Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 271 records · Page 15Linked to original sources

PubMed1997

Characterization of CD4+CD8+ thymocytes observed in SCID-bg mice.

Previously, we reported that a strain of severe combined immunodeficient (SCID) mice, namely SCID-bg, spontaneously develop CD4+CD8+ double positive (DP) thymocytes despite their scid mutation. In the present study, we intend to further characterize the DP thymocyte population in SCID-bg mice with Southern hybridization and flow cytometry. Southern hybridization analyses of sorted DP thymocytes in SCID-bg mice showed rearrangement of T cell receptor (TCR) beta and TCR gamma gene segments, although the expression of TCR beta and gamma delta TCR molecules was absent. The phenotype of the DP thymocytes in SCID-bg mice was CD44- heat-stable antigen (HSA)+CD25-, and they did not express CD69. Interestingly, the expression of thymus leukaemia (TL) antigen was observed in the DP thymocytes of SCID-bg mice but not in their CD4-CD8- double negative (DN) fraction. Fas expression was higher and bcl-2 expression was down-regulated in the DP thymocytes as compared to the DN thymocytes in SCID-bg mice, suggesting that they are not immortalized cells having escaped from apoptosis. Taken together, these results show that the phenotype of the DP thymocytes in SCID-bg mice is similar to that of the earliest phase of the DP thymocytes in normal mice, although the expression of the molecules in the pre-TCR complex is absent.

Animals↗

PubMed1997

An ultrastructural study of cartilage resorption at the site of initial endochondral bone formation in the fetal mouse mandibular condyle.

An ultrastructural study was undertaken on cartilage resorption at the site of initial endochondral bone formation in the mouse mandibular condyle on d 16 of pregnancy. After resorbing the bone collar, the osteoclasts extended their cell processes into the cartilage matrix and made contact with hypertrophic chondrocytes. By means of cell processes or vacuolar structures, these osteoclasts entrapped the calcified cartilage matrices, cell debris, and the degraded uncalcified cartilage matrices. In particular, since the calcified cartilage matrices were sometimes seen to be disrupted within the osteoclastic vacuolar structures, they were probably disposed of by the osteoclasts. Invading endothelial cells giving rise to capillaries also directly surrounded the degraded uncalcified cartilage matrices and small deposits of cell debris. In addition, hypertrophic chondrocytes that had attached to or were in the process of attaching to the invading osteoclasts often enclosed the small calcified cartilage matrices. Other cell types that have often been reported in other regions of cartilage resorption were not seen at the site of initial endochondral bone formation in this study. Our findings in relation to cartilage resorption may therefore represent unique features of the site of initial endochondral bone formation site. We consider that the manner of cartilage resorption is likely to vary by site, age, and species.

Animals↗

PubMed1997

Immunohistochemistry of collagen types II and X, and enzyme-histochemistry of alkaline phosphatase in the developing condylar cartilage of the fetal mouse mandible.

We investigated the immunohistochemical localisation of types II and X collagen as well as the cytochemical localisation of alkaline phosphatase in the developing condylar cartilage of the fetal mouse mandible on d 14-16 of pregnancy. On d 14 of pregnancy, although no immunostaining for types II and X collagen was observed, alkaline phosphatase activity was detected in all cells in the anlage of the future condylar process. On d 15 of pregnancy, immunostaining for both collagen types was simultaneously detected in the primarily formed condylar cartilage. Alkaline phosphatase activity was also detected in chondrocytes at this stage. By d 16 of pregnancy, the hypertrophic cell zone rapidly increased in size. These findings strongly support a periosteal origin for the condylar cartilage of the fetal mouse mandible, and show that progenitor cells for condylar cartilage rapidly or directly differentiate into hypertrophic chondrocytes.

Alkaline Phosphatase↗

PubMed1997

Effect of tumor necrosis factor-alpha on the permeability of bovine brain microvessel endothelial cell monolayers.

The administration of chemotherapy to patients with tumors of the central nervous system is often blocked by the blood-brain barrier. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that promotes vascular permeability in addition to its pro-inflammatory effects. However, no direct evidence exists as to whether TNF-alpha may increase permeability of the BBB. We evaluated the effect of TNF-alpha on the transport of cisplatin (CDDP) or high molecular weight dextran labeled with fluorescein isothiocyanate (FITC-dextran) across bovine brain microvessel endothelial cell (BMEC) monolayers that was conducted on side-by-side diffusion chambers in vitro. The permeability coefficient for the transport of CDDP across the untreated monolayer was 3.80 x 10(-5) cm sec-1 at 30 minutes. After treating the BMEC monolayer with TNF-alpha (50 U ml-1 and 500 U ml-1) for 36 hours, the PC of CDDP increased significantly to 8.94 x 10(-5), and 14.43 x 10(-5) cm sec-1 respectively (p < 0.01). TNF-alpha had no effect on the transport of FITC-dextran across the BMEC monolayers. Electron microscopy showed that the tight junctions between the BMECs persisted even after treatment with TNF-alpha, whereas they had been partially disrupted following exposure to mannitol, 1600 mOsm kg-1. TNF-alpha selectively promoted the in vitro permeability of the blood-brain barrier to CDDP without disrupting tight junctions. This system could be used as a model for experimental studies of chemotherapy. Findings suggested that the combined administration of TNF-alpha and CDDP may be clinically useful.

Animals↗

PubMed1997

Impaired relaxing response to isoprenaline in isolated thoracic aorta of nephrotic rats: decrease in release of EDRF from endothelial cells.

Isoprenaline-induced relaxation was investigated in aortas from control and daunomycin-induced nephrotic rats. In the endothelium-intact aortas precontracted with phenylephrine, the isoprenaline-induced relaxation and cyclic adenosine monophosphate (AMP) accumulation were significantly less in nephrotic rats than in control animals. Removal of the endothelium, pretreatment with methylene blue (MB), a guanylate cyclase inhibitor, or NW-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, markedly reduced the relaxation induced by isoprenaline in nephrotic and control animals. The increase in cyclic AMP content induced by isoprenaline also was inhibited by these treatments. In addition, the difference in the isoprenaline-induced relaxation and cyclic AMP accumulation between nephrotic and control preparations was abolished by these treatments. The tissue cyclic guanosine monophosphate (GMP) level was not affected by isoprenaline. In the presence of zaprinast (Zap), a cyclic GMP phosphodiesterase inhibitor, the cyclic GMP level in the endothelium-intact tissues was significantly lower in nephrotic rats than in control animals. Removal of endothelium or pretreatment with MB or L-NAME markedly reduced cyclic GMP content in nephrotic and control animals. In the endothelium-denuded tissues, the isoprenaline-induced relaxation and cyclic AMP accumulation were markedly potentiated by a low concentration of nitroprusside (NP). In the endothelium-intact aortas precontracted with phenylephrine, relaxations induced by dobutamine, salbutamol, and forskolin in nephrotic rats were not significantly different from those in control animals. In the endothelium-intact aortas precontracted with KCl, the isoprenaline-induced relaxation also was significantly less in nephrotic rats than in control animals. Pretreatment with prazosin, but not yohimbine, abolished this difference. These results indicate that nephrosis decreases the relaxing response of the endothelium-intact aortas to isoprenaline. In addition, these results suggest that the endothelium-derived relaxing factor (EDRF) released from the endothelial cells markedly enhances isoprenaline-induced increase in the tissue level of cyclic AMP. The decreased relaxing response to isoprenaline in nephrotic rats may be caused by the decrease in the endothelial-dependent cyclic GMP release caused by alpha 1-adrenoceptor activation by isoprenaline.

Animals↗

PubMed1997

The contractile mechanism of sodium metavanadate in isolated rat aortae.

The mechanism of contractile effect of vanadate was investigated in rat aortae. Sodium metavanadate (NaVO3; 10(-5)-3 x 10(-3) M) induced contractile responses in a concentration-dependent manner. Removal of endothelium did not affect the response to NaVO3. The response to NaVO3 was inhibited by nifedipine, a voltage-operated Ca2+ channel (VOC) inhibitor; NCDC, a phospholipase C inhibitor; and H-7, a protein kinase C inhibitor, but not by prazosin, an alpha1-adrenoceptor antagonist; methysergide, a serotonin-receptor antagonist; tripelennamine, a histamine-receptor antagonist; glibenclamide, an adenosine triphosphate (ATP)-dependent K+-channel inhibitor; or iberiotoxin, a large-conductance Ca2+-activated K+-channel inhibitor. In addition, genistein or tyrphostin A48, tyrosine kinase inhibitors, did not affect the contraction induced by NaVO3. Mg2+ removal or antimycin A, a Ca2+-ATPase inhibitor, did not cause any contraction. Ouabain, a Na+, K+-ATPase inhibitor, or K+-free medium caused the contraction of the aortae. The maximal contraction induced by NaVO3 plus ouabain was similar to that induced by NaVO3 alone. In addition, the response to NaVO3 was inhibited by AA861, a 5-lipoxygenase inhibitor, and RHC-80267, a diacylglycerol (DAG) lipase inhibitor. In the presence of AA861, either H-7 or nifedipine further inhibited the residual response to NaVO3. In the presence of NCDC, however, AA861 failed further to affect the residual response to NaVO3. In rat aortae, NaVO3 increased the levels of inositol monophosphate (IP) and prostaglandin F2alpha (PGF2alpha). AA861 and NCDC inhibited the IP increase. In addition, NCDC inhibited the PGF2alpha increase. These results suggest that the response to NaVO3 in rat aortae may be mainly the result of the increased phosphoinositide metabolism.

Animals↗

PubMed1997

Morphological changes of intraparenchymal arterioles after experimental subarachnoid hemorrhage in dogs.

OBJECTIVE: Morphological and microcirculatory changes in intraparenchymal vessels after subarachnoid hemorrhage (SAH) have not yet been fully clarified. We conducted this experimental study to investigate the serial morphological changes of intraparenchymal arterioles after SAH. METHODS: SAH was produced by injecting autologous arterial blood into the cisterna magna twice at 48-hour intervals in 30 dogs. The dogs were killed 3, 7, or 14 days after SAH, and then perfusion-fixed specimens of both anterior sylvian giri were obtained by using two methods. Microvascular corrosion casts produced by arterial injection of polyester resin were examined using scanning electron microscopy, and the widths of 40 arterioles of each animal were measured. Sectioned slices from the brain surface to 500 microns deep were examined by light microscopy, and external diameter, internal diameters, and wall thickness of the arterioles at depths of 50, 200, and 500 microns from the brain surface were morphometrically evaluated in 40 arterioles of each animal. In control animals receiving cisternal injections of mock cerebrospinal fluid (n = 10) and in healthy control animals (n = 10), the same examination and evaluation were performed. RESULTS: Corrosion casts of arterioles showed tapered narrowing with folding after SAH, and the width of the arterioles significantly decreased 3 and 7 days after SAH (P < 0.01). Morphometric examination by light microscopy showed a significant decrease of internal diameter of arterioles associated with a significant increase of wall thickness at any depth from the brain surface 3 and 7 days after SAH (P < 0.05 or P < 0.01). These findings improved 14 days after SAH. Control animals receiving cisternal injections of mock cerebrospinal fluid showed no significant differences compared with healthy control animals. CONCLUSION: These results suggest that constriction of intraparenchymal arterioles occurs after SAH and may contribute to delayed cerebral ischemia.

Animals↗

PubMed1997

Evaluation of enzyme-labeled oligonucleotide probes to identify enterohaemorrhagic Escherichia coli.

Alkaline phosphatase-conjugated oligonucleotide probes were developed to detect the gene coding for Vero toxin 1 (VT1) and Vero toxin 2 (VT2). Using these probes, 3 hr was enough to detect VT genes when suspicious colonies of enterohaemorrhagic Escherichia coli (EHEC) were obtained on an agar plate. The results of a hybridization test with 144 isolates of EHEC O157 and one isolate of Shigella dysenteriae Type 1 agreed exactly with the immunological detection, reversed passive latex agglutination (RPLA) test, of VTs in their culture supernatants. The sensitivity levels of these probes for the detection of VT genes were 100%. The specificity of these probes were also tested with a total of 1,002 strains of Escherichia coli other than EHEC and 8 strains of Shigella sp. other than Shigella dysenteriae Type 1; the results showed 100% specificity.

Alkaline Phosphatase↗

PubMed1997

In-vivo microdialysis study of the distribution of cisplatin into brain tumour tissue after intracarotid infusion in rats with 9L malignant glioma.

Simultaneous brain microdialysis in tumour and non-tumour tissues has been used for kinetic determination of the local distribution of an anticancer agent, cisplatin, in rats. Rat brain was implanted with 9L malignant glioma and cisplatin (3.5 mg kg-1) was administered as a selective intracarotid infusion for 30 min to rats prepared for brain microdialysis. The amount of platinum in the dialysate collected from tumour and non-tumour brain tissues was determined by atomic absorption spectrophotometry, as representative of cisplatin. Total and free platinum concentrations in plasma were also measured. Free platinum is accumulated preferentially in the tumour tissue and the brain tumour distribution coefficient (the ratio of brain tumour platinum AUC to plasma free platinum AUC, where AUC is the area under the platinum concentration-time curve) was 0.69, although there was little distribution into normal brain tissue. Drug binding to plasma proteins was 65%. It is concluded that simultaneous microdialysis is an easy and available method for assessing in-vivo local pharmacokinetics and distribution of cisplatin in tumour and non-tumour tissues of the brain.

Animals↗

PubMed1997

[Genome types of adenovirus type 37 with different pathogenicity isolated in Nagoya City].

Out of 217 strains of viruses isolated from patients with conjunctivitis at one ophthalmology clinic in Nagoya City from 1982 to 1995, 37 were adenovirus type 37 (Ad37). They were isolated mainly from patients with epidemic keratoconjunctivitis in summer-time. DNAs from all Ad37 isolates were extracted and analyzed by five restriction endonucleases (Bam H I, Eco R I, Hind III, Sal I and Sma I) in comparison with prototype strain. Thirty-seven isolates were divided into six genome types (Ad37a, Ad37c, Ad37d, Ad37e, Ad37f and Ad37p). The predominant genome type in 1987 was Ad37a by DNA cleavage pattern analysis with Eco R I. The symptoms of patients with Ad37a were severe compared with those of patients with Ad37p.

Adenoviruses, Human↗

PubMed1997

Western immunoblot analysis of Haemobartonella muris and comparison of 16S rRNA gene sequences of H. muris, H. felis, and Eperythrozoon suis.

Infectious agents were isolated from the spleens of three wild mice (Apodemus argenteus) by intraperitoneal inoculation of the spleen homogenate into laboratory mice. The laboratory mice developed clinical signs and splenomegaly, and three isolates were maintained by passage in mice. Tetracyclines were effective in preventing infection of mice with these agents, but streptomycin and penicillin were ineffective. The agents did not grow in bacterial growth media or chicken embryos. In smears of blood from infected mice stained by the Giemsa or the indirect immunofluorescence method, numerous organisms were found on the surfaces of erythrocytes. Electron microscopy revealed cell wall-less pleomorphic cocci of 350 to 700 nm in diameter. On the basis of these results, the isolates were identified as Haemobartonella muris. There was no antigenic cross-reactivity with Rickettsia or Ehrlichia spp. or other related organisms. Western immunoblot analysis of three strains of H. muris with mouse antisera to H. muris revealed identical major antigens of 118, 65, 53, 45, and 40 kDa. By heteroduplex analysis of the three PCR-amplified segments of the 16S rRNA genes, the three strains of H. muris were found to be identical. The 16S rRNA genes of one of the H. muris strains, four strains of H. felis, and two strains of Eperythrozoon suis were sequenced and compared. The sequences of two strains of H. felis from cats in California were identical, as were the sequences of a strain from a cat in Ohio and a strain from a cat in Florida, but the similarity of sequences between the California and the Ohio-Florida strains was only 85%. The sequence of an H. muris strain was unique and was more closely related to that of the Ohio-Florida strain of H. felis (89%) than to that of the California strain of H. felis (84%). The sequence of E. suis from a pig in Illinois was identical to that from another pig from Taiwan. The similarity of the 16S rRNA gene sequence of E. suis with those of three Haemobartonella strains was 84 to 92%, with that of E. suis being most similar to that of the H. felis strain from California. In the phylogenetic analysis based on 16S rRNA gene sequences, the Haemobartonella spp. and E. suis formed a distinct clade more closely related to Mycoplasma spp. (79 to 83% similarity) than to Anaplasma marginale (72 to 75% similarity). Our results suggest that the Haemobartonella spp. and E. suis may be reclassified in the same genus in the family Mycoplasmataceae.

Anaplasmataceae↗

PubMed1997

High-dose chemotherapy and stem-cell rescue in the treatment of high-risk breast cancer: prognostic indicators of progression-free and overall survival.

PURPOSE: To examine the predictive value of tumor- and treatment-specific prognostic indicators of relapse-free survival (RFS) and overall survival (OS) in patients with high-risk breast cancer (HRBC) treated with high-dose chemotherapy (HDCT) and stem-cell rescue. PATIENTS AND METHODS: Between June 1989 and September 1994, 114 patients with HRBC (stage II with > or = 10 axillary lymph nodes involved, stage IIIA, and stage IIIB inflammatory carcinoma) received adjuvant chemotherapy followed by HDCT with etoposide, cyclophosphamide, and either doxorubicin (CAVP) or cisplatin (CCVP). Variables analyzed included stage, tumor size, number of axillary nodes involved, grade and receptor status, and types of adjuvant chemotherapy and radiation therapy and HDCT. RESULTS: With a median follow-up time of 46 months (range, 23 to 93), Kaplan-Meier estimates of 3.5-year OS for stage II, IIIA, and IIIB HRBC are 82% (95% confidence interval [CI], 67% to 97%), 79% (95% CI, 67% to 91%), and 72% (95% CI, 53% to 91%); RFS estimates are 71% (95% CI, 56% to 85%), 57% (95% CI, 43% to 72%), and 50% (95% CI, 29% to 71%) irrespective of the HDCT regimen. In univariate analysis, the risk of relapse was lower for patients with progesterone receptor (PR)-positive tumors (risk ratio [RR], 0.43; 95% CI, 0.22 to 0.81; P = .01) and higher for patients with inflammatory carcinoma (RR, 2.20; 95% CI, 1.02 to 4.76; P = .05). OS was better for patients with PR (RR, 0.16; 95% CI, 0.05 to 0.55; P = .003) and estrogen receptor (ER)-positive tumors (RR, 0.42; 95% CI, 0.17 to 1.02; P = .05); OS was worse for patients with high-grade primary tumors (RR, 4.08; 95% CI, 1.21-13.7; P = .02). In multivariate analysis, PR positivity was associated with improved RFS (P = .01) and OS (P = .001). CONCLUSION: HDCT in selected patients with HRBC is safe and warrants further evaluation. Patients with receptor-negative, high-grade, or inflammatory tumors require improvement in their therapeutic options. Better assessment of the role of HDCT awaits completion of ongoing randomized trials.

Adult↗

PubMed1997

Antitumorigenic activities of chalcones (II). Photo-isomerization of chalcones and the correlation with their biological activities.

Some chalcones are known to be phototransformed in a solution from trans into cis isomers. 3-Hydroxy-3'-methylchalcone (3'Me-3-C) has been found to be isomerized from trans into cis by irradiation of daylight in the methanolic solution. The presence of a hydroxyl in the 2'- or 4-position in the trans-chalcone structure prevents phototransformation into cis isomers. The feasibility of phototransformation of chalcones was discussed using UV-spectral analysis. The phototransformed cis-3'Me-3-C showed more potent antitumorigenic activity than the original trans form. The generally recognized parallelism between antitumorigenic and antiinflammatory activities was not observed in trans and cis 3'-Me- and 4'-Me-3C, which are antitumorigenic but inactive in 12-O-tetradecanoylphorbol 13-acetate (TPA)- and arachidonic acid (AA)-induced mouse ear edema. However, inhibitory activity against ornithine decarboxylase (ODC) was commonly observed in both naturally occurring and synthetic antitumorigenic chalcones.

Animals↗

PubMed1997

Novel renin inhibitors containing (2S,3S,5S)-2-amino-1-cyclohexyl-6-methyl-3,5-heptanediol fragment as a transition-state mimic at the P1-P1' cleavage site.

A series of renin inhibitors containing the (2S,3S,5S)-2-amino-1-cyclohexyl-6-methyl-3,5-heptanediol (2-amino-3,5-anti-diol) fragment as a novel transition-state mimic was synthesized, and their biological activities were evaluated. All of the synthesized compounds containing the 2-amino-3,5-anti-diol fragment at the P1-P1' position showed high in vitro renin-inhibitory activity with IC50 values in the 10(-8)-10(-10) M range, and most of them caused a reduction of blood pressure when administered orally to salt-depleted, conscious marmosets. The inhibitor (29) with the 4-hydroxypiperidine residue at the P4 position showed the highest activity in terms of both potency and duration of the blood pressure-lowering effect.

Administration, Oral↗

PubMed1997

Methamphetamine-induced sensitization of dopamine release via a metabotropic glutamate receptor mediated pathway in rat striatal slices.

We studied the roles of metabotropic glutamate receptors in methamphetamine (MAP)-induced sensitization of dopamine (DA) release from striatal slices. Rats were first treated with MAP (1 mg/kg, i.p.) once daily for 6 consecutive days. After a 6-day withdrawal, DA release from striatal slices evoked by +/- (-)1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) was measured, trans-ACPD-induced DA release was significantly enhanced in MAP-sensitized rats, but the inactive form of trans-ACPD (1R,3S-ACPD) did not enhance DA release. The active form of trans-ACPD (1S,3R-ACPD) (0.1 mM)-evoked DA release was attenuated by treatment with 0.4 mM RS-alpha-methyl-4-carboxyphenylglycine, a metabotropic glutamate receptor antagonist. The present results suggest that metabotropic glutamate receptors play an important role in expression of MAP-induced sensitization.

Analysis of Variance↗

PubMed1997

SCID-bg mice as xenograft recipients.

SCID-bg (scid/scid, beige/beige) is a strain of double-mutant mice with impaired lymphoid development and reduced natural killer (NK) cell activity. The present study was undertaken to evaluate the usefulness of SCID-bg mice as xenograft recipients. Fetal guinea pig tissues (liver, thymus, spleen) were transplanted under the kidney capsule of the mice and their serum guinea pig IgG levels were measured weekly thereafter, C.B.-17-scid and anti-asialo GM1 antiserum-treated (NK-depleted) C.B.-17-scid (C.B.-17-scid-AGM1) mice that received the identical transplants were used as controls. Throughout the experimental period (1, 2, and 3 weeks after transplantation), the average serum guinea pig IgG concentrations was highest in C.B.-17-scid-AGM1 mice followed by SCID-bg mice and lowest in C.B.-17-scid mice without antiserum treatment, though we could not find any statistical significance among these groups. However, SCID-bg mice always showed the smallest within-group variance (individual difference) in the serum guinea pig IgG concentrations (P < 0.05, versus C.B.-17-scid-AGM1 mice at 1, 2, and 3 weeks and versus C.B.-17-scid mice at 2 weeks). The graft size was not significantly different among these three groups, but the spleen grafts in C.B.-17-scid mice contained fewer nucleate cells than the other two groups. These results indicate that the reduced NK cell activity by beige mutation is not crucial for the success of xenogenic transplantation, though SCID-bg mice may be useful as xenograft recipients with a consistent potential to retain the viability and function of engrafted tissues.

Animals↗

PubMed1997

Multitracer studies on the accumulation of radionuclides in mushrooms.

We used the multitracer technique to study the transfer of several radionuclides to two mushroom species. Radionuclides accumulated in the fruiting bodies of the mushrooms in the order of 83Rb > 65Zn > 54Mn > 22Na > 75Se and 85Sr > 60Co > 88Y, 102Rh, 139Ce, 143.144Pm, 146.153Gd and 173Lu > 175Hf. The concentration ratio values for 83Rb, 65Zn and 54Mn in the fruiting bodies were more than 10, whereas those for 60Co, 88Y, 102Rh, 121mTe, 175Hf and the rare earth elements were less than 1. There were major differences in the accumulations of the alkali elements.

Basidiomycota↗

PubMed1997

Simple i.v. inoculation of HIV-1 to Thy/Liv SCID-hu mice induce reproducible HIV infection with narrowing of medulla in human thymic implant.

Human fetal thymus/liver engrafted SCID mice were constructed and studied for its susceptibility to HIVBRU infection by i.v. inoculation which seemed to represent an appropriate route of HIV infection in vivo. By the i.v. inoculation of HIV, the medulla in the engrafted thymus narrowed significantly when compared with that of the human thymic implant from virus-uninoculated mice. Further, immunohistochemical staining indicated the presence of HIV antigen predominantly in thymic epithelial cells in medulla of the engrafted thymus. Polymerase chain reaction (PCR) assays resulted in amplifications of HIV genome in the implanted grafts as well as in lymph nodes and PBMC. The virus infections to the implants were confirmed biologically by coculturing with PHA-stimulated human PBMC and the graft cells from the HIV-inoculated SCID-hu mice. Thus, the i.v. inoculation of HIV into Thy/Liv SCID-hu mice induce narrowing of medulla of the engrafted thymus and may become an efficient and useful tool for screening candidate anti-HIV agents.

Acquired Immunodeficiency Syndrome↗