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Biomedical subjects

C Tran

Publications and source records attributed to C Tran.

At least 19 recordsLinked to original sources
PubMed2006

HSV-1-mediated NGF delivery delays nociceptive deficits in a genetic model of diabetic neuropathy.

A previous phase III clinical trial failed to show significant therapeutic benefit of repeated subcutaneous nerve growth factor (NGF) administration in the treatment of diabetic neuropathy. Animal studies have since shown that site-specific viral-mediated expression of NGF in the lumbar dorsal root ganglia prevents peripheral nerve dysfunction associated with chemically induced neuropathy. Using a Herpes simplex virus expression vector, we have investigated the effect of localized NGF expression in a genetic mouse model of progressive diabetic neuropathy, the +/+ Leprdb mouse. We found that site-specific delivery of NGF initially delayed the appearance of hypoalgesia, assessed by the Hargreaves test, by 1 month and effectively attenuated this deficit for 2 months over the approximately 10 months normal life-span of these animals. Once the disease progressed into its more severe stages, NGF, although still capable of altering the electrophysiological profile of the sensory A- and C-fibers and influencing the expression of p75 and substance P in the dorsal root ganglia, could no longer maintain normal nociception. These data suggest that maximal therapeutic benefit in future NGF-based gene therapy trials will be gained from early applications of such viral-mediated neurotrophin delivery.

Action Potentials↗
PubMed2005

The depigmenting effect of RALGA in C57BL/6 mice.

BACKGROUND: It has been known for a long time that the topical use of retinoic acid (RA) produces mild depigmentation of human skin. However, RA has two major disadvantages for its utilisation as a topical depigmenting compound. First, RA can act as an irritant and can produce considerable erythema and exfoliation of skin. Second, RA has a relatively weak depigmenting ability compared to other known depigmenting chemicals. OBJECTIVE: In this study, we show that RALGA, a combination of the less irritant retinoid retinaldehyde (RAL; 0.1%) and glycolic acid (6.4%), has a higher skin-depigmenting potential than RA 0.05% in the tail skin of C57BL/6 mice. This effect was observed in reducing the number of functioning melanocytes and/or in inhibiting their ability to synthesise melanin. In addition, the visually recognisable depigmenting effect of RALGA was evident earlier than that of RA, i.e. only after 1 week of application. RALGA may therefore serve as a depigmenting product for the treatment of skin hyperpigmentary disorders. Postacne hyperpigmented lesions represent a very common pigmentary problem among acne patients. RALGA may thus act as an anti-acne product, due to the presence of RAL--an RA precursor--which could simultaneously remove the postacne hyperpigmented lesions in such patients.

Acne Vulgaris↗
PubMed2002

Effects of liquid nitrogen cryotherapy and bone grafting on artificial bone defects in minipigs: a preliminary study.

Liquid nitrogen cryotherapy has been advocated as an adjunct in the enucleation and curettage of locally aggressive lesions of the jaws. Simultaneous autogenous bone grafting has also been advocated to accelerate bone formation and reduce morbidity. There is, however, relatively little scientific basis for either of these hypotheses. In this study, nine Yucatan minipigs had artificial defects created in the mandible, which were treated with liquid nitrogen spray. Half of the defects were grafted with autogenous bone from the chin and half were closed primarily. Two animals were sacrificed 3 days postoperatively to measure the width of necrosis and the rest were sacrificed at 3 months to assess healing and new bone formation. It was found that drilling the artificial defects alone caused bone necrosis for a mean depth of 0.09 mm. Liquid nitrogen cryospray caused a mean depth of bone necrosis of 0.82 mm (range 0.51-1.52 mm). The defects that were bone grafted healed well clinically. Defects not bone grafted showed a 50% rate of wound breakdown and sequestrum formation with delayed healing. Vital staining showed a non-significantly greater rate of bone formation in the grafted defects. Digitally superimposed radiography showed a non-significantly greater bone density in the non-grafted defects at 3 months postoperatively. It appears that liquid nitrogen cryospray does devitalize an area of bone around defects in the mandible. The width of necrosis is usually less than 1 mm and subsequent healing is enhanced by autogenous bone grafting. This has clinical implications.

Animals↗
PubMed2002

[Episcleral Miragel buckling elements removal. A clinical case-series].

INTRODUCTION: Due to a long-term alteration in their chemical composition, resulting in excessive swelling, Miragel scleral buckles are now commonly removed. The aim of this study was to determine the characteristics and the outcome of patients needing Miragel buckling removal. METHODS: Retrospective analysis between 1997 and 1999 of the charts of patients successfully treated for retinal detachment and in whom a Miragelepiscleral buckle was removed after surgery with a minimal follow-up of 6 months after removal. RESULTS: The study group consisted of 24 eyes of 13 women and 11 men. Their mean age at removal was 47.1+/-18.4 years. The removed buckle was encircling in nine cases (37.5%), circumferential (<180 degrees ) in 11 cases (45.8%) and radial in four cases (16.7%). An exposed buckle was observed in two cases (8.3%). Reasons for removal were excessive swelling of the buckle inducing ocular motility disturbance in 23 cases and infection of an extruded buckle in only one case. The mean time between implantation and removal was 91.9+/-28.7 months (range 20-120). One case of scleral perforation during removal and one case of retinal redetachment were observed. Three cases of persistent ocular motility disturbance after removal were also noted. CONCLUSION: Late swelling of the buckle was the main reason for removal. Patients undergoing Miragel buckling removal should be informed of scleral perforation during removal, retinal redetachment and persistence of ocular motility disturbance as possible complications.

Adolescent↗
PubMed2001

KSHV-K5 inhibits phosphorylation of the major histocompatibility complex class I cytoplasmic tail.

The carboxy-terminal region of major histocompatibility complex class I (MHC I) molecules is required for the rapid internalization mediated by Kaposi's sarcoma-associated herpesvirus (KSHV) proteins K3 and K5. The cytoplasmic tail of MHC I contains highly conserved serine phosphorylation sites that have been implicated in intracellular trafficking. Indeed, in vivo labeling experiments reveal a lack of MHC I phosphorylation in K5-transfected HeLa cells. Phosphorylation of the MHC I tail was restored upon mutation of the PHD/LAP domain of K5. However, deletion and mutation studies of the MHC I tail show that both K3 and K5 are able to downregulate MHC I lacking the conserved phosphorylation site. This result suggests that inhibition of phosphorylation reflects, but does not cause, MHC I internalization. Interestingly, K3 and K5 differ from each other, as well as from human immunodeficiency virus nef, with respect to the minimal MHC I tail sequences required for MHC downregulation. These data support the notion that K3 and K5 downregulate MHC I molecules by a distinct molecular mechanism that is different from other viral immune evasion molecules.

Cytoplasm↗
PubMed2001

Screening for foetal malformations: performance of routine ultrasonography in the population of the Swiss Canton of Vaud.

OBJECTIVE: To determine the sensitivity of ultrasonography in screening for foetal malformations in the pregnant women of the Swiss Canton of Vaud. STUDY DESIGN: Retrospective study over a period of five years. METHOD: We focused our study on 512 major or minor clinically relevant malformations detectable by ultrasonography. We analysed the global sensitivity of the screening and compared the performance of the tertiary centre with that of practitioners working in private practice or regional hospitals. RESULTS: Among the 512 malformations, 181 (35%) involved the renal and urinary tract system, 137 (27%) the heart, 71 (14%) the central nervous system, 50 (10%) the digestive system, 42 (8%) the face and 31 (6%) the limbs. Global sensitivity was 54.5%. The lowest detection rate was observed for cardiac anomalies, with only 23% correct diagnoses. The tertiary centre achieved a 75% detection rate in its outpatient clinic and 83% in referred patients. Outside the referral centre, the diagnostic rate attained 47%. CONCLUSIONS: Routine foetal examination by ultrasonography in a low-risk population can detect foetal structural abnormalities. Apart from the diagnosis of cardiac abnormalities, the results in the Canton of Vaud are satisfactory and justify routine screening for malformations in a low-risk population. A prerequisite is continuing improvement in the skills of ultrasonographers through medical education.

Central Nervous System↗
PubMed2001

Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR.

Recent evidence places the FRAP/mTOR kinase downstream of the phosphatidyl inositol 3-kinase/Akt-signaling pathway, which is up-regulated in multiple cancers because of loss of the PTEN tumor suppressor gene. We performed biological and biochemical studies to determine whether PTEN-deficient cancer cells are sensitive to pharmacologic inhibition of FRAP/mTOR by using the rapamycin derivative CCI-779. In vitro and in vivo studies of isogenic PTEN(+/+) and PTEN(-/-) mouse cells as well as human cancer cells with defined PTEN status showed that the growth of PTEN null cells was blocked preferentially by pharmacologic FRAP/mTOR inhibition. Enhanced tumor growth caused by constitutive activation of Akt in PTEN(+/+) cells also was reversed by CCI-779 treatment, indicating that FRAP/mTOR functions downstream of Akt in tumorigenesis. Loss of PTEN correlated with increased S6 kinase activity and phosphorylation of ribosomal S6 protein, providing evidence for activation of the FRAP/mTOR pathway in these cells. Differential sensitivity to CCI-779 was not explained by differences in biochemical blockade of the FRAP/mTOR pathway, because S6 phosphorylation was inhibited in sensitive and resistant cell lines. These results provide rationale for testing FRAP/mTOR inhibitors in PTEN null human cancers.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Topical delivery of retinoids counteracts the UVB-induced epidermal vitamin A depletion in hairless mouse.

UVB irradiation depletes all-trans-retinol (ROL) and all-trans-retinyl esters (RE) from the hairless mouse epidermis. Prevention of this may be of relevance in counter-acting the long-term side effects of UVB exposure. We studied the effects of a topical treatment with natural retinoids before and after UVB exposure on three parameters involved in vitamin A metabolism: the amount of epidermal ROL and RE, the level of functional cellular retinol-binding protein I (CRBP-I), which is likely to protect ROL from UVB, as well as the cytosolic and microsomal enzyme activities which generate ROL and RE, i.e. all-trans-retinaldehyde (RAL) reductase, acylCoA:retinol acyltransferase (ARAT) and retinyl-ester hydrolase (REH). Topical pretreatment with retinoids promoted a dramatic increase of epidermal ROL, RE and CRBP-I levels, a transient increase of RAL reductase and ARAT activities as well as a decreased activity of REH, indicating a direction of epidermal vitamin A metabolism toward storage. In untreated mice UVB irradiation induced a depletion of epidermal ROL and RE in 10 min and a 50% decrease of CRBP-I after 24 h. In mice treated with topical retinoids, and then exposed to UVB, epidermal RE levels were higher than in vehicle-treated, nonirradiated mice. In contrast, ROL was as much depleted after UVB in pretreated as in untreated animals in spite of an induction of CRBP-I, indicating that CRBP-I does not actually protect ROL from UVB-induced depletion in this model. However, the reconstitution of both epidermal ROL and RE, after their depletion induced by UVB, was accelerated by previous topical treatment with RAL. Our results indicate that topical delivery of retinoids partly counteracts UVB-induced vitamin A depletion and promotes recovery.

Acyltransferases↗
PubMed2000

c-Abl is required for development and optimal cell proliferation in the context of p53 deficiency.

The c-Abl tyrosine kinase and the p53 tumor suppressor protein interact functionally and biochemically in cellular genotoxic stress response pathways and are implicated as downstream mediators of ATM (ataxia-telangiectasia mutated). This fact led us to study genetic interactions in vivo between c-Abl and p53 by examining the phenotype of mice and cells deficient in both proteins. c-Abl-null mice show high neonatal mortality and decreased B lymphocytes, whereas p53-null mice are prone to tumor development. Surprisingly, mice doubly deficient in both c-Abl and p53 are not viable, suggesting that c-Abl and p53 together contribute to an essential function required for normal development. Fibroblasts lacking both c-Abl and p53 were similar to fibroblasts deficient in p53 alone, showing loss of the G(1)/S cell-cycle checkpoint and similar clonogenic survival after ionizing radiation. Fibroblasts deficient in both c-Abl and p53 show reduced growth in culture, as manifested by reduction in the rate of proliferation, saturation density, and colony formation, compared with fibroblasts lacking p53 alone. This defect could be restored by reconstitution of c-Abl expression. Taken together, these results indicate that the ATM phenotype cannot be explained solely by loss of c-Abl and p53 and that c-Abl contributes to enhanced proliferation of p53-deficient cells. Inhibition of c-Abl function may be a therapeutic strategy to target p53-deficient cells selectively.

Abnormalities, Multiple↗
PubMed2000

Nasal colonization by methicillin-resistant coagulase-negative staphylococcus in community skilled nursing facility patients.

BACKGROUND: Methicillin-resistant coagulase-negative staphylococci (MRCNS) are increasing nosocomial pathogens in acute care hospital patients. However, there is little information on the epidemiology of MRCNS in skilled nursing facilities (SNFs). We report a pilot survey of the prevalence of MRCNS colonization in SNF patients. METHODS: Anterior nasal swabs were plated on oxacillin salt screening agar for selection of MRCNS. Suspected MRCNS were confirmed by coagulase and catalase tests and standard disc-diffusion antimicrobial susceptibility tests. RESULTS: The overall prevalence of MRCNS was 40% for in-house continuing SNF patients, 49% for newly admitted patients, and 60% for SNF nursing personnel. The prevalence was 13% in a "control" group of nonmedical personnel. Forty-six percent of MRCNS were resistant to ciprofloxacin. The frequency of colonization with MRCNS increased over time. After an average 17 months of facility stay, 32% of noncarriers acquired MRCNS. High frequency of colonization was associated with greater disability. CONCLUSION: Colonization with MRCNS is common among SNF patients, who can serve as a reservoir for transfer of such strains to acute care hospitals. Careful infection control practice, including judicious use of antibiotics with frequent handwashing, will remain critical policies for limiting spread of such strains.

Carrier State↗
PubMed1999

Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process.

Prostate cancers require androgen for growth but progress to an androgen-independent stage under the selective pressure of androgen ablation therapy. Here we describe a novel human prostate cancer xenograft (LAPC-9) propagated by serial passage in male severe combined immunodeficient mice that expresses prostate-specific antigen and wild-type androgen receptor. In response to castration, LAPC-9 cells undergo growth arrest and persist in a dormant, androgen-responsive state for at least 6 months. After prolonged periods of androgen deprivation, spontaneous androgen-independent outgrowths develop. Thus, prostate cancers progress to androgen independence through two distinct stages, initially escaping dependence on androgen for survival and, subsequently, for growth. Through the use of serial dilution and fluctuation analysis, we provide evidence that the latter stage of androgen independence results from clonal expansion of androgen-independent cells that are present at a frequency of about 1 per 10(5)-10(6) androgen-dependent cells. We conclude that prostate cancers contain heterogeneous mixtures of cells that vary in their dependence on androgen for growth and survival and that treatment with antiandrogen therapy provides selective pressure and alters the relative frequency of these cells, thereby leading to outgrowths of androgen-independent cancers.

Androgens↗
PubMed1999

Nasal colonization by Staphylococcus aureus in active, independent, community seniors.

OBJECTIVE: to evaluate the prevalence of nasal colonization with Staphylococcus aureus (SA) in active, independent community seniors and old people in a nursing home. DESIGN: cross-sectional brief questionnaire and screening culture of anterior nares specimens from 165 elders at a community centre and cross-sectional data from a recent survey in a nursing home. RESULTS: the prevalence of SA colonization in community seniors (27%) was similar to that in the nursing home (29%). The proportion of SA isolates that were methicillin-resistant was much lower in the community seniors (2.3%) than in the nursing-home residents (31%). There was less antibiotic resistance in those living at home. CONCLUSION: in community seniors the prevalence of SA colonization was similar to that in nursing-home residents, but the prevalence of methicillin-resistant SA was lower. Susceptibility patterns of antibiotics tested against the SA showed less resistance than isolates from nursing-home patients.

Aged↗
PubMed1999

Perinatal outcome after in-vitro fertilization-surrogacy.

The perinatal outcome of pregnancies (both single and multiple) established after in-vitro fertilization (IVF)-surrogacy was evaluated and compared to the outcome of pregnancies that resulted from standard IVF. Analysis of medical records and a telephone interview with physicians, IVF-surrogates, and commissioning mothers were conducted to assess prenatal follow up and delivery care in several hospitals. 95 IVF-surrogates delivered 128 liveborn (65 singletons, 27 sets of twins and two sets of triplets). The commissioning mothers and the IVF-surrogates average ages were 37.7 +/- 5.0 and 30.4 +/- 4.7 years old respectively. IVF-surrogates carrying twin and triplet gestations delivered substantially earlier than those who gestated singleton pregnancies (36.2 +/- 0.4 versus 35.5 versus 38.7 +/- 0.3 weeks gestation respectively; P < 0.001). Twin newborns were significantly lighter than singleton infants born through IVF-surrogacy (2.7 +/- 0.06 versus 3.5 +/- 0.07 kg; P < 0.001). The incidence of low birth weight infants rose from 3.3% in the single births to 29.6% (P < 0.01) in the twins and to 33.3% in the triplets born through IVF-surrogacy. The incidence of prematurity was significantly greater in both twins delivered by IVF-surrogates (20.4%) and infertile IVF patients (58%). The occurrence of pregnancy-induced hypertension and bleeding in the third trimester was four to five times lower in the IVF-surrogates, independently of whether they were carrying multiples. The incidence of Caesarean section was 21.3% for singleton gestations, while two times higher in the IVF-surrogates carrying multiples (56.3%). Postpartum complications occurred in 6.3% of patients and the incidence of malformation was similar to those reported for the general population. The results provide general reassurance regarding perinatal outcome to couples who wish to pursue IVF-surrogacy.

Adult↗
PubMed1999

Retinol and retinyl ester epidermal pools are not identically sensitive to UVB irradiation and anti-oxidant protective effect.

BACKGROUND: UV irradiation can deplete epidermal vitamin A, thus the hypothesis that UV-induced depletion of vitamin A in sun-exposed skin is involved in the pathogenesis of skin cancers and skin ageing. OBJECTIVES: In this study we addressed two questions: (1) Are retinol (ROL) and retinyl esters (RE) - the two predominant forms of vitamin A - equally sensitive to the action of UVB, and (2) could the depletion be prevented by anti-oxidants? METHODS: Hairless mice were irradiated with a single UVB dose, corresponding to the maximum of ROL and RE absorption. Retinoid content, enzyme activities catalysing the esterification of ROL (ARAT and LRAT) and the hydrolysis of RE (REH), as well as retinol-binding protein (CRBP-1) expression were determined in the epidermis. RESULTS: A single UVB dose induced a rapid, dose-dependent decrease in both ROL and RE in the epidermis of hairless mice, with partial replenishment after 24 h. The dose-response curve for ROL showed a high sensitivity to UV at doses not exceeding 200 mJ/cm(2), followed by a plateau, whereas RE underwent a continuous dose-dependent decrease at UVB doses up to 1 J/cm(2). A topical anti-oxidant mixture containing 0.5% ascorbate, 0.25% tocopherol and 0.25% melatonin failed to protect epidermal RE from UVB-induced depletion, whereas it did prevent ROL depletion. ARAT and REH, as well as CRBP-1, were not affected by UVB in these conditions. CONCLUSION: Vitamin A storage in the epidermis comprises two forms, ROL and RE, that do not show similar sensitivity to acute UVB exposure. ROL stores comprise a UVB-resistant (possibly by CRBP) portion and a UVB-sensitive portion that can be protected by anti-oxidants. RE stores do not show such a pattern.

Animals↗
PubMed1999

Biological activities of topical retinaldehyde.

BACKGROUND: We had hypothesised that retinaldehyde (RAL) should be an interesting precursor for topical use. AIM: We review our observations about its biological activities. METHODS: We performed pilot studies to explore its biological effects and tolerability in human skin and compared the effects of topical RAL to that of all-trans-retinoic acid (RA) in the mouse tail test. RESULTS: The biological activities of RAL were found to be qualitatively identical to that of RA: (i) induction of cellular RA-binding protein type 2 mRNA and protein, (ii) increase in epidermal proliferation (increase in DNA synthesis, epidermal thickness, induction of 50-kD keratin mRNA and reduction in 70-kD keratin mRNA), and (iii) metaplastic effects (induction of orthokeratosis, reduction of 65-kD keratin mRNA, increase in filaggrin and loricrin mRNAs). When associated with RAL, citral (known for its capacity to inhibit the oxidation of retinol to RA in epidermis) counteracted the effects induced by RAL indicating that RAL exerts biological activities through transformation to RA. Hypothesizing that keratinocytes would metabolize 9-cis-RAL to 9-cis-RA, we compared the biological effects induced by topical 9-cis-RAL and found that hyperplastic and metaplastic responses were lower than those induced by all-trans-RAL or all-trans-RA at similar concentrations. This suggests that 9-cis-RAL has no advantage over all-trans-RAL for specific delivery of natural retinoids into the skin. As in clinical studies conducted in human skin, we also found topical RAL less irritant than RA. CONCLUSION: These studies indicate that topical RAL has biological activity and is well tolerated.

Acyclic Monoterpenes↗
PubMed1998

Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression.

The recently identified PTEN/MMAC1 gene is a candidate tumor suppressor implicated in multiple tumor types based on mutations or homozygous deletions of the gene in certain human cancers. No studies of PTEN/MMAC1 mRNA or protein expression in cancer cells have been reported, primarily because of significant numbers of normal cells contaminating most tumor samples and because of the lack of antibody reagents. We examined PTEN/MMAC1 in advanced prostate cancer for gene mutations or abnormalities in expression by using a series of recently derived xenografts free of normal human cells and a PTEN/MMAC1-specific antibody. Only 1 of 10 tumors contained a homozygous deletion of PTEN/MMAC1, and no mutations were detected in the entire coding region of the remaining nine xenografts. However, five of these showed reduced or absent PTEN/MMAC1 expression by Northern analysis and reverse transcription-PCR of mRNA. PTEN/MMAC1 mRNA expression was restored in nonexpressing prostate cancer cells by in vitro treatment with the demethylating agent 5-azadeoxycytidine. Alterations in PTEN/MMAC1 expression were confirmed at the protein level by immunoblot analysis, and immunohistochemical studies show that the endogenous wild-type PTEN/MMAC1 protein is localized exclusively in the cytoplasm. These results demonstrate that loss of PTEN/MMAC1 expression occurs frequently in advanced prostate cancer.

Azacitidine↗