The induction of operational tolerance is not prevented by simultaneous administration of cyclosporin A1

In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival. The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were used concurrently at the time of transplantation. Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997     

The biological characteristics and chemosensitivity of anaplastic thyroid carcinoma transplanted into nude mice

Three xenografts established from three patients with anaplastic thyroid carcinoma were investigated for their biological characteristics and chemosensitivity. The histological and immunohistochemical findings of these tumors were almost the same as those of the original tumors. Although the growth rate of each xenograft was constant, the tumor doubling time varied from 4.8 per 9.0 days, and the labeling indexes, determined using bromodeoxyuridine pulse labeling, varied from 11.4 to 25.1 per cent. The chemosensitivity tests were performed according to the Battelle Columbus Laboratories Protocol, with adriamycin, cyclophosphamide, cisplatin, mitomycin C and tegafur administered intraperitoneally to tumor-bearing nude mice in maximum tolerable doses. Tumors with slower growth rates tended to be sensitive to more drugs. Furthermore, cyclophosphamide showed antitumor effects against all the tumors tested. Although previous treatments of the original tumors may have affected the results, our results suggest that a more suitable chemotherapy for anaplastic thyroid carcinoma could be developed.     

Reduction of infarct size and infiltration of polymorphonuclear leukocytes by a thromboxane synthetase inhibitor. Studies in a rabbit ischemic heart model.

The effect of sodium 6-(2-(1-(1H)-imidazolyl)methyl-4,5-dihydrobenzo(b) thiophene)carboxylate (RS-5186), a potent and long acting thromboxane synthetase inhibitor in vitro and in vivo, on infarct size and on the infiltration of polymorphonuclear leukocytes (PMNs), was studied in a rabbit coronary artery occlusion (1 h)--reperfusion (0.5 h or 3 h) model. The infarcted region was stained with triphenyltetrazolium, and the ratio of infarcted area/left ventricular area was calculated. The infiltration of PMNs into the infarcted region was determined by measuring the PMNs specific enzyme, myeloperoxidase (MPO) activity. In the vehicle treated group, infarct size and MPO activity were increased with increased reperfusion time from 0.5 h to 3 h (infarct size: 15.3 +/- 2.7 to 25.2 +/- 3.2%; MPO activity: 255 +/- 51 to 825.3 +/- 169.4 units/g wet weight). There was also a significant correlation (r = 0.90, p less than 0.01) between the infarct size and MPO activity. In contrast, in the RS-5186 treated group (2 mg/kg i.v.), both infarct size and MPO activity did not increase with prolongation of the reperfusion period (infarct size: 12.8 +/- 5.5 to 10.3 +/- 3.6%; MPO activity: 318.8 +/- 36.7 to 381.2 +/- 72.6 units/g wet weight). In 0.5 h reperfused samples, there was no significant difference in infarct size or in MPO activity between the vehicle treated group and RS-5186 treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of renal pelvic carcinoma in situ]

A 72-year-old female visited our hospital with the complaint of macroscopic hematuria on Jan. 29, 1990. Cystoscopic examination revealed hematuria flowing out from the left ureteral orifice. A 1 cm mass was found in the left upper calyx by retrograde pyelography (RP). Urine cytology obtained by RP was class IIIb. Later, the mass was found in the left middle calyx by CT. Repeated RP revealed no mass and the wall of the left upper calyx was irregular. Washing cytology from the left renal pelvis was class V. Left total nephroureterectomy was performed on Feb. 2, 1990. Macroscopically, no tumor mass was apparent. Microscopically, transitional cell carcinoma in situ was widely spread from the left renal pelvis to the middle ureter. The preoperative upper calyceal mass was thought to have been a blood clot. At twelve months after the operation, there has been no evidence of tumor recurrence.     

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.     

Induction of gastric tumor and intestinal metaplasia in rats exposed to localized X-irradiation of the gastric region

The induction of gastric tumor and intestinal metaplasia was examined in 8-week-old male JCL/SD rats exposed to localized X-irradiation of the gastric region. The animals were each given two 20 Gy fractions of X-rays, with a one-week interval between fractions (total, 40 Gy). Nine atypical hyperplasias (20%) and 13 adenocarcinomas (28%) in the pyloric mucosa of the glandular stomach were found in 46 animals with X-irradiation. The incidence of intestinal metaplasia was 93% in the pyloric mucosa, 50% in the fundic mucosa and 96% in both the pyloric and fundic mucosa. Type B metaplasia (intestinal metaplasia without Paneth cells) was most common and type C (intestinal metaplasia with Paneth cells) was less frequent. No gastric tumor or intestinal metaplasia appeared in non-irradiated control rats. This study shows that local X-irradiation of the gastric region induced both gastric tumor and intestinal metaplasia independently.     

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.     

Arterial conduit shear stress following bypass grafting for intermediate coronary artery stenosis: a comparative study with saphenous vein grafts.

OBJECTIVES: Graft failure has been reported when the arterial conduit, such as the internal thoracic artery (ITA) or the right gastroepiploic artery (GEA), is grafted to a lower grade coronary artery stenosis. The shear stress as a significant factor affecting graft patency was compared between the arterial conduit and the saphenous vein graft (SVG) after surgery. METHODS: In 101 patients, 40 ITAs, 27 GEAs and 34 SVGs were examined using a Doppler-tipped guide wire during postoperative angiography. The graft flow volume and shear stress were calculated from velocity and diameter data. The study grafts were classified according to the grade of native coronary artery stenosis: group L had more than 50 up to 75% stenosis, and group H had more than 75% stenosis. Group H consisted of 25 ITAs, 17 GEAs and 21 SVGs, while group L consisted of 15 ITAs, 10 GEAs and 13 SVGs. RESULTS: In group H, graft flow volume did not significantly differ among the ITA (34+/-11 ml/min), GEA (36+/-16 ml/min) and SVG (41+/-15 ml/min), and graft shear stress significantly (ITA vs. GEA P<0.0001; GEA vs. SVG P<0.01) differed among the ITA (16.0+/-4.8dyn/cm(2)), GEA (9.1+/-3.2dyn/cm(2)) and SVG (4.8+/-1.6dyn/cm(2)). In group L, flow volume was lower (P<0.001) in the ITA (18+/-6 ml/min) and GEA (13+/-8 ml/min) than in the SVG (35+/-16 ml/min), and shear stress was significantly (P<0.001) greater in the ITA (13.7+/-4.9dyn/cm(2)) than the GEA (5.6+/-2.0dyn/cm(2)) or SVG (4.6+/-2.0dyn/cm(2)). CONCLUSIONS: These data suggest that shear stress of the ITA is superior and maintained despite the flow volume being reduced by flow competition. Lower shear stress of the GEA for intermediate stenosis may be associated with the development of conduit failure.     

Generalized eruptive histiocytoma: an ultrastructural study

A case of generalized eruptive histiocytoma (GEH) was evaluated and examined histopathologically and ultrastructurally. A 24-year-old male had an episode of high fever and drug-induced eruption prior to the appearance of multiple skin lesions. Uniform, red to dark-red papular lesions appeared on his cheeks and then became generalized. The lesions were composed of a massive dermal infiltrate of histiocytes, which had oval nuclei and amphophilic cytoplasm. The cytoplasm contained unique annular structures, myeloid bodies and vacuoles. The specificity of these structures is as yet unknown. Reactive stimulation rather than neoplastic proliferation may be a causative factor in GEH.