We investigated a large family with levodopa-responsive, Lewy body parkinsonism in which the disease segregates as an apparent autosomal dominant trait. After performing a genome screen, we identified a chromosome 4p haplotype that segregates with the disease. However, this haplotype also occurs in individuals in the pedigree who do not have clinical Lewy body parkinsonism but rather suffer from postural tremor, consistent with essential tremor. These data demonstrate a new locus for Lewy body parkinsonism and suggest that in some circumstances postural tremor can be an alternative phenotype of the samepathogenic mutation as Lewy body parkinsonism.

Institutionalized patients with HD are more motorically, psychiatrically, and behaviorally impaired than their counterparts living at home. However, motor variables alone predicted institutionalization. Treatment strategies that delay the progression of motor dysfunction in HD may postpone the need for institutionalization.

The purpose of this study to compare the long-term clinical outcome of early versus delayed rasagiline treatment in early Parkinson's disease (PD). Subjects (N = 404) were randomly assigned to initial treatment with rasagiline (early-start group) or placebo for 6 months followed by rasagiline (delayed-start group) in the TEMPO study. Subjects who chose to participate in an open-label extension (N = 306) continued to receive rasagiline as well as other PD medications as needed. Average (+/-SD) duration in the study was 3.6 +/- 2.1 years; 177 subjects received rasagiline for > or =5.0 years. Over the entire 6.5-year follow-up period, the adjusted mean difference in change from baseline in total UPDRS scores was 2.5 units (SE 1.1; P = 0.021) or 16% (SE 5.7; P = 0.006) in favor of the early-start versus delayed-start rasagiline group. Although the interaction between treatment and time was significant, values for the early-start group were better than the delayed-start group across all time points. Significantly less worsening (percent change) in total UPDRS scores was observed in the early-start group at the time points 0.5, 1.5, 2.0, 3.0, 4.5, 5.0, and 5.5 years (P < 0.05). Compared to delayed start, early initiation of rasagiline provided long-term clinical benefit, even in the face of treatment with other dopaminergic agents. This might reflect enduring benefits due to neuroprotection or effects on compensatory mechanisms in early PD.

Angiogenesis is one of the hallmarks of cancer. We hypothesized that intra-tumoral angiogenesis correlates with inflammation and metastasis in breast cancer patients. To test this hypothesis, we generated an angiogenesis pathway score using gene set variation analysis and analyzed the tumor transcriptome of 3999 breast cancer patients from The Cancer Genome Atlas Breast Cancer (TCGA-BRCA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), GSE20194, GSE25066, GSE32646, and GSE2034 cohorts. We found that the score correlated with expression of various angiogenesis-, vascular stability-, and sphingosine-1-phosphate (S1P)-related genes. Surprisingly, the angiogenesis score was not associated with breast cancer subtype, Nottingham pathological grade, clinical stage, response to neoadjuvant chemotherapy, or patient survival. However, a high score was associated with a low fraction of both favorable and unfavorable immune cell infiltrations except for dendritic cell and M2 macrophage, and with Leukocyte Fraction, Tumor Infiltrating Lymphocyte Regional Fraction and Lymphocyte Infiltration Signature scores. High-score tumors had significant enrichment for unfavorable inflammation-related gene sets (interleukin (IL)6, and tumor necrosis factor (TNF)α- and TGFβ-signaling), as well as metastasis-related gene sets (epithelial mesenchymal transition, and Hedgehog-, Notch-, and WNT-signaling). High score was significantly associated with metastatic recurrence particularly to brain and bone. In conclusion, using the angiogenesis pathway score, we found that intra-tumoral angiogenesis is associated with immune reaction, inflammation and metastasis-related pathways, and metastatic recurrence in breast cancer.