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.     

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.     

Clinical evaluation of 123I-MIBG for assessment of the sympathetic nervous system in the heart (multi-center clinical trial)

Multi-center clinical trial of 123I-metaiodobenzylguanidine (123I-MIBG) was carried out to assess its utility as a scintigraphic imaging agent reflecting sympathetic neuronal function in cardiovascular field. Studies were performed on patients with heart diseases of three categories, myocardial infarction, angina pectoris and cardiomyopathy. Scintigraphic images, reflecting sympathetic neuronal function were obtained with 123I-MIBG from all of those categories of patients and the efficacy of the imaging was revealed in 781 (95.0%) out of 822 patients. In some patients abnormality was suggested in sympathetic neuronal function with 123I-MIBG imaging, in spite of normal findings with myocardial perfusion scintigraphy by 201TlCl. In all 981 patients studied with 123I-MIBG, there have been no severe adverse reactions, except complaints of burning on injection site of the agent or nausea, etc. from 4 patients. We conclude that 123I-MIBG imaging is one of the effective tools for diagnostic use reflecting topical sympathetic neuronal function in the heart, judging from its safety and efficacy.     

CHARACTERISTICS OF HISTIOCYTIC LESIONS IN THE RETICULOENDOTHELIAL SYSTEM OF NZB MICE

The so-called Potter's lesion, previously described as preneoplastic in the lymph nodes of C58 mice, develops frequently in autoimmune NZB mice. These lesions were characterized in the present study by bands or sheets of palestaining histiocytic cells in the cortex and medulla of the lymph node, and multiple small nodules of the same cells were found in the red pulp of the spleen and the liver. Electron microscopically, the cells had pleomorphic cytoplasm with long processes, electron-dense bodies, abundant mitochondria, and a characteristic labyrinth structure with many C-type viruses. Mac-1 antigen, IgG-Fc receptor, ferritin, and ACPase activity were identified on these cells. Intraperitoneally-injected iron colloids were found in the lesions of the spleen and liver but not in those of the lymph nodes. The lymph node lesions appeared when the mice were about 3 months of age and enlarged until the mice were around 10 months old, after which they gradually receded and were replaced by small vessels and fibroblastic cells. These data indicate that the lesions represent reactive hyperplasia of the macrophage system and may have no direct association with the development of malignant lymphoma in NZB mice.     

Xylocandin: a new complex of antifungal peptides. I. Taxonomy, isolation and biological activity

Xylocandin is a complex of novel peptides with potent antifungal activity that is produced by Pseudomonas cepacia ATCC 39277. The complex was isolated from the fermentation broth by extraction with butanol-methanol, 9:1, followed by collection of the precipitate formed upon concentration of the solvent extract. Purification was effected by chromatography on reversed phase and size exclusion gels followed by TLC on silica gel. These techniques afforded eight components: A1, A2, B1, B2, C1, C2, D1 and D2. A mixture of the two closely related components, xylocandins A1 and A2, displayed potent anticandidal and antidermatophytic activities in vitro. The activity was diminished by the presence of serum or vaginal washings. No antibacterial activity was demonstrable.     

Clinical evaluation of tumor markers in breast cancer patients

During the past 4 years, the performances of various tumor markers such as CA15-3, CEA, ferritin, beta 2-microglobulin and TPA have been evaluated in 78 cases of mammary cancer. The results were categorised according to differences in stages, difference in values from patients with recurrent tumors, the incidence of abnormal values and differences in values before and after surgery. When the incidence of values higher than the cutoff value was determined for each of stage I, II and III + IV, the rates for CEA were 14.3%, 4.9% and 27.8%, respectively, whereas those for TPA were 25.0%, 22.2% and 26.7%, respectively. In addition, for CA15-3, the incidences were 0% in stage I, 5.0% in stage II and 57.1% for combined stages III + IV. The average values for patients with recurrent tumors were 3.2 ng/ml CEA, 194.5 ng/ml ferritin, 316.2 U/l TPA and 81.3 U/ml CA15-3. The rates of abnormal values were 40.0% for CEA, 40.0% for ferritin, 85.7% for TPA and 63.6% for CA15-3. Differences in the values after surgical removal of the tumor were observed with these tumor markers: the CEA value was reduced from 1.6 +/- 1.4 to 1.1 +/- 0.5 (p less than 0.01) and the CA15-3 value from 12.2 +/- 8.4 to 9.3 +/- 4.1 (p less than 0.05), respectively, whereas that for ferritin was conversely increased from 48.9 +/- 48.0 to 74.0 +/- 70.0 (p less than 0.01). However, the values for TPA, despite showing a tendency to decrease, did not show any statistically significant alteration. The fluctuations of these marker levels in patients with recurrent tumors reflects the progress of the disease, with a sudden elevation in values indicating imminent death. The diagnostic significance of these markers is not high, but they are considered to be useful in detecting the progress or condition of a recurrent tumor.