Differences in Psychological Inflexibility Among Men With Erectile Dysfunction Younger and Older Than 40 Years: Web-Based Cross-Sectional Study.

BACKGROUND: Psychological inflexibility is a core concept of acceptance and commitment therapy (ACT), which is a comprehensive, transdiagnostic interpretation of mental health symptoms. Erectile dysfunction (ED) is a condition that affects male sexual performance, involving the inability to achieve and maintain a penile erection sufficient for satisfactory sexual activity. Psychosocial factors primarily influence ED in men younger than 40 years, whereas biological factors are more likely to be the underlying cause in older men. OBJECTIVE: This web-based cross-sectional study examined differences in depression, anxiety, and psychological inflexibility among men with ED younger and older than 40 years in a Japanese population. METHODS: We used a web-based survey to gather data from various community samples. ED was assessed by the International Index of Erectile Function-5 (IIEF-5) questionnaire, while depression, anxiety, and psychological inflexibility were evaluated by the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Acceptance and Action Questionnaire-II (AAQ-II), Cognitive Fusion Questionnaire (CFQ), and Valuing Questionnaire-Obstacle Subscale (VQ-OB) questionnaires. The chi-square test estimated the scores of PHQ-9 and GAD-7 among men with ED, comparing those younger than 40 years and those older than 40 years. Additionally, a two-way ANOVA was conducted with ED severity and age group as independent variables, assessing psychological inflexibility. RESULTS: Valid responses from 643 individuals (mean age 36.19, SD 7.54 years) were obtained. Of these, 422 were younger than 40 years (mean age 31.76, SD 5.00 years), and 221 were older than 40 years (mean age 44.67, SD 2.88 years). There was a statistical difference in the prevalence of depression as judged by PHQ≥10 between men with ED younger and older than 40 years (P<.001). On the other hand, there was no difference in the prevalence of anxiety as judged by GAD≥10 (P=.12). The two-way ANOVA revealed that the interactions for CFQ (P=.04) and VQ-OB (P=.01) were significant. The simple main effect was that men with ED younger than 40 years had significantly higher CFQ (P=.01; d=0.62) and VQ-OB (P<.001; d=0.87) scores compared to those older than 40 years in moderate ED and severe ED. Additionally, it was found that men younger than 40 years with moderate to severe ED had significantly higher CFQ (P=.01; d=0.42) and VQ-OB (P=.02; d=0.38) scores compared to men younger than 40 years without ED. On the other hand, no interaction was found for AAQ-II (P=.16) scores. CONCLUSIONS: To the best of our knowledge, this web-based cross-sectional study is the first to examine the relationship between psychological inflexibility and ED. We conclude that men with moderate and severe ED younger than 40 years have higher psychological inflexibility and might be eligible for ACT.

An Acceptance and Commitment Therapy Smartphone Application for Erectile Dysfunction: A Feasibility Study.

Background: Erectile dysfunction (ED) is a multifactorial disorder with both psychogenic and organic components, but psychosocial factors are usually neglected. Objective: The purpose of this study was to develop a smartphone application targeting psychosocial factors of ED and to examine its feasibility, acceptability, and treatment response to determine the parameters for a larger clinical trial. Methods: In this single-arm feasibility study, 8 participants with situational ED were enrolled. Dr. App, a newly developed smartphone treatment application for patients with psychogenic ED consisting of 8 weekly modules based on Acceptance and Commitment Therapy, was delivered. The primary outcome was comparison of the International Index of Erectile Function-15 domain scores measured pre- and post-intervention. Results: Six out of 8 participants completed the Dr. App and the post-intervention measures. The Wilcoxon signed-rank test showed a significant change in erectile function (P < 0.05; r = -0.65) and a significant trend in intercourse satisfaction (P < 0.10; r = -0.47) and overall satisfaction (P < .10; r = -0.47). Additionally, the reliable change index values were used to calculate the number of participants for whom a clinically meaningful difference occurred. The results showed that 33.30% of the participants had clinically meaningful differences in erectile function and 66.70% in intercourse satisfaction and overall satisfaction. On the other hand, no significant differences were shown in orgasmic function and sexual desire. Conclusions: Findings from this study support the feasibility, acceptability, and potential usefulness of the smartphone application targeting psychosocial factors of ED and warrant a larger randomized clinical trial to confirm the results.

Accuracy of digital image enhancement in detection of vertical and horizontal root fracture.

BACKGROUND: Two-dimensional intraoral radiography is the most common tool for recognizing root fractures. Improving the quality of images by means of enhancement tools can increase the recognition power of them. The aim of this study is to evaluate the effect of digital image enhancement on vertical and horizontal root fractures (HRFs) diagnostic accuracy. MATERIALS AND METHODS: In this in vitro study, 100 human extracted teeth, involving 50 mandibular premolars and 50 maxillary incisors, were investigated. In total, 25 premolar teeth were vertically fractured and other 25 sound teeth served as testing group. According to the verified methods, 25 incisor teeth were fractured and other 25 teeth of this group served as testing ones. Following, by using the charge-coupled device sensor, preapical digital images were recorded. The original images were altered using reverse-contrast and colorization enhancement tools. Two different observers independently investigated all of the images. Receiver operating characteristic analysis was used to calculate the area under the curve (AUC) and sensitivity and specificity of all images. Data analyzde using receiver operating characteristic (ROC) analysis. Two-ways variance analysis was used to assess differences in the values (P = 0.05 ). RESULTS: AUC and sensitivity and specificity related to the original, reverse-contrast, and colorized images were calculated (0.84, 0.64, 0.99), (0.84, 0.64, 0.96), and (0.82, 0.64, 0.92) respectively, for vertically root fractured images. AUC and sensitivity and specificity related to the original, reverse-contrast, and colorized images were calculated (0.49, 0.44, 0.56), (0.50, 0.44, 0.60), and (0.48, 0.48, 0.48), respectively, for horizontally root-fractured images. CONCLUSION: The results of the present study revealed that reverse-contrast and colorized enhancement filters cannot be used as critical methods in detecting in vitro vertical and HRF.

Delayed Expression of Circulating TGF-ß1 and BMP-2 Levels in Human Nonunion Long Bone Fracture Healing.

BACKGROUND: The healing process of bone fracture requires a well-controlled multistage and sequential order beginning immediately after the injury. However, complications leading to nonunion exist, creating serious problems and costs for patients. Transforming growth factor-beta 1 (TGF-ß1) and bone morphogenic protein 2 (BMP-2) are two major growth factors involved in human bone fracture healing by promoting various stages of bone ossification. In this study, we aimed to determine the role of these factors during the fracture healing of human long bones and assess their impacts on nonunion condition. MATERIALS AND METHODS: We performed a comprehensive analysis of plasma TGF-ß1 and BMP-2 levels in blood samples from 10 patients with proved nonunion and 10 matched patients with normal union following a predetermined time schedule. The concentrations of TGF-ß1 and BMP-2 were measured at each time point using a solid-phase ELISA. RESULTS: TGF-ß1 and BMP-2 levels were detectable in all patients. For all patients, a maximal peak for TGF-ß1 was found at 3-week. In normal union group, TGF-ß1 showed a maximal peak at 2-week while nonunion group had a delayed maximal peak at 3-week. Plasma levels of BMP-2 for all patients and for normal union group reached a maximal peak at 1-week, but nonunion group showed a delayed maximal peak at 2-week. In general, plasma TGF-ß1 or BMP-2 level was not significantly different between normal union and nonunion groups. CONCLUSION: The expression levels of TGF-ß1 and BMP-2 appeared to be delayed in nonunion patients which could play an important role in developing an early marker of fracture union condition and facilitate improved patient's management.

Methionine Aminopeptidase 2 as a Potential Therapeutic Target for Human Non-Small-Cell Lung Cancers.

BACKGROUND: Methionine aminopeptidase 2 (MetAP2) is a bi-functional protein that plays a critical role in the regulation of post-translational processing and protein synthesis. OBJECTIVES: We studied whether MetAP2 is activated and expressed in human non-small-cell lung cancer (NSCLC) tissues and whether inactivation of MetAP2 activity, with its specific inhibitor fumagillin, potentially inhibits proliferation of NSCLC cells. MATERIAL AND METHODS: The expression and function of MetAP2 were evaluated in NSCLC tissues, primary cell cultures and cell lines using immunohistochemistry, RT-PCR, Western blot, aminopeptidase activity assay and flow cytometry. MetAP2 expression was also studied in relation to clinicopathological factors. RESULTS: MetAP2 expression in NSCLS, including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), showed a moderate to strong positive reaction while normal appearing bronchial epithelium showed weak staining and normal alveolar epithelial cells were widely negative. A high MetAP2 mRNA and protein expression was found in NSCLC tissues. The aminopeptidase activity in NSCLC was 2-fold higher than that in normal lung tissues. In a series of 41 ADC patients, MetAP2 expression was significantly correlated with patient's outcome or survival time. Inhibition of MetAP2 by fumagillin in SCC cell lines revealed a significant increase in caspase-3 activity as compared to the control (p = 0.001). CONCLUSIONS: Our results indicate that MetAP2 is involved in NSCLC and is an important regulator of proliferative and apoptotic targets. Thus inhibition of MetAP2, such as by fumagillin, may be a potential therapeutic modality for prevention of tumor cell growth, development and progression in NSCLC patients.

Microshear Bond Strength of OptiBond All-in-One Self-adhesive Agent to Er:YAG Laser Treated Enamel After Thermocycling and Water Storage.

Introduction: This study aimed to compare the microshear bond strength of composite to enamel treated with Erbium-Doped Yttrium Aluminum Garnet (Er:YAG) laser using a self-etch one step bonding agent. Methods: Seventy-six enamel surfaces were prepared from 38 sound human third molar teeth. Specimens were randomly divided into four groups of 18. The enamel surface in half the specimens was irradiated with Er:YAG laser. One extra specimen from each group was evaluated under a scanning electron microscope (SEM). Composite micro-cylinders were bonded to the specimen surfaces using OptiBond All-In-One (OB) adhesive agent and stored in distilled water for 24 hours. Half the specimens were thermocycled (2000 cycles) and stored in distilled water at 37°C for three months (TW). The microshear bond strength of composite to enamel was measured using a universal testing machine at a crosshead speed of 1 mm/min. The fractured surfaces were evaluated under a stereomicroscope at ×40 magnification to determine the mode of failure. Data were analyzed using repeated measures analysis of variance (ANOVA) and t test. Results: The mean values (±standard deviation) were 17.96 ± 2.92 MPa in OB group, 22.29 ± 4.25 MPa in laser + OB group, 18.11 ± 3.52 MPa in laser + OB + TW group and 9.42 ± 2.47 MPa in OB + TW group. Repeated measures ANOVA showed that laser irradiation increased the microshear bond strength (P < 0.001). Bond strength decreased when the samples were thermocycled and stored for three months (P < 0.001). The interaction effect of water storage and laser treatment on bond strength was significant (P < 0.05). Conclusion: Enamel surface preparation with Er:YAG laser is recommended to enhance the durability of the bond of self-etch bonding systems to enamel.

Identification and characterization of Wnt signaling pathway in keloid pathogenesis.

Keloid is characterized by fibroblastic cell proliferation and abundant collagen synthesis. Numerous studies have shown that the Wingless type (Wnt) signaling pathways play key roles in various cellular functions including proliferation, differentiation, survival, apoptosis and migration. The aim of this study was to clarify the role of Wnt signaling pathway in keloid pathogenesis. Primary fibroblast cultures and tissue samples from keloid and normal appearing dermis were used. The expression of Wnt family members, frizzled (FZD)4 receptor, receptor tyrosine kinase-like orphan receptor (ROR)2 and the Wnt signaling downstream targets, glycogen synthase kinase (GSK)3-ß and ß-catenin were assessed using semi-quantitative RT-PCR, Western blot, or immunohistochemical methods. Of the Wnt family members, Wnt5a mRNA and protein levels were elevated in keloid fibroblasts (KF) as compared to normal fibroblasts (NF). A higher expression of ß-catenin protein was also found in KF. No detectable levels of FZD4 receptor and ROR2 proteins were observed in both NF and KF. Functional analysis showed that treatment of NF and KF with recombinant Wnt5a peptide resulted in an increase in protein levels of total ß-catenin and phosphorylated ß-catenin at Ser33/37/Thr 41 but no significant change in phosphorylated ß-catenin at Ser45/Thr 41 positions. In addition, the expression of total GSK3-ß protein was not affected but its phosphorylated/inactivated form was increased in NF and KF. Our findings highlight a potential role for a Wnt/ß-catenin canonical signaling pathway triggered by Wnt5a in keloid pathogenesis thereby providing a new molecular target for therapeutic modulations.

Clinical improvement in psoriasis with treatment of associated hyperlipidemia.

Psoriasis is associated with an increased risk of cardiovascular disease, a principal cause of which is atherosclerosis caused by hyperlipidemia. However, it is not known whether treatment of hyperlipidemia in patients with psoriasis lead to clinical improvement in psoriasis condition. In this study, the authors summarize the existing literature relevant to this inquiry. They also describe the potential pathways believed to link psoriasis with atherosclerosis and the role of hyperlipidemia therapy in this setting. A few studies indicated clinical improvement in psoriasis with treatment of associated hyperlipidemia. Some studies showed that a low-fat diet improved psoriasis. Others indicated a decreased risk of psoriasis associated with intake of cholesterol-lowering drugs such as "statins." Treatment with statins increased lactate dehydrogenase level and diminished Psoriasis Area and Severity Index score, ie, reduced cutaneous lesion in psoriasis. Beneficial effects of statin therapy on psoriasis included downregulation of lymphocyte function-associated antigen-1, inhibition of leukocyte endothelial adhesion, extravasation and natural killer cell activity, inhibition of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin 1 and 6, lowering of C-reactive protein, promotion of a T(H)1 to T(H)2 cells and inhibition of T(H)1 cytokine receptors on T cells, leading to inhibition of activation of lymphocytes and infiltration into the inflammation sites. Taken together, current literature indicates clinical improvement in psoriasis condition with treatment of associated hyperlipidemia, particularly with statins of which the mechanisms could be attributed to immunomodulatory and anti-inflammatory effects.

RCAN1 regulates vascular branching during Xenopus laevis angiogenesis.

BACKGROUND/AIMS: The mechanisms that regulate the size-related morphologies of various blood vessels from the aorta to capillary vessels are still poorly understood. In this study, we evaluate the involvement of regulator of calcineurin 1 (RCAN1), a regulatory protein in the calcineurin/NFAT signal transduction pathway, in vascular morphology to gain further insight into these mechanisms. METHODS AND RESULTS: We first generated 2 types of vasculature in vitro from the same source of human umbilical vein endothelial cells by fibrin gel assay. We found that RCAN1 was significantly upregulated in large vessels with low branching frequencies when compared with small vessels with high branching frequencies. Next, to clarify whether RCAN1 regulates the branching of blood vessels in vivo, we injected RCAN1 mRNA into fertilized Xenopus laevis eggs. Overexpression of RCAN1 decreased the number of branching points that sprouted from intersomitic vessels during X. laevis angiogenesis. In addition, coexpression of calcineurin A, a target of RCAN1, could rescue RCAN1-suppressed vascular branching. CONCLUSIONS: These results provide in vivo evidence of RCAN1-regulated vascular branching which may play a role in the patterning of morphologically different vasculature.

Pathogenic mechanisms shared between psoriasis and cardiovascular disease.

Psoriasis is associated with an increased risk of cardiovascular disease, a hallmark of which is atherosclerosis. The objective of this study was to review the pertinent literature and highlight pathogenic mechanisms shared between psoriasis and atherosclerosis in an effort to advocate early therapeutic or preventive measures. We conducted a review of the current literature available from several biomedical search databases focusing on the developmental processes common between psoriasis and atherosclerosis. Our results revealed that the pathogenic mechanisms shared between the two diseases converged onto "inflammation" phenomenon. Within the lymph nodes, antigen-presenting cells activate naive T-cells to increase expression of LFA-1 following which activated T-cells migrate to blood vessel and adhere to endothelium. Extravasation occurs mediated by LFA-1 and ICAM-1 (or CD2 and LFA-3) and activated T-cells interact with dendritic cells (and macrophages and keratinocytes in psoriasis or smooth muscle cells in atherosclerosis). These cells further secrete chemokines and cytokines that contribute to the inflammatory environment, resulting in the formation of psoriatic plaque or atherosclerotic plaque. Additionally, some studies indicated clinical improvement in psoriasis condition with treatment of associated hyperlipidemia. In conclusion, therapeutic or preventive strategies that both reduce hyperlipidemia and suppress inflammation provide potentially useful approaches in the management of both diseases.

Validation of glomerular basement membrane thickness changes with aging in minimal change disease.

Measurement of the normal range of glomerular basement membrane (GBM) thickness by electron microscopy is required for the diagnosis of thin basement membrane disease or diabetic nephropathy; however, this measurement is influenced by aging. The aim of this study was to introduce a simple histogram plotting method for the validation of the results of the GBM thickness measurements by the accepted arithmetic mean ± SD method. We examined renal biopsy specimens obtained from 19 patients (10 males and 9 females) with minimal change disease, ranging in age from 3 to 70 years. Renal tissue samples obtained at autopsy from a male baby (3 months old) with no renal disease were also examined. For each case, GBM thicknesses at 10-15 evenly distributed points per glomerular loop were directly measured and the arithmetic mean ± SD was calculated. Subsequently, the arithmetic mean ± SD for each group of cases classified by age into 4 groups, i.e. babyhood (3 months old), childhood (3-11 years old), adulthood (12-57 years old), and old age (60-70 years old), was determined. On the other hand, a histogram of the frequency of GBM points measured against thickness was plotted to determine the distribution pattern and the range of measurements in each age group. The histogram plot showed 4 clearly divided modes for GBM thickness. Comparison of the results obtained by the 2 methods revealed a significant correlation indicating the feasibility of the histogram plotting method as a useful adjunct to validate GBM thickness measurements.

Lamellar body formation and dark multivesicular body pockets in fetal and postnatal normal rat alveolar type II cells: ultrastructural study.

To investigate the osmiophilic lamellar body (LB) formation in the alveolar type II cells, the authors examined lung tissues from fetal (day 19 of gestation) and postnatal normal rat by electron microscopy. Lamellar body formation was identical in fetal and postnatal rat lungs. Immature dark multivesicular body (MVB) showed incomplete formation of the limiting membrane and contained a cluster of vesicles and an electron-dense granule probably originated from Golgi complex. Dark and light MVBs were seen in alveolar type II cells. However, only dark MVB was involved in the production of LB. First, a drumstick-shaped projection arising from the surface of MVB appeared, which partly trapped cytoplasmic materials such as glycogen granules and ribosomes. The projection was ultimately fused with the MVB surface to form an MVB pocket described here for the first time. In prelamellar body, lamellar structures appeared to provide a communicative MVB pocket and even found in a drumstick-shape. Mature LBs showed disappearance of multivesicles, dense matrix, and MVB pocket. Thus, lamellar body formation might not only need MVB materials, but also glycogen granules and ribosomes in the MVB pocket.

Ischemic damage and subsequent proliferation of oligodendrocytes in hippocampal CA1 region following repeated brief cerebral ischemia.

Changes in oligodendrocytes and astrocytes following repeated brief periods of ischemia were studied in gerbils. The repeated brief periods of cerebral ischemia were produced by occlusion of bilateral common arteries for 3 x 3 min at 1-hour intervals. Oligodendrocytes and astrocytes in hippocampal CA1 regions were examined on 1, 3, 7 and 14 days after ischemia. Seven days after ischemia reperfusion, astrocytes, large pale and small dark oligodendrocytes entered the necrotic pyramidal neuron layer and coexisted with microglia. The necrotic matter of neurons and phagolysosome was observed in cytoplasm of some large pale and small dark oligodendrocytes. Most oligodendrocytes also intermingled with reactive astrocytes. These reactive astrocytes showed glial fibrillary acidic protein-positive reaction. Furthermore, proliferating cell nuclear antigen-positive cells increased markedly 7 days after reperfusion. We conclude that the repeated brief cerebral ischemia caused proliferation of oligodendrocytes and astrocytes, and oligodendrocytes may play a phagocytic role for clearance of necrotic matter of neurons.

Bronchoalveolar lavage fluid analysis provides diagnostic information on pulmonary Langerhans cell histiocytosis.

Histiocytes of Langerhans cell type are recovered from the bronchoalveolar lavage fluid (BALF) of patients with interstitial lung diseases in a nonspecific manner. Langerhans cells (LCs) can be identified through immunostaining for S-100, CD1a, and, more specifically, langerin. To evaluate the diagnostic value of BALF in pulmonary Langerhans cell histiocytosis (PLCH), we performed a retrospective clinicopathological study of 5 patients with biopsy-confirmed PLCH or Hand-Schüller-Christian disease involving the lung. As a control study, we examined BALF cells from 23 patients with various diseases, including sarcoidosis, hypersensitivity pneumonitis, collagen vascular disease, idiopathic pulmonary fibrosis, and adenocarcinoma of the lung. Cytospins obtained from BALF were stained with Giemsa or Papanicoloau and others were immunostained. In general, cytospins showed a monomorphous and dispersed cell population containing mononucleated or binucleated and occasionally multinucleated histiocytes. LCs recovered from BALF were characterized by clear and velvety cytoplasm; oval or kidney-shaped, vesicular nuclei with irregular shapes; nucleoli; and frequent grooves and indentations. Radiography and high-resolution computed tomography showed multiple bilateral nodular or cystic lesions in the middle and upper lung zones. The mean percentage of LCs in 9 lavages from the 5 patients was 8.0%, whereas that from the control group was only 0.3% (maximum, 1.6%). The percentage of cells positive for S-100 or CD1a was comparable to the percentage of Langerhans-like histiocytes stained with Giemsa stain. The present results indicate that the survey of LCs in BALF with the aid of immunocytochemical evaluation and corresponding clinical data could play a critical role in establishing the diagnosis of PLCH, thus providing a less invasive approach than lung biopsy, which carries a risk of complications.

Increased effect of fucoidan on lipoprotein lipase secretion in adipocytes.

AIMS: Fucoidan, a sulfated polysaccharide extracted from brown seaweed (F. vesiculosus) is recognized as an effective anticoagulant but its anti-lipidemic potency has not been well defined. We investigated the effect of fucoidan on lipoprotein lipase (LPL) secretion by human adipocytes. MAIN METHODS: LPL mRNA and protein expressions were measured using semi-quantitative RT-PCR, ELISA and immunohistochemistry in cultured adipocytes with or without fucoidan treatment. LPL enzyme activity was determined by a fluorometric assay. KEY FINDINGS: In cultured adipocytes, fucoidan induced LPL secretion in a dose- and time-dependent manner. An initial increase in LPL was maintained at a significant level but much slower than that in heparin-treated cells. Fucoidan also dose-dependently induced a cofactor of LPL, the apolipoprotein C-II (ApoC-II) secretion. In fucoidan-treated cells, LPL mRNA was time-dependently increased and LPL protein expression was also inceased. Treatment with both heparin and fucoidan showed no further increase in media LPL activity compared to heparin alone. In the conditioned medium from fucoidan-treated cells followed for 4 h, LPL activity decayed exponentially with half-life of about 180 min. In addition, the extracellular LPL mass in cycloheximide (a protein synthesis inhibitor) and fucoidan-treated cells did not change markedly, but LPL shifted significantly from active to inactive form. SIGNIFICANCE: These results suggest that fucoidan acts like heparin by releasing LPL in addition to increasing the intracellular transport and decreasing the degradation of LPL in the medium. Furthermore, LPL and ApoC-II secretion induced by fucoidan may be involved in regulating plasma triglyceride lowering clearance.

Chronologic change of the maximum dimension of Bacillus Calmette-Guerin-induced keloids.

BACKGROUND: Because keloids grow gradually, there is a long time lag until the patients visit the hospital. OBJECTIVE: To investigate the chronologic change of the maximum dimension of Bacillus Calmette-Guerin (BCG)-induced keloids to provide information on their nature and facilitate early treatment intervention. METHODS: Clinical records of patients with keloid treated between 1998 and 2005 were reviewed, and patients with BCG-induced keloids were assessed with reference to age at onset of keloid, age at first hospital visit, length of the major axis of keloid at first visit, growth rate, and histopathologic features. RESULTS: Of 716 patients with keloid, 60 (8.4%) had BCG-induced keloid. A significant difference was found between mean age at onset and at first visit. The mean length of maximum dimension was 42.4 mm and increased proportionally to age at first visit. Keloids grew rapidly between the ages of 20 and 40, during which time many patients did not seek therapy. Histopathologically, no significant differences were noted between BCG-induced keloid and non-BCG keloid. CONCLUSION: Early therapeutic intervention might prevent keloids from growing larger, emphasizing a need to provide adequate information on keloid behavior to patients and physicians involved in BCG vaccination.

Evaluation of fractional analysis of bronchoalveolar lavage combined with cellular morphological features.

BACKGROUND: The value of bronchoalveolar lavage (BAL) still remains controversial, prompting a need for further improvement. The purpose of this study was to develop and evaluate a sequential analysis of cell content in fractional BAL (FBAL) from the airways and alveolar sacs with incorporation of the cellular morphologic features. METHODS: Initially, 30 ml saline was infused into a subsegmental lobe of the lung and the recovered fluid was assigned as FBAL-I being mainly originated from whole airways. The second and third lavages (FBAL-II and FBAL-III) each were performed using 50 ml saline being from more distal portions of airways and alveolar sacs respectively in the same lobe. Total cell number/ml and percentages of macrophages, lymphocytes, neutrophils, and eosinophils in each fraction together with their morphological alterations and mast cells, basophils and Masson bodies were assessed. RESULTS: In the 12 controls, percentage of neutrophils was high and lymphocytes and macrophages were low in FBAL-I while in FBAL-III, neutrophils decreased to nearly nil and lymphocytes and macrophages were increased. Analysis of FBAL from 76 patients with sarcoidosis and 14 with hypersensitivity pneumonitis (HP) revealed that a predominance of small, round and well-differentiated lymphocytes with relative absence of neutrophils, basophils and Masson bodies correlated best with sarcoidosis. In contrast, neutrophil predominance and presence of lymphocytes having deep nuclear indentations and abundant cytoplasm with a process resembling a "hand-mirror" correlated well with HP. CONCLUSIONS: Evaluation of FBAL together with cellular morphological features especially characteristics of lymphocytes provides valuable information for establishing the diagnosis in interstitial lung diseases.

Interaction between beta-amyloid protein and heparan sulfate proteoglycans from the cerebral capillary basement membrane in Alzheimer's disease.

Proteoglycans are important in the pathogenesis of senile dementia of Alzheimer type (SDAT) by participating in amyloidogenesis. Knowledge about specific proteoglycan subtypes in SDAT may be of therapeutic advantage. In this study, we examined proteoglycan constituents of SDAT brains with reference to hyaluronic acid, heparan sulfate (HS), dermatan sulfate and chondroitin sulfate subtypes. Total proteoglycans showed a 1.6-fold increase in the hippocampus and 4.3-fold increase in the gyrus frontalis superior compared to non-demented elderly subjects. The HS subtype showed a 9.3-fold increase in hippocampus and a 6.6-fold increase in gyrus frontalis superior. Immunohistochemical studies of senile plaques revealed the expression of heparan sulfate proteoglycan (HSPG) in a portion of the core of typical plaques. beta-amyloid expression was positive in senile plaques and the degenerated neuronal processes and capillary basement membrane, but was negative in endothelial cells. Microglial cells adjacent to senile plaques were positive for HLA-DR expression, and astroglial cells positive for glial fibrillary acidic protein were scattered around the microglial cells. Immunoelectron microscopic examination showed an electron-dense reaction for HSPG in the thickened basement membrane adjacent to the endothelial cells of capillary vessels, but not inside the endothelial cells. These findings suggest that a markedly increased HSPG in SDAT brains is most likely caused by HSPG from the blood capillary basement membrane and that the degenerated processes around senile plaques may arise from microglial or astroglial cells.

Induction of pulmonary thromboembolism by neutrophil elastase in collagen-induced arthritis mice and effect of recombinant human soluble thrombomodulin.

We previously reported that during total knee arthroplasty in rheumatoid arthritis (RA) patients, the use of tourniquet might promote local release of neutrophil elastase (NE) from neutrophils, which may contribute to the development of pulmonary thromboembolism (PTE) and tissue injury. The aim of this study was to develop PTE by the use of NE in a mouse model of collagen-induced arthritis (CIA) and investigate the relationship between thrombus and endothelial cells as well as the effect of recombinant human soluble thrombomodulin (rhs-TM) in reducing the risk of PTE. Male DBA/1J mice were injected intracutaneously at several sites with an emulsion containing bovine collagen and later a booster shot to produce CIA mice. Subsequently, NE was injected intravenously 2 times a day for 3 days and after a further 4 days, mice were sacrificed. A group of mice received rhs-TM injections prior to NE injections. We divided the mice into four groups of normal, CIA control, CIA + NE, and CIA + rhs-TM + NE mice and evaluated thrombus formation status. All CIA + NE mice developed PTE. In contrast, no thrombosis was found in normal control, CIA control and CIA + rhs-TM + NE mice. Plasma thrombin level, fibrinogen expression and neutrophil count were increased in CIA + NE mice. Double staining for anticoagulant TM and procoagulant von Willebrand factor (vWF) in pulmonary endothelial cells in normal mice showed a TM-dominant expression while in both CIA control and CIA + NE mice a vWF-dominant expression compatible with coagulant status was observed. Injection of rhs-TM into CIA + NE mice resulted in a phenotypic conversion of endothelial cells from vWF-dominant to TM-dominant expression and a reduction in fibrinogen deposition. These findings demonstrate that by repeated use of NE in CIA mice, it is feasible to produce PTE and to study its pathogenesis and that rhs-TM reduces the risk of PTE. We suggest that in surgical operations of upper and lower extremities in RA patients, the use of a tourniquet should be avoided as it may trigger NE release.