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Background and Purpose: Data on health‐related quality of life (HRQoL) and mood in cerebral amyloid angiopathy (CAA), a disease characterized by stroke and cognitive decline, are limited. We aimed to investigate the impacted domains of life, value‐based HRQoL and the prevalence of depression and anxiety in patients with CAA. Methods: We conducted a cross‐sectional study of patients with sporadic (s)CAA, lobar dominant mixed CAA and hypertensive arteriopathy (mixed CAA‐HTA), or Dutch‐type hereditary (D‐)CAA, from prospective outpatient clinic cohorts. Participants completed four questionnaires: the EuroQoL 5 dimensions 5‐level questionnaire (EQ‐5D‐5L; EQ‐VAS for visual analogue scale; EQ‐Index for index rating), the Short‐Form 36 questionnaire (SF‐36), the Center for Epidemiologic Studies—Depression scale (CES‐D), and the Hospital Anxiety and Depression Scale (HADS; ‐D for depression and ‐A for anxiety subscales). The EQ‐5D‐5L assesses the domains mobility, self‐care, usual activities, pain/discomfort and anxiety/depression. The SF‐36 domains are physical functioning, social functioning, physical role limitations, emotional role limitations, mental health, vitality, bodily pain, and general health perceptions. We compared age‐ and sex‐ adjusted HRQoL (SF‐36 domain scores; EQ‐VAS; EQ‐Index) to the Dutch normative population, and estimated the prevalences of current depression (either: history of depression or current use of antidepressants, with high score on CES‐D [≥16] and/or HADS‐D [≥8]; or high score on both depression questionnaires) and anxiety (HADS‐A ≥ 8). Results: We included 179 patients: 77 with sCAA (mean age: 72 years, women: 36%), 31 with mixed CAA‐HTA (68 years, women: 29%), and 71 with D‐CAA (56 years, women: 52%, symptomatic: 35 [49%]). The SF‐36 profiles of all patient groups were similar, negatively differing from the norm in emotional role functioning, social functioning and vitality. The EQ‐VAS score of patients (mean [SD] sCAA: 76 [16], D‐CAA: 77 [15]) was similar to the norm, as was the EQ‐Index score. Fifteen patients with sCAA (23%; 95% confidence interval [CI] 13%–33%), seven with mixed CAA‐HTA (27%; 95% CI 10%–44%) and eight with D‐CAA (14%; 95% CI 5%–22%) were noted as having depression. The prevalences of anxiety and depression were equivalent. Conclusions: We found that CAA influenced emotional role functioning and aspects linked to social engagement consistently across its subtypes. One quarter of patients exhibited depressive or anxiety symptoms. Recognizing these impacted domains could enhance overall well‐being. [ABSTRACT FROM AUTHOR]

Research was conducted to characterize the regulatory components of the translocon that affect translocational pausing in the endoplasmic reticulum. Constructs were truncated at Stu1 before transcription to produce mRNA utilized in translocation intermediates while reconstitutions from crude detergent extracts were determined by modifying previous study procedures. Results identified a prerequisite for the membrane glycoprotein translocating chain-associated membrane protein to regulate the translocational pausing of a secretory protein.

Abstract Introduction Although systemic T-cell responses against tumor antigens and tumor infiltration by T cells have been investigated in colorectal cancer (CRC), the initiation of spontaneous immune responses in situ is not well understood. Macrophages and dendritic cells (DC) play an important role as a link between innate and adaptive immune response. The aim of the present study was to analyze macrophage and DC infiltration in CRC and to investigate whether there is a correlation to systemic T-cell response, regulatory T cell (Treg) infiltration, and survival. Methods Immunohistological staining was performed with nine markers for macrophages and DC (CD68, CD163, S100, CD11c, CD208, CD209, CD123, CD1a, Langerin) in 40 colorectal cancer samples from patients, in whom the state of systemic T-cell responses against tumor-associated antigens (TAA) and Treg infiltration had previously been determined. Results All specimens contained cells positive for CD68, CD163, S100 and CD1a in epithelial tumor tissue and tumor stroma. Only a very few (less than median 3/HPF) CD123+, CD1a+, CD11c+, CD 208+, CD209+, or Langerin+ cells were detected in the specimens. Overall, we found a trend towards increased infiltration by S100-positive DC and a significantly increased number of stromal S100-positive DC in patients without T-cell response. There was an increase of stromal S100 DC and CD163 macrophages in limited disease (S100: 11.1/HPF vs. 7.3/HPF, p = 0.046; CD163: 11.0/HPF vs. 8.1/HPF, p = 0.06). We found a significant, positive correlation between S100-positive DC and FOXP3-positive Tregs. Survival in patients with high DC infiltration was significantly better than that in those with low DC infiltration (p < 0.05). Furthermore, we found a trend towards better survival for increased infiltration with CD163-positive macrophages (p = 0.07). Conclusion The present in situ study adds new data to the discussion on the interaction between the innate and adoptive immune system. Our data strongly support the hypothesis that tumor-infiltrating DC are a key factor at the interface between innate and adaptive immune response in malignant disease. Tumor infiltrating S100-positive DC show an inverse relationship with the systemic antigen-specific T-cell response, a positive correlation with regulatory T cells, and a positive association with survival in CRC. These data put tumor-infiltrating DC at the center of the relevant immune response in CRC.

Introduction: Although systemic T-cell responses against tumor antigens and tumor infiltration by T cells have been investigated in colorectal cancer (CRC), the initiation of spontaneous immune responses in situ is not well understood. Macrophages and dendritic cells (DC) play an important role as a link between innate and adaptive immune response. The aim of the present study was to analyze macrophage and DC infiltration in CRC and to investigate whether there is a correlation to systemic T-cell response, regulatory T cell (Treg) infiltration, and survival. Methods: Immunohistological staining was performed with nine markers for macrophages and DC (CD68, CD163, S100, CD11c, CD208, CD209, CD123, CD1a, Langerin) in 40 colorectal cancer samples from patients, in whom the state of systemic T-cell responses against tumor-associated antigens (TAA) and Treg infiltration had previously been determined. Results: All specimens contained cells positive for CD68, CD163, S100 and CD1a in epithelial tumor tissue and tumor stroma. Only a very few (less than median 3/HPF) CD123+, CD1a+, CD11c+, CD 208+, CD209+, or Langerin+ cells were detected in the specimens. Overall, we found a trend towards increased infiltration by S100-positive DC and a significantly increased number of stromal S100-positive DC in patients without T-cell response. There was an increase of stromal S100 DC and CD163 macrophages in limited disease (S100: 11.1/HPF vs. 7.3/HPF, p = 0.046; CD163: 11.0/HPF vs. 8.1/HPF, p = 0.06). We found a significant, positive correlation between S100-positive DC and FOXP3-positive Tregs. Survival in patients with high DC infiltration was significantly better than that in those with low DC infiltration (p < 0.05). Furthermore, we found a trend towards better survival for increased infiltration with CD163-positive macrophages (p = 0.07). Conclusion: The present in situ study adds new data to the discussion on the interaction between the innate and adoptive immune system. Our data strongly support the hypothesis that tumor-infiltrating DC are a key factor at the interface between innate and adaptive immune response in malignant disease. Tumor infiltrating S100-positive DC show an inverse relationship with the systemic antigen-specific T-cell response, a positive correlation with regulatory T cells, and a positive association with survival in CRC. These data put tumor-infiltrating DC at the center of the relevant immune response in CRC. [ABSTRACT FROM AUTHOR]

The component proteins of the iron-only nitrogenase were isolated from Rhodobacter capsulatus (ΔniƒHDK, ΔmodABCD strain) and purified in a one-day procedure that included only one column-chromatography step (DEAE-Sephacel). This procedure yielded component 1 (FeFe protein, Rc1Fe), which was more than 95% pure, and an approximately 80% pure component 2 (Fe protein, Rc2Fe). The highest specific activities, which were achieved at an Rc2Fe/Rc1Fe molar ratio of 40:1, were 260 (C2H4 from C2H2), 350 (NH3 formation), and 2400 (H2 evolution) nmol product formed · min-1 · mg protein-1 · The purified FeFe protein contained 26 ± 4 Fe atoms; it did not contain Mo, V, or any other heterometal atom. The most significant catalytic property of the iron-only nitrogenase is its high H2-producing activity, which is much less inhibited by competitive substrates than the activity of the conventional molybdenum nitrogenase. Under optimal conditions for N2 reduction, the activity ratios (mol N2 reduced/mol H2 produced) obtained were 1:1 (molybdenum nitrogenase) and 1:7.5 (iron nitrogenase). The Rc1Fe protein has only a very low affinity for C2H2. The Km value determined (12.5 kPa), was about ninefold higher than the Km for Rc1Mo (1.4 kPa). The proportion of ethane produced from acetylene (catalyzed by the iron nitrogenase), was strictly pH dependent. It corresponded to 5.5 % of the amount of ethylene at pH 6.5 and was almost zero at pH values greater than 8.5. In complementation experiments, component 1 proteins coupled very, poorly with the ‘wrong’ component 2. Rc1Fe if complemented with Rc2Mo, showed only 10–15% of the maximally possible activity. Cross-reaction experiments with isolated polyclonal antibodies revealed that Rc1Fe and Rc1Mo are immunologically not related. The most active Rc1Fe samples appeared to be EPR-silent in the Na2S2O4-reduced state. However, on partial oxidation with K3[Fe(CN)6] or thionine several signals occurred. The most significant signal appears to be the one at g = 2.27 and 2.06 which deviates from all signals so far described for P clusters. It is a transient signal that appears and disappears reversibly in a redox potential region between -100 mV and +150 mV. Another novel EPR signal (g = 1.96, 1.92, 1.77) occurred on further reduction of Rc1Fe by using turnover conditions in the presence of a substrate (N2, C2H2, H+). [ABSTRACT FROM AUTHOR]

Background and Purpose: Although evidence accumulates that the cerebellum is involved in cerebral amyloid angiopathy (CAA), cerebellar superficial siderosis is not considered to be a disease marker. The objective of this study is to investigate cerebellar superficial siderosis frequency and its relation to hemorrhagic magnetic resonance imaging markers in patients with sporadic and Dutch-type hereditary CAA and patients with deep perforating arteriopathy-related intracerebral hemorrhage., Methods: We recruited patients from 3 prospective 3 Tesla magnetic resonance imaging studies and scored siderosis and hemorrhages. Cerebellar siderosis was identified as hypointense linear signal loss (black) on susceptibility-weighted or T2*-weighted magnetic resonance imaging which follows at least one folia of the cerebellar cortex (including the vermis)., Results: We included 50 subjects with Dutch-type hereditary CAA, (mean age 50 years), 45 with sporadic CAA (mean age 72 years), and 43 patients with deep perforating arteriopathy-related intracerebral hemorrhage (mean age 54 years). Cerebellar superficial siderosis was present in 5 out of 50 (10% [95% CI, 2-18]) patients with Dutch-type hereditary CAA, 4/45 (9% [95% CI, 1-17]) patients with sporadic CAA, and 0 out of 43 (0% [95% CI, 0-8]) patients with deep perforating arteriopathy-related intracerebral hemorrhage. Patients with cerebellar superficial siderosis had more supratentorial lobar (median number 9 versus 2, relative risk, 2.9 [95% CI, 2.5-3.4]) and superficial cerebellar macrobleeds (median number 2 versus 0, relative risk, 20.3 [95% CI, 8.6-47.6]) compared with patients without the marker. The frequency of cortical superficial siderosis and superficial cerebellar microbleeds was comparable., Conclusions: We conclude that cerebellar superficial siderosis might be a novel marker for CAA.

Objectives: The discussion about the effectivity of psychodynamic psychotherapy is being renewed by recent meta-analyses. Although some well-designed studies have been presented, there is still a dearth of research in this field., Methods: In a controlled prospective field study we investigated the outcome of outpatient psychodynamic psychotherapy in a pre-post design. This evaluation includes data from the symptom inventories VDS90, VDS30, and HEALTH for 90 patients with different mental disorders before therapy and after the regular end of therapy, compared to a waiting list control group., Results: We found a significant improvement in symptoms, dysfunctional personality features, and quality of life. Rates of statistically and clinically significant improvement were markedly higher after therapy than in the waiting list condition., Conclusions: Psychodynamic psychotherapy shows an effect on symptoms, dysfunctional personality features, and quality of life.