Initiation of skin basement membrane formation at the epidermo-dermal interface involves assembly of laminins through binding to cell membrane receptors

To study the mechanism of basement membrane formation, we determined by immunochemistry temporal and spatial expression of laminin-5 (Ln-5), laminin-1 (Ln-1) and their integrin receptors during early skin morphogenesis. A 3-dimensional skin culture was used that allows the study of the sequential molecular events of basement membrane formation at the epidermodermal interface. During early anchorage of keratinocytes to the extracellular matrix there is expression of Ln-5, BP-230 antigen and &#945;3, &#946;1 integrin subunits. During epidermal stratification and prior to the formation of the lamina densa there is assembly of Ln-5, Ln-1, collagen IV and nidogen accompanied by keratinocyte basal clustering of &#945;2, &#945;3, &#945;6, &#946;1, and &#946;4 integrin subunits. The assembly pattern of Ln-1 and Ln-5 can be disturbed with functional antibodies against the &#946;1 (AIIB2) and &#945;6 (GoH3) integrin subunits. Ln-1 assembly can also be disturbed with antibodies against its E8 domain and by competitive inhibition with a synthetic peptide (AG-73) derived from its G-4 domain. Quantitative RT-PCR showed that the dermis contributes about 80% of the laminin &#947;1 chain mRNA while 20% is produced by the epidermis which emphasizes its dual tissue origin and the major contribution of the mesenchyma in laminin production. The laminin &#947;2 chain mRNA, present in Ln-5, was mostly of epidermal origin. This study presents evidence that during the initiation of basement membrane formation, laminins bind to keratinocyte plasma membrane receptors and thus may serve as nucleation sites for further polymerization of these compounds by a self-assembly process.</p

Positive Therapeutic Response to Bevacizumab Plus Paclitaxel in a Patient with Advanced, Life-Threatening Breast Cancer and Carcinomatous Lymphangitis:a Subsequent Treatment Change to Hormone Therapy

We present a case of advanced, life-threatening breast cancer with carcinomatous lymphangitis treatedwith bevacizumab plus paclitaxel. A positive therapeutic response was achieved and the treatment was subsequentlychanged to hormone therapy.The patient was a 53-year-old postmenopausal woman with a non-contributory medical history. She presentedto a nearby hospital with chief complaints of continued exertional dyspnea and coughing since March2012. Physical findings included a palpable mass in the left breast, and the patient was referred and presentedto our hospital in May. Examinations at our hospital revealed left-sided breast cancer (estrogen receptorpositive, progesterone receptor positive, and no amplification of the human epidermal growth factorreceptor 2 by FISH). The patient had bone metastasis and carcinomatous lymphangitis (cT2N3cM1-stageIV). The condition was life threatening, and administration of bevacizumab plus weekly paclitaxel was initiatedwith the expectation of a high response rate. Coughing and dyspnea resolved two weeks later. CTscans were taken in August after the completion of 3 cycles and showed improvement in carcinomatouslymphangitis. No major side effects were observed due to bevacizumab plus weekly paclitaxel. When theCT scans were taken in December after the completion of 6 cycles, the primary lesion and lymph node metastaseswere reduced in size. In the lung field, there was no thickening of the interlobular septa or subpleuralinterstitium, and the findings of carcinomatous lymphangitis were improved. Thus, bevacizumab plus paclitaxelwere discontinued and the treatment was changed to oral letrozole (2.5 mg/day). The patient hasbeen followed up with no recurrence as of March 2013

A Case of Inflammatory Pseudotumor of the Breast after Augmentation Mammoplasty

Inflammatory pseudotumor is a benign reactive lesion which forms due to diverse tissue responses of inflammatory cells and mesenchymal cells. It can occur in various organs of the body but rarely in the breast. We report a case of inflammatory pseudotumor of the breast after augmentation mammoplasty. The patient was a 78-year-old woman who noticed a mass in her right breast in July 2012. She had a history of augmentation mammoplasty at age 24 years. She was referred to our hospital for thorough examination. A 3-cm immovable induration was palpated in the upper lesion of the right breast. Ultrasound examination revealed a hypoechoic mass at the same site. The mass was 2.9×1.7 cm with irregular, ill-defined borders. Mammography revealed some areas of elevated density with coarse, lucent-centered calcifications in bilateral breasts but no clear findings of malignancy. Core needle biopsy of this site revealed marked fibrous hyperplasia and proliferation of fibroblast-like spindle cells. Infiltration of neutrophils and plasma cells was observed in the stroma. There were spindle cells with no atypia and scarce mitotic figures. Thus, the patient was diagnosed with inflammatory pseudotumor. The patient received only follow-up observation without surgical resection as per the patient\u27s wishes. There has not been any change as of May 2013

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

Partitioning of Lead and Lead Compounds under Gasification-Like Conditions

An investigation of the chemical form, the concentration, and distribution of lead species between the gas and condensed phase was carried out under gasification-like conditions. The influence of hydrogen sulfide, hydrogen chloride, and steam on the speciation of lead was studied. The gaseous species were determined online by molecular-beam-mass-spectrometry. The condensates were analyzed by standard methods. The dominant chemical forms were metallic Pb, PbCl2, and PbS. The experimental data were compared with the results of thermodynamic Scheil–Gulliver cooling calculations. Further, the experimental data was used as an input for a pseudoequilibrium model aiming at the determination of kinetic information on the underlying transformations