The salience of gender in the illness experiences and care preferences of people with Parkinson's disease.

RATIONALE: In recent years, interest in sex characteristics and gender dimensions of Parkinson's disease (PD) has increased. Yet, much remains to be understood about how gender-related aspects specifically impact the illness and experiences of care in persons living with PD. OBJECTIVE: The purpose of this study was to explore the salience of gender-related aspects in the illness experiences and care provision preferences of people with PD. METHODS: A descriptive qualitative study including semi-structured life story interviews was conducted with men and women living with PD in the Netherlands. Between September 2020 and February 2021, forty people with PD (20 men and 20 women) participated in digital interviews of which thirty-one (18 men and 13 women) were included in the thematic analyses for this specific study. RESULTS: Overall, most participants did not consider gender-related aspects salient towards their illness experiences. However, when prompted, a number of participants described several stereotypical views about gender as related to the visibility of PD, emotional experiences, help seeking, role patterns and physical appearance. While most men and women with PD did not express specific gender-related preferences for their healthcare providers, those that did, all preferred women as healthcare providers. These preferences were generally related to attributed feminine traits which are considered relevant in routine, particularly sensitive, physical examinations of people with PD. CONCLUSION: This study demonstrates that although every person has a gender identity, the salience attributed to gender varies with illness experiences and in care provision preferences between people with PD. These findings highlight the need for precise and personalized methodologies to capture more nuanced insights into the impact of gender dimensions on PD. Furthermore, drivers behind gender-related preferences in care provision are multifactorial and warrant further investigation among people with PD.

Protein profiling of B-cell lymphomas using tissue biopsies: A potential tool for small samples in pathology.

Non-Hodgkin's lymphoma comprises many related but distinct diseases and diagnosis and classification is complex. Protein profiling of lymphoma biopsies may be of potential value for use in this lymphoma classification and the discovery of novel markers. In this study, we have optimized a method for SELDI-TOF MS based protein profiling of frozen tissue sections, without dissection of tumour cells. First we have compared chip surfaces and lysis buffers. Also, we have determined the minimal input using laser dissection microscopy. Subsequently, we have analyzed and compared protein profiles of diffuse large B-cell lymphoma (n=8), follicular lymphoma (n=8) and mantle cell lymphoma (n=8). Benign, reactive lymph nodes (n=14) were used as a reference group.CM10 chip surface in combination with urea lysis buffer and an input of approximately 50,000 lymphocytes allowed the detection of many differential peaks. Identification of the diffuse large B-cell lymphoma cases was reliably made in the supervised classification. Unsupervised clustering showed segregation into a benign/indolent cluster predominantly formed by benign, reactive lymph nodes and follicular lymphoma cases and into a more aggressive cluster formed by diffuse large B-cell lymphoma and mantle cell lymphoma cases. In conclusion, our protocol enables protein profiling of protein lysates derived from small histological samples and the subsequent detection of many differentially expressed proteins, without the need of tumour cell dissection. These results support further evaluation of protein profiling of small lymphoma biopsies as an additional tool in pathology.

Mapping of constitutional translocation breakpoints in renal cell cancer patients: identification of KCNIP4 as a candidate gene.

Our group and others had previously developed a high throughput procedure to map translocation breakpoints using chromosome flow sorting in conjunction with microarray-based comparative genomic hybridization (arrayCGH). Here we applied both conventional positional cloning and integrated arrayCGH procedures to the mapping of constitutional chromosome anomalies in four patients with renal cell cancer (RCC), three with a chromosome 3 translocation, and one with an insertion involving chromosome 3. In one of these patients, who was carrying a t(3;4)(p13;p15), the KCNIP4 gene was found to be disrupted. KCNIP4 belongs to a family of potassium channel-interacting proteins and is highly expressed in normal kidney cells. In addition, KCNIP4 splice variants have specifically been encountered in RCC.

Biomarkers as disease definition: mantle cell lymphoma as an example.

The introduction in pathology practice of a new biomarker that is contributing to define a disease requires a series of investigations. Now that new biomarkers are being discovered continuously it is important to learn from successful examples of markers that are presently widely used. In this historical account the steps are described that have led to the use of immunohistochemical staining of tissue samples with an antibody against cyclinD1 to diagnose mantle cell lymphoma. Furthermore, a short outlook is given on the introduction of proteomics as a tool in the diagnosis of lymphoma and the potential route to be taken for introducing this technology into clinical practice.

Protein profiling in pathology: analysis and evaluation of 239 frozen tissue biopsies for diagnosis of B-cell lymphomas.

PURPOSE: We determined the potential value of protein profiling of tissue samples by assessing how precise this approach enables discrimination of B-cell lymphoma from reactive lymph nodes, and how well the profiles can be used for lymphoma classification. EXPERIMENTAL DESIGN: Protein lysates from lymph nodes (n=239) from patients with the diagnosis of reactive hyperplasia (n=44), follicular lymphoma (n=63), diffuse large B-cell lymphoma (n=43), mantle cell lymphoma (n=47), and chronic lymphocytic leukemia/small lymphocytic B-cell lymphoma (n=42) were analysed by SELDI-TOF MS. Data analysis was performed by (i) classification and regression tree-based analysis and (ii) binary and polytomous logistic regression analysis. RESULTS: After internal validation by the leave-one-out principle, both the classification and regression tree and logistic regression classification correctly identified the majority of the malignant (87 and 96%, respectively) and benign cases (73 and 75%, respectively). Classification was less successful since approximately one-third of the cases of each group were misclassified according to the histological classification. However, an additional mantle cell lymphoma case that was misclassified as chronic lymphocytic leukemia/small lymphocytic B-cell lymphoma initially was identified based on the protein profile. CONCLUSIONS AND CLINICAL RELEVANCE: SELDI-TOF MS protein profiling allows for reliable identification of the majority of malignant lymphoma cases; however, further validation and testing robustness in a diagnostic setting is needed.

Identification of androgen-responsive genes that are alternatively regulated in androgen-dependent and androgen-independent rat prostate tumors.

The vast majority of androgen-dependent prostate tumors progress toward incurable, androgen-independent tumors. The identification of androgen-responsive genes, which are still actively transcribed in the tumors of patients who have undergone androgen ablation, may shed light on the molecular mechanisms underlying this phenomenon. To address this question, we chose the Dunning R3327 rat model system, in which the progression from androgen-dependent to -independent tumors is represented by several transplantable prostate-derived tumors. Gene expression profiles were analyzed in normal rat prostates and in the prostates of rats 14 days after castration by use of microarrays containing approximately 5,000 oligonucleotides, together representing more than 4,800 known rat genes. These expression profiles were compared with similarly obtained expression profiles of androgen-dependent and androgen-independent rat prostate tumors. By doing so, a series of known and novel prostate cancer-associated androgen-responsive genes was identified. Within this series, we were able to identify several clusters of genes that are differentially regulated in the various prostate tumors. These genes may serve as (i) novel prognostic identifiers and (ii) novel therapeutic targets.