Relationship of glycosaminoglycan and matrix changes to vascular smooth cell phenotype modulation in rabbit arteries after acute injury

Purpose: The phenotype of vascular smooth muscle cells (SMCs) is altered in several arterial pathologies, including the neointima formed after acute arterial injury. This study examined the time course of this phenotypic change in relation to changes in the amount and distribution of matrix glycosaminoglycans. Methods: The immunochemical staining of heparan sulphates (HS) and chondroitin sulphates (CS) in the extracellular matrix of the arterial wall was examined at early points after balloon catheter injury of the rabbit carotid artery. SMC phenotype was assessed by means of ultrastructural morphometry of the cytoplasmic volume fraction of myofilaments. The proportions of cell and matrix components in the media were analyzed with similar morphometric techniques. Results: HS and CS were shown in close association with SMCs of the uninjured arterial media as well as being more widespread within the matrix. Within 6 hours after arterial injury, there was loss of the regular pericellular distribution of both HS and CS, which was associated with a significant expansion in the extracellular space. This preceded the change in ultrastructural phenotype of the SMCs. The glycosaminoglycan loss was most exaggerated at 4 days, after which time the HS and CS reappeared around the medial SMCs. SMCs of the recovering media were able to rapidly replace their glycosaminoglycans, whereas SMCs of the developing neointima failed to produce HS as readily as they produced CS. Conclusions: These studies indicate that changes in glycosaminoglycans of the extracellular matrix precede changes in SMC phenotype after acute arterial injury. In the recovering arterial media, SMCs replace their matrix glycosaminoglycans rapidly, whereas the newly established neointima fails to produce similar amounts of heparan sulphates.

Establishment of native ecosystems after mining - Australian experience across diverse biogeographic zones

The Australian minerals industry, which is dominated by coal, gold, bauxite, iron ore, base metals and mineral sand operations, is widely scattered across a continent which has a wide range of climatic zones ranging from moist temperate in the south through hot deserts in the centre to moist tropical in the north. There is an emphasis at most mines on establishing native ecosystems after mining, and technologies have had to be developed to ensure successful establishment and stability of these ecosystems under often adverse climatic conditions. This paper describes some of the innovative practices used to establish native ecosystenms in bauxite, mineral sand and coal operations across diverse biogeographic zones. Additionally, brief reference is made to an ecosystem function analysis, which has been developed to assess the success of establishment of these ecosystems. (C) 2001 Elsevier Science B.V. All rights reserved.

Ethanol-related adaptive changes and physical dependence in rats after exposure to ethanol

Adaptive changes that occur after chronic exposure to ethanol are an important component in the development of physical dependence. We have focused our research on ethanol-induced changes in the expression of several genes that may be important in adaptation. In this article, we describe adaptive changes at the level of the N-methyl-D-aspartate receptor, in the protein expression and activity of the Egr transcription factors, and in the expression of a novel gene of unknown function. (C) 2001 Elsevier Science Inc. All rights reserved.

Randomized controlled trial of two cigarette quit programmes in coronary care patients after acute myocardial infarction

Background: Tobacco cessation after acute myocardial infarction (AMI) substantially improves outcome but how effective individual programmes are needs to be established. To date, few studies have examined this factor. Aims: To assess the outcome of two smoking cessation programmes after AMI. Methods: One hundred and ninety-eight current smokers admitted to coronary care with an AMI participated in a randomized controlled study comparing two outpatient tobacco interventions, the Stanford Heart Attack Staying Free (SF) programme and a Usual Care (UC) programme. Results: Log-rank analyses revealed that patients in the SF programme were retained longer (P < 0.001) and had higher cotinine validated abstinence rates (P < 0.001) compared with patients in the UC programme. Twelve months after intervention, 39% of the SF programme compared with 2% of the UC programme demonstrated cotinine validated tobacco cessation, representing a significant reduced relapse rate in the SF programme (chi (2), P < 0.001). Conclusions: The SF smoking cessation programme initiated in hospital can significantly reduce smoking rates at 12 months after myocardial infarction. Although superior to the UC quit programme, Australian outcomes were lower than the American programme originators' published outcomes.

Rapid onset of pituitary apoplexy after goserelin implant for prostate cancer: need for heightened awareness

No Abstract

Irritative symptoms after colposuspension: Are they due to distortion or overelevation of the anterior vaginal wall and trigone?

Symptoms of bladder irritability are common after incontinence surgery but their cause is unknown. This study tests the hypothesis that irritative symptoms after colposuspension are due to distortion of the trigone. As part of longitudinal follow-up studies, 175 women were examined 6 months to 12 years after either an open or a laparoscopic Burch colposuspension. The main outcome measures were symptoms of bladder irritability (frequency, nocturia and urge incontinence) and ultrasound findings (bladder neck position at rest and on Valsalva, the presence of a colposuspension ridge, ridge depth and ridge distance, and trigonal angle). Two positive associations between ultrasound parameters and symptoms of bladder irritability were observed: urge incontinence was more likely in the presence of bladder neck funneling, and women with nocturia had a higher trigonal angle. Increased distortion of the trigone was associated with a reduced incidence of urge incontinence in the subgroup of patients after laparoscopic colposuspension. The data presented in this study do not support the hypothesis that symptoms of bladder irritability are due to trigonal distortion or overelevation.

Chk2 activation dependence on Nbs1 after DNA damage

The checkpoint kinase Chk2 has a key role in delaying cell cycle progression in response to DNA damage. Upon activation by low-dose ionizing radiation (IR), which occurs in an ataxia telangiectasia mutated (ATM)dependent manner, Chk2 can phosphorylate the mitosis-inducing phosphatase Cdc25C on an inhibitory site, blocking entry into mitosis, and p53 on a regulatory site, causing G, arrest. Here we show that the ATM-dependent activation of Chk2 by gamma- radiation requires Nbs1, the gene product involved in the Nijmegen breakage syndrome (NBS), a disorder that shares with AT a variety of phenotypic defects including chromosome fragility, radiosensitivity, and radioresistant DNA synthesis. Thus, whereas in normal cells Chk2 undergoes a time-dependent increased phosphorylation and induction of catalytic activity against Cdc25C, in NBS cells null for Nbs1 protein, Chk2 phosphorylation and activation are both defective. Importantly, these defects in NBS cells can be complemented by reintroduction of wild-type Nbs1, but neither by a carboxy-terminal deletion mutant of Nbs1 at amino acid 590, unable to form a complex with and to transport Mre11 and Rad50 in the nucleus, nor by an Nbs1 mutated at Ser343 (S343A), the ATM phosphorylation site. Chk2 nuclear expression is unaffected in NBS cells, hence excluding a mislocalization as the cause of failed Chk2 activation in Nbs1-null cells, interestingly, the impaired Chk2 function in NBS cells correlates with the inability, unlike normal cells, to stop entry into mitosis immediately after irradiation, a checkpoint abnormality that can be corrected by introduction of the wild-type but not the S343A mutant form of Nbs1, Altogether, these findings underscore the crucial role of a functional Nbs1 complex in Chk2 activation and suggest that checkpoint defects in NBS cells may result from the inability to activate Chk2.

Role of cytokine gene polymorphisms in acute rejection and renal impairment after liver transplantation

Although immunosuppressive regimens are effective, rejection occurs in up to 50% of patients after orthotopic liver transplantation (OLT), and there is concern about side effects from long-term therapy. Knowledge of clinical and immunogenetic variables may allow tailoring of immunosuppressive therapy to patients according to their potential risks. We studied the association between transforming growth factor-beta, interleukin-10, and tumor necrosis factor alpha (TNF-alpha) gene polymorphisms and graft rejection and renal impairment in 121 white liver transplant recipients. Clinical variables were collected retrospectively, and creatinine clearance was estimated using the formula of Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain reaction-based methods. Thirty-seven of 121 patients (30.6%) developed at least 1 episode of rejection. Multivariate analysis showed that Child-Pugh score (P =.001), immune-mediated liver disease (P =.018), normal pre-OLT creatinine clearance (P =.037), and fewer HLA class 1 mismatches (P =.038) were independently associated with rejection, Renal impairment occurred in 80% of patients and was moderate or severe in 39%, Clinical variables independently associated with renal impairment were female sex (P =.001), pre-OLT renal dysfunction (P =.0001), and a diagnosis of viral hepatitis (P =.0008), There was a significant difference in the frequency of TNF-alpha -308 alleles among the primary liver diseases. After adjustment for potential confounders and a Bonferroni correction, the association between the TNF-alpha -308 polymorphism and graft rejection approached significance (P =.06). Recipient cytokine genotypes do not have a major independent role in graft rejection or renal impairment after OLT, Additional studies of immunogenetic factors require analysis of large numbers of patients with appropriate phenotypic information to avoid population stratification, which may lead to inappropriate conclusions.

Delayed emergence of bovine leukemia virus after vaccination with a protective cytotoxic T cell-based vaccine

In a previous study eight MHC class I-matched sheep were vaccinated with a minimal cytotoxic T lymphocyte (CTL) peptide epitope vaccine and were challenged with the retrovirus, bovine leukemia virus (BLV). Half the vaccinated animals remained PCR negative after challenge, whereas the remaining half and the placebo group became PCR positive within 4 weeks postchallenge (Hislop AD, Good MF, Mateo L, Gardner J, Gatei MH, Daniel RCW, Meyers BV, Lavin MF, and Suhrbier A: Nat Med 1998; 4: 1193). Here we show that neither epitope mutations nor processing differences explained why half the peptide-vaccinated animals failed to resist the BLV challenge. However, in these animals the development of BLV-induced lymphosarcomas was significantly delayed compared with the placebo group, suggesting a role for CTLs in preventing retrovirus-induced cancers. Importantly, two of the initially protected animals become PCR positive after similar to1.5 years, indicating extended suppression but not elimination of challenge virus by vaccine-induced CTLs. The late emergence of virus could not be explained by epitope escape mutations or the loss of memory CTL responses. We speculate that high levels of effector CTL may be needed to protect animals from a postchallenge viremia and maintenance of such effector CTLs, rather than memory CTLs, may be required to prevent subsequent emergence of virus from latent pools.

Muscle strength and function before and after anterior cruciate ligament reconstruction using semitendonosus and gracilis

This study assessed the quadriceps and hamstring strength before and 6 months after anterior cruciate ligament (ACL) reconstructive surgery using the hamstrings and related the findings to functional performance. Six months after surgery is a critical time for assessment as this is when players are returning to sport. Maximum isokinetic strength of 31 patients with complete unilateral ACL ruptures was measured at speeds of 60 degrees and 120 degrees per second. Functional assessment included the single hop, the triple hop, the shuttle run, side-step and carioca tests. All patients underwent a controlled quadriceps emphasized home-based physiotherapy program both before and after surgery. Results show that before surgery there was a 7.3% quadriceps strength deficit at 60 degrees per second compared to the uninjured leg but no hamstring strength deficit. After surgery there was a statistically significant but relatively small loss of muscle strength. The quadriceps strength deficit had increased to 12% and there was a 10% hamstring deficit. Post-operatively there was an 11% and 6.3% improvement in the hop tests, a 9% (P < 0.01) improvement in the shuttle run, a 15% (P < 0.001) improvement in the side step and a 24% (P < 0.001) improvement in the carioca tests (P < 0.001) despite the loss of muscle strength. (C) 2001 Elsevier Science B.V. All rights reserved.