Frequency response in bone joint acoustic sensor development.

BACKGROUND: Elderly people are often affected by age-related knee osteoarthritis (KOA). The development of sensors for measuring and diagnostic devices used in preventive healthcare of that illness therefore constitutes an urgent issue. OBJECTIVE: After developing a bone joint acoustic sensor (BJAS) that receives signals of mechanical vibrations in the knee joints during bending and stretching motions, we tested it and compared responses with those of an acceleration sensor used as a reference. METHODS: For six examinees in their 20 s, using an acceleration sensor as a reference for comparison with BJAS, we conducted two frequency-response tests of impact excitation and knee bending and stretching. For impact excitation tests, two transmission systems of hard materials and soft materials were applied. We examined the cross spectral density, coherence function, Fourier transform and quantified signal. RESULTS: Although BJAS detected signals of 0.5-15.0 kHz in impact excitation tests, considerably strong damping was found for soft specimens at higher frequencies. Therefore, acceleration sensors showed superiority over BJAS for impact excitation. However, for knee bending and stretching, BJAS detected signal frequencies of 0.5-8.0 kHz for all six examinees. BJAS demonstrated marked superiority over the acceleration sensor. Furthermore, we were able to quantify the signal intensity for each frequency for comparison. CONCLUSIONS: The BJAS frequency response was superior to that of the acceleration sensor for capturing signals from knee bending and stretching. This superiority suggests its promise for application to clarify mechanical signals from knees.

The "sliding door" technique for closure of abdominal wall defects after rectus abdominis musculocutaneous flap transposition.

Radical surgery is often necessary in patients with local recurrence of rectal cancer or in those with carcinoma associated with an anal fistula. The surgery may include extended excision of the perineal area and can create a large dead space in the pelvis and a large skin defect, often necessitating reconstruction of the pelvic floor using rectus abdominis musculocutaneous (RAM) flap transposition. Wound dehiscence and incisional hernia are common complications of RAM flap transposition. We report herein our encounter with 3 patients in whom we used a "sliding door" technique for reconstruction of the abdominal wall after the creation of a RAM flap. One patient underwent abdominoperineal resection with sacrectomy and RAM flap transposition; he experienced a postoperative surgical site infection and wound dehiscence, which we urgently repaired by reconstructing the abdominal wall using the sliding door technique. Two other patients underwent posterior pelvic exenteration with sacrectomy and RAM flap transposition. These patients underwent simultaneous abdominal wall reconstruction using the sliding door technique. No patient experienced postoperative pelvic sepsis, wound dehiscence, or incisional hernia. The sliding door technique might be useful for preventing wound dehiscence and incisional hernia in patients undergoing RAM flap transposition.

Survival of microencapsulated islets at 400 days posttransplantation in the omental pouch of NOD mice.

The long-term durability of agarose microencapsulated islets against autoimmunity was evaluated in NOD mice. Islets were isolated from 6-8-week-old prediabetic male NOD mice and microencapsulated in 5% agarose hydrogel. Microencapsulated or nonencapsulated islets were transplanted into the omental pouch of spontaneously diabetic NOD mice. Although the diabetic NOD mice that received nonencapsulated islets experienced a temporary reversal of their hyperglycemic condition, all 10 of these mice returned to hyperglycemia within 3 weeks. In contrast, 9 of 10 mice transplanted with microencapsulated islets maintained normoglycemia for more than 100 days. Islet grafts were removed at 100, 150, 200, 300, and 400 days posttransplantation. A prompt return to hyperglycemia was observed in the mice after graft removal, indicating that the encapsulated islet grafts were responsible for maintaining euglycemia. Histological examination revealed viable islets in the capsules at all time points of graft removal. In addition, beta-cells within the capsules remained well granulated as revealed by the immunohistochemical detection of insulin. No immune cells were detected inside the microcapsules and no morphological irregularities of the microcapsules were observed at any time point, suggesting that the microcapsules successfully protected the islets from cellular immunity. Sufficient vascularization was evident close to the microcapsules. Considerable numbers of islets showed central necrosis at 400 days posttransplantation, although the necrotic islets made up only a small percentage of the islet grafts. Islets with central necrosis also showed abundant insulin production throughout the entire islets, except for the necrotic part. These results demonstrate the long-term durability of agarose microcapsules against autoimmunity in a syngeneic islet transplantation model in NOD mice.

Primary leiomyoma of the liver: report of a case.

We report a case of primary leiomyoma of the liver. A 71-year-old man was admitted for investigation of a mass lesion in his liver, detected on ultrasonography. Computed tomography (CT) showed a solid tumor, 3 cm in diameter, in the caudate lobe of the liver. He underwent partial hepatectomy, and histological findings of the resected specimen revealed the proliferation of spindle cells, which formed a pattern of interlacing bundles, without any evidence of malignancy. The tumor cells were not immunoreactive to c-kit or S-100, but they were immunoreactive to alpha-smooth muscle actin. No other lesion was found elsewhere in the body. Thus, the tumor was diagnosed as a primary leiomyoma of the liver.

The membrane-anchored matrix metalloproteinase (MMP) regulator RECK in combination with MMP-9 serves as an informative prognostic indicator for colorectal cancer.

PURPOSE: RECK, a membrane-anchored regulator of matrix metalloproteinases (MMPs), is widely expressed in healthy tissue, whereas it is expressed at lower levels in many tumor-derived cell lines. Studies in mice and cultured cells have shown that restoration of RECK expression inhibits tumor invasion, metastasis, and angiogenesis. However, the clinical relevance of these findings remains to be fully documented. Here we examined the expression of RECK and one of its targets, MMP-9, in colorectal cancer tissue. EXPERIMENTAL DESIGN: The RECK and MMP-9 expression levels in colorectal cancer samples from 53 patients were determined by immunohistochemical techniques. The expression level of each protein was scored, and the patients were divided into two groups based on these scores. In 33 cases, we performed gelatin zymography to estimate the degree of MMP-2 and MMP-9 activation. Microvessel density and vascular endothelial growth factor (VEGF) expression were also evaluated histologically. RESULTS: RECK protein was detected in 30 of 53 (56.6%) specimens. Importantly, patients with tumors expressing relatively high levels of RECK (high-RECK group) had a significantly lower risk of recurrence than did patients with tumors expressing relatively low levels of RECK (low-RECK group; P = 0.011). Moreover, RECK-dominant (RECK score > or = MMP-9 score) patients showed a significantly lower incidence of recurrence than did MMP-9-dominant patients (P = 0.0003). Multivariate analysis revealed that the RECK/MMP-9 balance was an independent prognostic factor (P = 0.0122). The expression of VEGF and microvessel density were inversely correlated with the level of RECK expression. CONCLUSIONS: RECK/MMP-9-balance is an informative prognostic indicator for colorectal cancer. Our data also suggest that RECK suppresses tumor angiogenesis, probably by limiting the availability of VEGF in tumor tissues.

The breakdown of apoptotic mechanism in the development and progression of colorectal carcinoma.

BACKGROUND: Fas (APO-1/CD95) is a cell surface receptor that mediates apoptosis when it reacts with Fas ligand (FasL) or Fas antibody. Alterations of Fas and FasL expression have been demonstrated in various carcinomas. MATERIALS AND METHODS: We examined the alteration of Fas and FasL expression in seventy-eight specimens of colorectal adenoma and carcinoma by immunohistochemistry and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Our study revealed that the expression of Fas was reduced in colorectal adenoma and completely lost in some 60% of colorectal carcinomas. Fas expression was significantly down-regulated in liver metastasis compared with corresponding primary colorectal carcinoma. The expression of Fas significantly related to p53 status, tumor location and apoptosis in colorectal carcinoma. Up-regulation of FasL was not detected in colorectal adenoma, carcinoma cells and liver metastatic cancer cells. CONCLUSION: These results indicate that Fas may play an important role, not only in development but also progression, and that FasL is not always required for both development and progression in colorectal carcinomas.

Bone marrow chimerism and tolerance induced by single-dose cyclophosphamide.

BACKGROUND: Establishment of hematopoietic chimerism is the most stable strategy for donor-specific tolerance. Safer pretreatment regimens are needed for clinical application. We evaluated the efficacy of a simple protocol using cyclophosphamide (CYP) on induction of chimerism and organ transplant tolerance across major histocompatibility complex (MHC) barriers in the rat. MATERIALS AND METHODS: Bone marrow cells from BN (RT1(n)) donors were infused to LEW (RT1(l)) recipients on day 0 after a single injection of CYP at various doses on day -1. Donor-derived hematopoietic chimerism was evaluated by flowcytometry. The recipients received BN or third party (BUF) heart allografts on day 100. RESULTS: While pretreatment with 200 mg/kg of CYP induced high levels of hematopoietic chimerism, six of eight recipients died of severe graft-versus-host-disease (GVHD). CYP at dose of 150 mg/kg induced 36.5 +/- 24.1% of donor-derived chimerism on day 10, and sustained macrochimerism was seen until day 100 without GVHD. Pretreatment with 100 mg/kg of CYP resulted in only transient chimerism (4.8 +/- 5.2%) which disappeared by day 20. In the recipients with 50 mg/kg of CYP, donor bone marrow cells were rapidly rejected and no chimerism was observed. The recipients with 150 mg/kg of CYP accepted BN heart allografts (>100 days x 5), while rejecting BUF allografts by day 12 (n = 4). BN heart allografts were rejected in the recipients with 100 (MST: 57 days, n = 5) and 50 mg/kg (MST: 7 days, n = 5) of CYP. CONCLUSIONS: A single dose of CYP can induce hematopoietic chimerism across MHC-barriers. The dose of 150 mg/kg seems to be optimal to induce organ transplant tolerance without developing GVHD.

Prognostic significance of death-associated protein-kinase expression in hepatocellular carcinomas.

BACKGROUND: Disorder of programmed cell death (PCD) contributes to the pathogenesis and the progression of various cancers. Death-associated protein-kinase(DAP-kinase) was isolated as a positive mediator of apoptosis induced by IFN-gamma. It has been reported that the loss or reduction of DAP-kinase expression was detected in various human tumor cell lines and resulted from methylation of the DAP-kinase gene. MATERIALS AND METHODS: We investigated the expression of DAP-kinase protein by immunohistochemistry and Western-blotting in 43 patients with hepatocellular carcinoma (HCC). Additionally, we examined the methylation status of the DAP-kinase promoter region by methylation-specific polymerase chain reaction. RESULTS: In DAP-kinase-positive HCC cases(n = 16), serum AFP levels were lower (p = 0.009), tumor differentiation was higher (p = 0.048), histological portal invasion and metastatic foci were less (p = 0.004 and 0.016, respectively), apoptosis of tumor cells was more (p = 0.0009), and the disease-free survival rate and the overall survival rate were higher (p = 0.0057 and 0.0246, respectively), compared with DAP-kinase-negative cases. The status of DAP-kinase protein expression closely correlated with IFN-gamma-receptor and Fas expression (p = 0.038 and p < 0.0001, respectively), but not the methylation of promoter region. CONCLUSION: Hepatoma cells may escape from apoptosis through the loss or reduction of DAP-kinase expression, while the block of IFN-gamma signal transduction as well as the methylation of promoter region may reduce the expression of DAP-kinase protein.

Indefinite islet protection from autoimmune destruction in nonobese diabetic mice by agarose microencapsulation without immunosuppression.

BACKGROUND: The recurrence of autoimmunity and allograft rejection act as major barriers to the widespread use of islet transplantation as a cure for type 1 diabetes. The aim of this study was to evaluate the feasibility of immunoisolation by use of an agarose microcapsule to prevent autoimmune recurrence after islet transplantation. METHODS: Highly purified islets were isolated from 6- to 8-week-old prediabetic male nonobese diabetic (NOD) mice and microencapsulated in 5% agarose hydrogel as a semipermeable membrane. Islet function was evaluated by a syngeneic islet transplantation model, in which islets were transplanted into spontaneously diabetic NOD mice. RESULTS: The nonencapsulated islet grafts were destroyed and diabetes recurred within 2 weeks after transplantation in all 12 mice. In contrast, 13 of the 16 mice that underwent transplantation with microencapsulated islets maintained normoglycemia for more than 100 days after islet transplantation. Histologic examination of the nonencapsulated islet grafts showed massive mononuclear cellular infiltration with beta-cell destruction. In contrast, the microencapsulated islets showed well-granulated beta cells with no mononuclear cellular infiltration around the microcapsules or in the accompanying blood capillaries between the microcapsules. CONCLUSIONS: Agarose microcapsules were able to completely protect NOD islet isografts from autoimmune destruction in the syngeneic islet transplantation model.

Prognostic significance of HIF-1 alpha overexpression in human pancreatic cancer.

BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1 alpha) has been correlated with unfavorable prognosis in several cancers. The aim of this study was to investigate the impact of HIF-1 alpha expression on clinicopathological factors and to clarify whether or not HIF-1 alpha is correlated with angiogenesis and mutation of p53 in pancreatic cancer. MATERIALS AND METHODS: Using immunohistochemical methods, we examined the expression of HIF-1 alpha, vascular endothelial growth factor (VEGF), p53 and intratumoral microvessel density (IMD) in 55 cases of primary pancreatic cancer. RESULTS: Immunohistochemical studies showed that 40.0% cases were positive and the status of HIF-1 alpha was significantly correlated with metastatic status (p = 0.048), VEGF expression (p = 0.026) and IMD (p = 0.0061). HIF-1 alpha is significantly related to prognosis in pancreatic cancer. CONCLUSION: Our data demonstrate that pancreatic cancer widely expresses HIF-1 alpha, which contributes to angiogenesis and progression. Therefore, assessment of HIF-1 alpha expression might be useful for predicting the prognosis of pancreatic cancer patients.