Comparison between the effects of deep and moderate neuromuscular blockade during transurethral resection of bladder tumor on endoscopic surgical condition and recovery profile: a prospective, randomized, and controlled trial.

PURPOSE: To compare between deep neuromuscular blockade (NMB) and moderate NMB with respect to endoscopic surgical conditions and recovery profiles in patients with general anesthesia for transurethral resection of bladder (TURB). METHODS: 108 patients undergoing elective TURB were randomized into two groups: the moderate NMB (n = 54) or deep NMB (n = 54) group. After the operation, NMB was reversed with 2 mg/kg sugammadex at a train-of-four (TOF) count of 1 or 2 (moderate NMB group) or with 4 mg/kg sugammadex at post-tetanic count (PTC) of 2 (deep NMB group). Surgeons, who were blinded to the study design, rated the endoscopic surgical condition on a 5-point scale (1 = extremely poor, 2 = poor, 3 = acceptable, 4 = good, 5 = optimal) immediately following the operation. Recovery profiles, including postoperative residual curarization (PORC), respiratory complication, and recovery time, were recorded. RESULTS: No difference was observed between the two groups regarding patients and anesthesia characteristics. There were statistically significant differences in endoscopic surgical conditions between the two groups (P < 0.001). Thirty-eight patients in the deep NMB group (74%) showed optimal surgical conditions, whereas 16 patients in the moderate NMB group (30%) showed optimal endoscopic surgical conditions. No PORC and respiratory complications occurred in both groups, and no difference was found between the two groups in terms of recovery profiles, including recovery time and other adverse events. CONCLUSIONS: Deep NMB and reversal with sugammadex improved the endoscopic surgical condition without complications compared with moderate NMB and reversal with sugammadex in patients undergoing TURB.

Clinicopathological features and outcome of type 3 gastric neuroendocrine tumours.

BACKGROUND: With the widespread use of endoscopy, small and low-grade type 3 gastric neuroendocrine tumours (NETs) are increasingly being detected. The clinicopathological features, biological behaviour and appropriate treatment strategy for these NETs remain unclear. METHODS: Patients with biopsy-proven gastric NET and a normal fasting serum gastrin level were identified from a prospectively maintained database. Clinicopathological features and long-term outcome of local resection for type 3 NETs were reviewed retrospectively and compared according to tumour grade. RESULTS: Some 32 patients with type 3 gastric NETs were included (25 patients with NET grade G1, 5 with G2 and 2 with G3). Pathological tumour size was 2·0 cm or less in 30 patients. All tumours were well differentiated, even G3 lesions, and all tumours but one were confined to the submucosal layer. G1 NETs were significantly smaller and had a significantly lower lymphovascular invasion rate than G2 and G3 NETs. Twenty-two patients with a G1 NET without lymphovascular invasion were treated with wedge or endoscopic resection. After a median follow-up of 59 (range 6-102) months, no patient with a G1 NET of 1·5 cm or smaller developed recurrence and one patient with a G1 NET larger than 1·5 cm had recurrence in a perigastric lymph node. Among seven patients with a G2 or G3 NET, two had lymph node metastasis and one had liver metastases. CONCLUSION: Low-grade type 3 gastric NET has non-aggressive features and a favourable prognosis. Wedge or endoscopic resection may be a valid option for patients with type 3 gastric G1 NET no larger than 1·5 cm without lymphovascular invasion.

Granulocyte macrophage - colony stimulating factor (GM-CSF) significantly enhances articular cartilage repair potential by microfracture.

OBJECTIVE: To investigate whether granulocyte macrophage-colony stimulating factor (GM-CSF) can be used to increase the number of mesenchymal stem cells (MSCs) in blood clots formed by microfracture arthroplasty (MFX) and whether it can improve the therapeutic outcome for cartilage repair. METHODS: Thirty-six New Zealand white rabbits were divided into four groups: (1) control, (2) GM-CSF, (3) MFX, and (4) GM-CSF + MFX. GM-CSF was administrated intravenously (IV) at 10 µg/kg body weight 20 min before the MFX surgery. The repaired tissues were retrieved and examined by histological observation, quantitative assessment, and biochemical assays at 4, 8, and 12 weeks after treatment. The number of MSCs was measured in the blood clots by the colony forming unit-fibroblast (CFU-F) assay. The kinetic profile and distribution of GM-CSF in vivo was also evaluated by near-Infrared (NIR) fluorescence imaging and enzyme-linked immune sorbent assay. RESULTS: In the histological observations and chemical assays examined at 4, 8, and 12 weeks, the MFX after GM-CSF administration showed better cartilage repair than the one without GM-CSF. The CFU-F assay showed a significantly larger amount of MSCs present in the blood clots of the GM-CSF + MFX group than in the blood clots of the other groups. The blood concentration of GM-CSF peaked at 10 min and decreased back to almost the initial level after a couple of hours. GM-CSF was distributed in many organs including the bone marrow but was not observed clearly in the joint cavity. CONCLUSION: Intravenous administration of GM-CSF together with MFX could be a promising therapeutic protocol to enhance the repair of cartilage defects.

Influence of esophagectomy on the gastroesophageal reflux in patients with esophageal cancer.

This study aims to assess the influence of esophagectomy with gastric transposition on the gastroesophageal reflux (GER) and gastric acidity in patients with esophageal cancer. Data on 53 esophageal cancer patients who underwent 24-hour impedance-pH monitoring after esophagectomy were retrospectively analyzed. We used a solid-state esophageal pH probe in which the esophageal pH sensor is placed 1.5 cm distal to the upper esophageal sphincter and the gastric pH sensor is located 15 cm distal to the esophageal pH channel. 24-hour impedance-pH monitoring data and other clinical data including anastomosis site stricture and incidence of pneumonia were collected. We defined pathologic reflux with reference to known normative data. Stricture was defined when an intervention such as bougienage or balloon dilatation was required to relieve dysphagia. The esophageal and gastric mean pH were 5.47 ± 1.51 and 3.33 ± 1.64, respectively. The percent time of acidic pH (<4) was 6.66 ± 12.49% in the esophagus and 70.53 ± 32.19% in the stomach. Esophageal pathologic acid reflux was noticed in 32.1%, 20.8%, and 35.8% during total, upright, and recumbent time, respectively. Esophageal pathologic bolus reflux was noted in 83.0%, 77.4%, and 64.2% during total, upright, and recumbent time, respectively. Gastric acidity increased with time after esophagectomy. Esophageal acid exposure time correlated with intragastric pH. However, esophageal pathologic acid reflux was not associated with anastomosis site stricture or pneumonia. In conclusion, GER frequently occurs after esophagectomy. Thus, strict lifestyle modifications and acid suppression would be necessary in patients following esophagectomy.

Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets.

Pig islets are an alternative source for islet transplantation to treat type 1 diabetes (T1D), but reproducible curative potential in the pig-to-nonhuman primate (NHP) model has not been demonstrated. Here, we report that pig islet grafts survived and maintained normoglycemia for >6 months in four of five consecutive immunosuppressed NHPs. Pig islets were isolated from designated pathogen-free (DPF) miniature pigs and infused intraportally into streptozotocin-induced diabetic rhesus monkeys under pretreatment with cobra venom factor (CVF), anti-thymocyte globulin (ATG) induction and maintenance with anti-CD154 monoclonal antibody and low-dose sirolimus. Ex vivo expanded autologous regulatory T cells were adoptively transferred in three recipients. Blood glucose levels were promptly normalized in all five monkeys and normoglycemia (90-110 mg/dL) was maintained for >6 months in four cases, the longest currently up to 603 days. Intravenous glucose tolerance tests during the follow-up period showed excellent glucose disposal capacity and porcine C-peptide responses. Adoptive transfer of autologous regulatory T cells was likely to be associated with more stable and durable normoglycemia. Importantly, the recipients showed no serious adverse effects. Taken together, our results confirm the clinical feasibility of pig islet transplantation to treat T1D patients without the need for excessive immunosuppressive therapy.

Effect of rescue surgery after non-curative endoscopic resection of early gastric cancer.

BACKGROUND: Whether rescue surgery confers a survival benefit in patients undergoing non-curative endoscopic resection of early gastric cancer remains controversial. METHODS: This was a retrospective review of patients who underwent non-curative endoscopic resection of at least one lesion of differentiated-type early gastric cancer between 2000 and 2011. Patients with a positive lateral resection margin as the only non-curative factor were excluded. Outcome was investigated by univariable (Kaplan-Meier) and multivariable (Cox proportional hazards) analysis. RESULTS: Some 341 patients underwent non-curative endoscopic resection for at least one lesion of differentiated-type early gastric cancer. Sixty-seven patients with a positive lateral resection margin as the only non-curative factor were excluded, leaving 274 patients for analysis; 194 had rescue surgery and 80 had no additional treatment. The median duration of follow-up was 60·5 months. Patients who had rescue surgery were younger, had a lower Charlson co-morbidity index score, smaller tumours and a higher lymphovascular invasion rate than patients with no treatment. Among 194 patients who had rescue surgery, intragastric local residual tumours were found in ten (5·2 per cent) and lymph node metastases in 11 (5·7 per cent). Patients with lymph node metastasis were significantly older than those without metastasis; no other significant differences were found. Univariable analysis showed that patients aged less than 65 years, those with a Charlson co-morbidity index score below 4 and patients undergoing rescue surgery had significantly longer overall survival. Five-year overall survival rates in the rescue surgery and no-treatment groups were 94·3 and 85 per cent respectively. In multivariable analysis, rescue surgery was identified as the only independent predictor of overall survival after non-curative endoscopic resection of early gastric cancer. CONCLUSION: Rescue surgery confers a survival benefit after non-curative endoscopic resection of early gastric cancer.

Polyethylene wear particles play a role in development of osteoarthritis via detrimental effects on cartilage, meniscus, and synovium.

OBJECTIVE: While ultra-high molecular weight polyethylene (UHMWPE) wear particles are known to cause periprosthetic osteolysis, its interaction with other intra-articular tissues in the case of partial joint arthroplasties is not well understood. We hypothesized that UHMWPE particles per se would interact with intra-articular tissue, which by acting as inflammatory reservoirs, would subsequently induce osteoarthritic (OA) changes. Our goal was to assess the inflammatory response, phagocytic activity, as well as apoptosis of intra-articular cells in the presence of UHMWPE particles in vitro, and the in vivo response of those tissues after intra-articular injection of particles in a murine model. DESIGN: Three cell types were used for the in vitro study; chondrocytes, meniscal fibrochondrocytes, and synoviocytes. Each cell type was cultured with two different concentrations of UHMWPE particles. Pro-inflammatory cytokine production, phagocytosis, and apoptosis were analyzed. In vivo experiments were done by injecting two concentrations of UHMWPE particles into normal and murine OA model knee joints. RESULTS: In vitro experiments showed that UHMWPE particles increase pro-inflammatory cytokine and mediator (IL-1ß, IL-6, TNF-α, Nitric Oxide, and Prostaglandin E2) production, phagocytosis of particles, and apoptosis in all cell types. In vivo experiment showed degeneration of cartilage and meniscus, as well as synovitis after particle injection. CONCLUSIONS: UHMWPE wear particles per se exert detrimental effects in cartilage, synovium, and meniscus of the knee joint resulting in pro-inflammatory cytokine release, phagocytosis of particles and apoptosis. Particles induced and exacerbated OA changes in a murine model.

Establishment of a reliable and reproducible murine osteoarthritis model.

OBJECTIVE: Many osteoarthritis (OA) models have been developed in mice to understand OA progression and evaluate new OA therapies. However, the individual variation of the joint lesions remains a critical problem in most of the current OA models. We established an OA model in C57BL/6 mice that is more reproducible and amenable to therapeutic intervention by controlling their movement. DESIGN: OA was induced in 9-week-old C57BL/6 mice by destabilizing the medial meniscus. The mice were then raised in the standard cage for free movement or in a confined cage customized to restrict movement. Mice in the confined cage were subjected to no exercise or exercise of 400, 800, and 1200 m/day. RESULTS: OA lesions of mice in the confined cage were more severe in the exercise group and showed much less variation. However, the patterns of OA lesions over time were quite different depending on the amount of daily exercise; the patterns increased linearly until 8 weeks in 400 m/day exercise group, but showed plateauing after 4 weeks in 800 m/day and 1200 m/day groups. The validity of our novel OA model with movement control was proven by successfully discriminating the therapeutic effect of hyaluronic acid (HA) in histological scores, while the OA model using standard caging showed a statistically insignificant difference. CONCLUSION: The mouse OA model using the confine cage and enforced periodic exercise of mice is more reproducible and reliable than standard caging methods.

Feasibility and efficacy of argon plasma coagulation for early esophageal squamous cell neoplasia.

We present 19 cases in which argon plasma coagulation (APC) was used as curative initial treatment for 5 low-grade esophageal squamous intraepithelial neoplasias (ESINs), 12 high-grade ESINs, and 2 early esophageal squamous cell carcinomas (ESCCs). Complete response was defined as the absence of tumor from any biopsy taken from the ablated lesion. At follow-up endoscopy 2 - 4 months after APC, 94.7 % of patients had achieved complete response in a single treatment session. Only one patient with high-grade ESIN showed local recurrence. This patient underwent additional APC and showed complete response at 12 months after initial APC. At the 12-month follow-up endoscopy, again 94.7 % had a complete response. The exception was one patient with local recurrence, who underwent additional APC. After the 12-month follow-up endoscopy, no patient showed local recurrence during a median follow-up of 22 months. No stricture requiring endoscopic dilation occurred after the procedure. This study suggests that APC is a feasible and effective treatment modality for ESIN and early ESCC.

Anti-inflammatory effect of low intensity ultrasound (LIUS) on complete Freund's adjuvant-induced arthritis synovium.

OBJECTIVES: Arthritis with intra-articular inflammation was accompanied by joint pain, swelling, and stiffness leading to significant functional impairment. Thus, regulation of joint inflammation is a good therapeutic approach for patients with arthritis. In this study, the effect of low intensity ultrasound (LIUS) applied to an adjuvant-induced arthritic rat model on the synovium was investigated. DESIGN: Synovial inflammation was induced by complete Freund's adjuvant (CFA)-injection into the rat knee joint. LIUS (200 mW/cm(2)) was applied on the ipsilateral knee everyday for 10 min beginning 1 day after inflammation induction. The expression of proinflammatory factors and immunohistochemical staining pattern of the synovium were assessed. RESULTS: CFA induced an increase of the knee circumference that was significantly diminished by LIUS. Synovial membrane hyperplasia in the ipsilateral joint was also affected by LIUS. The inflammatory mediators, COX-1/2, IL-1ß, and iNOS, but not TNF-α, in the synovial membrane were induced after 3 days, and they closely correlated with the degree of edema. In the synovial membrane, the expression of inflammatory mediators was reduced by LIUS. The chemoattractant chemokine receptor CCR5 also was involved. On immunohistochemical analysis, CFA caused increased infiltration of CD11b-positive cells in the synovium. After 3 days, neutrophils, myeloperoxidase (MPO)-positive cells filled the inflammatory core; later, monocytes and macrophages, ionized calcium binding adaptor molecule 1 (Iba1)-positive cells in the periphery infiltrated the core by day 5. LIUS markedly reduced CFA-induced inflammatory cells infiltration. CONCLUSION: LIUS showed a potent anti-inflammatory effect in this animal arthritis model with reduced infiltration of inflammatory cells into the synovium.

Predictive factors for lymph node metastasis in patients with poorly differentiated early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection is gaining popularity in the treatment of early gastric cancer. This study aimed to identify clinicopathological factors predictive of lymph node metastasis in patients with the poorly differentiated early gastric cancer to assess the feasibility of using endoscopic submucosal dissection for these cancers. METHODS: The records of patients with poorly differentiated early gastric cancer who had undergone gastric cancer surgery between January 2002 and December 2009 were reviewed. Associations between clinicopathological factors and the presence of lymph node metastasis were analysed by univariable and multivariable logistic regression analysis. RESULTS: Some 1005 patients were included in the analysis. Univariable analysis indicated that lymph node metastasis was associated with sex, ulceration, tumour size, depth of invasion, macroscopic type, lymphatic invasion and venous invasion. Logistic regression revealed that lymph node metastasis was significantly associated with sex, tumour size, depth of tumour invasion and lymphatic involvement. In the group with none of these risk factors (men with mucosal tumour no larger than 2 cm in size, with no lymphatic involvement), lymph node metastasis was present in four (3·2 per cent) of 124 patients. CONCLUSION: In the present study 3·2 per cent of patients who were negative for all identified risk factors had lymph node metastasis. The use of endoscopic submucosal dissection should be considered carefully in the treatment of poorly differentiated early gastric cancer.

Gastric extremely well-differentiated intestinal-type adenocarcinoma: a challenging lesion to achieve complete endoscopic resection.

Extremely well-differentiated tubular adenocarcinomas (EWDAs) of the stomach are characterized by surface maturation and their mimicking of intestinal metaplasia. Endoscopically, intramucosal EWDAs are frequently ill defined with indistinct borders due to the pallor of the neoplastic mucosa and the lack of contrast against the background atrophic and metaplastic mucosa. We evaluated the effectiveness of endoscopic resection for EWDAs after endoscopic submucosal dissection (ESD). Among 872 patients with early gastric cancer, 17 EWDAs were identified (1.9 %). Endoscopically, the flat or depressed type was significantly more common among EWDAs (88.2 %) than among early gastric cancers of other histologies (37.8 %; P < 0.01). The discrepancy between endoscopically estimated tumor size and tumor size as confirmed in pathology reports was significantly greater among EWDAs (18.4 ±â€Š22.0  mm) than among others (5.8 ±â€Š7.5  mm). Involvement of the lateral resection margin was more common (29.4 % vs. 2.5 %; P < 0.05), and complete resection was achieved less often in EWDAs (47.1 % vs. 80.4 %; P = 0.01) compared to the others. EWDAs are associated with higher rates of incomplete resection after ESD, especially along the lateral margins. Pathologists should alert endoscopists when this diagnosis is made, with its associated risks; and endoscopists should pay particular attention to the extent of these tumors during resection.

Implantation of bone marrow-derived buffy coat can supplement bone marrow stimulation for articular cartilage repair.

OBJECTIVE: Bone marrow stimulation (BMS) has been regarded as a first line procedure for repair of articular cartilage. However, repaired cartilage from BMS is known to be unlike that of hyaline cartilage and its inner endurance is not guaranteed. The reason presumably came from a shortage of cartilage-forming cells in blood clots derived by BMS. In order to increase repairable cellularity, the feasibility of autologous bone marrow-derived buffy coat transplantation in repair of large full-thickness cartilage defects was investigated in this study. METHODS: Rabbits were divided into four groups: the defect remained untreated as a negative control; performance of BMS only (BMS group); BMS followed by supplementation of autologous bone marrow buffy coat (Buffy coat group); transplantation of autologous osteochondral transplantation (AOTS) as a positive control. RESULTS: Repair of cartilage defects in the Buffy coat group in a rabbit model was more effective than BMS alone and similar to AOTS. Gross findings, histological analysis, histological scoring, immunohistochemistry, and chemical assay demonstrated that supplementation of autologous bone marrow buffy coat after BMS arthroplasty effectively repaired cartilage defects in a rabbit model, and was more effective than BMS arthroplasty alone. CONCLUSION: Supplementation of autologous bone marrow-derived buffy coat in cases of BMS could be a useful clinical protocol for cartilage repair.

Comparison of a novel teeth-protecting mouthpiece with a traditional device in preventing endoscopy-related complications involving teeth or temporomandibular joint: a multicenter randomized trial.

BACKGROUND AND STUDY AIMS: After upper endoscopy, patients have complained of symptoms involving teeth or the temporomandibular joint; however, these endoscopy-related complications are usually ignored with few attempts to prevent them. The aim of this study was to identify the incidence of endoscopy-related complications involving teeth or temporomandibular joint, and to compare the effectiveness of a newly developed teeth-protecting mouthpiece (TPM) with a traditional mouthpiece (the MB-142) in preventing these complications. PATIENTS AND METHODS: 872 patients from 28 centers, who were undergoing their first upper endoscopy, were randomly assigned to TPM and MB-142 groups. At 3 - 4 days after the procedure, the occurrence of endoscopy-related complications involving the teeth or the temporomandibular joint was investigated using a structured questionnaire. Finally 865 patients (TPM group, n = 423; MB-142, n = 442) responded to this questionnaire and were included in the analysis. RESULTS: Overall, the incidence of complications was significantly lower in the TPM than in the MB-142 group (0.9% vs. 3.2%). With stratification according to sedation status, in nonsedated patients no significant difference was found between the two groups (0.7% vs. 0.9%). In sedated patients, however, the TPM group showed a significantly lower incidence of complication than the MB-142 group (1.7% vs. 11.6%). Clinically serious problems such as a tooth fracture or a loose tooth occurred only in sedated patients in the MB-142 group. CONCLUSIONS: The TPM showed an advantage over the MB-142 mouthpiece for preventing endoscopy-related complications involving teeth or the temporomandibular joint.

Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high-resolution manometry system.

BACKGROUND: Integrated relaxation pressure (IRP) is a key metric for diagnosing esophagogastric junction outflow obstruction (EGJOO). However, its normal value might be different according to the manufacturer of high-resolution manometry (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO in Sandhill HRM and to find clinicomanometric variables to segregate clinically relevant EGJOO. METHODS: We analyzed 262 consecutive subjects who underwent HRM between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but did not satisfy criteria for achalasia. Clinically relevant subjects were defined as follows: (i) subsequent HRM met achalasia criteria during follow-up (early achalasia); (ii) Eckardt score was decreased at least two points without exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii) significant passage disturbance on esophagogram without structural abnormality (possible achalasia). KEY RESULTS: Seven subjects were clinically relevant, including two subjects with early achalasia, four subjects with variant achalasia, and one subject with possible achalasia. All clinically relevant subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or more, clinically relevant group (n = 7) had significantly higher rate of dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7% vs 21.7%, P = .001) compared to clinically non-relevant group (n = 115). CONCLUSIONS & INFERENCES: Our results suggest that IRP of 20 mm Hg or higher could segregate clinically relevant subjects showing EGJOO in Sandhill HRM. Additionally, if subjects have both dysphagia and compartmentalized pressurization, careful follow-up is essential.

Mechanotransduction pathways of low-intensity ultrasound in C-28/I2 human chondrocyte cell line.

Low-intensity ultrasound (LIUS) has recently been considered to be an effective method to induce cartilage repair and/or regeneration after injury. Nevertheless, there is no study to provide a cellular mechanism or signal pathways of LIUS stimulation. The current study is designed to investigate the effects of LIUS on the mechanotransduction pathways in C-28/I2, an immortalized human chondrocyte cell line. C-28/I2 cells were treated with LIUS at an intensity of 200 mW/cm2 using Noblelife from Duplogen. The role of stretch-activated channels (SAC) and integrins that are most well-known mechanoreceptors on the chondrocyte cell surface was first examined in mediating the LIUS effects on the expression of type II collagen and aggrecan. When analysed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, gadolinium (a specific inhibitor of SACs) or GRGDSP (a peptide inhibitor of integrins) specifically reduced the LIUS-induced elevation of type II collagen and aggrecan expressions depending on the incubation time. In addition, the LIUS treatment of C-28/I2 cells induced the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) but not p38 kinase among the members of the mitogen-activated protein kinases (MAPKs). The phosphorylation of ERK by LIUS was repressed by a specific inhibitor of the ERK pathway and integrin function. These results suggest that the LIUS signal might be mediated via canonical mechanoreceptors of SACs and integrins and subsequently through JNK and ERK pathways. The present study provides the first evidence for the activation of the mechanotransduction pathways by LIUS in human chondrocytes.

The fate of implanted autologous chondrocytes in regenerated articular cartilage.

Autologous chondrocyte implantation (ACI) is used to treat some articular cartilage defects. However, the fate of the cultured chondrocytes after in-vivo transplantation and their role in cartilage regeneration remains unclear. To monitor the survival and fate of such cells in vivo, the chondrocytes were labelled with a lipophilic dye and the resultant regenerated tissue in dogs examined. It was found that, 4 weeks after implantation, the osteochondral defects were filled with regenerative tissue that resembled hyaline cartilage. Fluorescence microscopy of frozen sections of the regenerated tissue revealed that the majority of cells were derived from the DiI-labelled implanted chondrocytes. From these results, it was concluded that a large population of implanted autologous chondrocytes can survive at least 4 weeks after implantation and play a direct role in cartilage regeneration. However, it remains unknown whether other cells, such as periosteal cells or bone marrow stromal stem cells, are involved in the regeneration of cartilage after ACI.

The developmental biology of induced malignant melanoma in guinea pigs and a comparison with other neoplastic systems.

Malignant melanoma has been induced in the Weiser-Maple guinea pig by prolonged application of 7,12-dimethylbenz(a)anthracene. The tumor shows a biphasic growth pattern analogous to the radial and vertical growth phase of human cutaneous malignant melanoma. It evolves through a predictable series of cellular events classified as intraepidermal melanocytic hyperplasia, dermal melanocytosis, dermal melanocytoma, malignant melanoma without intralesional transformation, and, finally, malignant melanoma with intralesional transformation, which is characterized by the appearance of "new kinds of cells" and is associated with widespread metastases and massive lymph node involvement. Clinically, the lesions evolve from diffuse hyper-pigmentation to brown-black macules, to nodules of increasing size, to overt malignant melanoma associated with metastases, wasting, and death. Examples of intralesional transformation analogous to that in guinea pigs are found not only in human malignant melanomas, but in other human neoplastic systems, and such analogous cellular events are discussed in this paper.

Interplay of charge density wave and multiband superconductivity in 2H-PdxTaSe2.

2H-TaSe2 has been one of unique transition metal dichalcogenides exhibiting several phase transitions due to a delicate balance among competing electronic ground states. An unusual metallic state at high-T is sequentially followed by an incommensurate charge density wave (ICDW) state at ≈122 K and a commensurate charge density wave (CCDW) state at ≈90 K, and superconductivity at TC ~ 0.14 K. Upon systematic intercalation of Pd ions into TaSe2, we find that CCDW order is destabilized more rapidly than ICDW to indicate a hidden quantum phase transition point at x ~ 0.09-0.10. Moreover, TC shows a dramatic enhancement up to 3.3 K at x = 0.08, ~24 times of TC in 2H-TaSe2, in proportional to the density of states N(EF). Investigations of upper critical fields Hc2 in single crystals reveal evidences of multiband superconductivity as temperature-dependent anisotropy factor γH = , quasi-linear increase of , and an upward, positive-curvature in near TC. Furthermore, analysis of temperature-dependent electronic specific heat corroborates the presence of multiple superconducting gaps. Based on above findings and electronic phase diagram vs x, we propose that the increase of N(EF) and effective electron-phonon coupling in the vicinity of CDW quantum phase transition should be a key to the large enhancement of TC in PdxTaSe2.

The 7 × 1 Fermi Surface Reconstruction in a Two-dimensional f -electron Charge Density Wave System: PrTe3.

The electronic structure of a charge density wave (CDW) system PrTe3 and its modulated structure in the CDW phase have been investigated by employing ARPES, XAS, Pr 4 f RPES, and first-principles band structure calculation. Pr ions are found to be nearly trivalent, supporting the CDW instability in the metallic Te sheets through partial filling. Finite Pr 4 f spectral weight is observed near the Fermi level, suggesting the non-negligible Pr 4 f contribution to the CDW formation through the Pr 4 f -Te 5p hybridization. The two-fold symmetric features in the measured Fermi surface (FS) of PrTe3 are explained by the calculated FS for the assumed 7 × 1 CDW supercell formation in Te sheets. The shadow bands and the corresponding very weak FSs are observed, which originate from both the band folding due to the 3D interaction of Te sheets with neighboring Pr-Te layers and that due to the CDW-induced FS reconstruction. The straight vertical FSs are observed along kz, demonstrating the nearly 2D character for the near-EF states. The observed linear dichroism reveals the in-plane orbital character of the near-EF Te 5p states.