Human cyclovergence as a function of stimulus frequency and amplitude

Summary By the use of scleral search coils a continuous record of human cyclovergence was obtained while two identical 80° textured patterns, presented dichoptically, oscillated in the frontal plane in counterphase through 1, 3 and 6° of cyclorotation at frequencies between 0.05 and 2 Hz. The amplitude and gain of the response decreased exponentially with increasing stimulus frequency. As stimulus amplitude increased, response amplitude also increased but gain was highest for low-amplitude cyclorotations. For an amplitude of 1° and a frequency of 0.05 Hz the gain reached 0.87 for two subjects. The phase lag increased from a few degrees at a frequency of 0.05 Hz to over 100° at a frequency of 2 Hz. These results suggest that cyclovergence is designed to correct for small, slow drifts in the stereoscopic alignment of the images in the two eyes. Although the disparity in the textured display was not interpreted as slant, it provided a strong stimulus for cyclovergence. The cyclovergence caused a transfer of cyclodisparity into a superimposed vertical line, which was then perceived as slanting in depth.     

TEMPS-a scale in 'mixed' and 'pure' manic episodes: new data and methodological considerations on the relevance of joint anxious-depressive temperament traits

BACKGROUND: Temperament is an important factor in affective illness. There is some indication that mixed episodes result from an admixture of inverse temperamental factors (e.g. depressive and/or anxious) to a manic syndrome. To test this hypothesis, which has been first formulated by Akiskal [Clin. Neuropharmacol. 15 (Suppl. 1A) (1992) 632-633], we compared the temperament of non-acute bipolar affective patients with and without the history of a previous mixed episode. METHODS: Patients who had been hospitalized for a bipolar disorder were re-assessed at least 6 months after their last in-patient treatment. Those who met the criteria for a partially remitted or full affective or psychotic episode at re-assessment were excluded from the study. Data concerning illness history, current psychopathology (SCID-I interview), depression (BDI), mania (Self-Report Manic Inventory) and temperament (TEMPS-A scale) were obtained. Patients with and without a history of previous mixed episodes were compared. RESULTS: Of 49 eligible former patients, 22 subjects with and 23 subjects without a former mixed episode in bipolar affective disorder fulfilled the inclusion criteria. Subjects suffering from bipolar affective disorder exhibited significantly more depressive and anxious and less hyperthymic temperament, if they had experienced a mixed episode previously. Concerning cyclothymic and irritable temperament, bipolar affective patients with a former mixed episode presented non-significantly higher scores. Patients with a former mixed episode presented with higher depression scores than patients without such a history. No group differences were found concerning current mania scores. LIMITATIONS: (1). This is a preliminary report from an ongoing study. (2). Temperament had not been assessed premorbidly. (3). Although group comparisons revealed significant differences, these did not seem great enough to fully explain the emergence of a mixed episode. CONCLUSION: Our findings support the study's hypothesis that mixed episodes occur more often in subjects with an inverse temperament (e.g. depressive and anxious), although it cannot be ruled out that subsyndromal features of the bipolar illness had an effect on temperament assessment.     

Characterization of monocyte-derived dendritic cells in recent-onset diabetes mellitus type 1

Dendritic cells (DC) may play an important role in the immunopathogenesis of type 1 diabetes mellitus (DM-1). In this study, we have analyzed phenotypical changes during cytokine-driven maturation from CD14+ monocytes to mature DC and DC-dependent T-cell stimulation in recent-onset pediatric DM-1 patients and healthy controls. DC maturation was monitored by flow cytometric analyses for the expression of surface markers (HLA-DR, CD1a, CD40, CD80, CD86, CD83, CD14, CD32, mannose-receptor, and CD11c). Flow cytometric analysis of isolated peripheral blood monocytes did not reveal apparent differences between patients and controls. During DC maturation no obvious differences in the expression patterns of surface markers over time or evidence for maturation impairments in DM-1 patients could be appreciated. Solely, a marginal, but significant, transient down-regulation of CD1a on Day 3 (mean MDFI 3.82 vs 7.25; P = 0.021), which was accompanied by an increase of IL-6, could be observed. The comparison of mature DCs (Day 10) between patients and controls indicated no significant differences, except for CD83 (mean MDFI 1.7 vs 1.5; P = 0.042) and CD80 (mean MDFI 15.92 vs 12.73; P = 0.042). Moreover, no difference in T-cell stimulatory capacity was seen. In conclusion, our analysis of a cohort of recent-onset DM-1 patients and controls does not support a role for disease-related alterations in cytokine-driven maturation of monocyte-derived DC.     

Mycobacterium tuberculosis subverts the differentiation of human monocytes into dendritic cells

Intracellular pathogens have developed strategies for evading elimination by the defenses of the host immune system. Here we describe an escape mechanism utilized by Mycobacterium tuberculosis that involves the interference with the generation of fully competent DC from monocytes. We show that monocytes infected with live M. tuberculosis differentiated into mature, CD83+ and CCR7+ DC (Mt-MoDC), but were characterized by a selective failure in the expression of the family of CD1 molecules. These cells also showed levels of MHC class II and CD80 (B7.1) that were reduced in comparison with LPS-matured DC. In addition, Mt-MoDC produced TNF-alpha and IL-10, but were unable to secrete IL-12. The generation of Mt-MoDC required the infection of monocytes with live M. tuberculosis, since infection with heat-killed bacteria partially abrogated the effects on monocyte differentiation. Interestingly, Mt-MoDC revealed an impaired antigen-presentation function as assessed by the reduced capability to induce proliferation of cord blood T lymphocytes. Further, naive T lymphocytes expanded by Mt-MoDC were unable to secrete cytokines, in particular IL-4 and IFN-gamma, suggesting that they could be ineffective in helping the macrophage-mediated killing of intracellular mycobacteria. Our results suggest that the interference with monocyte differentiation into fully competent DC is an evasion mechanism of M. tuberculosis that could contribute to its intracellular persistence by avoiding immune recognition.     

Primary leiomyosarcoma of the skin: a comprehensive review on diagnosis and treatment

Sarcomas are a heterogeneous group of mesenchymal tumors which can affect bone and soft tissue. Leiomyosarcoma (LMS) is a rare subtype localized to the skin or subcutaneous tissue. Due to the heterogeneity of sarcomas, reviews and guidelines with an in-depth focus specifically on primary LMS of the skin are sparse. This article is intended to provide an up to date and systematic overview on diagnosis, treatment, and surveillance of this rare entity to provide a framework for decision making and management for dermato-oncologists. We discuss novel treatment options for advanced disease such as targeted therapy with kinase inhibitors and immune checkpoint blockade which may improve the prognosis even in advanced stages of LMS.     

Die Klinik „Heilanstalt Weidenplan“ in Halle (Saale), eine Pionierstätte der Deutschen Urologie

The routine use of cystoscope initiated the development of the modern urology. Otto Kneise (1875–1953) extended the targets of cystoscopy by including examinations of the male bladder and prostate. He achieved the goal that “cystoscopy is part of general work in urology and not a pure gynecological act”. He, thus, founded the specialty gynecological urology in the field urology, which prevented it from becoming an independent field. Under the leadership of Otto Kneise, the first independent urology department in Germany was created in the hospital Heilanstalt Weidenplan.     

Stimulation of collagenase 3 expression in synovial fibroblasts of patients with rheumatoid arthritis by contact with a three-dimensional collagen matrix or with normal cartilage when coimplanted in NOD/SCID mice

OBJECTIVE: To study the expression of collagenase 3 (matrix metalloproteinase 13 [MMP-13]) and collagenase 1 (MMP-1) in synovial fibroblasts from patients with rheumatoid arthritis (RA) when cultured within 3-dimensional collagen gels or coimplanted with normal cartilage in immunodeficient NOD/SCID mice. METHODS: Messenger RNA (mRNA) and protein expression of collagenase 3 and collagenase 1 were characterized in synovial and skin fibroblasts by Northern blot and Western blot analysis. The mRNA expression of both collagenases in cell-cartilage implants in NOD/SCID mice was investigated by in situ hybridization in combination with immunohistochemistry of human fibroblasts. RESULTS: Synovial fibroblasts coimplanted with normal cartilage in NOD/SCID mice deeply invaded adjacent cartilage tissue. In this in vivo system of cartilage destruction, collagenase 3 mRNA was induced in synovial fibroblasts at sites of cartilage erosion, while the expression of collagenase 1 mRNA could not be detected. Culture of synovial fibroblasts within 3-dimensional collagen gels was associated with a marked increase in collagenase 3 mRNA expression and proenzyme production. This stimulatory effect was 1 order of magnitude higher in comparison with a 2-4-fold increase upon treatment with interleukin-1beta or tumor necrosis factor a. In contrast, mRNA expression and proenzyme production of collagenase 1 were increased strongly, and to a similar extent, either by contact with 3-dimensional collagen or by proinflammatory cytokines. CONCLUSION: The expression of collagenase 3, in contrast to that of collagenase 1, is preferentially stimulated in synovial fibroblasts by 3-dimensional collagen rather than by proinflammatory cytokines. The induction of collagenase 3 by cell-matrix interactions represents a potential mechanism contributing to the invasive phenotype of synovial fibroblasts at sites of synovial invasion into cartilage in RA.     

Predictive biomarkers for the treatment of resectable esophageal and esophago-gastric junction adenocarcinoma: from hypothesis generation to clinical validation

Introduction: Esophageal and esophago-gastric junction (EGJ) adenocarcinomas remain a major health problem worldwide with a worryingly increasing incidence. Recent trials indicate survivals benefit for preoperative or perioperative chemoradiotherapy compared to surgery alone. Beside standard chemoradiotherapy regimens, new therapeutic approaches with targeted therapies have been proposed for the treatment of resectable disease. However, clinical outcomes remain extremely poor due to drug resistance phenomena. The failure of these approaches could be partially ascribed to their incorrect application in patients. Therefore, the identification of strong biomarkers for optimal patient management is urgently needed.

Areas covered: This review aims to summarize and critically discuss the most relevant findings regarding predictive biomarker development for neoadjuvant treatment of resectable esophageal and esophago-gastric junction adenocarcinoma patients.

Expert commentary: Optimizing the currently available therapeutic modalities through a more accurate selection of patients may avoid the use of ineffective and potentially toxic treatments. During the last decade, the advent of high-throughput ‘-omics’ technologies has set the basis for a new biomarker discovery approach from ‘molecule by molecule’ screening towards a large-scale systematic screening process with exponential increases in putative biomarkers, which often failed to provide adequate clinical validation.