Frequent inactivation of PTEN in prostate cancer cell lines and xenografts

Loss of chromosome 10q is a frequently observed genetic defect in prostate cancer. Recently, the PTEN/MMAC1 tumor suppressor gene was identified and mapped to chromosome 10q23.3. We studied PTEN structure and expression in 4 in vitro cell lines and 11 in vivo xenografts derived from six primary and nine metastatic human prostate cancers. DNA samples were allelotyped for eight polymorphic markers within and surrounding the PTEN gene. Additionally, the nine PTEN exons were tested for deletions. In five samples (PC3, PC133, PCEW, PC295, and PC324), homozygous deletions of the PTEN gene or parts of the gene were detected. PC295 contained a small homozygous deletion encompassing PTEN exon 5. In two DNAs (PC82 and PC346), nonsense mutations were found, and in two (LNCaP and PC374), frame-shift mutations were found. Missense mutations were not detected. PTEN mRNA expression was clearly observed in all cell lines and xenografts without large homozygous deletions, showing that PTEN down-regulation is not an important mechanism of PTEN inactivation. The high frequency (60%) of PTEN mutations and deletions indicates a significant role of this tumor suppressor gene in the pathogenesis of prostate cancer.     

Modulation of agonist and antagonist interactions in serotonin 1A receptors by alcohols

The serotonin type IA (5-HT1A) receptors are members of a superfamily of seven transmembrane domain receptors that couple to GTP binding regulatory proteins (G-proteins). Serotonergic signalling has been shown to play an important role in alcohol tolerance and dependence. We have studied the effects of alcohols on ligand (agonist and antagonist) binding to bovine hippocampal 5-HT1A receptor in native as well as solubilized membranes. Our results show that alcohols inhibit the specific binding of the agonist OH-DPAT and the antagonist p-MPPF to 5-HT1A receptors in a concentration-dependent manner.     

Global tuberculosis challenges

The authors report the case of a 49-year-old, insulin-dependent diabetic man treated by double kidney-pancreas transplantation. A T3, N3, M0 testicular tumour was discovered at the 8th month and treated by inguinal orchidectomy and 2 courses of chemotherapy. Immunosuppressant treatment was decreased without any consequences for the transplants. Seven years later, the patient was cured but still treated by haemodialysis for chronic rejection of the renal transplant. The pancreatic transplant was still functional and the patient is waiting for a second renal transplantation.     

Safety of a temperature-sensitive clone of Mycoplasma synoviae as a live vaccine

A temperature-sensitive (ts+) clone derived from the Australian Mycoplasma synoviae (MS) field isolate 86079/7NS was produced by chemical mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine and assessed for safety as a live vaccine. This clone, designated MS-H, was assessed for pathogenicity in three different models with air sac lesions as the criterion. No air sac lesions were observed when MS-H was administered to specific-pathogen-free hybrid white leghorn (HWL) chickens by eyedrop at 10 times the normal dose or directly into the thoracic air sacs or as an aerosol administered to specific-pathogen-free Webster white leghorn chickens with concurrent intratracheal T-strain infectious bronchitis virus (IBV). MS-H did not revert to virulence or lose the ts+ phenotype when passaged through five in vivo and 10 in vitro passages. No adverse effects were seen when HWL chickens were vaccinated concurrently with MS-H and combinations of Mycoplasma gallisepticum ts-11 vaccine, IBV vaccine, and infectious laryngotracheitis virus vaccine. Lateral transmission of MS-H was found to occur when vaccinated HWL chickens were mixed with unvaccinated chickens 2 wk after vaccination. At 1 wk after mixing, one out of two unvaccinated chickens had seroconverted to MS and was culture positive for MS. At 2 wk after mixing, both contact chickens were positive for MS by culture and serology.     

The chronic non-healing wound: how to make it better

Chronic wounds are a commonly encountered problem. An understanding of their aetiology, combined with a systematic approach to their management, is fundamental to achieving an optimal environment for healing to take place.     

Periurethral fat injection in the treatment of recurrent genuine stress incontinence

A benign, transient proliferation of atypical lymphocytes and a monoclonal rearrangement of the T-cell receptor beta (TRB) locus was found in a 60-year-old woman who presented with low-grade fever, anorexia and fatigue. A marked and transient atypical lymphocytosis (white blood cell count 90.5 x 10(9)/l) with CD8 surface antigen improved without specific treatment. Although tests for IgM antibodies to hepatitis A, varicella zoster, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all negative, a monoclonal gene rearrangement of TRB locus was observed in the DNA of the proliferated atypical lymphocytes by Southern blotting. The clonal rearrangement and the atypical lymphocytes disappeared after 14 d, and the patient has remained well for 7 years. These results suggest that monoclonal proliferation of CD8 lymphocytes can occur based on a non-neoplastic aetiology.     

Ductile crack growth in pre-cracked CVN specimens: numerical studies

This study describes plane strain, finite element analyses to model ductile crack extension in pre-cracked Charpy specimens subjected to static and impact loading. The Gurson–Tvergaard (GT) dilatant plasticity model for voided materials describes the degradation of material stress capacity. Fixed-size, computational cell elements defined over a thin layer along the crack plane provide an explicit length scale for the continuum damage process. Outside of this layer, the material remains undamaged by void growth, consistent with metallurgical observations. The finite strain constitutive models include the effects of high strain rates on the material flow properties. Parametric studies focusing on numerically generated R-curves quantify the relative influence of impact velocity, material strain rate sensitivity, and properties of the computational cells (thickness and the initial cell porosity). In all cases, impact loading elevates significantly the R-curve by increasing the amount of background plasticity. The strong effects of impact loading on the driving force for cleavage fracture are illustrated through evolution of the Weibull stress. The analyses suggest a negligible, additional effect of tearing on the Weibull stress under impact loading. Validation of the computational cell approach to predict loading rate effects on R-curves is accomplished by comparison to static and impact experimental sets of R-curves for three different steels.     

Studies of the distribution of lipofuscin in the retinal pigment epithelium using high-resolution TV laser scanning ophthalmoscopy

BACKGROUND: The fundus autofluorescence imaging technique has been modified allowing improved image resolution (768 x 572 pixel). We present results of fundus autofluorescence studies using this technique. MATERIALS AND METHODS: Fundus autofluorescence was studied in 286 eyes of 143 patients with retinitis pigmentosa, macular dystrophies and age-related macular degeneration using a confocal laser scanning ophthalmoscope prototype (Zeiss, Oberkochen; excitation wavelength: 488 nm, cut-off filter at 521 nm). RESULTS: The spatial distribution of autofluorescence was different in all diseased eyes investigated compared to the normal pattern of fundus autofluorescence. Each disorder showed a specific fundus autofluorescence appearance. CONCLUSIONS: The advanced technique of imaging fundus autofluorescence allows detailed studies of the lipofuscin distribution. In vivo analysis of the dynamics of accumulation and degradation of lipofuscin in eyes with tapeto-retinal dystrophies and age-related macular disease may contribute to elucidation of the pathogenesis of these disorders.