Proliferating cell nuclear antigen (PCNA) immunostaining--a prognostic factor in ovarian cancer?

The measurement of tumour cell proliferation is becoming increasingly recognised in defining prognostic groups. Proliferating cell nuclear antigen (PCNA) immunolocalisation can be used as an index of cell proliferation and may define the extent of departure from normal growth control. The monoclonal antibody PC10 stains PCNA in archival paraffin-embedded tissue. This study investigates its potential as a prognostic marker in early and advanced ovarian cancer. A three-stage immunoperoxidase technique was developed to detect the monoclonal antibody PC10. Archival paraffin-embedded tissue from 19 stage I ovarian tumours (13 malignant and six borderline) and 79 advanced (stage IIb-IV) ovarian tumours (patients entered into the Third North-West Thames Ovarian Cancer Trial) was immunostained with PC10. PC10 immunostaining was performed successfully in 91.8% of cases. The PC10 labelling index (PC10 LI) ranged from 1.5% to 88% with a mean value of 47.4%. Stage I borderline tumours had significantly lower PCNA labelling indexes than stage I malignant tumours (P < 0.048). In advanced disease there was an inverse correlation between PC10 and overall survival, and in those patients who underwent good debulking surgery (37 patients with disease < 2 cm diameter) a low PC10 value (< 36.5%) correlated with improved survival (log-rank trend test for survival, chi 2 = 5.75, P = 0.017). PCNA immunostaining defines a good prognostic subgroup in adequately debulked patients with ovarian cancer.     

Progressive aneurysmal degeneration of cortical venous drainage of dural arteriovenous malformations: case report

OBJECTIVE AND IMPORTANCE: The development of a venous aneurysm associated with dural arteriovenous malformations rarely has been documented in the literature. CLINICAL PRESENTATION: A 64-year-old man with known dural arteriovenous malformations developed a venous aneurysms, as shown on sequential angiograms obtained during 2 years. INTERVENTION: The dural arteriovenous malformations were treated with neuroendovascular embolization and then surgical excision. CONCLUSION: The clinical presentation, diagnosis, and treatment of this unusual case are presented.     

Improved atrial function in bicaval versus standard orthotopic techniques in cardiac transplantation

Atrial geometry is preserved in the bicaval technique of cardiac transplantation. Using Doppler echocardiography, we investigated the impact of this technique on preservation of atrial function and found that echocardiographic indexes of atrial function are improved in bicaval cardiac transplants versus the standard orthotopic transplants.     

Apparent first-order kinetics in the transformation of 1,1,1-trichloroethane in groundwater following a transient release

A transient release of 1,1,1-trichloroethane (TCA) to an otherwise uncontaminated aquifer at a manufacturing facility presented a useful opportunity to validate the results of previous laboratory and field studies on TCA transformation in groundwater. Abiotic TCA transformation to 1,1-dichloroethylene (DCE) and acetic acid at the site exhibited first-order kinetics with half-life of 2.9 years 15 degrees C. Degradation effects were seen to overwhelm chemical retardation effects on the DCE/TCA concentration ratio in groundwater. The kinetic data was sufficient to date the release to within one week of when it actually occurred. A kinetic approach may be applicable to dating the releases on other contaminated sites where a single transient release is indicated. The transformation of dissolved TCA in groundwater with a half-life of several years can be expected at many contaminated sites.     

High density lipoprotein particle size restriction in apolipoprotein A-I(Milano) transgenic mice

Human carriers of apolipoprotein A-I(Milano) (Arg173 --> Cys substitution in apolipoprotein A-I) are characterized by an HDL deficiency in which small, dense HDL accumulate in plasma. Because affected individuals are heterozygous for this mutation, the full impact of apolipoprotein A-I(Milano) (apoA-I(Milano)) on HDL-cholesterol metabolism is unknown. In this study, apoA-I(Milano) transgenic mice were used to evaluate the extent of apoA-I(Milano) dimerization and HDL particle size restriction in the absence of wild-type apoA-I. Murine apoA-I knockout mice were utilized to express apoA-I(Milano) and human apoA-II in the presence of wild-type, human apoA-I (apoA-IMilano/A-Iwt/A-II) and in its absence (apoA-IMilano/A-II). Plasma HDL-cholesterol concentrations were similar (30 mg/dl) in both lines of apoA-I(Milano) transgenic mice. In the apoA-IMilano/A-Iwt/A-II phenotype, 14% of the apoA-I(Milano) formed homodimers and 33% formed heterodimers with apoA-II. ApoA-I(Milano) homodimers increased by 71% in the apoA-IMilano/A-II transgenics and was associated with an abundance of small, 7.6-nm HDL3-sized particles compared to the 9.5, 8.3, and 7.6-nm-sized particles in apoA-IMilano/A-Iwt/A-II mice. The unesterified cholesterol/cholesteryl ester mole ratio of HDL was elevated by 45% in apoA-IMilano/A-Iwt/A-II mice and by 90% in apoA-IMilano/A-II transgenics compared to wild-type (human apoA-I/A-II). Both apoA-I(Milano) transgenics possessed normal levels of plasma LCAT activity, but endogenous cholesterol esterification rates were reduced by 50% compared to controls. Thus, HDL particle size restriction was not the result of impaired LCAT activation; rather, dimerization of apoA-I(Milano) limited the esterification of cholesterol on endogenous HDL. In the absence of wild-type apoA-I, the more extensive dimerization of apoA-I(Milano) severely limited cholesteryl ester accumulation on plasma HDL accounting for the abundance of small, 7.6-nm HDL3 particles in apoA-IMilano/A-II mice.     

Physiological effects of medetomidine-zolazepam-tiletamine immobilization in black bears

Proteasomes are nonlysosomal multicatalytic proteases involved in antigen processing. Three of the 10 mammalian proteasome beta subunits (LMP2, LMP7, and LMP10) are induced by IFN-gamma. Two of these (LMP2 and LMP7) are encoded in the major histocompatibility complex of both human (chromosome 6) and mouse (chromosome 17). However, the human homologue of Lmp10, MECL1, is found on chromosome 16. Here we show that in mice, Lmp10 is a single-copy gene localized to chromosome 8, in a region of conserved synteny with human chromosome 16. Sequencing of a 129/SvJ strain genomic clone revealed that the gene has eight exons spanning 2.3 kb. Characterization of a full-length mouse cDNA clone indicates that Lmp10 encodes a protein of 273 amino acids with a calculated molecular weight of 29 kDa and an isoelectric point of 6.86. Northern analysis of Lmp2, Lmp7, and Lmp10 showed expression in heart, liver, thymus, lung, and spleen, but not in brain, kidney, skeletal muscle, or testis.