Aging Effects on the Mongolian Gerbil Female Prostate (Skene's Paraurethral Glands): Structural,Ultrastructural, Quantitative,and Hormonal Evaluations

Different from the classic view, the prostate is not a gland exclusive to the male, also being an organ of the female genital system presenting morphofunctional similarity between human and rodent. Thus structural, ultrastructural, morphometric‐stereological features of the female prostate (Skene's paraurethral gland) and steroid serological levels were evaluated during young, adult, and senile ages in the Mongolian gerbil. The morphofunctional precocity of the female gland in comparison with the male gland occurring in young gland is probably associated with the female circulating steroid levels. The hormonal imbalance in senesce coincides with its susceptibility to histopathological lesions, such as epithelial hypertrophy, metaplasia, and intraepithelial neoplasia. Differently than that of males, the aging degeneration of the female gland involves the accumulation of lipofuscin granules. However, the alterations in senile prostate did not damage its functionality. These analyses reinforce the use of this experimental model for the comprehension of glandular morphofunctional aspects with special attention to senescence. Thus, the appreciation of this organ becomes relevant to avoid future discomfort to women's health. Anat Rec, 291:463–474, 2008. © 2008 Wiley‐Liss, Inc.     

Age-related histopathological lesions in the Mongolian gerbil ventral prostate as a good model for studies of spontaneous hormone-related disorders

The Meriones unguiculatus (Mongolian) gerbil has demonstrated significant prostatic responses to hormonal treatments, and to drugs against human prostatic hyperplasia Spontaneous neoplasia develops in the older animals. Thirty gerbils (age 18 months) were divided into non-affected and prostatic lesion bearers and the prostate lesions were evaluated morphologically, immunohistochemically and quantitatively. The most frequent changes were in epithelial sites and, namely prostatic intraepithelial neoplasias, microinvasive carcinomas and adenocarcinomas. In the stromal compartment, cellular hyperplasia, when verified, was always associated with the sites of anomalous epithelium. Additionally, larger deposition of collagen fibrils, generating stromal fibrosis, was found in all the old gerbils analysed. The quantitative analysis showed that prostatic tissue proportions differed in altered areas, being specific for each lesion type. Isolated nuclear and nucleolar parameters were not effective in diagnosing the malign potential of lesions. However, the cellular proliferation and death indexes indicated larger cellular turnover in invasive lesions such as carcinomas. With these analyses, it could be verified that old gerbils present high propensity to develop spontaneous prostate changes and this may aid in a better understanding of the biological behaviour of human prostate cancer.     

Sarcoglycan Complex in Human Normal and Pathological Prostatic Tissue: An Immunohistochemical and RT‐PCR Study

The sarcoglycan complex is a trans‐membrane system playing a key role in mechano‐signaling the connection from the cytoskeleton to the extracellular matrix. While β‐, δ‐, and ε‐sarcoglycans are widely distributed, γ‐ and α‐sarcoglycans are expressed exclusively in skeletal and cardiac muscle. Insufficient data are available on the distribution of sarcoglycans in nonmuscular tissue. In the present study, we used immunohistochemical and RT‐PCR techniques to study the sarcoglycans also in normal human glandular tissue, a type of tissue never studied in relation to the sarcoglycan complex, with the aim of verifying the real wider distribution of this complex. To understand the role of sarcoglycans, we tested specimens collected from patients affected by benign prostatic hyperplasia and adenocarcinoma. For the first time, our results showed that all sarcoglycans are detectable in normal samples both in epithelial and in myoepithelial cells; in pathological prostate, sarcoglycans appeared severely reduced in number or were absent. These data demonstrated that all sarcoglycans have a wider distribution suggesting a new unknown role for these proteins. The decreased number of sarcoglycans, containing cadherin domain homologs in samples of prostate affected by hyperplasia, and the absence of proteins in prostate biopsies, in cases affected by adenocarcinoma, could be responsible for the loss of adhesion between epithelial cells, which in turn facilitates the progression of benign tumors and the invasive potential of malignant tumors. Anat Rec, 297:327–336, 2014. © 2013 Wiley Periodicals, Inc.     

Relationship between Androgen Deprivation Therapy and Normal-Tension Glaucoma in Patients with Prostate Cancer: A Nationwide Cohort Study

PurposeThis study assessed the relationship between newly developed normal-tension glaucoma (NTG) and androgen deprivation therapy (ADT) in patients with prostate cancer.Materials and MethodsA retrospective population-based cohort study was performed. During the period between 2008 and 2017, a total of 218203 prostate cancer patients were identified in a nationwide claims database in the Republic of Korea. The final analysis included 170874 patients (42909 in the ADT group, 127965 in the control group) after applying the inclusion and exclusion criteria. The incidences of NTG according to ADT duration were compared with controls. Exact matching was conducted to adjust comorbidities between cohorts. Cox proportional hazard regression models were performed after controlling for latent confounding factors, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of NTG according to ADT were obtained.ResultsIn the matched cohort, the ADT group was associated with a significantly reduced risk of NTG in multivariable analysis compared to the control group. The risk of NTG decreased in patients who underwent ADT for less than 2 years (HR=0.824; 95% CI, 0.682–0.995; p=0.0440) and in those using ADT over 2 years (HR=0.796; 95% CI, 0.678–0.934; p=0.0051), compared to the controls.ConclusionMedical castrations for patients with prostate cancer results in a lower incidence of newly diagnosed NTG compared to no ADT. These findings suggest that testosterone may be involved in the pathogenesis of NTG.     

Supporting Patients Treated for Prostate Cancer: A Video Vignette Study With an Email-Based Educational Program in General Practice

Background

Men who have been treated for prostate cancer in Australia can consult their general practitioner (GP) for advice about symptoms or side effects at any time following treatment. However, there is no evidence that such men are consistently advised by GPs and patients experience substantial unmet need for reassurance and advice.

Objective

The intent of the study was to evaluate a brief, email-based educational program for GPs to manage standardized patients presenting with symptoms or side effects months or years after prostate cancer treatment.

Methods

GPs viewed six pairs of video vignettes of actor-patients depicting men who had been treated for prostate cancer. The actor-patients presented problems that were attributable to the treatment of cancer. In Phase 1, GPs indicated their diagnosis and stated if they would prescribe, refer, or order tests based on that diagnosis. These responses were compared to the management decisions for those vignettes as recommended by a team of experts in prostate cancer. After Phase 1, all the GPs were invited to participate in an email-based education program (Spaced Education) focused on prostate cancer. Participants received feedback and could compare their progress and their performance with other participants in the study. In Phase 2, all GPs, regardless of whether they had completed the program, were invited to view another set of six video vignettes with men presenting similar problems to Phase 1. They again offered a diagnosis and stated if they would prescribe, refer, or order tests based on that diagnosis.

Results

In total, 64 general practitioners participated in the project, 57 GPs participated in Phase 1, and 45 in Phase 2. The Phase 1 education program was completed by 38 of the 57 (59%) participants. There were no significant differences in demographics between those who completed the program and those who did not. Factors determining whether management of cases was consistent with expert opinion were number of sessions worked per week (OR 0.78, 95% CI 0.67-0.90), site of clinical practice (remote practice, OR 2.25, 95% CI 1.01-5.03), number of patients seen per week (150 patients or more per week, OR 10.66, 95% CI 3.40-33.48), and type of case viewed. Completion of the Spaced Education did impact whether patient management was consistent with expert opinion (not completed, OR 0.88, 95% CI 0.5-1.56).

Conclusions

The management of standardized patients by GPs was particularly unlikely to be consistent with expert opinion in the management of impotence and bony metastasis. There was no evidence from this standardized patient study that Spaced Education had an impact on the management of patients in this context. However, the program was not completed by all participants. Practitioners with a greater clinical load were more likely to manage cases as per expert opinion.     

Localization of Prostate Cells in Human Semen: A Comparison of the Burstone Technique and the Prostatic Specific Antigen Staining Method

Abstract

Our laboratory had reported a method for the localization and quantitation of exfolhted prostate cells found in semen of vasectomized and nonvasectomized men using the Burstone enzymatic histochemical stain. Recently, such enzymatic histochemical stains for the localization of acid phosphatase have given way to more specific immunoperoxidase stains. This study compared both enzymatic and immunoperoxidase staining reactions on histologic and cytologic prostate specimens. We fixed semen samdes in 10% neutral buffered formaldehvde (NBF) and collectd the exfoliated prostate cells using eiiher cytocentrifugation or 8 μm polycarbonate filters. The prostate cells collected on filters and the histologic sections of prostate stained with either acid phosphatase or prostatic specific anti gen (PSA) showed few cells with positive staining. In contrast, centrifuged specimens stained with either technique revealed positivestaining in most cells and secretions, indicating that the Burstone techniaue is as s~ecificas PSA for exfoliated Drostate prostate cells collected from semen. (The J of Histotechnol 10: 169, 1987).     

Protofilament and Hexagon: A Three-Dimensional Mechanical Model for the Junctional Complex in the Erythrocyte Membrane Skeleton

It is a long-standing mystery why erythrocyte actin filaments in the junctional complex (JC) are uniformly 37 nm and the membrane skeleton consists of hexagons. We have previously proposed that a molecular ruler formed by E-tropomodulin and tropomyosin 5 or 5b functions to generate protofilaments of 12 G actin under mechanical stress. Here, we illustrate that intrinsic properties of actin filaments, e.g., turns, chemical bonds, and dimensions of the helix, also favor fragmentation into protofilaments under mechanical stress. We further construct a mechanical model in that a pair of G actin is wrapped around by a split and spectrin, which may spin to two potential positions, and stabilize to one when the tail end is restricted. A reinforced protofilament may function as a mechanical axis to anchor three (top, middle, and bottom) pairs of Sp. Each Sp pair may wrap around the protofilament with a wide dihedral angle (166.2°) and a minimal axial distance (2.75 nm). Such three Sp pairs may spiral down (right handed) the protofilament from the pointed end with a dihedral angle of 55.4° in between the Sp pairs. This first three-dimensional model of JC may explain the hexagonal geometry of the erythrocyte membrane skeleton. © 2003 Biomedical Engineering Society. PAC2003: 8716Ka, 8716Dg, 8714Ee, 8716Ac     

A Filiform Large Cell Lymphoma in the Spleen: A Case Report with Immunohistochemical and Electron Microscopic Study

We describe histological, immunohistochemical, and ultrastructural findings in a filiform large cell lymphoma of the spleen in a 73-year-old man. The spleen weighed 300 g and contained a nodular mass of dimensions 4 × 2.8 × 3 cm that was lobular, raised, and well circumscribed. Light microscopically, the lesion was composed of compact cellular aggregates having large nuclei with evenly dispersed chromatin and a single large nucleolus or occasionally two to three small nucleoli. Immuno histochemically, the tumor cells were reactive to antibodies to leukocyte common antigen and MBI. Electron microscopically, most tumor cells were covered with tall, delicate, filiform cytoplasmic projections resembling microvilli in number and distribution. Filiform cytoplasmic projections varied from 50 to 200 nm in width and were at right or oblique angles to the surface. They appeared to be parallel but were frequently undulated, curved, or branching, forming in places small tufts. The pattern was more clearly noted on thick sections examined at an accelerating voltage of 200 kV.     

A Filiform Large Cell Lymphoma in the Spleen: A Case Report with Immunohistochemical and Electron Microscopic Study

We describe histological, immunohistochemical, and ultrastructural findings in a filiform large cell lymphoma of the spleen in a 73-year-old man. The spleen weighed 300 g and contained a nodular mass of dimensions 4 × 2.8 × 3 cm that was lobular, raised, and well circumscribed. Light microscopically, the lesion was composed of compact cellular aggregates having large nuclei with evenly dispersed chromatin and a single large nucleolus or occasionally two to three small nucleoli. Immuno histochemically, the tumor cells were reactive to antibodies to leukocyte common antigen and MBI. Electron microscopically, most tumor cells were covered with tall, delicate, filiform cytoplasmic projections resembling microvilli in number and distribution. Filiform cytoplasmic projections varied from 50 to 200 nm in width and were at right or oblique angles to the surface. They appeared to be parallel but were frequently undulated, curved, or branching, forming in places small tufts. The pattern was more clearly noted on thick sections examined at an accelerating voltage of 200 kV.     

Ciliated Cells in the Main Excretory Duct of the Submandibular Gland in Obstructive Sialadenitis: A SEM and TEM Study

The epithelium of the main excretory duct of the submandibular gland in five cases of obstructive sialadenitis was studied by TEM and SEM. In three cases we found a considerable increase in goblet and ciliated cells. As well as normal cilia, different kinds of ciliary anomalies, especially compound cilia, were noticed. Images of centriole formation and of ciliogenesis, both normal and abnormal, were also observed. Several hypotheses concerning the mode of formation of the compound cilia are discussed.     

Modulation of c-kit expression in pancreatic adenocarcinoma: A novel stem cell marker responsible for the progression of the disease

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of late symptoms and resistance to chemotherapy and radiation therapy. We have investigated the appearance of c-kit, a stem cell marker, in both normal adult pancreatic tissue and in cancerous tissue. Apart from some very pale staining of islets of Langerhans, normal pancreas was devoid of staining with antibodies to c-kit. In contrast, in cancerous tissue that still preserves the overall integrity of the pancreatic tissue, there was a clear labeling in islets of Langerhans, which seemed to be co-localized with insulin containing β cells. In other cases, where the pancreatic tissue was completely deteriorated, intensive labeling was clearly evident in remnants of both the exocrine and the endocrine tissues. The duct cells of the adenocarcinoma were moderately but clearly labeled with antibodies to c-kit. In contrast, in metastasis of PDAC, very intensive labeling of c-kit was evident. The location of KRAS, which is strongly associated with PDAC, was also analyzed at the initial stages of the disease, when islets of Langerhans still preserve their integrity to a large extent. KRAS was found exclusively in islets of Langerhans and overlapped in its location with insulin and c-kit expressing cells. It is suggested that the modulation of the expression of c-kit, visualized by antibodies to the oncogene molecule, may play an important role in the formation and progression of PDAC. The absence of c-kit in normal pancreas and its appearance in PDAC is probably due to a mutational event, which probably allows conversion of the β cells into cancer stem cells (CSC). Co-expression of both c-kit and KRAS, typical markers for CSC with overlapping with insulin in islets of Langerhans, strongly support the notion that β-cells play a central role in the development of PDAC. The use of specific drugs that can attenuate the kinase activity of c-kit or target KRAS expressing cancer cells should be tested in order to attenuate the progression of this lethal disease.     

Validation and Reliability of a Smartphone Application for the International Prostate Symptom Score Questionnaire: A Randomized Repeated Measures Crossover Study

Background

Smartphone-based assessment may be a useful diagnostic and monitoring tool for patients. There have been many attempts to create a smartphone diagnostic tool for clinical use in various medical fields but few have demonstrated scientific validity.

Objective

The purpose of this study was to develop a smartphone application of the International Prostate Symptom Score (IPSS) and to demonstrate its validity and reliability.

Methods

From June 2012 to May 2013, a total of 1581 male participants (≥40 years old), with or without lower urinary tract symptoms (LUTS), visited our urology clinic via the health improvement center at Soonchunhyang University Hospital (Republic of Korea) and were enrolled in this study. A randomized repeated measures crossover design was employed using a smartphone application of the IPSS and the conventional paper form of the IPSS. Paired t test under a hypothesis of non-inferior trial was conducted. For the reliability test, the intraclass correlation coefficient (ICC) was measured.

Results

The total score of the IPSS (P=.289) and each item of the IPSS (P=.157-1.000) showed no differences between the paper version and the smartphone version of the IPSS. The mild, moderate, and severe LUTS groups showed no differences between the two versions of the IPSS. A significant correlation was noted in the total group (ICC=.935, P<.001). The mild, moderate, and severe LUTS groups also showed significant correlations (ICC=.616, .549, and .548 respectively, all P<.001).There was selection bias in this study, as only participants who had smartphones could participate.

Conclusions

The validity and reliability of the smartphone application version were comparable to the conventional paper version of the IPSS. The smartphone application of the IPSS could be an effective method for measuring lower urinary tract symptoms.     

An Experimental Model for the Study of Underwater Pressure Waves on the Central Nervous System in Rodents: A Feasibility Study

Annals of Biomedical Engineering - Underwater blast differs from blast in air. The increased density and viscosity of water relative to air cause injuries to occur almost exclusively as primary...     

A noninvasive examination for the diagnosis of pulmonary alveolar proteinosis: induced sputum in conjunction with transmission electron microscopy

Transmission electron microscopy (TEM) of sputum deposition (SD) is an important method to assist in the diagnosis of pulmonary alveolar proteinosis (PAP). However, the low positive rate and poor quality of slices restrict the application of sputum samples in the diagnosis of PAP. Furthermore, it can be more difficult to obtain a sufficient amount of sample for TEM if the patients have little or no sputum. In this paper, we successfully diagnosed a patient with PAP using induced sputum deposition (ISD) with TEM, which is a novel and noninvasive method for PAP diagnosis. Therefore, ISD combined with TEM can be an effective method for PAP diagnosis, especially when a lung biopsy and bronchoalveolar lavage (BAL) cannot be performed, or little or no sputum can be obtained.     

A Prospective Korean Multicenter Study for Infectious Complications in Patients Undergoing Prostate Surgery: Risk Factors and Efficacy of Antibiotic Prophylaxis

This multicenter study was undertaken to determine the efficacy of antibiotic prophylaxis and identify the risk factors for infectious complications after prostate surgery in Korean patients. A total of 424 patients who underwent surgery of the prostate were reviewed. All patients underwent urinalysis and urine culture preoperatively and postoperatively. Efficacy of antibiotic prophylaxis and risk factors for infectious complications were investigated. Infectious complications were observed in 34.9% of all patients. Factors independently associated with infectious complications were diabetes mellitus (adjusted OR, 1.99; 95% CI, 1.09-3.65, P=0.025) and operation time (adjusted OR, 1.08; 95% CI, 1.03-1.13, P=0.004). Clinicians should be aware of the high risk of infectious complications in patients with diabetes and those who undergo a prolonged operation time. Neither the type nor duration of prophylactic antibiotics resulted in differences in infectious complications.

Graphical Abstract

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Direct Measurement of Peptide-Specific CD8+ T Cells Using HLA-A2:Ig Dimer for Monitoring the In Vivo Immune Response to a HER2/neu Vaccine in Breast and Prostate Cancer Patients

HER2/neu is a proto-oncogene and a member of the epidermal growth factor receptor family of proteins that is overexpressed in numerous types of human cancer. We are currently conducting clinical trials with the HER2/neu E75 peptide vaccine in breast and prostate cancer patients. We have evaluated the use of HLA-A2 dimer molecule for the immunological monitoring of cancer patients receiving the E75 peptide vaccine. Peripheral blood samples from patients receiving the vaccine were stained with HLA-A2 dimers containing the vaccine peptide E75 or control peptides and analyzed by flow cytometry. We compared the HLA-A2 dimer assay to standard methods of immunologic monitoring (IFN-gamma release, lymphocyte proliferation, and cytotoxicity). The HLA-A2 dimer assay was also compared with the HLA-A2 tetramer assay. E75 peptide-specific CD8 T cells were detected directly in the peripheral blood of patients by staining with E75-HLA-A2 dimers and CD8 antibodies. T cell cultures generated by repeated stimulations using E75 peptide-pulsed dendritic cells showed increased staining with E75-peptide loaded HLA-A2 dimers. Simultaneously analysis by the dimer assay and standard immunologic assays demonstrated that the dimer-staining assay correlated well with these methods of immunologic monitoring. A direct comparison using E75-specific HLA-A2 tetramers and HLA-A2 dimers for the detection of E75-specific CD8 T cells in peripheral blood showed comparable results with the two assays. Our findings indicate that the HLA-A2 dimer is a powerful new tool for directly quantifying and monitoring immune responses of antigen-specific T cells in peptide vaccine clinical trials.     

Morphology of the Bearded Seal (Erignathus barbatus) Muscular–Vibrissal Complex: A Functional Model for Phocid Subambient Pressure Generation

Bearded seals possess a broad muscular snout with large mystacial vibrissal fields that are involved in tactile sensation and prey identification. Although the microstructure of bearded seal vibrissae and their feeding performance have been investigated their orofacial morphology has not. Such morphological studies are important to understand the underlying mechanisms of feeding performance and to test proposed functional hypotheses. Therefore, the facial musculature was examined in bearded seals to test functional hypotheses regarding feeding performance. The orofacial musculature is composed primarily of three enlarged muscular layers, the M. levator nasolabialis, M. orbicularis oris, and M. buccinatorius (superficial), M. maxillonasolabialis (intermediate), and the M. lateralis nasi and M. dilator nasi (deep). The expansion of these muscles, the three dimensionality of the entire muscular array, the soft tissue insertions, and constant volume fit the model of a muscular hydrostat, and explains the detailed and varied mobility of their snout. An anastomosing network of CN VII innervates these facial muscles. The disproportionately large infraorbital nerve of CN V courses toward the snout and divides into numerous branches that penetrate the external capsule of every Follicle Sinus‐Complex. The anatomical evidence support that the M. orbicularis oris, M. buccinatorius, and M. maxillonasolabialis form a robust lateral lip complex that can occluded lateral gape during subambient pressure generation. The rostral portion of the M. orbicularis oris, M. dilator nasi, and M. mentalis function to pursue the rostral lips to form a circular aperture important for projecting steep pressure gradients rostral to the lips for prey acquisition. Anat Rec, 299:1043–1053, 2016. © 2016 Wiley Periodicals, Inc.     

A New Model for Calculating the Lumbar Lordosis Angle in Early Hominids and in the Spine of the Neanderthal From Kebara

The debate over the posture of early hominids is longstanding, perhaps because the absence of a reliable method for reconstructing the lumbar lordosis angle (LA) in early hominid spines has made it difficult to determine whether their posture resembled or differed from that of modern humans. We have developed a new model for predicting the lordotic curvature of the lumbar spine of early hominids based on the relationship between the lordotic curvature and the orientation of the articular processes in the lumbar spines of living primates (modern humans and nonhuman primates). The orientation of the inferior articular processes explains 89% of the variation in lordotic curvature among living primates and, thus, should be a reliable predictor of the lumbar LA in disarticulated hominid spines. Based on this model, we calculated a LA of 25–26 degree angle for the Kebara 2 Neanderthal. The calculated value for Kebara 2 is below the normal range of lordosis for modern humans (30–79 degree angle). Anat Rec 293:1140–1145, 2010. © 2010 Wiley‐Liss, Inc.