Two T-cell lines with immature phenotypes, CD4-8- and CD4+8+, were found among HTLV-I-transformed T-cell lines obtained during experiments using a rabbit model of adult T-cell leukemia. Persistence and differentiation of these clones in vivo were examined by retrospectively analysing a series of cell lines from individual animals and by adoptive transfer of these cells into syngeneic hosts. The double negative cell line did not differentiate and remained double negative in adoptive transfer into neonates and in long-term in vitro culture, while the double positive cell line differentiated both in vivo and in vitro into CD8+ cell, as if the fate of this cell line had been predetermined. Cells of the same clone as this double positive cell line persisted for more than one year in the peripheral blood of the animal. Long-term persistence was not observed for five cell lines of CD4 single positive phenotype, which were obtained from another carrier rabbit. These results suggested that HTLV-I-transformed immature T-cells persist in neonatally infected carriers, continuously giving rise to mature T-cells harboring HTLV-I.

Animals↗

PubMedDate not supplied

Probucol treatment affects the cellular composition but not anti-oxidized low density lipoprotein immunoreactivity of plaques from Watanabe heritable hyperlipidemic rabbits.

Use of the antioxidant probucol has been associated with a reduction in the development of atherosclerotic lesions in Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia. In this study, atheromatous lesions from control or probucol-treated WHHL rabbits were probed with monoclonal antibodies to evaluate whether use of this drug either affected the presence or distribution of epitopes recognized by an antibody against oxidized low density lipoprotein or altered the cellular makeup of lesions. Although probucol-treated animals had much less aortic atherosclerosis than did controls, equivalent immunoreactivity for the anti-oxidized LDL antibody (OXL 41.1) was demonstrated in atherosclerotic lesions of both groups of animals, consistent with a role for oxidative modification of lipoproteins in atherogenesis in this animal model. Use of smooth muscle cell-specific (HHF-35) and macrophage-specific (RAM-11) antibodies demonstrated that lesions from probucol-treated animals were significantly smaller (p less than 0.01) and less cellular (p less than 0.05) than were control lesions. In addition, smooth muscle cells were the predominant cell type in lesions from probucol-treated animals, whereas macrophages predominated in lesions from controls (p less than 0.01). These findings are consistent with a reduction of monocyte/macrophage recruitment into or retention in lesions in probucol-treated animals, or with probucol-induced alterations in the production of growth factors or cytokines that might influence the cellular makeup of atherosclerotic lesions.

Animals↗

PubMedDate not supplied

Probucol does not affect lipoprotein metabolism in macrophages of Watanabe heritable hyperlipidemic rabbits.

We recently reported that the antioxidant action of probucol inhibited the progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. In this study, we investigated another possible action of probucol: its action as an antiatherogenic agent on macrophages. When WHHL rabbit peritoneal macrophages were pre-incubated in vitro with probucol and then incubated with several atherogenic lipoproteins, the incorporation of the lipoproteins was not significantly prevented. In the case of mouse peritoneal macrophages, pre-incubation with probucol showed slight, although not statistically significant, changes in the amount of lipoprotein incorporations. We also used macrophages obtained from mice and WHHL rabbits fed with probucol, but the amount of uptake of lipoproteins by these cells was not less than that by control macrophages. Furthermore, to investigate the incorporation of atherogenic lipoproteins into these cells, we prepared probucol-containing macrophages; however, probucol in macrophages failed to prevent the uptake of such lipoproteins. In conclusion, probucol did not prevent foam cell transformation of macrophages of WHHL rabbit or mice directly, and the effect of probucol against atherogenesis in WHHL rabbits was due mainly to its inhibitory effect on the oxidative modification of low density lipoprotein, as previously reported.

Animals↗

PubMedDate not supplied

Adult Fanconi syndrome in primary amyloidosis with lambda light-chain proteinuria.

A 57-year-old woman who had had renal amyloidosis with nephrotic syndrome for five years was found to have the Fanconi syndrome and monoclonal lambda light-chain proteinuria. The amyloidosis of this patient was of primary type on the basis of the permanganate-resistant amyloid, the presence of monoclonal light-chain proteinuria, and the absence of clinical and histologic evidence of multiple myeloma. To best of our knowledge, this is the first case report in which primary amyloidosis with monoclonal lambda light-chain proteinuria was accompanied by adult Fanconi syndrome.

Amyloidosis↗

PubMedDate not supplied

Establishment of an in vivo human myeloid leukemia model in the SCID mouse.

We succeeded in establishing a human myelogenous leukemia model in severe combined immunodeficient (SCID) mice by transplanting 2 x 10(7) ML-2 cells intraperitoneally (i.p.) with cyclophosphamide (CTX) pretreatment. Two months after transplantation, 9 of 10 mice developed leukemia and leukemia cells were detected in the peripheral blood (PB) and bone marrow (BM). The main findings at autopsy were peritoneal and pleural effusions and large tumor masses involving the peritoneal organs. However, successful transplantation required injection of a large number of cells. We therefore established a new cell line, ML-2S, from the PB of a mouse with ML-2 leukemia. Although only 2 x 10(6) ML-2S cells were inoculated, ML-2S induced the same pattern of leukemic dissemination reminiscent of the parent ML-2 cells. Compared to ML-2, progression of ML-2S was slow, suggesting that ML-2S is suitable as a leukemia model to study treatment. Furthermore, we confirmed that ML-2S cells are of human origin using isoenzyme analysis and also that ML-2S and ML-2 cells have the same phenotypic character by cell surface marker analysis.

Animals↗

PubMedDate not supplied

In vivo therapeutic effects of IFN-gamma on human myelogenous leukemia in a severe combined immunodeficiency mouse model.

BACKGROUND: Results of clinical trials of IFN-gamma on the treatment of various types of leukemia are not so promising, regardless of the antiproliferative activity against leukemic cells and expected immunomodulatory effects. In this study, we have re-evaluated the anti-leukemic effects of natural human IFN-gamma (nHuIFN-gamma) using an established human myelogenous leukemia model in SCID mice. MATERIALS AND METHODS: SCID mice transplanted with human myelogenous leukemia cell line ML-2S received subcutaneously 5 x 10(4) IU/mouse of nHuIFN-gamma at 5 times/week for 5 weeks. RESULT: nHuIFN-gamma significantly prolonged the lifespan of SCID mice in leukemic crisis. Percentages of ML-2S cells in the peripheral blood were also significantly decreased by the IFN-gamma treatment. Histopathological examination revealed that IFN-gamma treatment suppressed the replacement of pancreatic cells by tumor cells and the formation of tumor masses in the intestine. CONCLUSIONS: These results suggest that IFN-gamma is effective against human myeloid leukemia, especially extramedullary tumor mass-forming type in the peritoneal organs. Our results further suggest that studies employing SCID mice leukemia model would help in devising appropriate therapeutic strategies of IFN-gamma based on the specific characteristics of each leukemia subtype.

Animals↗

PubMedDate not supplied

Indications for posthepatectomy hepatic vein reconstruction from functional and morphological studies: clamping test and hepatic vein branch distribution determined by three-dimensional computed tomography.

BACKGROUND/AIMS: Indications for hepatic vein reconstruction for preserving remnant liver function after hepatectomy were assessed using the clamping test and the findings of preoperative 3D-CT (3-dimensional computed tomography). METHODOLOGY: Fifteen patients who underwent hepatectomy for malignant tumors in segment VII or VIII, or both, were examined with preoperative 3D-CT and an intraoperative clamping test. RESULTS: On the basis of changes in right hepatic venous pressure during clamping, we classified all patients into 3 types: the persistent elevation type (P-type, 8 patients), the no elevation type (N-type, 3 patients) and the transitory elevation type (T-type, 4 patients). Hepatic venous hemoglobin oxygen saturation (ShvO2) decreased significantly in the P type but hardly changed in the T and N types during the clamping test. Both the inferior right hepatic vein (IRV6) and the tributary of the middle hepatic vein draining segment V (MV5) were detected by preoperative 3D-CT in the T and N types. CONCLUSIONS: Assessments of hepatic vein branch distribution using preoperative 3D-CT served to predict the results of the hepatic vein clamping test. The results of preoperative 3D-CT were useful as indications for hepatic vein reconstruction.

Adult↗

PubMedDate not supplied

Adenosine A3 receptor-mediated airway microvascular leakage: role of mast cells and tachykinins.

To determine whether adenosine A3 receptor stimulation produces airway inflammation and, if so, what the mechanism of action is, we studied microvascular permeability in the rat trachea. After intravenous injection of Evans blue dye, adenosine and various adenosine analogues were given by inhalation, and the tracheal microvascular permeability was determined by a photometric measurement of extravasated dye. N6-2-(4-aminophenyl)-ethyladenosine (APNEA), an adenosine A3 receptor agonist, dose dependently increased plasma protein extravasation, whereas adenosine, the A1-receptor agonist N6-(R-phenylisopropyl)-adenosine, or the A2-receptor agonist 5'-N-ethyl-carboxamidoadenosine had no effect. The effect of APNEA was not altered by the adenosine A1/A2 receptor antagonist 8-(p-sulphophenyl)-theophylline, but was reduced by depletion of mast cell-derived mediators with compound 48/80 or pretreatment with the tachykinin NK1 receptor antagonist CP99,994. These results suggest that activation of A3 receptor specifically increase airway microvascular permeability probably via mast cell-derived mediators and tachykinins.

Adenosine↗

PubMedDate not supplied

Primary intracardiac tumors in magnetic resonance imaging.

Fifteen patients suspected of having 18 intracardiac masses by two-dimensional echocardiography underwent MR imaging. In MR imaging, intracardiac masses were evaluated on both short TE (TE = 20-35 msec) and long TE (TE = 50-80 msec) spin echo sequences, and were differentiated from myocardium or papillary muscle. Three masses were excluded (they were papillary muscle) by MR imaging, and three were additionally found in patients with tuberous sclerosis. Fifteen masses were found by both echocardiography and MR imaging, one of which was stagnant blood. Cine MR imaging was needed to differentiate between thrombus and stagnant blood. MR imaging is useful for the evaluation of intracardiac masses. It is recommended in addition to echocardiography when cardiac tumors are suspected, especially in patients with tuberous sclerosis.

Adolescent↗