Patterns of cognitive change over time and relationship to age following successful treatment of Cushing's disease.

Chronically elevated levels of cortisol have been associated with changes in cognitive functioning and brain morphology. Using Cushing's disease as a model to assess the effects of high levels of cortisol on cognitive functioning, 27 patients with Cushing's disease were examined at baseline and three successive follow-up periods up to 18 months after successful surgical treatment. At all follow-up periods, patients were administered cognitive tests as well as measures of plasma and urinary free cortisol. Structural MRIs and a depression measure were taken at baseline and one-year follow-up. Results showed that there is a specific pattern of significant cognitive and morphological improvement following successful treatment. Verbal fluency and recall showed recovery, although brief attention did not. Age of participants was a significant factor as to when recovery of function occurred; younger patients regained and sustained their improvement in cognitive functioning more quickly than older participants. Improvement in verbal recall also was associated with a decrease in cortisol levels as well as an increase in hippocampal formation volume one year after treatment. Overall, these findings suggest that at least some of the deleterious effects of prolonged hypercortisolemia on cognitive functioning are potentially reversible, up to at least 18 months post treatment.     

In vitro degradation of silk fibroin

A significant need exists for long-term degradable biomaterials which can slowly and predictably transfer a load-bearing burden to developing biological tissue. In this study Bombyx mori silk fibroin yarns were incubated in 1mg/ml Protease XIV at 37 degrees C to create an in vitro model system of proteolytic degradation. Samples were harvested at designated time points up to 12 weeks and (1) prepared for scanning electron microscopy (SEM), (2) lyophilized and weighed, (3) mechanical properties determined using a servohydraulic Instron 8511, (4) dissolved and run on a SDS-PAGE gel, and (5) characterized with Fourier transform infrared spectroscopy. Control samples were incubated in phosphate-buffered saline. Fibroin was shown to proteolytically degrade with predictable rates of change in fibroin diameter, failure strength, cycles to failure, and mass. SEM indicated increasing fragmentation of individual fibroin filaments from protease-digested samples with time of exposure to the enzyme; particulate debris was present within 7 days of incubation. Gel electrophoresis indicated a decreasing amount of the silk 25 kDa light chain and a shift in the molecular weight of the heavy chain with increasing incubation time in protease. Results support that silk is a mechanically robust biomaterial with predictable long-term degradation characteristics.     

Neutrophils Injure Bronchial Epithelium after Ozone Exposure

Neutrophil (PMN) influx is an early, prominent finding in the airways of humans after experimental inhalation of ozone (O3), however the potential for PMN to contribute to epithelial injury in this setting is unknown. Bronchial epithelial cells of the human BEAS 2B R1.4 cell line or primary human bronchial epithelial cells underwent DNA labeling by incubation with BrdU. Monolayers were exposed to O3 (0.05 to 1 ppm) or filtered air for 60 min., and subsequently incubated with PMN for 2 h. Epithelial cell cytolysis was significant only in BEAS exposed to O3 and co-cultured with PMN. Apoptosis was maximal in BEAS exposed to O3 + PMN. Primary bronchial epithelial cells were resistant to injury; no cytolysis was detected, and apoptosis was detected only after treatment with 10 mM H₂O₂. Neutrophils may increase damage to the respiratory epithelium after O3 exposure, but primary bronchial epithelial cells are resistant to PMN and ozone induced injury.     

Isolated asymptomatic hematuria in the adult

The term "isolated asymptomatic hematuria," as it relates to both gross and microscopic hematuria, is defined; and the pros and cons of detection techniques used to localize the source of the hematuria are discussed. An algorithm is provided to optimize detection of structural defects and intrinsic renal disease in an effort to avoid subjecting the patient with this difficult-to-diagnose problem to unnecessary invasive tests. Although invasive tests should be performed where deemed necessary in the clinician's aggressive search to detect any structural abnormality, controversial areas of the evaluation of these patients are addressed. To justify various branch points of the algorithm, a discussion of both renal cell carcinoma and primary renal hematuria is proffered.     

Transformation and tumor promoter sensitive phosphoproteins in JB-6 mouse epidermal cells: one is also sensitive to heat stress

JB-6 mouse epidermal cells undergo irreversible transformationwhen exposed to tumor-promoting agents such as 12-O-tetradecanoyl-phorbol-13-acetate(TPA). Phosphoprotein changes related to transformation weresought in four tumor cell lines related to JB-6 cells. Two dimensionalpolyacrylamide gel electrophoresis showed altered abundancesof five phosphoproteins in the tumor cell lines compared withfive untransformed clones. The mol. wt. in Kilodaltons and isoelectricpoints in pH units were: 120/6.0, 80/ 4.5, 55/6.5, 37/5.0 and23–25/4.5. In all four transformants pp80 was markedlydecreased and the pp23–25 doublet increased. In two ofthe four transformants pp120 and pp55 were increased and pp37decreased. Treatment of untransformed clones with TPA affectedonly one of the phosphoproteins altered in the transformants.Treatment of untransformed clones with TPA produced a 2-foldincrease in pp80 after 5 h. pp80 returned to baseline levelsby 24 h and changed little in the continuous presence of TPAfor up to 96 h. The increase in pp80 with short term TPA treatmentoccurred in all of the untransformed clones but none of fourtransformants. Late preneoplastic (P +) JB-6 cells only requiretreatment with a tumor promoter to transform. Early preneoplastic(P – ) JB-6 cells require prior transfection of DNA fromlate preneoplastic JB-6 cells to transform in response to tumorpromoter treatment. Quantitative analysis of pp80 in early preneoplastic,late preneoplastic, and tumor cell lines showed an inverse relationshipbetween the level of pp80 and degree of preneoplastic progressionin these cells. pp80 represents 2% of total cellular phosphoproteinin JB-6 cells, shows microheterogeneity of both mol. wt. andisoelectric point, occurs in the particulate fraction of cellsand is readily solubilized by 1% Triton. pp80 is increased byheat stress and shares other properties with the recently describedmammalian heat stress protein, hsp 80. pp80's decrease in fourout of four tumor cell lines, inverse correlation with stageof preneoplastic progression and responsiveness to TPA in preneoplasticbut not in tumor cell line suggest that pp80 may be closelylinked to biochemical mechanisms underlying transformation inthis cell system.