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Biomedical subjects

G Weinberg

Publications and source records attributed to G Weinberg.

At least 19 recordsLinked to original sources
PubMed2005

Receptor-independent actions of PPAR thiazolidinedione agonists: is mitochondrial function the key?

Agonists of the peroxisome proliferator activated receptor gamma (PPAR(gamma)) are currently used for treatment of type 2 diabetes due to their insulin sensitizing and glucose metabolism stabilizing effects. More recently some of these same agonists were shown to exert anti-inflammatory and anti-proliferative effects as well. Although PPAR(gamma) agonists can operate via receptor-mediated events occurring at the genomic level, thereby causing long lasting changes in gene expression patterns, recent studies demonstrate non-genomic as well as genomic actions, and receptor-dependent as well as receptor-independent effects of the thiazolidinedione (TZD) class of PPAR(gamma) agonists. In this review we will summarize data describing some of these novel, receptor independent actions of TZDs, review evidence that TZDs directly influence mitochondrial function, and attempt to reconcile how changes in mitochondrial function could contribute to other receptor-independent actions of these drugs.

Animals↗
PubMed2002

The utility of buccal mucosa graft in salvage urethroplasty.

OBJECTIVE: To evaluate our results with buccal mucosa free grafts in salvage urethroplasty. PATIENTS AND METHODS: Retrospective chart review of autologous buccal mucosa grafts for urethral reconstruction at Winnipeg Children's Hospital and Children's Hospital of Eastern Ontario between November 1992 and March 2000. RESULTS: Nine patients (median age 4 years) underwent such reconstruction. Seven of the nine patients had experienced failed previous attempts at hypospadias repair. Onlay grafts were used in all but one patient who required a tube graft. Urethrocutaneous fistula was the most common post-operative complication, affecting four of nine patients. Two patients developed urethral strictures and one a meatal stenosis. Satisfactory functional results were ultimately achieved in all patients. Harvest site complications were minimal. CONCLUSIONS: Buccal mucosa is a readily available and useful source for urethral grafting material, but should only be used in patients with insufficient penile skin. Grafts may be used as onlays or tubes. It is our experience that despite precautionary measures, fistulae and strictures are common.

Child↗
PubMed2001

A 27-bp region of the inducible nitric oxide synthase promoter regulates expression in glial cells.

The expression of inducible nitric oxide synthase (NOS2) in glial cells is inhibited by neurotransmitters such as norepinephrine (NE) which elevate cAMP levels. We examined the molecular basis for this effect using a 2.2-kb fragment of the rat NOS2 promoter transfected into rat C6 glioma cells. Promoter activation (up to six-fold) by lipopolysaccharide (LPS) and interferon-gamma (IFNgamma) was reduced by NE, which alone had no effect. However, a promoter construct extending to bp -130 and containing the proximal nuclear factor-kappa B (NF-kappaB) binding site was minimally activated by LPS and cytokines, but activated up to three-fold by NE. Deletion analysis identified a 27-bp region (bp -187 to -160) as critical for mediating this suppressive effect. This region also enhanced promoter activation by LPS and cytokines, and prevented activation by NE alone. Gel shift analysis revealed constitutive binding to this region, and induction by NE of additional complexes which could be blocked by an antibody against CREB. NE also increased levels of the IkappaBalpha protein which could contribute to its suppressive effects. These results identify a critical role for this 27-bp region in regulation of NOS2 promoter activation and suppression by cAMP.

Animals↗
PubMed2001

Local anesthetics potentiate nitric oxide synthase type 2 expression in rat glial cells.

Expression of the calcium-independent nitric oxide synthase (NOS2) contributes to damage in neurologic disease and trauma. The effects of local anesthetics on NOS2 expression have not been examined. The authors tested the effects of four local anesthetics on the expression of NOS2 in immunostimulated rat C6 glioma cells. Incubation with local anesthetics alone did not induce nitrite accumulation; however, the nitrite production induced by stimulation with bacterial endotoxin lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) was increased in a dose-dependent manner by bupivacaine (maximal 3-fold at 360 microM), tetracaine (maximal 7-fold at 360 microM), and lidocaine at higher doses (5-fold increase at 3.3 mM). Significant increases in nitrite production were observed in concentrations of bupivacaine or tetracaine as low as 120 microM, which correspond to 30 microg/mL (.003% weight/volume). In contrast, ropivacaine had little effect on nitrite production (160% of control values) and only at the highest concentration (3.3 mM, corresponding to 890 microg/mL or 0.089% w/v) tested. Increased nitrite production was not caused by cytotoxic effects of the drugs used, as assessed by release of intracellular lactate dehydrogenase. Increased nitrite production was accompanied by increased NOS2 catalytic activity, steady state mRNA levels, and promoter activation. These results demonstrate that submillimolar doses of two commonly used local anesthetics can increase glial NOS2 expression.

Anesthetics, Local↗
PubMed1999

Effects of ZDV-based patient education on intentions toward ZDV use, HIV testing and reproduction among a US cohort of women.

This study examined the immediate effects of exposure to a patient education brochure concerning the risks and benefits of zidovudine (ZDV) therapy during pregnancy to reduce perinatal HIV transmission (protocol ACTG 076) on related knowledge, behavioural intentions and attitudes of women with and at-risk for HIV-infection. Self-reports were collected from 653 women of childbearing age from community family planning clinics and hospital-based HIV centres in 19 sites from nine US cities between May and November 1995. The intervention was a nine-page patient education brochure in Spanish, Creole and English versions, evently presenting the pros and cons of ZDV therapy to reduce perinatal HIV-transmission. Brochure exposure increased knowledge (p < 0.001) for all but one scale concerning ZDV resistance and increased the likelihood of women reporting intentions to take ZDV during pregnancy (p < 0.001) and to believe ZDV reduced transmission (p < 0.001). Brochure exposure had differential effects for some subpopulations. Intentions to have or terminate current or future pregnancies, knowledge about ZDV and attitudes toward ZDV varied mostly by ethnicity/race, language preference and HIV status. Pregnancy status, age, education and having an HIV-positive child had less impact on the brochure's effect, while income had no impact.

Anti-HIV Agents↗
PubMed1999

Factors influencing participation in weekly support groups among women completing an HIV/STD intervention program.

Over the past three decades, the influence and importance of social support has been well documented and the findings have suggested a beneficial effect on stress-related situations, mental and physical health, and social functioning. More recently, small group/skills training behavioral interventions have demonstrated success in changing behaviors which affect the transmission of sexually transmitted diseases, including HIV among populations at risk for these diseases. Studies of support groups to date have been conducted exclusively in research settings where women are offered financial incentives for participation. Little is known about the willingness of women to participate in ongoing support groups after successfully completing a skills training intervention. The present study examines the factors that may influence participation among women in a weekly support group after completing a structured, six session HIV/STD intervention. Both quantitative and qualitative data are collected from 265 women in the intervention arm of a multi-site randomized controlled behavioral intervention trial. Results reveal that less than a quarter (22%) of women participated in at least one support group. Participation varied significantly by site, ranging from 34% to 15% (p = .008). Participation was also strongly linked to recent use of domestic violence services. Qualitative data indicated that although monetary incentives play some role in the woman's decision to participate, other factors are also important. These include program outreach, support group size, salience of the group content, consistency of group leadership from the intervention to the support group, and use of peer leaders along with professional facilitators. Implications for design of post-intervention support groups programs are discussed.

Adolescent↗
PubMed1998

MRA of the intracranial circulation in asymptomatic patients with sickle cell disease.

BACKGROUND: MR angiography (MRA) provides a mechanism for non-invasively studying blood flow, thus providing a new opportunity to study the intracranial circulation in asymptomatic sickle cell disease (SCD) patients. Although conventional angiography is the gold standard for the depiction of vascular anatomy, this is too invasive for an asymptomatic population. OBJECTIVE: To establish the range of appearances in asymptomatic SCD patients and to correlate brain MRI results (either sub-clinical abnormalities or normal brain parenchyma) with the MRA findings. MATERIALS AND METHODS: Brain MRI and MRA of the intracranial circulation was performed on 22 patients (13 male and 9 female, median age 7.5 years, range 1.3-20 years). Fourteen were homozygous SS and eight were SC. The median haematocrit at the time of MRI was 25.9 (range 13.8-33.3). RESULTS: On MR imaging, four patients had infarcts in eight vascular territories (six anterior and two posterior). In 3/4 of anterior vascular territories with infarction, long ( >/= 6 mm) segments of abnormal signal were seen at the internal carotid artery bifurcation with associated reduced distal flow. Short focal areas of abnormal signal were commonly seen where vessels branched, bifurcated or curved and were not associated with infarcts. These areas probably represent turbulence-related dephasing secondary to high velocity flow found in SCD. CONCLUSION: Long segments ( >/= 6 mm) of abnormal signal with reduced distal flow correlated with sub-clinical infarction.

Adolescent↗
PubMed1998

Seat belt injury presenting as bilateral abdominal wall herniations in a child.

The constellation of abdominal injuries caused by seat belts in automobile accidents usually consists of intraabdominal solid organ and hollow viscus injuries. We present a two-and-one-half-year-old patient with an unusual constellation of seat belt injuries that presented as bilateral abdominal herniations. We feel that an abdominal hernia caused by a seat belt injury should alert the clinician to the probability of other severe intraabdominal injuries. The uniqueness of this case is compounded by the way in which the seat belt was misused.

Abdominal Injuries↗
PubMed1993

Detection of a deep lipoblastoma by MRI and ultrasound.

Lipoblastoma is a rare benign tumor of the soft tissue occurring predominantly during the first two years of life. We report here the application of MRI and ultrasound to the detection of a soft tissue lipoblastoma. By MRI and ultrasound, we precisely evaluated the extent of the tumor, the presence of atypical areas of cystic and mucoid degeneration within the tumor, and its lack of vascularity. Our patient's lipoblastoma did not demonstrate the signal characteristics of a fatty tumor on MRI.

Humans↗
PubMed1992

Observation of atomic steps on single crystal surfaces by a commercial scanning electron microscope.

Atomic steps on (111) and (100) crystal surfaces of Pt were observed using a commercial scanning electron microscope (SEM) in secondary electron mode. By comparing the SEM images and those by reflection electron microscopy (REM), the observed contrast was confirmed to be that from atomic steps on crystal surfaces. The contrast mechanism is briefly discussed. One application of this imaging technique is also shown.

Gold↗
PubMed1992

Necrotizing enterocolitis in infancy.

The most common gastrointestinal emergency in the newborn is necrotizing enterocolitis. Premature babies are the most likely victims, but it also occurs in full-term infants. Although great strides have been made in elucidating some of the factors responsible for necrotizing enterocolitis, such as intestinal ischemia, bacterial overgrowth, and feeding dysfunction, the exact etiology is as yet unclear. The timing and indications for surgery differ from institution to institution, but the long-term outcome is similar in most large series. The overall mortality rate remains about 20% to 40%, and of the survivors, about one half seem to have no sequelae, the remaining infants having neurologic and gastrointestinal deficits of various degrees of significance.

Enterocolitis, Pseudomembranous↗