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Objective 18F-labeled prostate-specific membrane antigen (PSMA) ligand, [18F]PSMA-1007, has the benefit of a higher synthetic yield and minimal excretion in the urine. High detection efficacy was reported in biochemical recurrence (BCR) of prostate cancer after radical prostatectomy. Thus, we evaluated the preliminary diagnostic utility of [18F]PSMA-1007 PET in patients with prostate cancer, focusing on the BCR which is not detected on conventional imaging. Methods We enrolled a total of 28 patients (age 51–79 years) with BCR of prostate cancer. BCR was defined as a continuous increase in PSA after radical prostatectomy or radiation therapy without any apparent recurrent lesions on conventional diagnostic imaging (CT and bone scintigraphy). PSMA-PET scanning was performed approximately 60 min after intravenous injection of [18F]PSMA-1007 (259 ± 37 MBq). PSMA-PET images were evaluated for lesion detection as well as its relation to PSA values and location. Results Abnormal uptake, which was suspected to be recurrence or metastasis, was detected in 92.9% (26/28) of patients with BCR. The SUVmax was 8.4 ± 6.4 in local recurrence, 11.5 ± 11.8 in pelvic lymph nodes (LN), and 4.1 ± 1.6 in bone metastasis. The detection rates were 66.7% in the PSA group-1 (0.1–0.5 ng/mL), 85.7% in the PSA group-2 (0.5–1.0 ng/mL), and 100% in the PSA group-3 (above 1.0 ng/mL). Among the PET-positive BCR patients (n = 26), local recurrence was detected in 57.7% (15/26), pelvic LN in 42.3% (11/26), and bone metastasis in 15.4% (4/26). In 53% (8/15) of BCR patients who were suspected of local recurrence, focal uptake was detected adjacent to the bladder on [18F]PSMA-1007 PET. This suggested the significant advantage of having minimal physiological urine excretion. Conclusions [18F]PSMA-1007 PET showed a high detection rate in recurrent and metastatic lesions. In patients with BCR, its high detection led to suitable treatment strategies, such as salvage radiation therapy or surgical removal of recurrent lymph nodes. Trial registration (UMIN Clinical Trials Registry) UMIN000037697.

A 68-year-old man with sarcoidosis showed high 18F-FDG uptake in the mediastinal and hilar lymph nodes on 18F-FDG PET, suggesting active inflammation. 18F-fluoro-boronophenylalanine (FBPA) PET showed no significant uptake in the mediastinal and hilar lymph nodes, suggesting its cancer specificity as a substrate of l-type amino acid transporter 1. 18F-fluoro-boronophenylalanine PET can be used for precise evaluation in oncology when the differentiation between inflammation and metastasis is inconclusive on 18F-FDG PET.

Generally, FDG-PET/CT image is acquired at the 60th minute after tracer administration. Depending on the clinical case, additional delayed scans may be useful. However, it is difficult to judge whether additional delayed scan is useful or not. The purposes of this study were creation and evaluation of educational programs to help radiological technologists to decide the usefulness of additional delayed scan of FDG-PET/CT. METHODS Educational programs consisted of the instructional materials and the judgment test of clinical cases. The instructional materials provided the valuable findings for differentiation between uptake in the wall of the colon and colon content, distinction between uptake in the lymph node and urinary tract, and evaluation of malignancy. The judgment test of clinical cases consisted of 10 cases selected by a nuclear medicine physician (for 5 of that cases additional delayed scan was decided to be useful). Five experienced technologists and five inexperienced technologists scored the volubility of additional delayed scan pre- and post-training using the instructional materials (the full marks of score is 5). RESULTS After the educational programs using the instructional materials, the score was improved with the significant difference in both experienced (pre: 3.6±1.4, post: 4.0±1.2) and inexperienced (pre: 2.8±1.5, post: 3.7±1.5) groups (p

Aims: To determine the effect of low-intensity pulsed ultrasound (LIPUS) on cyclooxygenase-2 (COX-2) expression and related mechanisms by using cultured articular chondrocytes derived from porcine mandibular condyles after treatment with interleukin-1 beta (IL-1?). Methods: Chondrocytes were derived from porcine mandibular condylar cartilage and cultured. The cells were treated with or without 10 ng/mL IL-1?. At the same time, the cells were exposed to LIPUS for 20 minutes. After LIPUS exposure, the conditioned medium was changed to a fresh one without IL-1?, and the cells were incubated for 0 to 24 hours. The effects of LIPUS on IL-1?-treated chondrocytes were examined in terms of the expression of p-integrin ?1, COX-2, and phosphorylated extracellular signal-related kinase (p-ERK) 1/2 by real-time polymerase chain reaction (PCR) and Western blot analyses. Differences in the means among multiple groups were examined by oneway analysis of variance (ANOVA) for all groups at each time point, followed by a Scheffe multiple comparison test as a post-hoc test; Student t test was also used. Results: COX-2 mRNA level was upregulated by the treatment with IL-1? and was suppressed significantly (P < .01) by LIPUS exposure. Furthermore, LIPUS enhanced gene expression and phosphorylation of integrin ?, and it inhibited the expression of p-ERK 1/2. Conclusion: LIPUS exposure inhibited IL-1?-induced COX-2 expression through the integrin ?1 receptor followed by the phosphorylation of ERK 1/2. Despite the restricted duration of its effect, LIPUS is suggested to be a potential candidate as a preventive and auxiliary treatment to suppress the degradation of articular chondrocytes in temporomandibular joint osteoarthritis. Keywords: cyclooxygenase-2 (COX-2), low-intensity pulsed ultrasound (LIPUS), mandibular condylar cartilage, mechanical stress, osteoarthritis (OA)

Crohn's disease is treated by medication, operation, and alimentary therapy, and among of them the usefulness of enteral nutrition has been pointed out. Not only elemental diet (ED) but also low residue diets have been reported to be useful, however, there are few cases of long-term use of such digested diets. We have successfully managed a postoperative patient with Crohn's disease involving the small intestine and colon by enteral nutrition mainly with digested diets which are rich in lipids, especially medium-chain triglyceride (MCT) at home. The enteral nutrition was started in a remission period after operation for peritonitis due to perforation of the ileum. About three years have elapsed up to now, and normalization and maintenance of inflammatory reaction, disappearance of the subjective symptoms, maintenance of good nutritional status and weight gain were observed. The patient has recovered normal social activities without any recurrence. Low molecular peptides and MCT in the digested diet are excellent in the digestion and absorption in the body. It is thought that this digested diet regimen involving such peptides and MCT might contribute to the good nutritional management in this case.

A case of preoperatively diagnosed early carcinoma of the appendix is reported. A 78-year-old woman was admitted to the hospital complaining of lower abdominal pain. Barium enema revealed an elevated lesion of the cecum, and adenocarcinoma of the appendix was diagnosed by colon fiberscopy. Right hemicolectomy with D3 lymph node disection was subsequently carried out. Pathological examination demonstrated intramucosal adenocarcinoma limited to the mucosa. This case of early cancer of the appendix is the second case diagnosed preoperatively. We must be careful in treating appendicitis, taking the possibility of carcinoma into consideration.

Total knee arthroplasty nowadays becomes a common procedure to restore the knee function for patients who suffered either natural knee diseases or injuries. The procedure effectively reduces pain and improves knee function with high rate of success. However, the risk of failure is still a problem despite this particular issue has been discussed for the past decades by researchers all over the world. The current implementation of the procedures relies heavily on the feel of the surgeons to ensure the right implantation of the prosthesis on the tibiofemoral component. A force distribution measurement system which has a sufficient accuracy for determining the location of tibiofemoral contact forces is being developed to address this concern. The system consisted of two pressure sensitive sensors, embedded in the trial insert for each condyle. The sensors were made up of pressure-conductive rubber with 8 x 16 of electrodes arrays at the front and backside of the rubber. The current study focuses on the reliability and validity of the measurement performed using the developed sensors. The results indicate good response of the rubber against constant applied force within the first two minutes before the measurement error start increasing over time.

A rare case of cavernous hemangioma rupture in the liver following a blunt abdominal trauma is reported. A 42-year-old male was brought to the hospital in shock following a blunt trauma to his right hypochondral region during a softball game. Ultrasonography and computed tomography of the abdomen demonstrated intraabdominal massive bleeding and injury to the right lobe of the liver. The lesion was highly enhanced by contrast medium. Upon laparotomy which was done under a diagnosis of hemorrhagic shock due to the hepatic injury, bleeding about 6000cc in volume was noted. Right lobectomy was carried out and the patient recovered well. Microscopic examination revealed the ruptured cavernous hemangioma, 2×3cm in size. In a review of clinical cases of traumatic or spontaneous rupture of hemangioma, most lesion were more than 5cm in diameter and such small lesion as the patient had was rare. In emergency cases of hepatic rupture, we must consider a possible basal disease of the liver.

Extracellular matrix degradation in mandibular condylar cartilage is mediated by various cytokines in the temporomandibular joint (TMJ). Interleukin-1 beta (IL-1β) is detected in joint structures with pathologic status, and participates in catabolic action in the extracellular matrix. The purpose of this study was to investigate the effects of IL-1β on cyclooxygenase-2 (COX-2) expression and cartilage metabolism using cultured chondrocytes from mandibular condyle. Articular chondrocytes from the porcine mandibular condylar cartilage around the surface were cultured and treated with 0–10 ng/ml IL-1β or 0–1000 ng/ml prostaglandin (PGE 2 ) for 0–24 h. The mRNA levels of COX-2, MMP-1, -3, and -13 were evaluated by real-time PCR analysis. The protein levels of PGE 2 and MMPs were examined by ELISA and Western blot analysis, respectively. The expression levels of COX-2 and PGE 2 were enhanced by exogenous IL-1β in chondrocytes. The mRNA levels of MMP-1, -3, and -13 were up-regulated by PGE 2 treatment dose-dependently. It is shown that the expression of COX-2/PGE 2 was enhanced by IL-1β in articular chondrocytes from mandibular condyle, and that MMP-1, -3, and -13 were induced by PGE 2 , suggesting that IL-1β-induced COX-2/PGE 2 play a crucial role in catabolic processes of mandibular condylar cartilage under inflammatory conditions.

Osteoarthritis (OA) in the temporomandibular joint (TMJ) is a degenerative disease caused by excessive external loading. Recently, it was reported that the damage in the mineralized subchondral bone caused by traumatic impact-loading is responsible for the initiation and progression of cartilage degeneration. Thus far, we have hypothesized that cytokines released from damaged subchondral bone from impact-loading affect the cartilage catabolism under pathological conditions. An impactor of 200 gw was dropped onto the top of a porcine mandibular condyle. After organ culture for 2 days, we investigated the association between the subchondral bone and cartilage using histological and biochemical experiments. The impact-loading induced the expression of IL-1beta immunohistochemically and prominently up-regulated IL-1alpha and IL-1beta mRNA levels in subchondral bone. We confirmed a significant decrease in type II collagen and aggrecan mRNA expressions in chondrocytes by co-culture with osteoblasts after impact-loading, and significant increase in mRNA and protein expressions of IL-1beta in subchondral osteoblasts from impact-loaded subchondral bone. The mRNA expressions of type II collagen, aggrecan, and type X collagen in chondrocytes were decreased significantly by the co-culture with osteoblasts pre-treated by IL-1beta, -6, and TNF-alpha. Among them, osteoblasts pre-treated by IL-1beta affected chondrocytes most strongly. It was also shown that IL-1beta-treated osteoblasts enhanced the MMP-1 mRNA level most markedly in chondrocytes among the four cytokines. These results suggest that the TMJ subjected to impact-loading can increase directly IL-1beta synthesis in the subchondral region, subsequently altering the metabolism of adjacent cartilage and may eventually resulting in the onset and progression of TMJ-OA.

Vascular endothelial growth factor A (VEGF-A) plays an essential role in tumor progression through stromal neovascularization in malignant solid tumors. Neuropilin (NRP) is considered to be the specific receptor for limited types of VEGF-A isoform, VEGF165. The clinicopathological implications of NRP are not well understood in colon cancer, while almost all colon cancers overexpressed VEGF-A. We examined the expression levels of NRP1 and NRP2 genes in 54 colon cancer cases and paired extraneoplastic tissue with quantitative real-time polymerase chain reaction. The gene expression levels of NRP1 in the tumor (0.431+/-0.583) were significantly decreased compared to those in the extraneoplastic tissue (0.754+/-0.799) (paired t-test, p=0.0208). On the other hand, the gene expression levels of NRP2 in the tumor (0.763+/-0.791) were not decreased compared to those in the extraneoplastic tissue (0.508+/-0.386) (paired t-test, p=0.0511). Twenty cases, with preserved expression of the NRP1 gene in the tumor, showed a better prognosis as compared to the 34 cases with decreased NRP1 expression (p=0.0258, log-rank test). No significant relationship was noted between NRP2 gene expression and prognosis. The results suggested that preserved NRP1 expression provides colon cancer patients with a better prognosis.

Background: The type 2 cytokine interleukin (IL)-10 has been reported to inhibit the antitumour activity of the regional immunity against various neoplasms. Certain lung cancers produce IL-10, but the clinical significance of IL-10 expression is not well understood. Patients and methods: We examined IL-10 and IL-10 receptor (IL-10R) mRNA expression in 82 non-small-cell lung cancers (NSCLC) by reverse transcription-polymerase chain reaction (RT-PCR) assay. Immunohistochemistry (IHC) and enzyme immunoassay ( EIA) were applied to evaluate the cellular localisation and the serum levels of IL-10. Results: RT-PCR assay revealed IL-10 mRNA expression in 68 (83%) of 82 NSCLC surgical specimens (40 of 50 adenocarcinomas, 22 of 26 squamous cell carcinomas, 5 of 5 large-cell carcinomas, 1 of 1 adenosquamous-cell carcinoma). RT-PCR assay also revealed IL-10R mRNA expression in 79 cases of NSCLC (96.1%). IL-10 expression was confirmed within tumour cells by 1HC. EIA showed no significant serum IL-10 elevation in the 12 NSCLC positive for IL-10 mRNA expression (0-2.99 pg/ml). The NSCLC patients with IL-10 production showed significantly poorer prognosis than those without IL-10 production (P < 0.05, Kaplan-Meier, log-rank test). Conclusions: These results suggested that the cytoplasmic IL-10 correlated to clinical prognosis, and that IL-10 expression is a prognostic factor for NSCLC.

We have studied the effects of urokinase (UK) on concentration changes of α2-antiplasmin (α2-AP) and on fibrinogenolysis. Medium dose (480.000u) or large dose (960, 000u) of UK was given to each of seven normal volunteers by intravenous drip infusion within six hours, and then blood and urine analyses were carried out. Total α2-AP, which includes free α2-AP and α2-AP-plasmin complex, decreased about 50 per cent of the original value with large dose of UK. α2-AP-plasmin complex appeared in the plasma one hour after UK infusion and increased up to 50 per cent of total α2-AP at the end of UK infusion. Bβ1-42, which liberated from fibrinogen at the very early stage of fibrinogenolysis, increased significantly with UK infusion, and was 65 times as much as the normal range at the end of UK infusion. Urinary Bβ1-42 increased as well as plasma Bβ1-41. On the other hand, fibrinogen degradation products (FDP) measured with enzyme immunoassay (ETA) increased only slightly, and moreover, urinary FDP was not detectable at any time. Plasma fibrinogen level did not decrease and it changed within the normal range in both groups. We then gave 960, 000u of UK to three patients with deep vein thrombosis and blood analysis was carried out as with normal volunteers. The most significant observation different from that of normal volunteers was shown in FDP levels. Serum FDP levels of three patients increased significantly in comparison with normal volunteers. Urinary FDP increased as significantly as plasma FDP.In conclusion, we consider that infusion of 960, 000u of UK is enough to neutralyze α2-AP and enough to express thrombolytic activity. It causes only very early stage of fibrinogenolysis without advanced fibrinogenolysis which may result in bleeding tendency in normal volunteers. On the other hand, in thrombotic patients, advanced fibrinolysis was observed with UK infusion.

Monoclonal antibodies (MAbs) were obtained from hybridoma clones established by cell fusion between P3X63Ag8.653 mouse myeloma cells and spleen cells of mice or rats hyperimmunized against human bladder cancer tissue or BC47 rat bladder cancer cells. RBS-31 and RBS-85 mouse MAbs and RBA-1 rat MAb were raised against BC47 cells and HBP-1 MAb was raised against human bladder cancer tissues. Urinary antigens detected by these MAbs were quantitatively assayed by means of ELISA using 50 microliters of 1:2 diluted urine samples. The cut-off value of the assay was set up as the mean + 4 X SD of the mean using data from the healthy individual urine samples. The reactivity of all healthy control urine samples were under the cut-off value (negative). By contrast, urine from bladder cancer patients reacted positively with the RBS-31 MAb at 72%, with the RBS-85 MAb at 63%, with the RBA-1 MAb at 51% and with the HBP-1 MAb at 35%. The urine samples from some patients with renal calculi, acute cystitis or complicated urinary tract infections showed only a weak reactivity with our MAbs. As for extra-bladder cancers, some patients with renal, renal pelvis, prostate or ureter cancer, but no patients with esophageal, gastric, colon or liver cancer or leukemia, had reactive urinary antigens.

Summary Objective Superficial zone protein (SZP) has been shown to function in the boundary lubrication of articular cartilages of the extremities. However, the expression of SZP has not been clarified in mandibular cartilage which is a tissue that includes a thick fibrous layer on the surface. This study was conducted to clarify the distribution of SZP on the mandibular condyle and the regulatory effects of humoral factors on the expression in both explants and fibroblasts derived from mandibular condyle. Methods The distribution of SZP was determined in bovine mandibular condyle cartilage, and the effects of interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β) on SZP expression were examined in condyle explants and fibroblasts derived from the fibrous zone of condyle cartilage. Results SZP was highly distributed in the superficial zone of intact condyle cartilage. The SZP expression was up-regulated by TGF-β in both explants and cultured fibroblasts, whereas the expression was slightly down-regulated by IL-1β. A significant increase in accumulation of SZP protein was also observed in the culture medium of the fibroblasts treated with TGF-β. Conclusions These results suggest that SZP plays an important role in boundary lubrication of mandible condylar cartilage, is synthesized locally within the condyle itself, and exhibits differential regulation by cell mediators relevant to mandibular condyle repairing and pathologies.

We have studied the effects of urokinase (UK) on concentration changes of alpha 2 antiplasmin (alpha 2 AP) and on fibrino(geno)lysis. Medium dose (480,000 u) or large dose (960,000 u) of UK was given to each of seven normal volunteers by intravenous drip infusion within six hours, and then blood and urine analyses were carried out. Total alpha 2 AP, which includes free alpha 2 AP and alpha 2 AP-plasmin complex, decreased to about 50% of the original value with large dose of UK. alpha 2 AP-plasmin complex appeared in the plasma one hr after UK infusion and increased up to 50% of total alpha 2 AP at the end of UK infusion. B beta peptides, which are liberated from fibrin(ogen) at the very early stage of fibrino(geno)lysis, increased significantly with UK infusion, and was 65 times as much as the normal range at the end of UK infusion. Urinary B beta peptides increased as well as plasma B beta peptides. On the other hand, fibrin(ogen) degradation products (FDP) measured with enzyme immunoassay (EIA) increased only slightly, and moreover, urinary FDP was not detectable at any time. Plasma fibrinogen levels did not decrease and changed within the normal range in both groups. We then gave 960,000 u of UK to four patients with deep vein thrombosis and blood analyses were carried out as with normal volunteers. The most significant observation different from that of normal volunteers was shown in FDP levels. Serum FDP levels of four patients increased significantly in comparison with normal volunteers. Urinary FDP increased as significantly as plasma FDP. In conclusion, the infusion of 960,000 u of UK caused only very early stage of fibrinogenolysis without advanced fibrinogenolysis in normal volunteers, but in thrombotic patients, advanced fibrinolysis was observed.

The ankle systolic pressure was measured by the Doppler flow detector during the postoperative course after arterial reconstructive surgery in 61 limbs. The ankle systolic pressure was expressed as a pressure index (PI). There were 2 patterns in the recovery of PI after successful reconstructions. In one of these patterns, PI returned to the normal level within 24 hours. The other group represented a delayed recovery of PI. A comparative study between these 2 groups indicated that the delay in the recovery of PI may be chiefly related to a poor distal run-off. There was no relationship between the recovery pattern of PI and the late patency of reconstructed arteries. On the other hand, follow-up examination by means of the ankle pressure measurement was useful to detect new occurrences of stenotic lesions in the postoperative period.