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T Okano

Publications and source records attributed to T Okano.

At least 127 records · Page 7Linked to original sources
PubMed2000

[Effectiveness of docetaxel plus cisplatin in large cell lung cancer showing little response to prior chemotherapy with MVP].

The present patient was a 53-year-old male who had large cell lung cancer of c-T4N1M0. We administered multi-drug regimen including mitomycin C, vindesine and cisplatin (CDDP) because of cancer invasion into the great vessels seen on a chest CT. After 3 courses, the cancer showed no change in size. Therefore, we adopted chemotherapy of docetaxel (Taxotere: TXT) and CDDP. After 4 courses, the size of the mass had decreased (partial response). The only major toxic defect was grade 3 neutropenia. A good response to TXT and CDDP could lead to complete resection of lung cancer. It is suggested that TXT is effective in the treatment of large cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Autoantibodies define a family of proteins with conserved double-stranded RNA-binding domains as well as DNA binding activity.

Cellular responses to viral infection are signaled by double-stranded (ds) RNA, which is not found in substantial amounts in uninfected cells. Although cellular dsRNA-binding proteins have been described, their characterization is incomplete. We show that dsRNA-binding proteins are prominent autoantigens. Sera from B6 and B10.S mice with pristane-induced lupus and human autoimmune sera immunoprecipitated a novel set of 130-, 110-, 90-, 80-, and 45-kDa proteins. The proteins were all major cellular poly(IC)-binding factors. N-terminal amino acid sequences of p110 and p90 were identical and matched nuclear factor (NF) 90 and M phase phosphoprotein 4. p45 and p90 were identified as the NF45.NF90 complex, which binds the interleukin-2 promoter as well as certain highly structured viral RNAs. NF90.NF45 and M phase phosphoprotein 4 belong to a large group of proteins with conserved dsRNA-binding motifs. Besides binding dsRNA, NF90.NF45, p110, and p130 had single-stranded and dsDNA binding activity. Some sera contained autoantibodies whose binding was inhibited by poly(IC) but not single-stranded DNA or vice versa, suggesting that the DNA- and RNA-binding sites are different. These autoantibodies will be useful probes of the function of dsRNA-binding proteins. Their interaction with dsRNA, an immunological adjuvant, also could promote autoimmunity.

Amino Acid Sequence↗
PubMed1999

High resolution neutron fibre diffraction data on hydrogenated and deuterated cellulose.

High-resolution fibre neutron diffraction data were recorded from cellulose samples on a D19 diffractometer at the Institut Laue-Langevin (Grenoble). Highly crystalline cellulose I samples from Cladophora (cellulose I alpha + I beta) or Halocynthia (cellulose I beta) origin were prepared in the form of oriented films. Samples were studied in a hydrogenated form and in a hydrogen-deuterium exchanged deuterated form corresponding to all OH moieties being replaced by ODs. These samples, which diffracted to a resolution of around 0.9 A, gave diffraction diagrams consisting of several hundred independent diffraction spots. Crystalline cellulose II fibres resulting from the mercerization of flax were also studied in a hydrogenated form using NaOH/H2O as mercerizing medium and in a deuterated form using NaOD/D2O. Both of these samples diffracted to around 1.2 A, giving fibre diffraction diagrams slightly less resolved than those of cellulose I, but still consisting of more than one hundred independent diffraction spots. For cellulose I as well as for cellulose II, significant differences between the hydrogenated and deuterated patterns were observed and recorded. These new data should lead to improved structures for cellulose and direct identification of the position of hydrogen atoms involved in hydrogen bonding.

Cellulose↗
PubMed1999

Chimeric nature of pinopsin between rod and cone visual pigments.

Chicken pineal pinopsin is the first example of extra-retinal opsins, but little is known about its molecular properties as compared with retinal rod and cone opsins. For characterization of extra-retinal photon signaling, we have developed an overexpression system providing a sufficient amount of purified pinopsin. The recombinant pinopsin, together with similarly prepared chicken rhodopsin and green-sensitive cone pigment, was subjected to photochemical and biochemical analyses by using low-temperature spectroscopy and the transducin activation assay. At liquid nitrogen temperature (-196 degrees C), we detected two kinds of photoproducts, bathopinopsin and isopinopsin, having their absorption maxima (lambda(max)) at 527 and approximately 440 nm, respectively, and we observed complete photoreversibility among pinopsin, bathopinopsin, and isopinopsin. A close parallel of the photoreversibility to the rhodopsin system strongly suggests that light absorbed by pinopsin triggers the initial event of cis-trans isomerization of the 11-cis-retinylidene chromophore. Upon warming, bathopinopsin decayed through a series of photobleaching intermediates: lumipinopsin (lambda(max) 461 nm), metapinopsin I (460 nm), metapinopsin II (385 nm), and metapinopsin III (460 nm). Biochemical and kinetic analyses showed that metapinopsin II is a physiologically important photoproduct activating transducin. Detailed kinetic analyses revealed that the formation of metapinopsin II is as fast as that of a chicken cone pigment, green, but that the decay process of metapinopsin II is as slow as that of the rod pigment, rhodopsin. These results indicate that pinopsin is a new type of pigment with a chimeric nature between rod and cone visual pigments in terms of the thermal behaviors of the meta II intermediate. Such a long-lived active state of pinopsin may play a role in the pineal-specific phototransduction process.

Amino Acid Sequence↗
PubMed1999

Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate).

To achieve a combination of spatial specificity in a passive manner with a stimuli-responsive targeting mechanism, a temperature-responsive polymeric micelle is prepared using block copolymers of (poly(N-isopropylacrylamide-b-butylmethacrylate) (PIPAAm-PBMA)). The micelle inner core formed by self-aggregates of PBMA segments successfully loaded with a drug (adriamycin), and the outer shell of PIPAAm chains played a role of stabilization and initiation of micellar thermo-response. Optimum conditions were investigated for the micelle formation and drug loading into the inner cores in a view of micellar stability and function as drug carriers. Outer shell hydrophilicity that prevents inner core interaction with biocomponents and other micelles can be suddenly switched to hydrophobic at a specific site by local temperature increase beyond the LCST (lower critical solution temperature) (32.5 degrees C). These micelles showed reversible structural changes allowing drug release upon heating/cooling thermal fluctuations through the LCST. Polymeric micelles incorporated with adriamycin showed a dramatic thermo-responsive on/off switching behavior for both drug release and in vitro cytotoxicity according to the temperature responsive structural changes of a micellar shell structure. The reversible and sensitive thermo-response of the micelle opens up opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia.

Acrylic Resins↗
PubMed1999

Two-Layer Structure of Microcapsule Membrane as Predicted from Electrophoretic Studies.

Four types of hydrophilic gel microcapsules containing water have been prepared by an interfacial polymerization method. Each type of microcapsules has membranes of different compositions. Using three kinds of monomers, N,N-dimethylacrylamide (DMAAm), 4-aminomethylstyrene (AmSt), and N,N-dimethylaminopropylacrylamide (DMAPAA), two types of water-soluble copolymers with different compositions having primary and tertiary amino groups were obtained. Two more types of copolymers were synthesized by copolymerization of alpha-acryloxy-omega-methoxy-poly(ethylene glycol) (a-PEG) with the above two kinds of monomer mixtures. These copolymers were polymerized with terephthaloyldichloride at the water/oil interface to prepare four types of microcapsules containing water. By electrophoretic mobility measurements of these microcapsules and the analyses of the data, it was found that the surface layer of the microcapsule membranes were composed of two sublayers, each of which has different charge density and softness. The outer sublayer was negatively charged and inner sublayer was positively charged. By PEGylation, the charge density in the outer sublayer decreased, while that in the inner sublayer was not affected. Also, the surface layer became softer by PEGylation. The effects of membrane composition upon the swellability of the microcapsule membrane were studied. It was found that the asymmetrical structure of the microcapsule membranes causes the nonuniform distribution of charges and then the swellability of the microcapsule membrane changes depending on the permittivity of the dispersing medium. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Decrease in culture temperature releases monolayer endothelial cell sheets together with deposited fibronectin matrix from temperature-responsive culture surfaces.

Bovine aortic endothelial cells were cultured on surfaces grafted with a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm), in the presence of serum. Cells adhered, spread, proliferated, and reached confluency as observed on ungrafted tissue culture polystyrene dishes. A decrease in culture temperature released cells only from the grafted surfaces without enzymatic or ethylenediaminetetraacetic acid treatment. Upon lowering temperature, the culture surfaces changed from hydrophobic to hydrophilic owing to the hydration of grafted PIPAAm and thus weakened the cell attachment to the dishes. Released cells maintained cell-cell junctions composing monolayer cell sheets. Immunoblotting and immunofluorescence microscopy revealed that fibronectin (FN) was deposited and accumulated on the grafted surfaces during the culture. Furthermore, the deposited FN matrix adhering to cell sheets was also recovered from temperature-responsive surfaces by low-temperature treatment, while trypsin treatment destroyed the matrix. The recovery of FN by low-temperature treatment was as high as by physical scraping with a rubber blade. Temperature-responsive surfaces can provide a novel method to use cultured confluent cell sheets for tissue engineering, and also to elucidate structure and function of deposited extracellular matrix during cell culture.

Acrylamides↗
PubMed1999

Effect of Ca2+-alginate gel dissolution on release of dextran with different molecular weights.

Release of macromolecular drug from calcium-alginate gel beads was investigated. Fluorescein isothiocyanate-labeled dextrans with molecular weight ranging from 9400 to 145000 were used as a model macromolecular drug. Dextran release was observed to be molecular weight-dependent, with the release pattern changing from pseudo first-order for dextran with 9400 molecular weight to sigmoidal for dextran with molecular weight of 145000. Release of a lower molecular weight dextran is mainly governed by the drug diffusion through the calcium-alginate gel matrix. With increasing dextran molecular weights, dextran release was strongly influenced by the dissolution of alginate matrix through the exchange of Ca2+ ions which act as a cross-linker. Rapid and complete release was achieved for dextran with 145000 molecular weight in a "burst" fashion showing a initial lag time. Minimal dextran release was observed in pseudo-gastric fluid at pH 1.2, while rapid dextran release within a narrow time range was achieved in simulated intestinal fluid at pH 6. 8. These results strongly suggest that calcium-alginate gel is a useful vehicle for pulsatile release of macromolecular drugs in oral drug delivery.

Alginates↗
PubMed1999

Signal transduction and cytoskeletal reorganization are required for cell detachment from cell culture surfaces grafted with a temperature-responsive polymer.

We have developed a new cell culture substrate grafted with a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm) using an electron beam irradiation method. These surfaces are hydrophobic in culture at 37 degrees C due to the hydration/dehydration changes intrinsic to PIPAAm at 32 degrees C, and they become highly hydrophilic below 32 degrees C. At 37 degrees C grafted and ungrafted surfaces showed no difference with regard to attachment, spreading, growth, confluent cell density, and morphology of bovine aortic endothelial cells. Stress fibers, peripheral bands, and focal contacts were established in similar ways. After the medium temperature was decreased to 20 degrees C, spread cells lost their flattened morphology, acquiring a rounded cell appearance similar to that of cells immediately after plating. After mild agitation cells floated free from the dish surface without trypsin treatment. Neither cell morphological changes nor cell detachment occurred on ungrafted surfaces. An ATP synthesis inhibitor, sodium azide, and a tyrosine kinase inhibitor, genistein, suppressed cell morphological changes and cell detachment while a protein synthesis inhibitor, cycloheximide, slightly enhanced cell detachment. An actin filament stabilizer, phalloidin, and its depolymerizer, cytochalasin D, also inhibited cell detachment. These findings suggest that cell detachment on grafted surfaces is mediated by intracellular signal transduction and reorganization of the cytoskeleton. While trypsinization causes damage to the cell membrane surface and extracellular matrix proteins, this alternative low temperature treatment is exceptionally noninvasive. The temperature-responsive cell culture surface also should prove useful for investigating the molecular machinery involved in cell-surface detachment.

Acrylic Resins↗
PubMed1999

Experimental study of ectopic-free tissue transfer of rabbit epigastric flap using small-caliber vascular grafts.

Ectopic intraperitoneal free-tissue grafting using small-caliber artificial vascular grafts is reported. The vascular grafts were polyurethane tubes (inner diameter 1.4 mm; outer diameter 1.9 mm; length 15 mm) with a coating of the antithrombotic agents argatroban and 2-hydroxyethylmethacrylate-styrene block copolymer (HS)on the inner surface. The patency of the artificial vessels was investigated in an ectopic-free rabbit epigastric flap in which grafts were used for anastomosis between the femoral and renal vessels. The mean patent duration of uncoated controls (n = 10) was 128 +/- 37 min. Flap viability after one week (n = 17) and the patency of the coated grafts were investigated histologically. The flap take rate was 65%, the arterial graft patency rate 41%, and the venous graft patency rate 24%. The HS-treated surface combined with the argatroban slow-release system exhibited improvement of flap survival in an intraperitoneal ectopic -free grafting model.

Animals↗
PubMed1999

Maintenance of retinoid metabolism in human retinal pigment epithelium cell culture.

If transplantation of cultured retinal pigment epithelium (RPE) or iris pigment epithelium (IPE) is to be successful in the treatment of ocular disease, it is imperative to demonstrate that these cells can perform all of their necessary metabolic functions. Unfortunately, a critical function of the RPE, retinoid metabolism, is often lost rapidly in culture. We have examined whether or not nonspecific proteolytic enzymes commonly used in cell isolation and serial passaging may be responsible for this loss of function, and we have investigated novel isolation and passaging techniques which can alleviate this loss of retinoid metabolism.RPE cells were obtained from human donor eyes by enzymatic and nonenzymatic methods. Cells were cultured either on control tissue culture inserts or on inserts coated with a layer of thermally responsive poly(N -isopropylacrylamide-co-cinnamoylcarbamidemethylstyrene). Upon confluence, cells were detached either by trypsinization or by lowering dish temperature. Retinoid metabolism of cells was assessed after isolation and culture by incubating membrane fractions with3H-all- trans -retinol. Retinoid metabolism was also measured in freshly isolated IPE, corneal endothelium (CE), an RPE cell line (D407), and two hepatocyte cell lines (Hepa 6 and HepG2). Membrane fractions from cells isolated nonenzymatically or using collagenase/hyaluronidase formed 11- cis -retinol, retinal isomers and retinyl esters. Retinoid metabolism of RPE cells freshly isolated by trypsinization showed no 11- cis -retinal and little 11- cis -retinol formation. Nondamaged cells cultured on thermally responsive surfaces detached in sheets upon temperature change. They showed metabolism similar to that of cells freshly isolated by nonenzymatic means. After trypsinization, confluent cultures dissociated into individual cells, but these cells showed poor retinoid metabolism, including no detectable retinyl esters or 11- cis -retinoid isomers. IPE, CE and Hepa 6 did not show any retinoid metabolism. D407 and HepG2 produced retinals, but not the 11- cis isomer.RPE cells isolated using trypsin lose the ability to form critical intermediates in the visual cycle. Collagenase/hyaluronidase or nonenzymatic cell isolation techniques enable these functions to be maintained. After cell culture, thermally responsive surfaces allow nonenzymatic cell detachment and excellent maintenance of retinoid metabolism.

Adolescent↗
PubMed1999

Differentiation of pinopsin-immunoreactive cells in the developing quail pineal organ: an in-vivo and in-vitro immunohistochemical study.

The avian pineal organ contains several types of photoreceptors with different photopigments: rhodopsin, iodopsin, and pinopsin. We have previously examined the differentiation of both rhodopsin-like and iodopsin-like immunoreactive cells during pineal development in quail embryos to determine the onset of synthesis of specific proteins and their cellular localization. In the present study, we have performed pinopsin immunohistochemistry on in-vivo developing and in-vitro cultured pineal organs of quail embryos. The results were compared with those obtained with rhodopsin and iodopsin immunohistochemistry. In the developing pineal organs, pinopsin immunoreactivity was detected at embryonic day 8, i.e. five days earlier than rhodopsin-like and iodopsin-like immunoreactivities. It was localized exclusively in the protrusions extending into the lumen throughout development, whereas rhodopsin-like and iodopsin-like immunoreactivities were usually found both in cell bodies and processes. These differences were also observed under two different types of culture conditions (dissociated cell culture and organ culture) indicating that, in the avian pineal organ, the expression pattern of the pinopsin gene is basically different from those of the other two pineal photopigments. The present study suggests that pineal cells have a mechanism for the polarized transport of pinopsin molecules.

Animals↗
PubMed1999

Intestinal absorption of calcium from calcium ascorbate in rats.

The intestinal absorption of calcium (Ca) from Ca ascorbate (Ca-AsA) was investigated in normal rats. Each animal was perorally administered either 5mg (low dose) or 10mg (high dose) of Ca in 1ml of distilled water as Ca-AsA, Ca carbonate (CaCO3), or Ca chloride (CaCl2), which were intrinsically labeled with 45Ca using 45CaCl2. The amount of radioactivity in plasma was measured periodically up to 34h after dosing, and pharmacokinetic parameters were calculated from the radioactivity in plasma. The time taken to reach the maximum 45Ca level (Tmax) did not differ among the three groups. The area under the plasma 45Ca level/time curve (AUCinfinity) value for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups. The radioactivity at Tmax (Cmax) for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups for the low dose, and comparable with or significantly higher than those for the CaCl2 and CaCO3 groups for the high dose. Similar results were observed for whole-body 45Ca retention. Radioactivity in the femur 34h after dosing was the highest in the Ca-AsA group and the lowest in the CaCO3 group. The rank order of solubility in water, the first fluid (pH 1.2, JP-1) of JPXIII disintegration medium, acetate buffer solution (pH 4.0), triethanolamine-malate buffer solution (pH 7.0) and ammonium chloride buffer solution (pH 10.0) at 37 degrees C was CaCl2 > Ca-AsA > CaCO3. In contrast, the rank order of the solubility in the second fluid (pH 6.8, JP-2) of JPXIII disintegration medium at 37 degrees C was Ca-AsA > CaCl2 > CaCO3. These results indicate that the absorbability of Ca from Ca-AsA is almost comparable with, or higher than, that from CaCl2 and significantly higher than that from CaCO3 because of its high degree of solubility in the intestine. Therefore, Ca-AsA would be useful as a Ca supplement with relatively high absorption from intestine.

Animals↗
PubMed1999

ProMMP-9 (92 kDa gelatinase) in vitreous fluid of patients with proliferative diabetic retinopathy.

Matrix metalloproteinases (MMPs) are implicated in tissue destruction during various pathophysiologic conditions. The vitreous body is a gel-like extracellular matrix that undergoes liquefaction during aging and pathological processes. To investigate the pathogenic role of MMPs in proliferative diabetic retinopathy (PDR), we studied 73 eyes from PDR patients and 25 eyes from patients with non-diabetic ocular diseases. Vitreous MMPs were measured by zymography. Retinopathy was assessed by ophthalmoscopy and PDR was classified into 3 stages, 'naked', 'active', and 'quiescent'. Although proMMP-9 was expressed in only 8% (2/25) of non-diabetic patients, it was expressed in more than 80% (38/47) of 'active' PDR patients and still expressed in 60% (9/15) of those with 'quiescent' PDR. Vascular endothelial growth factor (VEGF) in vitreous fluids was undetectable (<0.16 ng/ml) in most of the non-diabetic patients, and was maximally elevated in the 'active' PDR patients (mean=2.20 ng/ml, range; 0.16-7.61), declining in patients with 'quiescent' PDR (1.04 ng/ml, 0.16-3.77). These results suggest that MMP-9 is one of the noteworthy factors in relation to the progress of PDR, as well as angiogenic cytokines such as VEGF.

Adolescent↗
PubMed1999

Effect of ED-71 on modeling of bone in distraction osteogenesis.

We investigated the effect of 2-beta-(3-hydroxypropoxy)-1alpha,25-dihydroxyvitamin D3 (ED-71) on the modeling of bone in distraction osteogenesis. The tibiae of 30 rabbits were lengthened by 10 mm in 10 days. Following osteotomy, ED-71 (0.05 microg/kg) was administered subcutaneously twice a week to the ED-71 group until necropsy. The bone mineral content (BMC) of the lengthened callus was measured by dual-energy X-ray absorptiometry (DXA). Five rabbits per group were killed at 1, 3, and 8 weeks after completion of lengthening, and the lengthened callus was examined histologically and histomorphometrically. Bone volume of the lengthened callus was measured by peripheral quantitative computed tomography (pQCT) at 8 weeks after the completion of lengthening. At all timepoints the BMC in the ED-71 group was significantly higher than that in the untreated group. The mineral apposition rate and bone formation rate were higher in the ED-71 group than in the untreated group at 1 and 3 weeks after the completion of lengthening on the coronal section. In cross sections, the cortical area and width in the ED-71 group showed significantly higher values than in the untreated group at 8 weeks after the completion of lengthening. Both the endosteal osteoid surface and endosteal eroded surface showed no differences between groups. However, the endosteal mineral apposition rate and endosteal bone formation rate were significantly higher in the ED-71 group. At 8 weeks after completion of lengthening, the intracortical area and intracortical BMC were significantly greater in the ED-71 group than in the untreated group, but no significant difference was noted in intracortical BMD. These findings indicate that ED-71 increases callus volume during the early period after the completion of lengthening, resulting in thick cortical bone formation.

Absorptiometry, Photon↗
PubMed1999

Permeation of PEO-PBLA-FITC polymeric micelles in aortic endothelial cells.

PURPOSE: To determine aortic endothelial cells permeation ability and mechanisms of the aqueous block copolymeric micelles, poly(ethylene oxide)-poly (beta-benzyl L-aspartate) (PEO-PBLA) chemically conjugated with fluroescein isothiocyanate (FITC) by transport study and confocal laser scanning microscopy. METHODS: The block copolymers' PEO-PBLA-FITC was first synthesized and characterized by gel permeation chromatography (GPC) reflect index, UV, fluorescence detectors, and critical micelles concentrations (CMC), and atomic force microscopy (AFM). Permeation ability and mechanisms of polymeric micelles in aortic endothelial cells were evaluated by incubating with NaF, NaN3, wortmannin, cytochalasin B inhibitors, at 20 degrees C, and under reverse conditions. FITC and latex particles (40 nm) were also used for comparison of transport ability. The extent of localization of uptake polymeric micelles was established by confocal laser scanning microscopy. RESULTS: The size of the aqueous PEO-PBLA-FITC polymeric micelles was detected at around 56 nm with unimodal distribution by AFM. The CMC test revealed the fluorescence intensity increased to around 0.01-0.05 mg/ml. NaF, NaN3, wortmannin, cytochalasin B, 20 degrees C, and reverse experiments inhibited the absorption of polymeric micelles through aortic endothelial cells with apparent permeability coefficients (P) of 18.07 +/- 1.03 to 12.98 +/- 0.93, 11.31 +/- 0.77, 12.44 +/- 1.23, 6.40 +/- 0.23, 11.11 +/- 0.46, and 10.22 +/- 1.09 x 10(-7) cm/sec, respectively. Also, the permeation of FITC and latex on aortic endothelial cells was 70.02 +/- 4.71, and 2.05 +/- 0.41 x 10(-7) cm/sec, respectively. Confocal laser microscopy showed that fluorescent compounds were distributed in the intracellular cytoplasm and nucleus. CONCLUSIONS: PEO-PBLA-FITC copolymeric micelles in an aqueous system were transported by energy-dependent endocytosis with 18.07 x 10(-7) cm/sec penetrated range and were localized on intracellular and nucleus endothelial cells.

Animals↗
PubMed1999

Disparate T cell requirements of two subsets of lupus-specific autoantibodies in pristane-treated mice.

Intraperitoneal injection of pristane induces a lupus-like disease in BALB/c and other non-autoimmune mice characterized by autoantibody production and the development of immune complex disease closely resembling lupus nephritis. Two subsets of autoantibodies are induced by pristane: IgG anti-DNA DNA and -chromatin autoantibodies are strongly IL-6-dependent, whereas IgG anti-nRNP/Sm and -Su antibodies are not. The present studies were carried out to examine the role of T cells in establishing this dichotomy between the production of anti-nRNP/Sm/Su versus anti-DNA/chromatin autoantibodies. Autoantibody production and renal disease were evaluated in athymic (nude) mice treated with pristane. BALB/c nu/nu mice spontaneously developed IgM and IgG anti-single-stranded (ss)DNA and -chromatin, but not anti-nRNP/Sm or -Su, autoantibodies. Pristane treatment increased the levels of IgG anti-chromatin antibodies in nu/nu mice, but did not induce production of anti-nRNP/Sm or -Su antibodies. In contrast, BALB/c nu/+ and +/+ control mice did not spontaneously produce autoantibodies, whereas anti-nRNP/Sm and -Su autoantibodies were induced by pristane in approx. 50% of nu/+ and +/+ mice and anti-DNA/chromatin antibodies at lower frequencies. Nude mice spontaneously developed mild renal lesions that were marginally affected by pristane, but were generally milder than the lesions developing in pristane-treated nu/+ and +/+ mice. The data provide further evidence that two distinct pathways with different cytokine and T cell requirements are involved in autoantibody formation in pristane-induced lupus. This dichotomy may be relevant to understanding differences in the regulation of anti-DNA versus anti-nRNP/Sm autoantibodies in systemic lupus erythematosus, as well as the association of anti-DNA, but not anti-nRNP/Sm, with lupus nephritis.

Animals↗