Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 145 records · Page 8Linked to original sources

PubMed2000

[Activities of antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. Levofloxacin--Surveillance Group].

The surveillance study was conducted to determine the antimicrobial activity of fluoroquinolones (ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin) and other 20 antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. The resistance to fluoroquinolones was remarkable in Enterococci, methicillin-resistant staphylococci and Pseudomonas aeruginosa from UTI. However, many of the common pathogens such as Streptococcus pneumoniae including penicillin-resistant isolates, methicillin-susceptible Stahylococcus aureus, Moraxella catarrhalis, the family of Enterobacteriaceae, Haemophilus influenzae including ampicillin-resistant isolates have been kept to be susceptible to fluoroquinolones. About 90% of P. aeruginosa isolates from RTI were susceptible to fluoroquinolones. In conclusion, the results from this surveillance study suggest that fluoroquinolones are useful in the treatment of various bacterial infections including respiratory infections.

Anti-Infective Agents↗

PubMed2000

[Risk factors and physical activity levels at the onset of acute myocardial infarction in young men].

OBJECTIVES: The pathogenesis and triggering factors of acute myocardial infarction in young men remain unknown. To clarify the pathogenesis of acute myocardial infarction in young Japanese men, we compared the clinical features of patients with acute myocardial infarction in 2 age groups in Japan. METHODS: There were 37 male patients aged < 40 years (Young group; mean age 36 +/- 4 years, range 23-39 years) among 2,879 patients with acute myocardial infarction admitted to the coronary care unit of the National Cardiovascular Center, Japan, from 1977 through 1996. The clinical features of this group were compared with those of 110 consecutive male patients with acute myocardial infarction aged > or = 65 years (Old group; mean age 72 +/- 6 years, range 65-96 years) admitted in 1993-1994. Demographic features, physical activity levels at or within 2 hours before the onset of acute myocardial infarction, and coronary angiographic findings were analyzed. RESULTS: Compared with the Old group, the Young group had lower incidences of hypertension (p < 0.01) and diabetes mellitus (p < 0.01), a higher incidence of smoking (p < 0.01), higher levels of total cholesterol (p < 0.05) and body mass index (p < 0.05), and a lower level of high-density lipopotein (HDL)-cholesterol (p < 0.01). Also, the Young group had a higher prevalence of 0-1 vessel disease than the Old group (72% vs 35%, p < 0.01). The physical activity level was significantly higher in the Young group than in the Old group (2.6 +/- 2.2 vs 1.8 +/- 1.1 METs, p < 0.01). Furthermore, patients with multivessel disease in the Young group had a higher incidence of hypertension, a higher level of total cholesterol and a lower level of HDL-cholesterol (all p < 0.05), whereas those with 0-1 vessel disease had a higher incidence of heavy smoking (73% vs 50%, p = 0.1) and a tendency to higher physical activity level at the onset (2.7 +/- 2.2 vs 2.4 +/- 2.3, NS). CONCLUSIONS: Young male patients with acute myocardial infarction may be characterized by 2 distinctive patterns: one associated with smoking and a higher physical activity level at the onset of acute myocardial infarction with 0-1 vessel disease and the other with hypertension and hypercholesterolemia with multivessel disease.

Adult↗

PubMed2000

[A preliminary study on dihydropyrimidine dehydrogenase activity in breast cancer].

We studied dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS), key enzymes in regulating the pharmacokinetics and chemosensitivity to 5-FU, in 36 breast cancer patients as a control group and 18 patients as a 5-FU group, in which 5-FU was given orally for 2 weeks before surgery at a dose of 200 mg/day. Cancer tissues with adjacent normal tissue were sampled and stored until the assay. The DPD activity and TS amount were determined according to the radio-enzymatic assay and radiobinding assay, respectively. The DPD activity was significantly higher in breast cancer than in the adjacent breast tissue. This finding was observed in T1 and T2, node negative and ER positive breast cancers in the control group as well as in the 5-FU group. The DPD activity in T3 was significantly lower than in T1, and that of the adjacent breast tissue in T3 was significantly higher than in T1; therefore, the tumoral/non-tumoral ratio of DPD activity was significantly lower in T3 than T1. TS was significantly elevated in both groups, without significant differences. The clinical implication of elevated DPD activity in T1, T2, node negative or ER positive breast cancer compared to the respective normal breast tissue activity remains to be studied, because it is still unclear whether or not the tumoral DPD activity regulates the local concentration of 5-FU within the tumor. The amount of TS and DPD activity was not influenced by the oral administration of 5-FU for 2 weeks at the dose of 200 mg/day.

Antimetabolites, Antineoplastic↗

PubMed2000

Bacterial adherence in a rat bladder augmentation model: ileocystoplasty versus colocystoplasty.

PURPOSE: Various intestinal segments are used to reconstruct the urinary tract. For unclear reasons asymptomatic chronic bacteriuria is common in patients treated with reconstruction. We compared bacterial adherence in ileum, colon and bladder in rats with ileal and colonic bladder augmentation. MATERIALS AND METHODS: Bladder augmentation using ileum or colon was performed in 8-week-old rats. After 3 months urinary pH was measured and urine was cultured. Urovirulence factors of Escherichia coli aspirated from the augmented bladders were detected by polymerase chain reaction. In rats with negative urine culture after augmentation experimental cystitis was induced by the transurethral inoculation of E. coli C5, with type I pili and aerobactin or E. coli C92 with type I pili, P fimbriae and aerobactin at a concentration of 10(5) colony forming units per 0.3 ml. After 14 days we counted the colony forming units per cm.(2) of bladder and cm.(2) of intestinal augmentation tissue. RESULTS: When cultures were negative, mean urinary pH plus or minus standard deviation for ileocystoplasty (7.35 +/- 0.33) was significantly higher than that for colocystoplasty (6.80 +/- 0.45) or in controls (6.67 +/- 0.30). Bacterial colonization occurred in 60 of 96 ileocystoplasties (62.5%) and 36 of 68 colocystoplasties (52.9%). All 32 E. coli strains aspirated from ileocystoplasties had type I pili. In colocystoplasties 14 strains had type I pili, 4 had P fimbriae and type I pili, and 1 had no virulence factor. In experimental cystitis in the ileal patch and bladder there were 10(3.2) to 10(6.2) (log mean 4.9) and 10(1.1) to 10(5.1) (log mean 3.5) colony forming units of E. coli C5, respectively. In the colonic patch and bladder there were 10(2.2) to 10(6.2) (log mean 3.9) and 10(2.1) to 10(5.1) (log mean 3.7) colony forming units of E. coli C5, respectively. In the ileal patch and bladder versus the colonic patch and bladder there were 10(3.2) to 10(6.2) (log mean 5.0) and 10(3.1) to 10(6.1) (log mean 4.5) versus 10(3.2) to 10(6.2) (log mean 4.3) and 10(2.1) to 10(6.1) (log mean 3.8) colony forming units of E. coli C92, respectively. E. coli C5 adhered to more ileum than bladder, while bacterial adherence did not differ for colon and bladder. Adherence of E. coli C92 did not differ significantly in bladder and implanted ileum or colon. CONCLUSIONS: The colonic segment offers more resistance to E. coli than the ileal segment in urinary diversion.

Animals↗

PubMed2000

A prospective, randomized trial of conventional, dose-accelerated corticosteroids and intravenous immunoglobulin in children with newly diagnosed idiopathic thrombocytopenic purpura.

To determine the minimal essential treatment for childhood acute idiopathic thrombocytopenic purpura (ITP), a prospective, randomized trial was conducted focusing on hemorrhagic manifestation as well as platelet count. Subjects with a platelet count of <10 x 10(3)/microL or 10 to 29 x 10(3)/microL and mucosal bleeding (group 1) were randomly assigned to receive intravenous immunoglobulin (IVIg) at 1 to 2 g/kg, conventional oral prednisolone (o-PSL) (2 mg/kg for 2 weeks). parenteral methylprednisolone (mPSL) (5 mg/kg for 5 days), or pulsed parenteral methylprednisolone (PmPSL) (30 mg/kg for 3 days). Subjects with a platelet count of 10 to 29 x 10(3)/microL without mucosal bleeding (group 2) were randomized to receive either o-PSL or no treatment. In subjects with a platelet count of 30 x 10(3)/microL or higher (group 3), patients undergoing no specific treatment were monitored. In group 1, IVIg offered faster platelet enhancement compared with o-PSL and mPSL, although neither mPSL no PmPSL showed any advantage, even over o-PSL. Platelet response was uniformly excellent when pretreatment platelet coun was > or = 10 x 10(3)/microL. Furthermore, the presence or absence of mucosal bleeding in subjects with a platelet count <10 x 10(3)/microL had no effect on the response to treatment. In group 2, platelet increase was indifferently attained with or without o-PSL. These data suggest that childhood acute ITP with a platelet count > or = 10 x 10(3)/microL may be left untreated or may be treated with o-PSL when mucosal bleeding is evident, whereas for those with a platelet count <10 x 10(3)/microL, IVIg is the most predictable platelet enhancer. Thus, a platelet count of 10 x 10(3)/microL seems to be informative enough to decide whether to treat childhood acute ITP.

Adolescent↗

PubMed2000

[In vitro and in vivo antibacterial activities of azithromycin].

In Vitro and in vivo antibacterial activities of azithromycin were compared with those of macrolides and other antimicrobial agents. In the in vitro activity azithromycin has a potent activity against both gram-positive and gram-negative bacteria, but against the latter organisms the other macrolides have little potent activity. The in vitro results demonstrate that azithromycin has a high potent activity against respiratory pathogens such as erythromycin-susceptible staphylococci, streptococci (except for organisms possessing erm gene), H, influenzae, B. prtussis, Legionella spp., M. pneumoniae, C. trachomatis. In the pharmacokinetic of azithromycin in mice, it is found that its half life is longer than the other macrolides and the concentration of it in polymorphonuclear leukocytes and lung tissues is higher than the other macrolides. These specific properties in the pharmacodynamic and the in vitro antibacterial activities reflect the therapeutic efficacies in experimental infection models. Finally, the therapeutic efficacies of azithromycin in various infection models better than those of the other macrolides.

Animals↗

PubMed1999

Auranofin inhibits interleukin-1beta-induced transcript of cyclooxygenase-2 on cultured human synoviocytes.

The aim of this study was to characterize the effects of auranofin (2,3,4,6-tetra-O-acetyl-l-thio-beta-D-gluco-pyranosato-S) on cyclooxygenase expression and prostaglandin E(2) synthesis on cultured human synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with auranofin in the presence or absence of interleukin-1beta. Cultured supernatants were harvested for prostaglandin E(2) synthesis. Cyclooxygenase-1 and -2 expression was analyzed with Western and Northern blotting. Translocation of nuclear factor-kappa B p65 was determined by immunostaining. Cytotoxicity was measured with 51Cr release assay. Auranofin attenuated interleukin-1beta-induced prostaglandin E(2) production of the cells in a dose-dependent fashion. Auranofin selectively suppressed interleukin-1beta-induced cyclooxygenase-2 mRNA and protein expression of the cells without alteration of cyclooxygenase-1 expression. Also, auranofin interfered with interleukin-1beta-induced translocation of nuclear factor-kappa B. These inhibitory effects did not originate in the cytotoxicity of the agent. Our data indicate that auranofin inhibits interleukin-1beta-induced prostaglandin E(2) synthesis and cyclooxygenase-2 expression via suppression of nuclear factor-kappa B activation on synoviocytes.

Auranofin↗

PubMed1999

Influence of warfarin therapy on left atrial spontaneous echo contrast in nonvalvular atrial fibrillation.

To examine whether warfarin therapy had any influence on left atrial spontaneous echo contrast, we performed serial transesophageal echocardiography with integrated backscatter analysis in 12 patients with non-valvular atrial fibrillation. We found that the integrated backscatter intensity of the left atrial cavity did not change after 1 to 2 months of warfarin therapy, and concluded that this therapy does not influence spontaneous echo contrast.

Aged↗

PubMed1999

Clonal expansion of alphabeta-T lymphocytes with inverted Jbeta1 bias in familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare but fatal disease in infancy. There are no previous reports on the clonality of T cells in FHL patients. We analyzed here the clonality of alphabeta-T cells in 5 FHL patients using an inverse reverse transcriptase-polymerase chain reaction (RT-PCR) of the T-cell receptor variable region gene (TCR V), a joining region gene of the beta chain (Jbeta)-PCR, a single-strand conformation polymorphism (SSCP), and sequence analysis. A high frequency (15%) of Vbeta and Valpha families was observed in 3 of 5 and 4 of 4 patients examined, respectively. In 19 Vbeta repertoires, including all highly frequent Vbeta, the Jbeta-PCR analysis showed restricted usage of the Jbeta family, indicating a marked bias to Jbeta1 subsets (the mean rate of Jbeta1:Jbeta2 was 87:13 in 65% of the alphabeta-T cells) in widespread alphabeta-T cells (in all patients but 1). In all patients, the clonality of specific Vbeta-Jbeta fragment expanded was confirmed by SSCP and sequence analysis. These results suggest that the existence of clonal expansion and restricted Jbeta1 usage of T cells in FHL is genetically associated with the pathogenesis and the immunodysfunction of the disease. These results help to explain some of the abnormal functional behaviors of T cells in FHL and raise new questions regarding the mechanisms responsible for the restricted clonal diversity.

Amino Acid Sequence↗

PubMed1999

In situ-gelling gellan formulations as vehicles for oral drug delivery.

Gels formed in situ following oral administration of 1% (w/v) aqueous solutions of gellan to rats and rabbits were evaluated as sustained-release vehicles. The formulation contained calcium ions in complexed form, the release of which in the acidic environment of the stomach caused gelation of the gellan gum. The in vitro release of theophylline from the rigid gellan gels followed root-time kinetics over a period of 6 h. Plasma levels of theophylline after oral administration of gellan solutions and a commercial oral sustained-release liquid dosage form containing an identical drug concentration were compared in both rats and rabbits. Bioavailability of theophylline from gellan gels formed by in situ gelation in the animal stomach was increased by four-fivefold in rats and threefold in rabbits compared with that from the commercial oral formulation. There was no significant difference in the mean residence times of theophylline when administered by these two vehicles.

Administration, Oral↗

PubMed1999

Characterization of the Drosophila ortholog of mouse eIF-3p48/INT-6.

The mouse mammary tumor virus (MMTV) has been shown to integrate frequently into INT-6 in MMTV-induced mouse mammary tumors. The INT6 gene has been highly conserved through evolution and has recently been shown to encode the p48 component of the eucaryotic translation initiation factor 3 (eIF-3) complex. We report here the isolation of the Drosophila eIF-3p48/INT-6. The gene comprises three exons within 1.8kb of genomic DNA located at cytogenetic position 73C2 in the Drosophila genome. The 1.5kb eIF-3p48/INT-6 RNA species encodes a protein composed of 364 amino-acid residues whose sequence is 71% similar to that of the mouse/human eIF-3/INT-6 amino-acid sequence. eIF-3p48/INT-6 RNA is expressed throughout development in Drosophila and the encoded protein is associated with the microsomal subcellular fraction.

Amino Acid Sequence↗

PubMed1999

Spatiotemporal dynamics of the [Ca2+]i rise induced by microinjection of sperm extract into mouse eggs: preferential induction of a Ca2+ wave from the cortex mediated by the inositol 1,4,5-trisphosphate receptor.

Hamster sperm extract (SE) possessing Ca2+ oscillation-inducing activity was microinjected into the peripheral or central region of mouse eggs, and the first increase in intracellular Ca2+ concentration ([Ca2+]i), together with the spread of fluorescence-labeled SE in the ooplasm, was investigated by imaging with confocal microscopy. Injection into the periphery always induced a Ca2+ wave that started from the injection site after a delay of 5 to 30 s depending on the concentration of SE. The diluted SE caused a wave of two-step [Ca2+]i rises, which was always observed at fertilization. Injection into the center could induce a radial Ca2+ wave with relatively high dose of SE, but lower dose of SE caused a [Ca2+]i rise after a longer delay which was initiated synchronously over the ooplasm or was preceded in a peripheral area. Injection of diluted SE remarkably prolonged the delay time and reduced the rate of [Ca2+]i rise. The critical concentration of SE needed to induce [Ca2+]i rise was significantly lower in the periphery. These results indicate that the sensitivity to SE is higher in the cortex. SE-induced [Ca2+]i rises were blocked by an antibody against the type 1 inositol 1,4,5-trisphosphate receptor (InsP3R). The cortex was substantially more sensitive to injected InsP3 induction of Ca2+ release than the center. It is suggested that the cortex of mouse eggs may involve a functionally specialized organization of InsP3Rs and Ca2+ pools in which a cytosolic sperm factor(s) could act upon sperm-egg fusion to cause Ca2+ release, leading to the Ca2+ wave at fertilization.

Animals↗

PubMed1999

Effects of aspirin and trapidil on cardiovascular events after acute myocardial infarction. Japanese Antiplatelets Myocardial Infarction Study (JAMIS) Investigators.

Aspirin therapy confers conclusive net benefits in the acute phase of evolving myocardial infarction, but no clear evidence of benefit from the long-term use of aspirin after acute myocardial infarction (AMI) has been shown in any single study. This multicenter study, the Japanese Antiplatelets Myocardial Infarction Study, was performed to find out whether aspirin or trapidil would improve clinical outcome compared with no antiplatelets in postinfarction patients. The study was a multicenter, open-label, randomized controlled trial of aspirin 81 mg/day, trapidil 300 mg/day, and no antiplatelets in patients with AMI admitted within 1 month from the onset of symptoms. Seven hundred twenty-three patients were enrolled at 70 hospitals in 18 prefectures of Japan; 250 were randomly assigned to treatment with 81 mg aspirin (aspirin group), 243 to that with trapidil (trapidil group), and 230 were not given antiplatelet agents. The mean follow-up period was 475 days. This study demonstrated that long-term use of aspirin at the dose of 81 mg/day reduced the incidence of recurrent AMI compared with the group receiving no antiplatelets after AMI (p = 0.0045) and that trapidil also reduced the occurrence of reinfarction compared with the group receiving no antiplatelets, but the difference was not significant (p = 0.0810). The incidence of cardiovascular events including cardiovascular death, reinfarction, uncontrolled unstable angina requiring admission to hospital, and nonfatal ischemic stroke was reduced in the group receiving 300 mg trapidil daily compared with the group receiving no antiplatelets (p = 0.0039). The use of aspirin 81 mg/day provided almost no benefit over no antiplatelets therapy in the incidence of cardiovascular events. In conclusion, low-dose aspirin (81 mg) effectively prevented recurrent AMI in postinfarction patients after thrombolysis or coronary angioplasty when used over a long term. Furthermore, the long-term use of trapidil resulted in a significant reduction in the incidence of cardiovascular events.

Aged↗

PubMed1999

Thermally reversible xyloglucan gels as vehicles for oral drug delivery.

The potential, as sustained release vehicles, of gels formed in situ following the oral administration of dilute aqueous solutions of a xyloglucan polysaccharide derived from tamarind seed has been assessed by in vitro and in vivo studies. Aqueous solutions of xyloglucan that had been partially degraded by beta-galactosidase to eliminate 44% of galactose residues formed rigid gels at concentrations of 1.0 and 1.5% w/w at 37 degrees C. The in vitro release of indomethacin and diltiazem from the enzyme-degraded xyloglucan gels followed root-time kinetics over a period of 5 h at 37 degrees C at pH 6.8. Plasma concentrations of indomethacin and diltiazem, after oral administration to rats of chilled 1% w/w aqueous solutions of the enzyme-degraded xyloglucan containing dissolved drug, and a suspension of indomethacin of the same concentration were compared. Constant indomethacin plasma concentrations were noted from both formulations after 2 h and were maintained over a period of at least 7 h. Bioavailability of indomethacin from xyloglucan gels formed in situ was increased approximately threefold compared with that from the suspension. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for oral delivery of drugs.

Administration, Oral↗

PubMed1999

Spatiotemporal characterization of intracellular Ca2+ rise during the acrosome reaction of mammalian spermatozoa induced by zona pellucida.

The mammalian sperm acrosome reaction (AR) is an essential event prior to sperm-egg fusion at fertilization, and it is primarily dependent on an increase in intracellular Ca2+ concentration ([Ca2+]i). Spatiotemporal aspects of the [Ca2+]i increase during the AR induced by solubilized zona pellucida (ZP) in hamster spermatozoa were precisely investigated with a Ca2+ imaging technique using confocal laser scanning microscopy with two fluorescent Ca2+ indicators. A rapid rise in [Ca2+]i occurred immediately after the application of ZP solution through a micropipette. The rise was always initiated in the sperm head, even when the application was directed toward the tail. The elevated [Ca2+]i was little attenuated during measurement for 30-40 s. Acrosomal exocytosis was detected as a sudden decrease of fluorescence in the acrosomal vesicle approximately 20 s after the onset of the [Ca2+]i rise. High-resolution imaging revealed that the [Ca2+]i rise in the sperm head began at the region around the equatorial segment and spread over the posterior region of the head within 0.6 s, whereas Ca2+ concentration in the acrosomal vesicle appeared to be unaltered. The [Ca2+]i rise was completely abolished under Ca2+-free extracellular conditions, indicating that it is totally attributable to Ca2+ influx. Nifedipine, an inhibitor of L-type Ca2+ channels, did not affect the rising phase of the ZP-induced Ca2+ response, but accelerated the decline of the [Ca2+]i rise and inhibited acrosomal exocytosis. The present study provides implicative information about the spatial organization of functional molecules involved in the signal transduction in mammalian AR.

Acrosome↗

PubMed1999

A novel role of IL-15 in the development of osteoclasts: inability to replace its activity with IL-2.

IL-15 shares many activities with IL-2 on stimulating lymphocytes, hematopoietic progenitor cells, and macrophages. However, the role of IL-15 in osteoclastogenesis has not been elucidated. The recent finding of abundant IL-15 in rheumatoid arthritis synovial fluids suggested a possible role for this cytokine in the pathological destruction of bone and prompted us to determine whether IL-15 stimulates osteoclast formation. IL-15 stimulated the formation of multinucleated osteoclast-like cells in rat bone marrow cultures. In stroma-free cultures, IL-15 increased the number of mononuclear preosteoclast-like cells in the early stage of osteoclast formation. The stimulation was observed even after treatment with IL-15 for only 24 or 48 h of culture. Moreover, low IL-15 concentration (0.1 ng/ml) strongly increased the level of calcitonin receptor mRNA of mononuclear preosteoclast-like cells. Although IL-15 is known as a potent stimulator of TNF-alpha, its activity was not abolished by addition of anti-TNF-alpha Ab. Interestingly, IL-2 and IL-7, which utilize some IL-15R components, had no effect on osteoclast differentiation, but pretreatment with IL-2 or IL-7 of bone marrow cells before the addition of IL-15 inhibited the enhancing activity of IL-15. In summary, IL-15 has a novel activity to stimulate the differentiation of osteoclast progenitors into preosteoclasts, which cannot be replaced by IL-2 but may use components in common with IL-2R to mediate its effects.

Animals↗

PubMed1999

DNA Data Bank of Japan dealing with large-scale data submission.

The DNA Data Bank of Japan (DDBJ) (http//:www.ddbj.nig.ac.jp) has developed a software system for mass submissions to cope with a recent expansion of EST and genome data submissions. The system is composed of four parts, the WWW data submission, large-scale submission, submission management and storing. Using this system one can submit data on a large number of sequences or a very long sequence while checking the consistency between the annotation and sequence without much effort. DDBJ has received large scale data of Homo sapiens, Arabidopsis and Pyrococcus from Japanese researchers who made full use of the new submission system.

Animals↗

PubMed1999

Clonal dissemination of T-lymphocytes in scid mice from familial hemophagocytic lymphohistiocytosis.

BACKGROUND: Although familial hemophagocytic lymphohistiocytosis (FHL) has been considered a disorder of T-cell dysfunction, there is no evidence of the clonal origin of T-cells in this disease. PROCEDURE: We engrafted mononuclear cells (MNCs) from five FHL patients into scid mice and examined the infiltration of human cells in mouse organs. The characterization of human cells that infiltrated in the mouse organs was then performed. RESULTS: A diffuse infiltration of human lymphoid cells was detected in scid mice treated with 1 x 10(6) MNCs from one of the five patients. These cells were positive for HLA-DR and CD3, but negative for CD4, CD8, CD20, and CD68, suggesting the infiltration of double negative (DN) T-cells. The MNCs from the other four patients induced murine lymphoma-like disease; T-cell lymphoma in one and lymphoma of unknown origin in three. The characterization of these human DN T-cells was performed. The analysis of the Vbeta repertoire showed no preferential usage of the Vbeta family in MNCs, while the dominant expression of Vbeta13 was detected in T-cells infiltrating in the spleen and lung. A Jbeta analysis showed the restricted usage of Jbeta1.2 for Vbeta13 in these cells, and the clonality of Vbeta13-Jbeta1.2 fragment was confirmed by a single-strand confirmation polymorphism analysis. The analysis of the Valpha repertoire showed that Valpha24 was exclusively used in these DN T-cells, but no usage of JalphaQ for Valpha24 was observed. CONCLUSIONS: A clonal expansion of T-cells was induced in scid mice by the engraftment of MNCs from an FHL patient. The infiltration of DN alphabeta T-cells bearing invariant Valpha24 T-cell receptor in mouse organs may provide a useful clue to the pathogenesis of FHL. In the patients whose MNCs induced murine lymphoma-like disease, some cytokines or unknown factors that stimulate the growth and the tumorigenicity of murine lymphocytes might be produced by the MNCs engrafted in scid mice. Further study is needed to confirm the validity of our experimental approach and the findings observed in scid mice by using more FHL samples.

Animals↗