Sequential changes in transforming growth factor (TGF)-β1 concentration in synovial fluid and mRNA expression of TGF-β1 receptors in chondrocytes after immobilization of rabbit knees

We have previously reported that a combination of transforming growth factor (TGF)-β1 and basic fibroblast growth factor (bFGF) synergistically increases the proliferation of chondrocytes obtained from knee joint immobilized for 7–14 days in male Japanese white rabbits. In the present study, we performed experiments with chondrocytes and synovial fluid obtained from rabbit knees immobilized for 0–42 days, to clarify the sequential changes in TGF-β1 and bFGF concentrations in synovial fluid and the mRNA expression of TGF-β1 receptor type I (RI) and II (RII) in chondrocytes after immobilization. The combination of TGF-β1 and bFGF had a synergistic effect on the proliferation of chondrocytes obtained from knee joints immobilized for 7–14 days. The concentration of TGF-β1 in synovial fluid was significantly higher (up to 3.6-fold) at 7–28 days after immobilization compared with that at 2 days. The mRNA for RI and RII was expressed during the whole immobilization period. The concentration of bFGF was kept at the same level at 2–7 days after immobilization, and gradually decreased thereafter. In the early stages of degenerated cartilage, up to 14 days after immobilization, the concentrations of both TGF-β1 and bFGF were higher in the synovial fluid and mRNA expression of TGF-β1 receptors in chondrocytes was kept. Received: September 22, 2000 / Accepted: December 19, 2000     

Advanced adenocarcinoma of the urinary bladder successfully treated by the combination of cisplatinum, mitomycin-C, etoposide and tegafur-uracil chemotherapy

Primary adenocarcinoma of the urinary bladder has shown an extremely poor response to radiation or chemotherapy. Therefore, radical surgery is the only therapeutic treatment for it. A case report is presented of a primary advanced adenocarcinoma of the urinary bladder invaded into the uterus with distant metastases which responded completely to systemic combination chemotherapy including tegafur-uracil. The patient was a 53-year-old woman with a history of asymptomatic macrohematuria. She was treated with the combination of cisplatinum, mitomycin-C, etoposide and tegafur-uracil chemotherapy. After four courses of the chemotherapy, computed tomography showed marked regression of the primary tumor of the urinary bladder and the complete disappearance of the distant metastases in the liver, lung and para-aortic lymph node. Subsequently, she underwent radical cystectomy and cutaneous ureterostomy. Pathologically, no viable cancer cells were detected. Three years after the operation, she has no evidence of disease recurrence. Treatment of advanced adenocarcinoma of the urinary bladder by this combination chemotherapy is of benefit.     

Human atrial natriuretic peptide is a useful criterion in treatment of nocturia.

BACKGROUND: Nocturia is one of the major problems of elderly people. The possible causes of nocturia include irritation of lower urinary tract obstruction, disturbance of the fluid balance, and sleep disturbance. In a significant proportion of patients, the mechanism of nocturia is still unclear and a definitive method of treatment has yet to be determined. This study investigated how to treat nocturia. MATERIALS AND METHODS: We analyzed 51 patients who visited Kobe City General Hospital between January 1998 and June 1999 with nocturia (three or more nocturnal voidings) and no daytime urological problems. Twenty-two of these patients were given daytime diuretic therapy (azosemide 60 mg), while 29 other patients received a minor tranquilizer. The method of treatment was selected randomly. Correlations between the plasma level of atrial natriuretic peptide (hANP) and the effect of treatment were analyzed. RESULTS: Daytime diuretics decreased the nocturnal frequency of voiding in 10 out of 22 patients. The plasma hANP level at the first visit was significantly higher in the patients with improvement (p = 0.0026). Furthermore, the plasma hANP level was significantly decreased after daytime diuretic therapy in patients who showed improvement of nocturia with diuretic therapy (p = 0.0180). Minor tranquilizer administration decreased nocturia in 22 out of 29 patients. The plasma hANP level at the first visit was significantly lower in the patients who improved (p = 0.0021). CONCLUSIONS: These findings suggest that patients with higher plasma hANP levels should be treated as having subclinical heart failure, while nocturia in patients with a normal plasma hANP level might be caused by sleep disturbance.     

Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases.

BACKGROUND: We previously reported that glomerular changes in the renal specimen of a human case with heme oxygenase-1 (HO-1) deficiency were mild, but tubulointerstitial injury advanced progressively. This study examined the patterns of HO-1 production in the kidney in various renal diseases. Furthermore, the critical cytoprotective roles of HO-1 were evaluated in the kidney by comparing HO-1 production and expressions of carboxymethyllysine (CML) and pentosidine, both of which are markers of oxidative stress. METHODS: Renal biopsy or autopsy materials were obtained from a total of 74 patients. Degrees of hematuria and proteinuria and the levels of urinary N-acetyl-beta-D-glucosaminidase (NAG), beta2-microglobulin (beta2m), and creatinine were evaluated. Immunohistochemical studies for HO-1, CML, and pentosidine expressions were performed with their specific antiserum. RESULTS: HO-1 staining was observed within tubular epithelial cells in all of the renal diseases, but was not detected within intrinsic glomerular cells. HO-1 staining tended to be more intense within distal tubuli than in proximal tubuli. Within distal tubuli, there was no significant correlation between intensity of HO-1 staining and degree of hematuria or presence of proteinuria. Within proximal tubuli, HO-1 staining tended to be more intense with greater degrees of hematuria, presence of proteinuria, and moderate tubulointerstitial damage. Intense staining of CML and pentosidine was observed within renal tubular epithelial cells only in HO-1-deficient patients. CONCLUSIONS: HO-1 plays important roles in protecting renal tubuli from oxidative injuries, as these cells are constantly exposed to various oxidative stresses. It is suggested that renal tubular epithelia are more susceptible to oxidative stress due to the lack of this critical enzyme in HO-1 deficiency.     

Long-term outcomes of vitrectomy with or without arteriovenous sheathotomy in branch retinal vein occlusion

PURPOSE: To evaluate the long-term effect of vitrectomy with or without arteriovenous sheathotomy for macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: The study was a prospective, randomized, comparative, interventional case series of 36 patients (36 eyes) who underwent pars plana vitrectomy with or without arteriovenous sheathotomy for macular edema due to BRVO of 相似文献   

Morphological characteristics of basal-like subtype of breast carcinoma with special reference to cytopathological features

Expression profiling of invasive breast carcinomas by DNA microarray techniques has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpression, and basal-like) that are associated with different clinical outcomes and with different chemotherapy. Basal-like carcinoma is associated with younger patient age, high histological grade, aggressive clinical course, development of distant metastasis, poor prognosis, and relatively high mortality rate. Basal-like carcinomas do not express estrogen receptor, progesterone receptor, or HER2 (triple-negative phenotype). Therefore, patients with basal-like carcinomas are not likely to benefit from endocrine therapies or trastuzumab, but are likely to benefit from systemic chemotherapy. Although genetic, morphological, and immunohistochemical features of basal-like carcinomas have been reported, there is no universal definition for those tumors. Furthermore, there are no specific morphological and immunohistochemical features that can identify those tumors in routine diagnostic materials. In the present paper, we present data of histological and cytological features of basal-like breast carcinoma, and discuss about its morphological spectrum.     

Mammary ductoscopy: current issues and perspectives

Until recently, the mammary duct had not been directly observed in vivo. Starting with the success of Teboul et al., studies of mammary ductoscopy (MD) for nipple discharge have been performed in Japan and other East Asian countries. Ductal lavage screening trials for breast cancer started in the 2000s. Concurrently, the number of English-language articles about MD increased. Sixty-nine English-language and 74 Japanese-language papers published in the last 19 years were reviewed. Important reports and studies were analyzed. MD has undergone significant technological development, and studies of MD have taken place in many countries. As a result, endoscopic images of the mammary duct have developed, and the endoscopic diagnosis for nipple discharge has become possible. MD-guided biopsy and surgery have been studied. Findings of MD are useful for diagnosing intraductal lesions with nipple discharge. As a result, MD has reduced the number and extent of microdochectomies. MD is also helpful in guiding breast-conserving surgery. Many pioneers have tried direct biopsy or interventions under MD, but further developments are necessary for its practical use.     

MR Venography of Deep Veins: Changes with Uterine Fibroid Embolization

Deep veins (DVs) can be compressed by a uterus enlarged with fibroids. The purpose of this study was to assess the degree of luminal narrowing of DVs caused by a myomatous uterus, and the change in DV narrowing in women with symptomatic fibroids after embolization using time-of-flight (TOF)-magnetic resonance venography (MRV). Twenty-nine consecutive women with symptomatic uterine fibroids underwent TOF-MRV and pelvic MRI before and 4 months after embolization. Based on the TOF-MRV, we evaluated the luminal narrowing of three DVs, including the inferior vena cava, and the bilateral common and external iliac veins, and divided the findings into three grades. The scores for each DV were added for each patient (lowest, 0; highest, 6). DV scores and symptom severity (SS) scores were compared between the baseline and 4 months after embolization using the paired t-test. The relationship between DV scores and uterine volume was investigated using Pearson’s test. DV scores decreased significantly, from 1.52 ± 1.70 at baseline to 0.93 ± 1.56 at 4 months after embolization (p = 0.004). The uterine volume decreased from 948 ± 647 mL at baseline to 617 ± 417 mL at 4 months after embolization (p < 0.001). DV score correlated with uterine volume (r = 0.856, p < 0.001). SS scores decreased from 54.5 ± 14.6 at baseline to 26.8 ± 15.4 at 4 months after embolization (p < 0.001). In conclusion, the degree of luminal narrowing of DVs caused by a uterus with fibroids is correlated with the uterine volume. Uterine artery embolization may induce an improvement of luminal narrowing of DVs due to a reduction of the myomatous uterus volume.     

Second myeloablative allogeneic stem cell transplantation (SCT) using cord blood for leukemia relapsed after initial allogeneic SCT

There are many reports of second allogeneic stem cell transplantation (allo-SCT) using cord blood (CB) for graft failure after initial allo-SCT. However, the efficacy of second allo-SCT using CB for patients with leukemia relapsed after initial allo-SCT is unknown. We report the results of second allo-SCT using CB in seven adult patients with leukemia relapsed after initial allo-SCT. All patients received a myeloablative conditioning regimen including oral busulfan 16 mg/kg, intravenously fludarabine 100mg/m(2) and cyclophosphamide 120 mg/kg. All but one patient had myeloid reconstitution and four patients remain alive at between 4 and 40 months after second SCT. We conclude that second myeloablative allo-SCT using CB may be feasible in selected patients with the relatively younger age, less organ damage and longer time interval between first and second allo-SCT.     

Topotecan and small interfering RNA suppress survivin expression synergistically in Caki-1 renal cancer cells: Direct suppression of survivin and enhancement of transfection efficiency by topotecan

Survivin is an apoptosis inhibitor found in many tumors but not in most normal differentiated tissues, which makes it an exciting target for cancer therapy. Survivin expression has been shown to be associated with cell proliferation in renal cancer and we previously demonstrated the possibility of treating renal cancer with survivin-specific siRNA and topotecan, which increased the uptake of siRNA by KU19-20 renal cancer cells. We found in the present study that the combination of siRNA and topotecan inhibits survivin expression in Caki-1 renal cancer cells by another mechanism. Caki-1 renal cancer cells expressed higher level of survivin than KU19-20 cells did and survivin-specific siRNA alone suppressed survivin expression only slightly. The combination of topotecan and siRNA suppressed survivin expression completely and inhibited cell proliferation. Topotecan itself did not increase cellular uptake of siRNA but suppressed survivin expression. It also increased transfection efficiency without increasing cellular uptake of siRNA. Although the mechanism of action varies between cell lines, combination therapy using topotecan and siRNA should offer an attractive approach for treatment of advanced renal cancer.