Complete remission of refractory gestational trophoblastic disease with brain metastases treated with multicycle ifosfamide, carboplatin, and etoposide (ICE) and stem cell rescue

Patients with chemotherapy-refractory gestational trophoblastic disease and brain metastasis are considered to have a very poor prognosis. We present the case of a patient who had failed several chemotherapeutic regimens. Despite transient responses to chemotherapy, she had not achieved a complete remission in 3 years, and had developed systemic disease and recurrent brain metastasis. She was treated with four cycles of high-dose ifosfamide, carboplatin, and etoposide with blood progenitor cell support. She tolerated this regimen well and has obtained a complete remission that is ongoing for 12 months.     

Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha1beta1 and alpha2beta1 integrins

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a cytokine of central importance for the angiogenesis associated with cancers and other pathologies. Because angiogenesis often involves endothelial cell (EC) migration and proliferation within a collagen-rich extracellular matrix, we investigated the possibility that VEGF promotes neovascularization through regulation of collagen receptor expression. VEGF induced a 5- to 7-fold increase in dermal microvascular EC surface protein expression of two collagen receptors-the alpha1beta1 and alpha2beta1 integrins-through induction of mRNAs encoding the alpha1 and alpha2 subunits. In contrast, VEGF did not induce increased expression of the alpha3beta1 integrin, which also has been implicated in collagen binding. Integrin alpha1-blocking and alpha2-blocking antibodies (Ab) each partially inhibited attachment of microvascular EC to collagen I, and alpha1-blocking Ab also inhibited attachment to collagen IV and laminin-1. Induction of alpha1beta1 and alpha2beta1 expression by VEGF promoted cell spreading on collagen I gels which was abolished by a combination of alpha1-blocking and alpha2-blocking Abs. In vivo, a combination of alpha1-blocking and alpha2-blocking Abs markedly inhibited VEGF-driven angiogenesis; average cross-sectional area of individual new blood vessels was reduced 90% and average total new vascular area was reduced 82% without detectable effects on the pre-existing vasculature. These data indicate that induction of alpha1beta1 and alpha2beta1 expression by EC is an important mechanism by which VEGF promotes angiogenesis and that alpha1beta1 and alpha2beta1 antagonists may prove effective in inhibiting VEGF-driven angiogenesis in cancers and other important pathologies.     

An analysis of test bias and differential item functioning due to race on the Mattis Dementia Rating Scale

The Mattis Dementia Rating Scale (MDRS) is a commonly used cognitive measure designed to assess the course of decline in progressive dementias. However, little information is available about possible systematic racial bias on the items presented in this test. We investigated race as a potential source of test bias and differential item functioning in 40 pairs of African American and Caucasian dementia patients (N = 80), matched on age, education, and gender. Principal component analysis revealed similar patterns and magnitudes across component loadings for each racial group, indicating no clear evidence of test bias on account of race. Results of an item analysis of the MDRS revealed differential item functioning across groups on only 4 of 36 items, which may potentially be dropped to produce a modified MDRS that may be less sensitive to cultural factors. Given the absence of test bias because of race, the observed racial differences on the total MDRS score are most likely associated with group differences in dementia severity. We conclude that the MDRS shows no appreciable evidence of test bias and minimal differential item functioning (item bias) because of race, suggesting that the MDRS may be used in both African American and Caucasian dementia patients to assess dementia severity.     

Aminopeptidase N purified from gypsy moth brush border membrane vesicles is a specific receptor for Bacillus thuringiensis CryIAc toxin

We have evaluated the binding of Bacillus thuringiensis Cry toxins to aminopeptidase N (APN) purified from Lymantria dispar (gypsy moth) brush border membrane vesicle (BBMV). CryIAc toxin bound strongly to APN, while either the structurally related CryIAa and CryIAb toxins or CryIC, CryIIA, and CryIIIA toxins showed weak binding to APN. An in vitro competition binding study demonstrated that the binding of CryIAc to L. dispar BBMV was inhibited by APN. Inhibition of short circuit current for CryIAc, measured by voltage clamping of whole L. dispar midgut, was substantially reduced by addition of phosphatidylinositol-specific phospholipase C, which is known to release APN from the midgut membrane. In contrast, addition of phosphatidylinositol-specific phospholipase C had only a marginal effect on the inhibition of short circuit current for CryIAa. These data suggest that APN is the major functional receptor for CryIAc in L. dispar BBMV. A ligand blotting experiment demonstrated that CryIAc recognized a 120-kDa peptide (APN), while CryIAa and CryIAb recognized a 210-kDa molecule in L. dispar BBMV. In contrast, CryIAa and CryIAb bound to both the 120- and 210-kDa molecules in Manduca sexta BBMV, while CryIAc recognized only the 120-kDa peptide. The 120-kDa peptide (APN) in L. dispar BBMV reacted with soybean agglutinin, indicating that N-acetylgalactosamine is a component of this glycoprotein.     

Physiologic and hygienic characteristics of work conditions of miners in the Far North

Workers engaged into subsurface extraction of sand containing gold were proved to work in difficult conditions characterized by stable negative temperatures, high concentrations of dust, elevated levels of noise and vibration. The drill operators demonstrated extremely unfavorable changes of physiologic processes within a shift. Those changes were compromised cardiovascular regulation, early occurrence and intensive progress of fatigue. The authors provide recommendations to normalize the work conditions and to create rational scheme of work and rest for the occupations.