Gene amplification as a prognostic factor in primary and secondary high-grade malignant gliomas

ND10 are recently characterized nuclear domains that are composed of 0.5 microm sized, precisely circumscribed dots in cultured human cell lines. To investigate the distribution and number of ND10 on various types of normal and neoplastic human tissues, we carried out immunostaining and immunoprecipitation analyses with monoclonal antibodies 138 and 1150. The number of ND10 varied from 1 to 10 or more in various tissues as did their size. ND10 were diffusely located in early embryonic and normal tissues, except for the exocrine and endocrine cells of the pancreas and for hepatocytes. In normal squamous mucosa, basal cells had more ND10 than did differentiated superficial squamous cells. The number and size of ND10 were markedly increased in malignant neoplasms but were similar in benign tumors and corresponding normal tissues. Sex hormone-related normal tissues, such as the endometrium or myometrium, and neoplasms strongly stained for ND10. The distribution pattern of ND10 in human tissues indicates that they are conserved nuclear substructures that are closely associated with cellular differentiation, hormonal stimulation, and oncogenesis.     

Efficacy of monensin for the prevention of subclinical ketosis in lactating dairy cows

A total of 1010 dry cows and pregnant heifers was randomly selected from 25 dairy farms near Guelph, Ontario, Canada to receive either a controlled-release capsule of monensin or a placebo at 3 wk prior to expected calving. Serum samples were obtained at the time of treatment administration, and both serum and milk samples were collected at wk 1, 2, 3, 6, and 9 postcalving. The threshold used to define subclinical ketosis was selected a priori at a concentration of > or = 1200 mumol/L of beta-hydroxybutyrate. Using this threshold, the prevalence and incidence of subclinical ketosis were significantly reduced (50%) by monensin treatment. The duration of subclinical ketosis for cows that had been treated with monensin was also shorter than that for cows treated with the placebo. Monensin treatment significantly reduced the incidence of subclinical ketosis when the threshold was defined using higher concentrations of serum beta-hydroxybutyrate (1400 and 2000 mumol/L). In addition, monensin significantly reduced the prevalence of positive milk ketone tests.     

Structure of d(GT)n.d(GA)n sequences: formation of parallel stranded duplex DNA

Alternating polypurine sequences exhibit remarkable polymorphism. In this study, we report that dGA.dGT sequences form parallel stranded duplex DNA at neutral pH. Using two model hairpins, 3'-d(GT)3-5'5'-T4(AG)3-3' (I) and 3'-d(GT)4-5'5'-T4(AG)4-3' (II), containing 5'5' linkages which direct parallel strand formation, we systematically explored the spectroscopic and thermodynamic properties of parallel stranded d(GA)n.d(GT)n. The parallel stranded hairpins are remarkably stable structures with TM's of 41.5 and 47.5 degreesC (in 0.4 M NaCl) for the shorter and longer hairpins, respectively. The van't Hoff enthalpies of 80.7 and 114 kJ mol-1 are relatively low but are comparable to a parallel stranded d(GA)n duplex. On the basis of the spectroscopic and electrophoretic characteristics, we conclude that parallel strand formation is not restricted to hairpin systems, but also readily occurs in unconstrained dimeric duplexes with the appropriate sequence homologies. Both melting curves and electrophoretic analyses of parallel stranded heteroduplexes in which the sequence enforces specific base pairing demonstrate that G-G and A-T base pairs are formed in d(GA)n.d(GT)n segments.     

Detection and characterization of the electron paramagnetic resonance-silent glutathionyl-5,5-dimethyl-1-pyrroline N-oxide adduct derived from redox cycling of phenoxyl radicals in model systems and HL-60 cells

Rapidly growing knowledge about the nature and behaviour of breast cancer has led to many treatment modalities. Consequently, the possibilities of individualizing the treatment of breast cancer increase. The major tool for the determination of an optimal treatment plan is the estimation of the extent of the disease: in other words, staging. As a consequence, together with the expected result of the treatment, the stage of the disease gives information on the prognosis of the patient. Current staging systems insufficiently describe the clinically important features of breast cancer with respect to management and outcome: local and regional extent, invasiveness, aggressiveness, the state of dissemination, and the effectiveness of different treatment modalities. For staging of the local and regional extent, histology plays a prominent role and should be incorporated in future staging systems. Histological workup therefore needs standardisation. Histological parameters as tumour size, grade, nodal status, and vascular invasion are also the most important prognostic factors. Many so-called biological prognostic factors are related to the invasiveness and aggressiveness (metastatic potential) of the tumour, and therefore to the prognosis of the patient. However, these factors do not necessarily predict the effectiveness of certain systemic treatments. Only if the biological foundation of a prognostic factor is completely clarified can treatment be based on this knowledge, and the factor will become a predictor for the treatment effect. Many "biological" prognostic factors do not fulfil this main criterion and are therefore not useful for clinical decision making. A clinically useful staging system covers three primary aims: (1) to guide locoregional treatment, (2) to prognosticate the chance of survival, and (3) to indicate who needs what kind of adjuvant treatment. For the conception of a new staging system the following steps should be taken: standardization of all aspects of histology, identification of regional nodal involvement, and validation of prognostic factors with respect to their predictive value to treatment outcome.     

4-Defect repair of grade 4 cystocele

PURPOSE: The 4-defect repair of grade 4 cystocele corrects discrete and severe deficiencies of vesicourethral support. We describe this technique used during pelvic reconstruction in 130 women. MATERIALS AND METHODS: During a 3-year period 130 patients (age range 35 to 96 years) underwent repair of grade 4 cystocele using the 4-defect repair technique. Cystocele repair had been performed in 60 patients (46%) and hysterectomy had been performed in 85 (65%). A "goalpost incision" is used in the vaginal wall to facilitate separation of the wall from underlying perivesical fascia, entry into the retropubic space, and exposure of the urethropelvic ligament, cardinal ligament and perivesical fascia. The 4 polypropylene sutures are used to provide an anterior vaginal wall sling which is modified to incorporate perivesical fascia and cardinal ligaments. Central defect repair is achieved by approximation of the cardinal ligaments and midline plication of the perivesical fascia over absorbable mesh. RESULTS: A total of 112 patients were available for followup which ranged from 6 to 42 months (mean 21). Repair of grade 4 cystocele was accompanied by other transvaginal repairs in 94 patients (83%), including rectocele repair in 81, hysterectomy in 22 and enterocele repair in 31. Of the patients 92% had excellent objective and subjective results for anatomical cystocele repair. Of the patients with preoperative stress urinary incontinence 90% had excellent or good subjective results. De novo urge incontinence was seen in 7% of patients. CONCLUSIONS: The 4-defect repair technique relies on anatomical restoration of 4 distinct deficiencies of pelvic support and is highly effective for relief of symptoms of grade 4 cystocele.     

Polycyclic aromatic hydrocarbon-degrading capabilities of Phanerochaete laevis HHB-1625 and its extracellular ligninolytic enzymes

The ability of Phanerochaete laevis HHB-1625 to transform polycyclic aromatic hydrocarbons (PAHs) in liquid culture was studied in relation to its complement of extracellular ligninolytic enzymes. In nitrogen-limited liquid medium, P. laevis produced high levels of manganese peroxidase (MnP). MnP activity was strongly regulated by the amount of Mn2+ in the culture medium, as has been previously shown for several other white rot species. Low levels of laccase were also detected. No lignin peroxidase (LiP) was found in the culture medium, either by spectrophotometric assay or by Western blotting (immunoblotting). Despite the apparent reliance of the strain primarily on MnP, liquid cultures of P. laevis were capable of extensive transformation of anthracene, phenanthrene, benz[a]anthracene, and benzo[a]pyrene. Crude extracellular peroxidases from P. laevis transformed all of the above PAHs, either in MnP-Mn2+ reactions or in MnP-based lipid peroxidation systems. In contrast to previously published studies with Phanerochaete chrysosporium, metabolism of each of the four PAHs yielded predominantly polar products, with no significant accumulation of quinones. Further studies with benz[a]anthracene and its 7,12-dione indicated that only small amounts of quinone products were ever present in P. laevis cultures and that quinone intermediates of PAH metabolism were degraded faster and more extensively by P. laevis than by P. chrysosporium.     

Potato gun ocular injury

PURPOSE: This study aimed to identify a dangerous new weapon capable of causing damage to the ocular and periocular regions. METHODS: The authors report two patients who had penetrating ocular injury in the past year because of homemade recreational potato guns. RESULTS: In one 14-year-old boy, projectiles from the firing of a potato gun resulted in orbital and cranial injuries that were life threatening with widespread fractures, marked disruption of facial structures, a cerebrospinal fluid fistula requiring bifrontal surgical repair, and loss of one eye. In a separate accident with a different potato gun, a 14-year-old boy who was wearing glasses at the time of injury had a sight-threatening perforating corneal laceration. CONCLUSION: Practitioners must be aware of the existence of these new, homemade unregulated devices. Information about the use and construction of these guns is widespread on the Internet, but no injuries resulting from these guns currently are documented in the medical literature.