation of the superficial, transitional, radial, and calcified cartilage zones through the cartilage thickness. The histomorphological, biological, and mechanical characteristics of these zones can be correlated with the distributions of pressures, deformations, and pressure-induced fluid flow that are created in vivo. In a mature joint, cyclic loads produce cyclic hydrostatic fluid pressure through the entire cartilage thickness that is comparable in magnitude to the applied joint pressure. Prolonged physical activity can cause the total cartilage thickness to decrease about 5%, although the consolidation strains vary tremendously in the different zones. The superficial zone can experience significant fluid exudation and consolidation (compressive strains) in the range of 60% while the radial zone experiences relatively little fluid flow and consolidation. The topological variation in the histomorphologic appearance of articular cartilage is influenced by the local mechanical loading of chondrocytes in the different zones. Patterns of stress, strain, and fluid flow created in the joint result in spatial and temporal changes in the rates of synthesis and degradation of matrix proteins. When viewed over the course of a lifetime, even subtle difference in these cellular processes can affect the micro- and macro-morphology of articular cartilage. This hypothesis is supported by in vivo and ex vivo experiments where load-induced changes in matrix synthesis and catabolism, gene expression, and signal transduction pathways have been observed.

Animals↗