Evidence that monoclonal antibodies against the 55kD subunit of the rat IL-2 receptor do not inhibit the development of suppressor cells generated in mixed lymphocyte culture

Although the ability of Ts to prevent allograft rejection has been well established, their intrinsic characteristics and dependence upon lymphokines remain poorly defined. The cells from unmodified LEWxBN bulk 5-day rat MLR inhibit both proliferation in test MLR and generation of CTL, as well as prolonging the survival of donor-specific test cardiac allografts following adoptive transfer. We have examined the effects of a panel of mAb directed against functionally distinct epitopes on the p55 subunit of rat IL-2R on the generation and in vitro/in vivo activity of MLR-generated Ts. ART-18 (which blocks IL-2-dependent T cell growth) was the only mAb from the panel that profoundly suppressed alloreactive T cell proliferation in primary MLR (47.5%). However, the generation of Ts was never affected by any mAb (% suppression in test MLR = 40-60%). Neither ART-18 nor ART-65 (which does not affect T cell proliferation) interfered with the efficacy of Ts to inhibit CTL generation in fresh bulk MLR. Adoptive transfer of cells (3-10 x 10(6] from ART-18 or ART-65-modulated MLR into naive LEW rats prolonged (LEW x BN)F1 test cardiac allograft survival to 11-13 days (P less than 0.05 as compared with acutely rejecting hosts). All in vitro and in vivo effects exerted by MLR-generated cells were antigen-specific. In unmodified MLR, Ts were IL-2R+ (ca. 50% of total blasts), as shown by cell separation using magnetic beads. In contrast, in MLR with ART-18 added, Ts were primarily IL-2R- (ca. 10% of blasts). Thus, antirat p55 subunit IL-2R mAb do not inhibit MLR-generated Ts functionally operative in vitro and in vivo. IL-2R- Ts precursors requiring lymphokine(s) other than IL-2 may differentiate into IL-2-dependent Ts effectors. Such divergent IL-2 requirements for Ts growth in vitro may explain the Ts-sparing effects in allograft recipients treated with anti-IL-2R mAb.     

31P nuclear magnetic resonance study of intrahepatic energy metabolism in acute liver failure

Changes in phosphorus metabolites and intracellular pH in acute liver failure induced by D-galactosamine (GAL) were evaluated non-destructively and continuously using 31P-NMR spectroscopy. Furthermore, changes in these parameters under ischemia were also examined. GAL(1.0g/kg) was injected intravenously to male Wistar rats. NMR measurements in perfused livers were performed with a GX-270FT NMR spectrometer (JEOL). Typical changes in 31P-NMR spectra were observed after GAL administration. ATP levels decreased to 57.4 +/- 12.4% at 12 hours and to 65.4 +/- 7.7% at 24 hours after the administration compared with that in control rats. Pi levels increased remarkably to 632.1 +/- 76.4% at 3 hours and recovered to 127.5 +/- 22% at 24 hours. NAD+/NADH and UDP-sugar levels gradually increased to 253.5 +/- 33.4 and 456.3 +/- 60.9%, respectively, at 24 hours. In GAL treated livers, ATP levels fell rapidly and Pi levels rose correspondingly during ischemia, and they rapidly recovered by reperfusion. The intracellular pH decreased to 7.16 +/- 0.032 from 7.38 +/- 0.065 at 3 hours after GAL administration. However, significant changes in pH were not observed until 24 hours. In GAL treated livers, slight changes in pH were observed under ischemia. These results indicate that 31P-NMR is a useful method to evaluate the damage of acute liver failure, and to diagnose liver diseases involving the intrahepatic energy metabolism.     

Expression of matrix metalloproteinase matrilysin (mmp-7) was induced by activated ki-ras via ap-1 activation in sw1417 colon cancer cells

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metallo-proteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.     

Groove pancreatitis associated with true pancreatic cyst

We report a case of groove pancreatitis (GP) associated with a true pancreatic cyst. An 81-year-old man who had suffered epigastric pain for 4 months was referred to Saisekai Kure Hospital. Computed tomography and endoscopic retrograde pancreatography showed a cystic lesion in the groove area of the pancreas. Serum amylase elevation and imaging findings suggested GP due to the cyst. Six weeks of medical treatment did not improve the clinical symptoms. Therefore, pancreatoduodenectomy was performed. Histologic examination revealed a true cyst with intraluminal necrosis, which produced a protein plug that obstructed the Santorini duct. The parenchyma surrounding the groove area showed marked fibrosis and inflammatory cell infiltration. GP due to true pancreatic cyst was diagnosed. Although GP is usually caused by overconsumption of alcohol, which leads to changes in the pancreatic juice and the ultimate blockage of pancreatic outflow, the histologic features in our patient suggest that true pancreatic cyst stands as a secondary cause of GP.     

The use of frame fixation in the management of open distal extensor mechanism avulsion fracture in a dislocated knee

An avulsion fracture of the tibial tubercle is a common injury in traffic accident. If the fracture is closed, then a comparatively good prognosis can be expected through reinforcement of the bone via osteosynthesis and the use of artificial ligaments. In this case, an open wound was observed in the tibial tubercle, and the wound was so polluted that the healing process was significantly delayed. It was therefore difficult to provide simultaneous surgical treatment and so three operations were required to perform the reconstruction of the extensor mechanism. The reconstruction of extensor mechanism and the frame fixation between the patella and tibia was performed. Six months after the injury, the patient was able to walk without aid, had a range of movement from 5°to 130°, and did not show any indications of ADL disorder. Using this method of frame fixation between the patella and tibia proved to be an effective technique for the reconstruction of the open knee extension mechanism injury.     

A case of supravalvular aortic stenosis with spontaneous remission of peripheral pulmonary stenosis

A 14-year-old junior high school boy was admitted to our institute. Previously he had been diagnosed as having peripheral pulmonary stenosis (Gay's classification, type IV) at the age of 2 years and 10 months. On this occasion, however, a diagnosis of supravalvular aortic stenosis was made, with a pressure gradient of about 120 mmHg, and all examinations showed spontaneous remission of peripheral pulmonary stenosis. He underwent a successful standard aortoplasty. This is the first reported case of spontaneous remission of peripheral pulmonary stenosis.     

Skip mediastinal nodal metastases in non-small cell lung cancer

Objective: To reveal the incidence and clinical significance of mediastinal nodal metastases without N1-station nodal metastases (‘skip-N2 metastases’) in non-small cell lung cancer (NSCLC). Methods: A total of 450 NSCLC patients who underwent tumor resection with a systemic mediastinal nodal dissection were retrospectively reviewed. p53 status and proliferative activity represented as proliferative index (PI) were also examined immunohistochemically. Results: Skip-N2 metastases were documented in 49 (13%) patients of all 450 patients; among 334 patients without N1-nodal involvement, 18% patients had skip-N2 metastases. The postoperative survival of skip-N2 patients was almost same as that for patients with metastases to both N1 and N2 nodes. Skip-N2 metastases were significantly more frequent in male patients and squamous cell carcinoma patients. In addition, the mean PI for tumor with skip-N2 metastases was significantly higher than that for any other pathologic nodal (pN)-status diseases. Combined with histologic type and PI, the incidences of skip-N2 metastases for adenocarcinoma showing lower PI were only 5% (7/137) of all patients and 7% (7/94) of patients without N1-nodal involvement. Conclusions: N1 nodal status is not a useful predictor of N2 nodal status in NSCLC, because skip-N2 metastases were documented in 18% patients showing no N1-nodal involvement. However, N1 node-guided dissection might be performed in patients with adenocarcinoma showing lower PI, because the incidence of skip-N2 metastases was extremely low.     

Microheterogeneity of regional myocardial blood flows in low-perfused rat hearts evaluated by double-tracer digital radiography.

Using (3)H- and (125)I-labeled desmethylimipramine (DMI) for regional flow tracers, we established a two-time measurement method for the spatial pattern of myocardial perfusion in cross-circulated rat hearts. Myocardial extractions and retentions of these tracers were confirmed to be satisfactory; however, the latter were less than 90% after 3 min at a perfusion rate of 2.9 ml/min/g, limiting the present application to a short-time perfusion measurement. Distributions of myocardial depositions were separated by subtraction digital radiography with 400-microm pixel resolution. Its feasibility was examined by regression analysis between local deposition densities of (3)H- and (125)I-DMI injected simultaneously. The slope, y-intercept, and correlation coefficient (r) of the regression line were 0.98+/-0.04, 0.02+/-0.04, and 0.95+/-0.03, respectively, indicating the validity of the present image subtraction technique. The spatial pattern of myocardial perfusion in response to flow reduction was evaluated by the injections of (3)H- and (125)I-DMI, respectively, before and after a nearly 70% flow reduction. A significant correlation between normalized density distributions of these tracers was found in both subepicardium (r=0.77+/-0.12) and subendocardium (r=0.73+/-0.20), indicating the stable pattern of myocardial perfusion. However, the coefficient of variation of tracer densities showed a decrease of subendocardial flow heterogeneity from 35+/-15% to 31+/-16%. Thus, flow differences between originally high- and low-flow regions in subendocardium were reduced on a relative basis during low perfusion.     

Adamantinoma of the proximal femur: a case report

Adamantinoma is a rare low-grade malignant bone tumor with an indolent course. The tibia is involved in 85%–90% of long-bone cases. We encountered a patient with primary adamantinoma of the proximal femur. A 60-year-old woman fell and fractured her proximal left femur in the area of a cystic lesion. She underwent an osteosynthesis procedure, and bone union was obtained. After 3 years she developed pain in the left thigh, and a radiographic abnormality was found at the fracture site. A metastatic bone tumor was suspected, and curettage and cementing were carried out. Histologically, we found an epithelial component but failed to detect any primary cancer. Local recurrence became evident after another 6 years. A marginal excision was performed and a bipolar femoral prosthesis was implanted. We finally diagnosed the patient with adamantinoma. In this report we describe the characteristics of this tumor and discuss the reasoning concerning the differential diagnosis and therapeutic plan.