Benign breast changes and the risk for subsequent breast cancer: an update of the 1985 consensus statement. Cancer Committee of the College of American Pathologists

The Cancer Committee of the College of American Pathologists has prepared an update of the consensus statement on premalignant breast lesions and breast cancer risk that was originally published in the Archives of Pathology & Laboratory Medicine in 1986. The objective of this publication is to better define the relative breast cancer risk associated with specific histologic abnormalities by incorporating data derived from recent case-control studies. Explanatory notes are used to document and explain specific risk classifications. In addition to refining the degree of risk associated with individual lesions, such as fibroadenoma and atypical hyperplasia, this update includes a discussion of age-specific breast cancer risk and provides examples that can be used when counseling patients.     

On Linear Copositive Lyapunov Functions and the Stability of Switched Positive Linear Systems

We consider the problem of common linear copositive Lyapunov function existence for positive switched linear systems. In particular, we present a necessary and sufficient condition for the existence of such a function for switched systems with two constituent linear time-invariant systems. Several applications of this result are also given.     

Hematopoietic precursor cell exhaustion is a cause of proliferative defect in primitive hematopoietic stem cells (PHSC) after chemotherapy

The aim of the present study is to determine the possibility of measuring the bone mineral density (BMD) around implants by dual energy X-ray absorptiometry (DEXA). Therefore, the trabecular BMD was measured close to 127-600 microns and at a distance from various uncoated and Ca-P-coated implants inserted into the femoral condyle of goals. The implants were left in situ for 12 weeks. In addition, the bone-implant interface was evaluated histologically. For comparative reasons the BMD of non-implanted lateral and medial femoral condyles was also measured. The reproducibility of the measurements, expressed as a coefficient of variation, was found to be 0.44%. Moreover, the regions closest to the implants exhibited a higher BMD than all other regions, and the regions located in the medial condyle showed a higher BMD than the lateral condylar regions. Although the histological sections of the implants in the medial condyle demonstrated more bone contact with the coated than with the uncoated implants, a higher density was measured around the uncoated implants. The results regarding the non-implanted condyles indicated a higher density in the medial than in the lateral condyle. In view of these results, we conclude that BMD around dental implants depends on the location of the implant and that DEXA appears to be an excellent tool for analysing bone-implant reactions.     

Molecular recognition of diketide substrates by a beta-ketoacyl-acyl carrier protein synthase domain within a bimodular polyketide synthase

BACKGROUND: Modular polyketide synthases (PKSs) are large multifunctional proteins that catalyze the biosynthesis of structurally complex bioactive products. The modular organization of PKSs has allowed the application of a combinatorial approach to the synthesis of novel polyketides via the manipulation of these biocatalysts at the genetic level. The inherent specificity of PKSs for their natural substrates, however, may place limits on the spectrum of molecular diversity that can be achieved in polyketide products. With the aim of further understanding PKS specificity, as a route to exploiting PKSs in combinatorial synthesis, we chose to examine the substrate specificity of a single intact domain within a bimodular PKS to investigate its capacity to utilize unnatural substrates. RESULTS: We used a blocked mutant of a bimodular PKS in which formation of the triketide product could occur only via uptake and processing of a synthetic diketide intermediate. By introducing systematic changes in the native diketide structure, by means of the synthesis of unnatural diketide analogs, we have shown that the ketosynthase domain of module 2 (KS2 domain) in 6-deoxyerythronolide B synthase (DEBS) tolerates a broad range of variations in substrate structure, but it strongly discriminates against some others. CONCLUSIONS: Defining the boundaries of substrate recognition within PKS domains is crucial to the rationally engineered biosynthesis of novel polyketide products, many of which could be prepared only with great difficulty, if at all, by direct chemical synthesis or semi-synthesis. Our results suggest that the KS2 domain of DEBS1 has a relatively relaxed specificity that can be exploited for the design and synthesis of medicinally important polyketide products.     

Approach to the patient with pulmonary disease

The approach to the HIV-infected patient with pulmonary disease is summarized by the algorithms in Figures 3 and 4. These are not intended to be followed in a rigid step-wise fashion. Rather, the practitioner's knowledge of the patient with his or her accompanying medical risks influences the path taken, including the depth and the speed of the evaluation. For example, the patient with cough who is afebrile and breathing at 18 breaths a minute, with a normal chest radiograph and a CD4 count of 350 cells/mm3, is reasonably treated with a macrolide or cephalosporin for bacterial bronchitis and clinical follow-up while awaiting cultures (see Fig. 4). A febrile patient with a cough productive of thin mucus, but known to have a CD4 count of 60 cells/mm3 should be started on anti-PCP therapy while being evaluated for PCP with an induced sputum and if nondiagnostic, a bronchoscope despite a normal chest radiograph. Screening can be as simple as placing an oximeter on the patient's finger in the clinic. If the oxygen saturation of a patient with a normal chest radiograph is low, then the patient should be hospitalized and begun on treatment for PCP while diagnostic evaluation is initiated. If the oxygen saturation is normal, the patient can be exercised to elicit desaturation. If there is no desaturation, PCP is unlikely. If the results are equivocal (i.e., a decrease in saturation, but less than 3%), rest and exercise arterial blood gases can be performed, along with a Dlco-Gallium scanning can be done in patients known to have abnormal Dlco or those who cannot exercise. Patients with focal infiltrates who have acute onset of symptoms (see Fig. 4) commonly have bacterial infections, but the possibility of PCP or TB should not be dismissed. Induced sputum should be examined if TB or PCP is suspected. Patients who are severely ill might go quickly to bronchoscopy without awaiting improvement on empiric therapy. The patient with diffuse infiltrates (see Fig. 4) needs no screening because the presence of disease is apparent from the radiograph. The diagnostic part quickly leads to bronchoscopy for these patients and the initiation of therapy for PCP when suspected. In patients with known pulmonary KS, gallium scanning can be helpful to rule out acute infection, but bronchoscopy is warranted if the patient is severely ill, or at high risk for PCP. This approach should avoid unnecessary procedures in patients with simple bacterial infections, without missing opportunistic infections and tumors.     

Biophysical Model of Larval Yellow Perch Advection and Settlement in Lake Michigan

Potential for large-scale physical transport processes to affect recruitment of Lake Michigan yellow perch (Perca flavescens) was studied by examining the variation in larval distribution, growth rate, and settlement during June–August 1998–2003 using a 3D particle transport model linked with an individual-based bioenergetics growth model. In all years, virtual larvae were released nearshore in southwestern Lake Michigan, a known and important spawning region for yellow perch. For any given year, the same circulation pattern and water temperature either promoted or reduced yellow perch settlement depending on the consumption rates and settlement size chosen in the growth model. Increased consumption increased the number of settled larvae and expanded the total area where larvae settled, whereas increased settlement size reduced the number of settled larvae and reduced the overall settlement area. Interannual variability in circulation patterns and water temperature also resulted in contrasting larval settlement rates, settlement locations, and size of settlement areas between years. Model predictions were most consistent with field observations of age-0 yellow perch from Illinois and Michigan waters when settlement was assumed to occur at 50 mm. Moreover, our model suggests that larvae originating from southwestern Lake Michigan can recruit anywhere within the southern basin and even in the northern basin. Future model improvement will require information on the relative contribution of various sectors to the larval pool, their distribution with reference to the hydrodynamic landscape, the feeding and growth of yellow perch during their pelagic phase, and the size at transition to demersal stage.     

Correlation study between standard plate count and flow cytometry for determination of raw milk total bacterial count

Milk samples were collected in the dry season ( n =  155) and in the rainy season ( n =  68) to establish a correlation between electronic flow cytometry and standard plate count for the determination of total bacterial count of raw milk. Results were expressed in individual bacterial count (ibc) and colony forming unit (cfu) for electronic flow cytometry (Bactocount) and standard plate count, respectively. The accuracy of Bactocount, denoted by the residual standard deviation ( s ( y,x )), was 0.309 log cfu/mL. The predictive interval of estimated values was broad and it is suggested that total bacterial count should be expressed in ibc without transformation to cfu.     

Gene expression in brain during cuprizone-induced demyelination and remyelination

When C57BL/6J mice, 8 weeks of age, received 0.2% Cuprizone in their diet, extensive demyelination in corpus callosum was detectable after 3 weeks, and there was massive demyelination by 4 weeks. As expected, the accumulation of phagocytically active microglia/macrophages correlated closely with demyelination. When Cuprizone was removed from the diet, remyelination was soon initiated; after 6 weeks of recovery, myelin levels were near-normal and phagocytic cells were no longer prominent. Steady-state levels of mRNA for myelin-associated glycoprotein, myelin basic protein, and ceramide galactosyltransferase were already profoundly depressed after 1 week of Cuprizone exposure and were only 10-20% of control values after 2 weeks. Unexpectedly, upregulation of mRNA for these myelin genes did not correlate with initiation of remyelination but rather with accumulation of microglia/macrophages. After 6 weeks of exposure to Cuprizone, mRNA levels were at control levels or higher-in the face of massive demyelination. This suggests that in addition to effecting myelin removal, microglia/macrophages may simultaneously push surviving oligodendroglia or their progenitors toward myelination.