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PubMed1997

Iron-Sulfur Clusters with SiMe(2)-Bridged Cyclopentadienyl Ligands: [Me(2)Si(eta(5)-C(5)H(4))(2)](2)Fe(5)S(12), [Me(2)Si(eta(5)-C(5)H(4))(2)](2)Fe(4)S(6), and [Me(2)Si(eta(5)-C(5)H(4))(2)](2)Fe(4)S(6)(CO).

The synthesis and characterization of iron-sulfur clusters stabilized by dimethylsilyl-bridged cyclopentadienyl groups are reported. The thermal reaction of Me(2)Si(eta(5)-C(5)H(4))(2)Fe(2)(CO)(4) (1) with S(8) yields the tetranuclear cubane-type cluster compound [Me(2)Si(eta(5)-C(5)H(4))(2)](2)Fe(4)S(6) (4) and the pentanuclear cluster compound [Me(2)Si(eta(5)-C(5)H(4))(2)](2)Fe(5)S(12) (3) in high yields. The photochemical reaction of 1 with S(8) yields the tetranuclear cluster compound [Me(2)Si(eta(5)-C(5)H(4))(2)](2)Fe(4)S(6)(CO) (5), which contains one residual terminal carbonyl. The crystal structures of 3 and 4 have been determined. Crystal data: 3.CH(2)Cl(2), monoclinic, C2/c, a = 23.480(13) Å, b = 11.192 (4) Å, c = 17.84 (3) Å, beta = 118.58(9) degrees, V = 4118(7) Å(3), Z = 4, R = 0.078; 4, triclinic, P&onemacr;, a = 8.4787(7) Å, b = 12.9648(9) Å, c = 13.4990(9) Å, alpha = 79.857(8) degrees, beta = 75.293(8) degrees, gamma = 74.041(11) degrees, V = 1370.9(2) Å(3), Z = 2, R = 0.0447. The Fe(5)S(12) core of 3 has a bowtie structure in which a central iron atom is octahedrally coordinated by six sulfur atoms from one tetrasulfido and four disulfido groups. The structure of 4 resembles the structure of the known iron-sulfur cluster Cp(4)Fe(4)S(6). However, 4 shows a markedly enhanced thermal stability compared to Cp(4)Fe(4)S(6). In their cyclic voltammograms, 4 and 5 exhibit electrochemical behavior typical of cubane-type Cp-iron-sulfur clusters, whereas the cyclic voltammogram of 3 is quite different. The nu(CO) mode of 5 has been measured for four different oxidation states of the cluster by means of IR spectroelectrochemical methods. The Mössbauer spectra of 3 and 3(+) are in accordance with their pentanuclear structure.

Journal Article↗
PubMed2006

Characterisation by X-ray microanalysis of metal granules in the mucus trails of Littorina littorea (Gastropoda) along a putative pollution gradient.

Metal-containing granules in the mucus trails of the marine gastropod Littorina littorea from nine sites in north-east England were analysed for elemental composition by X-ray microanalysis and characterised relative to a putative gradient of pollution. Overall granule density varied significantly between sites, means of 6.5-17.0 per field of view (2688 microm2). Most granules found (64%) were poly-metal of a wide variety of compositions, but could be classified as Si+X, Mg+X, S+X, Na+X, P+Ca, P+Al, where X indicates any other combination of elements. Si+Al+X accounted for 61% of the poly-metal granules found and was considered to be contamination from the beach substratum. In single-metal granule form only Ca, Si, Fe, Ti, Al and Na were found. The most common single-metal granule at each site was of Ca, except at two sites, where the most common single-metal granule was of Si. The densities of these granule types varied between sites but differences were found to be significant only in the case of Si granules. Across all sites, single-metal granules of Si (mean = 2.49 microm +/- 1.44 SD, n = 141) and Ca (2.22 microm +/- 1.08 SD, n = 147) were significantly larger than granules of Fe (1.74 microm +/- 0.95 SD, n = 63) and Ti (1.24 microm +/- 0.52 SD, n = 18). The range of sizes was large: Ca (0.5-6 microm), Si (0.5-10 microm), Fe (0.3-4.1 microm), Ti (0.5-2.5 microm). Between the sites there were significant differences in the size of Fe and Si granules but not Ca or Ti granules. Despite these variations in granule type and size, there was no evidence of a relationship with pollution and consequently a detoxifying function of the mucus trail in metal polluted environments is not apparent.

Animals↗
PubMed1982

Collagens act as ligands to stimulate human monocytes to produce mononuclear cell factor (MCF) and prostaglandins (PGE2).

Blood mononuclear cells from patients with rheumatoid arthritis produce the lymphokine, leukocyte inhibitory factor (LIF) in response to collagens in vitro, and blood monocytes release prostaglandins (PGE2) and a factor, mononuclear cell factor (MCF) which stimulates collagenase and PGE2 production by cultured synovial cells. We therefore examined the effect of collagens on the production of PGE2 and MCF. Blood mononuclear cells from 6 patients with rheumatoid arthritis and 6 normal subjects were cultured in native human types I, II, or III collagen-coated tubes, or with streptokinase-streptodornase (SK-SD), and the supernatant media derived from these cultures analyzed for the presence of MCF, PGE2, and LIF. Types II and III collagens, as well as SK-SD, markedly stimulated MCF production by the cells from all 12 subjects (MCF activity, expressed as a mean stimulation index (SI) +/- SEM, was 43 +/- 12 for type II, 33 +/- 7 for type III, and 37 +/- 23 for SK-SD). Type I collagen was less stimulatory (mean SI 10 +/- 7). Cells from the patients with rheumatoid arthritis, but not the normal subjects, produced LIF in response to types II or III collagens but not to type I collagen. PGE2 production by blood mononuclear cells paralleled that of MCF, although abrogation of PGE2 release with indomethacin did not reduce MCF production. alpha chains purified from denatured collagens also stimulated MCF production. Using cells from patients with rheumatoid arthritis, type II collagen stimulated production of all three factors in the presence of polymyxin B or fibronectin-depleted serum, suggesting, respectively, that neither endotoxin nor fibronectin were responsible for their generation. Monocytes, purified from normal blood by an adherence technique, but not lymphocytes depleted of monocytes, released MCF and PGE2 when cultured with type II collagen. These results demonstrate that collagens can act as ligands to stimulate monocytes, as well as antigens to stimulate sensitized lymphocytes, to produce soluble factors that may contribute to the destruction of connective tissue.

Arthritis, Rheumatoid↗
PubMed2004

[Biofeedback as a conservative treatment of fecal incontinence].

Faecal incontinence (SI) is defined as uncontrolled evacuation of stool in an inappropriate time or place, occurring at least two times a month. The other definition of SI is an inability to refrain from defecation till the moment thought to be appropriate from sociologic point of view. SI is an extremely stressful disease, which according to different sources, concerns about 2.5 to 7% of the adult population. The frequency of SI incidence raises with age, and it concerns about 60% of patients in geriatric health--care institutions. Nowadays there are many types of casual treatment of SI. One of the "first line" methods, if there is no extensive mechanical injury of sphincteric complex, is biofeedback (BF) training. In our study we presented principles of biofeedback treatment, a historical outline of the mentioned method and other conservative methods of SI treatment. We also presented, on the basis of literature, actual state of art concerning effectiveness and possibilities of therapeutic application of BF and results of clinical research, concerning application of BF training in faecal continence impairment in the adult population.

Adult↗
PubMed1987

Type A behavior pattern, parental history of hypertension, and cardiovascular reactivity in college males.

Two risk factors for cardiovascular disorders, parental history of hypertension and the Type A behavior pattern, were investigated concurrently with respect to cardiovascular reactivity to challenging situations. Sixty-four college males were given both the Structured Interview (SI) and Jenkins Activity Survey (JAS) for the Type A behavior pattern and a family health questionnaire to determine parental history of hypertension. The students were monitored for blood pressure (BP), heart rate (HR), and pulse transit time (PTT) response to four tasks: cold pressor, isometric handgrip exercise, a reading comprehension task, and backwards digit span. Type As based on SI classification had significantly higher HR levels across all tasks than did Type Bs, as well as higher diastolic BP levels in the cold pressor task. No main effects for Type A-B using JAS classification were found. Positive parental history students had higher HR and shorter PTT levels across all the tasks. Type A and parental history did interact in a limited way on some tasks, but the interactions were also dependent on the Type A classification used.

Adolescent↗
PubMed1999

T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides.

T cell responses to peptide epitopes of the 60 kDa heat shock protein (hsp60) have been shown to play a role in the pathogenesis of type 1 insulin-dependent diabetes mellitus (IDDM) in mice. To test whether hsp60 autoimmunity might be involved in human type 1 diabetes, we studied T cell proliferative responses (stimulation index; SI) to intact human hsp60, to hsp60 peptides and to a recall antigen (tetanus toxoid) in 25 newly diagnosed type 1 diabetes patients, in 22 type 2 (non-insulin-dependent diabetes mellitus, NIDDM) patients, and in 25 healthy blood donors. There were no significant differences between the T cell responses of the three groups to tetanus toxoid. However, the responses to hsp60 of the type 1 diabetes group (median SI=5) were significantly greater (P<0. 01) than those of the type 2 group (median SI=1.67) and of the blood donors (median SI=1.7). Epitope mapping revealed significant responses to at least seven different peptides, with prevalent responses to the p277 peptide previously mapped in NOD mice and to peptide p32. Thus, newly diagnosed type 1 diabetes patients, similar to prediabetic and newly diabetic NOD mice, show heightened autoimmunity to hsp60 and hsp60 peptides.

Adolescent↗
PubMed1999

Sucrase-isomaltase and hexose transporter gene expressions are coordinately enhanced by dietary fructose in rat jejunum.

We previously demonstrated that the levels of mRNAs of both sucrase-isomaltase (SI) and sodium/D-glucose transporter (SGLT1) are modulated by dietary sucrose in the rat jejunum. In the present study, we investigated whether the transcription of the gene coding SI is regulated by certain types of monosaccharides. Force-feeding a fructose and sucrose diet, (40% energy as fructose or sucrose) gave rise to parallel increases in the transcripts of SI and intestinal hexose transporters (SGLT1, GLUT5, and GLUT2) within 12 h. Force-feeding a glycerol-containing diet also caused an enhancement of SI, SGLT1, and GLUT2 mRNA levels. However, feeding the diet containing glucose or alpha-methylglucoside generally did not increase the transcript levels of SI or the intestinal hexose transporters. Nuclear run-on assays revealed that fructose as well as sucrose increased the transcription of both SI and GLUT5 genes and that the transcription rates of these genes were unaffected by glucose. These results suggest that fructose (or a metabolite) is capable of increasing the mRNA levels of SI and hexose transporters in the small intestine and that transcriptional regulation might play a pivotal role in the carbohydrate-induced coordinate enhancement of SI and fructose transporter gene expression

Animals↗
PubMed1985

Development of a brief self-report measure of the type A (coronary prone) behavior pattern.

This study reports the development of a brief self-report measure of the Type A behavior pattern based upon a set of adjectives derived from the Gough Adjective Checklist (ACL). Previous work from our laboratory established a set of adjectives identified by experts as being relevant to the Type A construct that subsequently was found to successfully distinguish Type A individuals from their Type B counterparts. In the present study, a Type A self-rating scale based on these adjectives was found to be significantly related to an established Type A self-report instrument, the Jenkins Activity Survey (JAS), and to an independent behavioral rating based upon a standard structured interview (SI). However, no measure of Type A was related to the severity of coronary artery disease (CAD) as documented by coronary angiography. The advantages and disadvantages of the various Type A measures are discussed in the context of their ability to identify individuals at risk for the development of CAD.

Coronary Disease↗
PubMed2001

Intramedullary high signal intensity on T2-weighted MR images in cervical spondylotic myelopathy: prediction of prognosis with type of intensity.

PURPOSE: To examine whether the different appearances of intramedullary high signal intensity (SI) on T2-weighted MR images in cervical spondylotic myelopathy are related to differences in surgical prognosis. MATERIALS AND METHODS: The magnetic resonance (MR) findings and Japanese Orthopedic Association (JOA) score of 64 cervical spondylotic myelopathy patients, who underwent decompression surgery, were evaluated. SIs were classified as type 0 if no intramedullary high SI on T2-weighted MR images was noted, type 1 if a predominantly (>50%) faint and fuzzy border of high SI was noted, or type 2 if a predominantly (>50%) intense and well-defined border of high SI was noted. Postoperative JOA scoring and MR imaging were also performed 6 months after surgery. Recovery ratios were calculated. RESULTS: There were 20 type 0, 23 type 1, and 21 type 2 cases. Statistical analyses showed no significant difference in age, sex, cervical curvature, and preoperative JOA score between the three groups. Statistical analyses of the recovery ratio showed significantly poor prognosis of type 2 compared with type 1 (P < .001) and type 0 (P =.001), but no difference between types 0 and 1 (P = .317). After controlling for factors of age, sex, preoperative JOA score, cervical curvature, and cord compression ratio, analysis of covariance showed the same result. CONCLUSION: Type 1 intramedullary high SI on T2-weighted MR images indicates a better surgical outcome than does type 2.

Adult↗
PubMedDate not supplied

Familial resemblance in components of the type A behavior pattern: a reanalysis of the California type A twin study.

Rosenman and colleagues reported no heritability of global Type A behavior assessed by the Structured Interview (SI) method, although some of the self-report scales correlated with global Type A behavior did have heritable components. Recent factor analyses of coded SI responses revealed four independent dimensions: clinical ratings, primarily of speech stylistics; and self-reports of pressured drive, anger, and competitiveness. It may be that some of these dimensions have a heritable base, whereas others do not. We report here reanalyses of the available SI responses from the Rosenman sample. In this subsample, tape recorded interviews with 80 monozygotic and 80 dizygotic twin pairs were scored for the extent of self-reported Type A behaviors, the major speech stylistics considered to be indicative of Pattern A, and the observable Type A behaviors (e.g., signs of hostility). Then scores for the major dimensions measured by the SI were calculated and scores for which there were sufficient data were subjected to twin analyses by the method of Christian et al. These analyses showed that individual differences in the clinical ratings factor and certain ratings loading on it--specifically, loudness of speech, competition for control of the interview, and potential for hostility--might have a heritable component. These results are discussed in the context of the importance of hostility as a predictor of subsequent coronary heart disease events as well as of total mortality, other data on the heritability of emotionality, and a temperament approach to understanding the origins of the Type A behavior pattern.

Adult↗
PubMed1980

Synthesis and characterization of a photosensitive interface for hydrogen generation: Chemically modified p-type semiconducting silicon photocathodes.

p-Si photocathodes functionalized first with an N,N'-dialkyl-4,4'-bipyridinium redox reagent, (PQ(2+/+-))(surf), and then with a Pt precursor, PtCl(6) (2-), give significant efficiency (up to 5%) for photoelectrochemical H(2) generation with 632.8-nm light. Naked p-Si photocathodes give nearly zero efficiency, owing to poor H(2) evolution kinetics that are improved by the (PQ(2+/+-))(surf)/Pt modification. The mechanism of H(2) evolution from p-Si/(PQ(2+/+-))(surf)/Pt is first photoexcitation of electrons to the conduction band of Si followed by (PQ(2+))(surf) --> (PQ(+-))(surf) reduction. The dispersion of Pt then catalyzes H(2)O reduction to give H(2) and regeneration of (PQ(2+))(surf). The overall energy conversion efficiency rivals the best direct optical to chemical conversion systems reported to date.

Journal Article↗
PubMed2006

The chemisorption of coronene on Si(001)-2 x 1.

Coronene (C24H12) adsorption on the clean Si(001)-2 x 1 surface was investigated by scanning tunneling microscopy and by density-functional calculations. The coronene adsorbed randomly at 25 degrees C on the surface and did not form two-dimensional islands. The scanning tunneling microscopy measurements revealed three adsorption sites for the coronene molecule on the Si(001) surface at low coverage. The major adsorption configuration involves coronene bonding to four underlying Si atoms spaced two lattice spacings apart in a dimer row. The two minor adsorption configurations involve asymmetrical bonding of a coronene molecule between Si dimer rows and form surface species with a mirror plane symmetry to their chiral neighbor species. The two minor bonding arrangements are stabilized by a type-C defect on the Si(001) surface.

Journal Article↗
PubMed2006

Unique {H(SiR(3))(2)}, (H(2)SiR(3)), H(HSiR(3)), and (H(2))SiR(3) ligand sets supported by the {Fe(Cp)(L)} platform (L=CO, PR(3)).

This work deals with the type and incidence of nonclassical Si--H and H--H interactions in a family of silylhydride complexes [Fe(Cp)(OC)(SiMe(n)Cl(3-n))H(X)] (X=SiMe(n)Cl(3-n), H, Me, n=0-3) and [Fe(Cp)(Me(3)P)(SiMe(n)Cl(3-n))(2)H] (n=0-3). DFT calculations complemented by atom-in-molecule analysis and calculations of NMR hydrogen-silicon coupling constants revealed a surprising diversity of nonclassical Si--H and H--H interligand interactions. The compounds [Fe(Cp)(L)(SiMe(n)Cl(3-n))(2)H] (L=CO, PMe(3); n=0-3) exhibit an unusual distortion from the ideal piano-stool geometry in that the silyl ligands are strongly shifted toward the hydride and there is a strong trend towards flattening of the {FeSi(2)H} fragment. Such a distortion leads to short Si--H contacts (range 2.030-2.075 A) and large Mayer bond orders. A novel feature of these extended Si--H interactions is that they are rather insensitive towards the substitution at the silicon atom and the orientation of the silyl ligand relatively the Fe--H bond. NMR spectroscopy and bonding features of the related complexes [Fe(Cp)(OC)(SiMe(n)Cl(3-n))H(Me)] (n=0-3) allow for their rationalization as usual eta(2)-Si--H silane sigma-complexes. The series of "dihydride" complexes [Fe(Cp)(OC)(SiMe(n)Cl(3-n))H(2)] (n=0-3) is different from the previous two families in that the type of interligand interactions strongly depends on the substitution on silicon. They can be classified either as usual dihydrogen complexes, for example, [Fe(Cp)(OC)(SiMe(2)Cl)(eta(2)-H(2))], or as compounds with nonclassical H--Si interactions, for example, [Fe(Cp)(OC)(H)(2)(SiMe(3))] (16). These nonclassical interligand interactions are characterized by increased negative J(H,Si) (e.g. -27.5 Hz) and increased J(H,H) (e.g. 67.7 Hz).

Journal Article↗
PubMed2006

Arylthiopyrrole (AThP) derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors: synthesis, structure-activity relationships, and docking studies (part 2).

Arylthio isopropyl pyridinylmethylpyrrolemethanols (AThPs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleoside binding site (NNBS) of this enzyme. Docking experiments of the potent inhibitors 4k (IC(50) = 0.24 microM, SI = 167) and 5e (IC(50) = 0.11 microM, SI > 1667) of wild-type RT prompted the synthesis and biological evaluation of novel AThP derivatives featuring a number of polar groups in position 3 of the pyrrole ring and larger and more hydrophobic alicyclic substituents in place of the isopropyl group at position 4. Among the compounds synthesized and tested in cell-based assays against HIV-1 infected cells, 19b was the most active, with EC(50) = 0.007 microM, CC(50) = 114.5 microm, and SI = 16357. This compound and its precursor 18b retained interesting activities against clinically relevant drug-resistant RT forms carrying K103N, Y181I, and L100I mutations. Docking calculations of 10, 14, 18b, and 19b were also performed to investigate their binding mode into the RT NNBS and to rationalize both structure-activity relationship and resistance data.

Binding Sites↗
PubMed2006

Comparative study of LiF:Mg,Cu,Na,Si and Li2B4O7:Cu,Ag,P TL detectors.

Recently, two new types of 'tissue equivalent' thermoluminescent detectors (TLDs) have aroused attention: LiF:Mg,Cu,Na,Si and Li2B4O7:Cu,Ag,P. In this work the characteristics of both detectors were compared with the characteristics of the well-known type LiF:Mg,Ti detector, TLD-100. The following properties were investigated: the glow curve structures, relative sensitivity, batch homogeneity and uniformity, detection threshold, reproducibility of the response, linearity in the wide dose range and fading. Also, the energy dependence for medium and low energy X rays was determined in the range of mean energies between 33 and 116 keV. The results confirmed 'tissue equivalency' of both new types in the investigated range of photon energies. LiF:Mg,Cu,Na,Si detector has very high sensitivity (approximately 75 times higher than that of TLD-100) and is convenient for use in a very low range of doses. Li2B4O7:Cu,Ag,P detector shows some improvements in comparison with the previously prepared types of lithium borate. The most important is the five times higher sensitivity than that of TLD-100. This detector is also very promising, especially in medical dosimetry.

Borates↗
PubMed2001

The role of root exudates in aluminium resistance and silicon-induced amelioration of aluminium toxicity in three varieties of maize (Zea mays L.).

Aluminium (Al) toxicity is widely considered to be the most important growth-limiting factor for plants in strongly acid soils (pH<5.0). The inhibition of root elongation in three varieties of maize (Zea mays L. vars Clavito, HS701b and Sikuani) was followed over the first 48 h of Al treatment, and during the initial 10 h elongation was determined on an hourly basis. The silicon (Si)-induced amelioration of Al toxicity was investigated by pre-treating seedlings for 72 h in nutrient solutions with 1000 microM Si before transfer into solutions with 0, 20 or 50 microM Al (without Si). Plants were either grown in complete low ionic strength nutrient solutions (CNS) or in low salt solutions of 0.4 mM CaCl2 (LSS). In addition, the role of root exudation of organic compounds as a mechanism of Si-induced alleviation of Al toxicity was investigated. Aluminium-induced inhibition of root elongation in the maize var. HS701b was observed within 1 h of Al exposure. After a lag time of at least 8 h, Si-induced alleviation of Al toxicity was observed in this variety when grown in LSS. In the Al-resistant var. Sikuani, Al-resistance was only observed after exposure to 50 microM Al, and not after exposure to 20 microM Al, suggesting that there exists a threshold Al concentration before the mechanisms of Al resistance are activated. Aluminium stimulated root exudation of oxalic acid in all three varieties, but exudate concentrations did not increase with either Al resistance or with Si pretreatment. Aluminium and Si triggered release of catechol and of the flavonoid-type phenolics: catechin, and quercetin. In the Al-resistant variety, Sikuani, Al-exposed plants pretreated with Si exuded up to 15 times more phenolics than those plants not pretreated with Si. The flavonoid-type phenolics, to date unconsidered, appear to play a role in the mechanism(s) of Si-induced amelioration of Al toxicity.

Aluminum↗
PubMed1995

Adaptations of diaphragm neuromuscular junction following inactivity.

We hypothesized that differences exist in the morphological adaptations of neuromuscular junctions (NMJs) on different fiber types in response to prolonged inactivation. Two weeks of inactivity of both phrenic motoneurons and diaphragm muscle was induced by spinal cord hemitransection at C2 (spinal isolation; SI). A three-color fluorescent immunocytochemical technique, combined with laser-scanning confocal microscopy, was used to create two- (2D) and three-dimensional (3D) images of NMJs and obtain morphological information concerning: (1) innervating axons and presynaptic nerve terminals; (2) motor endplates (postsynaptic apparatus consisting of acetylcholine receptors), and (3) myosin heavy chain (MHC) phenotype of muscle fibers. In both sham controls (CTL) and SI animals, planar (2D) and surface (3D) areas of motor endplates and nerve terminals on type II muscle fibers (anti-fast MHC immunoreactive) were smaller than on type I (nonimmunoreactive to anti-fast MHC) fibers, when normalized for fiber diameter. The number of branches, total branch length and perimeter of both motor endplates and nerve terminals were greater for NMJs on type II fibers than on type I fibers. The extent of overlap between nerve terminal and endplate was greater on type I fibers than on type II fibers. After SI, there was a significant expansion of NMJs on type II fibers. Planar and surface areas of motor endplates and nerve terminals, number of endplate and nerve terminal branches, total branch length, and perimeter were all increased on type II fibers following SI. The extent of overlap of nerve terminal and endplate increased on type II fibers, approaching that observed in type I fiber NMJs. These results indicate that neuromuscular inactivation leads to a selective expansion of type II fiber NMJs through addition of new terminal area, and elongation of existing terminal branches. These changes may represent a compensatory effort to improve neuromuscular transmission.

Adaptation, Physiological↗
PubMed1995

Malignant lymphoma induction in rabbits by intravenous inoculation of Epstein-Barr-virus-related herpesvirus from HTLV-II-transformed cynomolgus leukocyte cell line (Si-IIA).

Malignant lymphomas, which were usually of T-cell type, were induced in 10 of 13 (77%) male rabbits (Japanese white, 8/10; New Zealand white, 2/3) inoculated i.v. with HTLV-II-transformed simian (Cynomolgus) leukocyte cell line (Si-IIA) cells. Of 7 rabbits injected with cell-free pellets from Si-IIA cultures, 5 also developed malignant lymphoma (15-28 days). Lymphoma development was completely inhibited by inactivation of cell-free pellets from Si-IIA culture with ethyl ether and was almost suppressed by neutralization of the cell-free pellets with anti-Si-IIA sera. Herpesvirus particles were discovered very rarely in Si-IIA cells, in addition to C-type virus particles, by electron microscopy. Si-IIA cells were positive for Epstein-Barr-virus (EBV)-associated nuclear antigen (EBNA) by immunofluorescence (IF) test. Antibody response to viral capsid antigen of EBV was also detected in sera from rabbits inoculated with Si-IIA. EBV-encoded RNA-1 (EBER-1) was demonstrated in Si-IIA, the tumor tissues and all rabbit tumor cell lines by in situ hybridization. EBV DNA was also detected in Si-IIA and rabbit lymphoma cell lines by polymerase chain reaction (PCR) and Southern blotting. However, EBV DNA was amplified only by some primers complementary to human EBV sequence (B95-8), but not by other primers. Integration of HTLV-II provirus genome could not be detected in Si-IIA-induced rabbit tumor cells. Moreover, no lymphoma was induced by inoculation of HTLV-IIC and MOT (other HTLV-II-producing human cell lines), B95-8(EBV-producing cell line) or TALL-1 and peripheral leukocytes from normal Cynomolgus (controls). Neither Herpesvirus saimiri nor H. ateles (simian oncogenic viruses) were detected in Si-IIA cells by IF test. These data suggest that the high rate of lymphoma induction in rabbits may not be caused by HTLV-II, human EBV (B95-8) or well-known simian oncogenic viruses, but by EBV-related herpesvirus derived from Si-IIA cells or HTLV-IIA cells, with which Si-IIA was established. The availability of this animal model promises to clarify the role of EBV in human lymphoma and provides a means of studying prophylactic and therapeutic regimens.

Animals↗