Changes in blood pressure and arterial stiffness monitored using the cardio-ankle vascular index during hemodialysis.

During hemodialysis (HD), blood pressure (BP) changes are frequently observed. However, the mechanism of BP changes during HD has not been fully clarified. The cardio-ankle vascular index (CAVI) reflects the arterial stiffness of the arterial tree from the origin of the aorta to the ankle independent from BP during measurement. Additionally, CAVI reflects functional stiffness in addition to structural stiffness. We aimed to clarify the role of CAVI in regulating the BP system during HD. We included 10 patients undergoing 4-hour HD (total 57 HD sessions). Changes in the CAVI and various hemodynamic parameters were evaluated during each session. During HD, BP decreased and CAVI significantly increased (CAVI, median [interquartile range]; 9.1 [8.4-9.8] [0 min] to 9.6 [9.2-10.2] [240 min], p < 0.05). Changes in CAVI from 0 min to 240 min were significantly correlated with water removal rate (WRR) (r = -0.42, p = 0.002). Changes in CAVI at each measurement point were negatively correlated with ΔBP (Δsystolic BPeach MP, r = -0.23, p < 0.0001; Δdiastolic BPeach MP, r = -0.12, p = 0.029). Whereas one patient exhibited a simultaneous decrease in BP and CAVI during the initial 60 min of HD. Arterial stiffness monitored with CAVI generally increased during HD. CAVI elevation is associated with decreased WWR and BP. An increase in CAVI during HD may reflect the contraction of smooth muscle cells and play an important role in BP maintenance. Hence, measuring CAVI during HD may distinguish the cause of BP changes.

Modeling Low Muscle Mass Screening in Hemodialysis Patients.

INTRODUCTION: Computed tomography (CT) can accurately measure muscle mass, which is necessary for diagnosing sarcopenia, even in dialysis patients. However, CT-based screening for such patients is challenging, especially considering the availability of equipment within dialysis facilities. We therefore aimed to develop a bedside prediction model for low muscle mass, defined by the psoas muscle mass index (PMI) from CT measurement. METHODS: Hemodialysis patients (n = 619) who had undergone abdominal CT screening were divided into the development (n = 441) and validation (n = 178) groups. PMI was manually measured using abdominal CT images to diagnose low muscle mass by two independent investigators. The development group's data were used to create a logistic regression model using 42 items extracted from clinical information as predictive variables; variables were selected using the stepwise method. External validity was examined using the validation group's data, and the area under the curve (AUC), sensitivity, and specificity were calculated. RESULTS: Of all subjects, 226 (37%) were diagnosed with low muscle mass using PMI. A predictive model for low muscle mass was calculated using ten variables: each grip strength, sex, height, dry weight, primary cause of end-stage renal disease, diastolic blood pressure at start of session, pre-dialysis potassium and albumin level, and dialysis water removal in a session. The development group's adjusted AUC, sensitivity, and specificity were 0.81, 60%, and 87%, respectively. The validation group's adjusted AUC, sensitivity, and specificity were 0.73, 64%, and 82%, respectively. DISCUSSION/CONCLUSION: Our results facilitate skeletal muscle screening in hemodialysis patients, assisting in sarcopenia prophylaxis and intervention decisions.

Occult hepatitis B virus infection in Japanese chronic hemodialysis patients.

We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti-HBc) was determined by various chemiluminescent immunoassays. HBV-DNA was quantified in patients positive for anti-HBc using quantitative real-time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg-positive and 218 (20.9%) were anti-HBc-positive. All HBsAg-positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg-negative and anti-HBc-positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.

Expression of Hepatocyte growth factor activator inhibitor type-1 (HAI-1) in prostate cancer.

BACKGROUND: Hepatocyte growth factor activator inhibitor type-1 (HAI-1) inhibits hepatocyte growth factor activator and matriptase. In the present study it was investigated whether the expression of HAI-1 is associated with the progression of prostate cancer. PATIENTS AND METHODS: The expression of HAI-1 was evaluated by immunohistochemistry (IHC) of samples from 51 patients with negative prostate biopsies and 75 patients with untreated prostate cancer. Furthermore, the expression of HAI-1 was evaluated in 24 patients with castration-resistant prostate cancer (CRPC), and the relationship between HAI-1 expression and the prostate-specific antigen (PSA) progression-free rate was investigated. RESULTS: Expression of HAI-1 by IHC in patients with prostate cancer was significantly higher than in those with negative prostate biopsy. CRPC exhibited significantly lower HAI-1 expression than untreated metastatic prostate cancer. The PSA progression-free rate was worse in patients without HAI-1 expression than in those with positive HAI-1 expression. CONCLUSION: It is suggested that HAI-1 may play an important role in the pathogenesis of CRPC.

Serum active hepatocyte growth factor (AHGF) in benign prostatic disease and prostate cancer.

BACKGROUND: Hepatocyte growth factor (HGF) is secreted as an inactive single-chain precursor called pro-HGF. Pro-HGF is converted to an active two-chain form by HGF activator and matriptase. We attempted to clarify whether serum levels of active HGF (AHGF) could be used as a marker of prostate cancer. METHODS: Serum levels of AHGF and total HGF (THGF; pro-HGF + AHGF) were measured by enzyme-linked immunosorbent assay in 38 patients with benign prostatic disease and 160 patients with prostate cancer. RESULTS: Serum levels of AHGF in patients with untreated prostate cancer (0.37 +/- 0.12 ng/ml) were significantly higher than those in patients with benign prostatic disease (0.28 +/- 0.08 ng/ml) (P = 0.0001). Serum AHGF levels were increased in patients with stage D or D3 compared with stage B. In addition, there were significant differences in serum AHGF levels between patients with well-differentiated and poorly differentiated adenocarcinoma. Furthermore, the mean serum AHGF/THGF ratio in patients with stage D3 prostate cancer was significantly higher than that in patients with stage B. CONCLUSIONS: AHGF may be a potential tumor marker for prostate cancer. Further studies in large groups of patients are needed to define the clinical value of AHGF.

Androgen receptor negatively influences the expression of chemokine receptors (CXCR4, CCR1) and ligand-mediated migration in prostate cancer DU-145.

We previously reported that androgen receptor (AR) plays a role in the regulation of adhesion to the extracellular matrix and invasion of human prostate cancer cells by influencing the expression of specific integrin subunits. It is now considered that chemokines play a significant role in organ-selective cancer metastasis. In this study, we hypothesized that AR may influence the expression of these chemokine receptors and cell function. The mRNA expression of chemokine receptors in human prostate cancer cell line DU-145 and DU-145 cells expressing AR (DU-145/AR) was investigated by RT-PCR. DU-145 cells selectively expressed CXCR4 and CCR1 mRNA at high levels compared with DU-145/AR cells. DU-145 showed vigorous migratory responses to its ligand CXCL12 (also called stromal-derived factor-1alpha, SDF-1alpha) and CCL3 (also called macrophage inflammatory protein-1, MIP-1alpha). In contrast, neither CXCL12 nor CCL3 affected the migration of DU-145/AR cells. These results indicate that expression of AR down-regulates the migratory responses of human prostate cancer cells via chemokine and its receptor systems.

[The efficacy of Gosyajinkigan for pollakisuria].

We investigated the efficacy of Gosyajinkigan in 20 patients with prostatic disease, in whom pollakisuria was not improved by treatment with drugs for lower urinary tract symptoms. Four and 8 weeks after treatment, the urinary frequency was significantly improved during both daytime and night. The efficacy rates for diurnal frequency and nocturia were 45% and 65%, respectively. The International Prostate Symptom Score (IPSS) was decreased 4 weeks after treatment, and the parameters of uroflowmetry, the residual urine volume and quality of life score were improved 8 weeks after therapy. It was concluded that Goshajinkigan was effective for pollakisuria with prostatic disease, and the administration of the agent for 8 weeks or longer was needed to improve lower urinary tract symptoms.

Serum hepatocyte growth factor activator inhibitor type I (HAI-I) and type 2 (HAI-2) in prostate cancer.

BACKGROUND: Hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) are Kunitz-type serine protease inhibitors for hepatocyte growth factor activator (HGFA). We attempted to clarify whether serum levels of HAI-1 and HAI-2 could be a useful marker in patients with prostate cancer. METHODS: Serum levels of HAI-1 and HAI-2 were measured by enzyme-linked immunosorbent assay in 27 patients with benign prostatic hyperplasia (BPH) and 118 patients with prostate cancer. RESULTS: The mean serum levels of HAI-1 in patients with prostate cancer were significantly higher than those in patients with BPH. Furthermore, the serum HAI-1 levels in patients with distant metastasis and hormone resistant prostate cancer were significantly elevated compared with those in patients with organ-confined diseases. There were no significant differences in serum HAI-2 levels among prostate cancer subgroups according to clinical stage. Significantly elevated levels of HAI-1 were detected in 38 patients with prostate cancer before any treatment. CONCLUSIONS: HAI-1 may be a potential tumor marker for prostate cancer. Further studies in large groups of patients are needed to define the clinical value of HAI-1.

Percutaneous endoscopic treatment for calyceal diverticular calculi.

A 29-year-old man complaining of gross hematuria was referred to our department. DIP demonstrated calyceal diverticular calculi of the left kidney. The patient requested ESWL, but the stone had not been discharged after two treatments. He then underwent PNL with dilation of the narrow neck of the calyceal diverticulum under fluoroscope. The neck of the diverticulum was dilated using an amplats dilator. Three months after the surgery, DIP demonstrated that the diverticulum was completely free from calculi and the size of the diverticulum was reduced. He was doing well 24 months after the operation. Calyceal diverticular calculi should be managed not only with ESWL and PNL but also with dilation of the narrow neck of the calyceal diverticulum.

Serum interleukin-11 in patients with benign prostatic hyperplasia and prostate cancer.

To clarify whether serum levels of interleukin-11 (IL-11) could be a useful marker in patients with prostate cancer, serum IL-11 was determined in 73 and 23 men with prostate cancer and benign prostate hyperplasia (BPH), respectively, before treatment. There were no statistical differences of IL-11 levels between patients with prostate cancer and BPH. Patients with hormone-resistant prostate cancer had a significantly higher level of IL-11 than those with untreated cancer. Serum IL-11 levels may be a potential tumor marker for prostate cancer progression.

Serum hepatocyte growth factor activator (HGFA) in benign prostatic hyperplasia and prostate cancer.

OBJECTIVES: Hepatocyte growth factor activator (HGFA) is responsible for proteolytic activation of the precursor form of hepatocyte growth factor (HGF). We attempted to clarify whether serum levels of HGFA could be used as a marker for prostate cancer. MATERIAL AND METHODS: Serum levels of total HGF and HGFA were measured by enzyme-linked immunosorbent assay in 99 healthy controls, 27 patients with benign prostatic hyperplasia (BPH) and 119 patients with prostate cancer. RESULTS: : The mean+/-S.D. serum levels of HGFA in untreated prostate cancer and BPH cases were 0.42+/-0.24 and 0.50+/-0.26 ng/ml, respectively (no significant difference). Serum HGFA was significantly elevated in hormone-refractory prostate cancer (stage D3) compared to other stages, while HGF did not significantly differ with regard to clinical stage. CONCLUSIONS: Serum HGFA tends was elevated in patients with advanced stage prostate cancer. Further studies in large groups of patients are needed to clarify the clinical value of HGFA.

Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide stimulate interleukin-6 production in prostate cancer cells and prostatic epithelial cells.

We investigated the effect of the vasoactive intestinal (VIP) and pituitary adenylate cyclase activating peptides (PACAP) on the production of interleukin-6 (IL-6) in normal prostate epithelial and stromal cells and prostate cancer cells. We performed RT-PCR analysis to assess the expression of VIP receptor (VPAC1, VPAC2 and PAC1) mRNA in normal prostate epithelial and stromal cells and prostate cancer cells, and investigated the effect of VIP and PACAP on the production of IL-6. VPAC1, VPAC2 and PAC1 receptor mRNAs were expressed in LNCaP and DU-145/AR prostate cancer cells and PrEC cells (prostate epithelial cells). VIP stimulated the production of IL-6 in DU-145/AR prostate cancer and PrEC cells. PACAP showed a similar effect on IL-6 production in PrEC cells. VIP stimulated IL-6 promoter transcriptional activity in DU-145/AR cells. These results indicate that VIP and PACAP may modulate the IL-6 production of normal prostate epithelial and prostate cancer cells.

Relationship between penile hemodynamic parameters assessed by color Doppler ultrasonography and penile rigidity recorded by the RigiScan Plus.

OBJECTIVE: We studied the relationship between penile hemodynamic parameters assessed by color Doppler ultrasonography and penile rigidity estimated by objective measurement. PATIENTS AND METHODS: A total 37 patients with erectile dysfunction were examined. After intracavernous injection of 20 microg prostaglandin E1, we measured their penile hemodynamic parameters in the cavernous arteries by color Doppler ultrasonography. Simultaneously, the RigiScan Plus device was used for real-time evaluation of penile rigidity. Hemodynamic parameters were correlated with penile rigidity. RESULTS: Peak systolic velocity and resistive index were significantly correlated with penile tip (r = 0.54, r = 0.72, respectively) and base (r = 0.55, r = 0.76, respectively) rigidity; there was no significant correlation between end-diastolic velocity and penile rigidity. CONCLUSIONS: Peak systolic velocity and resistive index were strongly correlated with penile rigidity in patients with erectile dysfunction during intracavernous pharmacological testing. The resistive index in particular appeared to be the most valid parameter for assessment of penile rigidity.

Differential expression of integrin subunits in DU-145/AR prostate cancer cells.

We have established a clonal DU-145 prostate cancer cell line (DU-145/AR) stably transfected with androgen receptor cDNA. We investigated the expression of integrin subunits, adhesion to extracellular matrices, the invasion of DU-145/AR prostate cancer cells. The expression of various integrin subunits and adhesion to various extracellular matrices in DU-145, DU-145/Neo and DU-145/AR cells were examined. The haptoinvasion and the haptotactic migration of these cells were investigated using a Transwell cell culture chamber assay. DU-145/AR cells exhibited lower expression of alpha6 and beta4 integrin subunits and higher expression of alpha2 and alpha5 than DU-145 cells. DU-145/AR cells showed significantly lower adhesion to fibronectin, laminin-1 and laminin-5 than DU-145/ Neo cells, whereas DU-145/AR cells showed higher adhesion to type I and type IV collagen. Haptoinvasion of DU-145/AR cells into Matrigel/fibronectin-coated filter was significantly reduced as compared with DU-145/Neo or DU-145 cells, but there was no significant difference between DU-145/AR and control cells in the haptotactic migration to fibronectin. Dihydrotestosterone (DHT) inhibited the invasive ability of DU-145/AR cells. These results indicate that androgen receptor may play a role in the regulation of adhesion to the extracellular matrices and invasion of prostate cancer cells through influencing the expression of specific integrin subunits.

Telomerase activity is correlated with lower grade and lower stage bladder carcinomas.

BACKGROUND: Telomerase is a ribonucleoprotein enzyme that compensates for the progressive erosion of telomeres. The increasing interest in telomerase is motivated by the demonstration that most human carcinomas are telomerase positive. The potential use of telomerase activity in bladder carcinomas using a urine sample has been reported in several studies. However, little is known about the detection of telomerase activity in bladder carcinoma tissues. Herein, we investigate telomerase activity in bladder carcinoma tissues according to grade (G) and stage. MATERIAL AND METHODS: Telomerase activity was assayed by polymerase chain reaction enzyme-linked immunosorbent assay methods. Malignant lesions were assessed in 37 patients with bladder carcinoma and no malignant lesions were assessed in five patients with dysplasia or inflammatory bladder lesions. RESULTS: Twenty-three out of 37 carcinoma samples were telomerase-positive and one out of five control samples without carcinoma was telomerase-positive. The positive rates according to stage and grade were 83.3% for superficial and 42.1% for invasive stages and 83.3% for G1, 66.7% for G2 and 40.0% for G3. Telomerase activity was correlated with lower grade and lower stage bladder carcinomas. CONCLUSION: These results strongly suggest that reactivation of telomerase may differ between superficial and invasive bladder carcinomas and also between low grade and high grade bladder carcinomas.

Prognostic significance of serum soluble Fas level and its change during regression and progression of advanced prostate cancer.

To evaluate the clinical usefulness of serum soluble Fas (sFas) and sFas ligand as a prognostic factor and for monitoring the regression and progression of metastatic prostate cancer treated with endocrine therapy, sFas and sFas ligand were measured in sera collected from 30 patients with untreated metastatic prostate cancer. sFas levels were measured sequentially in 16 patients who had progressed to a state of elevated prostate-specific antigen (PSA) and 5 patients who were in regression following endocrine therapy. Serum sFas levels in patients with metastatic prostate cancer were found to be significantly higher than that of control patients with benign prostate hyperplasia. Patients with low levels of serum sFas had a higher cause-specific survival rate and a higher PSA progression-free rate compared with patients with high levels of serum sFas. In patients who suffered PSA progression following endocrine therapy, serum sFas increased in parallel to the increase in PSA levels although the magnitude of change in sFas was very small. In patients whose tumor regressed following therapy, sFas levels did not change. sFas ligand levels were very low or below measurable levels in all specimens. sFas levels might be associated with poor prognosis in metastatic prostate cancer. Serum sFas ligand appears to have limited clinical relevance.

Clinical significance of expression of urokinase-type plasminogen activator in patients with prostate cancer.

BACKGROUND: Urokinase-type plasminogen activator (u-PA) has been reported to overexpress in several types of human cancers and correlate with cancer progression. The present study was performed to evaluate the significance of expression of u-PA on the progression of prostate cancer. MATERIALS AND METHODS: Expression of u-PA protein was investigated immunohistochemically on paraffin-embedded section from 61 patients with untreated prostate cancer. The correlation between the u-PA expression and clinical outcome was examined. RESULTS: u-PA was expressed in the cytoplasm of glandular cells of 56% patients. Higher expression of u-PA protein was positively correlated with bone metastasis (p = 0.011). The cause-specific survival rate was significantly lower in u-PA-positive patients than that in u-PA-negative patients (p = 0.0012). In those with bone metastasis, patients with u-PA expression had worse cause-specific survival than those without u-PA expression (p = 0.030). CONCLUSION: Increased expression of u-PA is a feature of bone metastasis in patients with prostate cancer. u-PA expression is a prognostic factor in patients with prostate cancer.

Differential effect of chromogranin A fragments on invasion and growth of prostate cancer cells in vitro.

OBJECTIVES: To investigate the effect of various chromogranin A (CgA) fragments on the invasion, haptotactic migration, and growth of prostate cancer cells. METHODS: We investigated the effect of five kinds of CgA fragments (79-115, 286-301, 324-341, 344-374, and 356-374) on the invasion of PC-3 and DU-145 prostate cancer cells through a reconstituted basement membrane (matrigel) and the haptotactic migration of these cells using a Transwell cell culture chamber assay. Cell growth was assessed by the WST-1 Cell Counting Kit. RESULTS: CgA (79-115) inhibited the invasive ability of PC-3 and DU-145 cells (P = 0.035 and P = 0.037, respectively). CgA (79-115) also inhibited the haptotactic migration of these cells (P = 0.031 and P = 0.021). On the other hand, other CgA fragments had no significant effect. CgA (79-115) also inhibited the cell growth of PC-3 cells (P = 0.012) and DU-145 cells (P < 0.001). CgA (324-341), CgA (344-374), and CgA (356-374) inhibited the cell growth of DU-145 cells (P < 0.001, P < 0.001, and P < 0.001, respectively). CONCLUSIONS: These results indicate that some CgA fragments may affect the invasion and growth of prostate cancer cells.

Effect of hepatocyte growth factor on invasion of prostate cancer cell lines.

Hepatocyte growth factor (HGF) was suggested to play an important role in the regulation of mitogenesis, motogenesis, angiogenesis, migration and invasion for various types of cells, and acts through a specific membrane receptor encoded by c-met proto-oncogene. However, the mechanism of the effect of HGF on tumor invasion of prostate cancer cells remains unclear. We investigated the effect of HGF on the invasion of PC-3 and DU-145 prostate cancer cells through a reconstituted basement membrane (Matrigel), the haptotactic migration to fibronectin substrate, the expression of protein and mRNA for matrix metalloproteinases (MMP)-1 and -9, membrane-type 1-MMP (MT1-MMP), urokinase-type plasminogen activator (u-PA) and its receptor (uPAR). HGF increased both Matrigel invasion and haptotactic migration of prostate cancer cells. Furthermore, HGF also increased the production of MMP-1 and -9, MT1-MMP, u-PA and uPAR of these cells. These results suggested that HGF increased the invasive potential of prostate cancer cells probably through enhancement of cell motility and the production of MMPs and u-PA.