Local outbreak of Streptococcus pneumoniae serotype 12F caused high morbidity and mortality among children and adults.

Pneumococcal serotype replacement is an important issue after the introduction of pneumococcal conjugate vaccine (PCV) in children. After the introduction of 13-valent PCV, the incidence of invasive pneumococcal diseases (IPD) caused by Streptococcus pneumoniae serotype 12F (Sp12F) have increased in some countries; however, an outbreak of Sp12F has not reported in the post-13-valent PCV era. We experienced a local outbreak of Sp12F during March through May 2016 in Tsuruoka city, Japan after the introduction of 13-valent PCV in 2013. The IPD patients were two children and seven adults, three of whom died with a rapid disease progress. Although the clear transmission route was not determined, eight of the nine patients (89%) had close contact with children, which suggests that transmitted colonisation of Sp12F among children and adults might be the source of transmission. Continuous monitoring of IPDs, along with the determination of pneumococcal serotypes, is warranted in the post-13-valent PCV era. New IPD control strategies may be needed if this fatal outbreak continues to occur.

High rate of vaccine failure after administration of acellular pertussis vaccine pre- and post-liver transplantation in children at a children's hospital in Japan.

We assessed the serological response to pertussis vaccines administered pre- and post-liver transplantation in 58 pediatric patients at a children's hospital in Japan. A high rate of pertussis vaccine failure was observed, 44.8% against the pertussis toxin and 69.0% against filamentous hemagglutinin, with no difference in the seropositivity rate with respect to the timing of the vaccination during the peritransplant period.

Intermediate length scale organisation in tin borophosphate glasses: new insights from high field correlation NMR.

The structure of tin borophosphate glasses, considered for the development of low temperature sealing glasses or anode materials for Li-batteries, has been analysed at the intermediate length scale by a combination of high field standard and advanced 1D/2D nuclear magnetic resonance techniques. The nature and extent of B/P mixing were analysed using the (11)B((31)P) dipolar heteronuclear multiple quantum coherence NMR sequence and the data interpretation allowed (i) detecting the presence and analysing the nature of the B-O-P linkages, (ii) re-interpreting the 1D (31)P spectra and (iii) extracting the proportion of P connected to borate species. Interaction between the different borate species was analysed using the (11)B double quantum-simple quantum experiment to (i) investigate the presence and nature of the B-O-B linkage, (ii) assign the different borate species observed all along the composition line and (iii) monitor the borate network formation. In addition, (119)Sn static NMR was used to investigate the evolution of the chemical environment of the tin polyhedra. Altogether, the set of data allowed determining the structural units constituting the glass network and quantifying the extent of B/P mixing. The structural data were then used to explain the non-linear and unusual evolution of the glass transition temperature.

Development of a high-hydrous gel phantom for human body communication based on electrical anisotropy.

In this study, we investigated a highly hydrated gel phantom with electrical anisotropy that can be used at 18.375 MHz to 23.625 MHz. This is one of the frequency bands used for human body communication. To achieve the communication, the electrical characteristics of the quadriceps femoris muscle of the rat were measured immediately after sacrifice. These were used to obtain an indicator of electrical characteristics to be satisfied by the phantom. Electrical anisotropy was realized by adding carbon fiber to the phantom and controlling its direction. We were able to develop a high hydrated gel phantom for human body communication with a maximum error of 8.1% assuming its use at 18.735 MHz to 23.625 MHz.

Induction of recipient cell-specific donor T-cell anergy by UV-C-irradiated recipient immature monocyte-derived dendritic cells.

The induction of donor T-cell anergy to recipient cells for reducing GVHD could be one way of expanding donor candidates for HLA-mismatched hematopoietic SCT. The present study was designed to clarify whether recipient cell-specific T-cell anergy could be induced by priming donor lymphocytes with recipient monocyte-derived DCs (mo-DCs) irradiated with ultraviolet-C (UV-C). By irradiation of mo-DCs with UV-C, the expression of DC-associated surface phenotypes such as CD83, CD80, CD86 and CD40 was reduced and the antigen-presenting ability of UV-C-irradiated mo-DCs was clearly decreased. By co-culturing normal donor 1 lymphocytes with UV-C-irradiated donor 2 immature mo-DCs, the response of the lymphocytes to donor 2 mature mo-DCs was markedly reduced as compared with that of the lymphocytes prestimulated with non-irradiated donor 2 immature mo-DCs or UV-C-irradiated mo-DCs derived from a different individual donor 3. The present study demonstrated that recipient cell-specific T-cell anergy could be induced by priming donor lymphocytes with UV-C-irradiated recipient immature mo-DCs in hematopoietic SCT. These data suggest the applicability of donor graft cells, which have been prestimulated with UV-C-irradiated recipient immature mo-DCs, for expanding donor candidates in HLA-mismatched hematopoietic SCT.

A role for TGFbeta1 in langerhans cell biology. Further characterization of the epidermal Langerhans cell defect in TGFbeta1 null mice.

Previous studies of TGFbeta1 null (-/-) mice indicated that the epidermis was devoid of Langerhans cells (LC) and that the LC deficiency was not secondary to the inflammation that is the dominant feature of the -/- phenotype (Borkowski, T.A., J.J. Letterio, A.G. Farr, and M.C. Udey. 1996. J. Exp. Med. 184:2417-2422). Herein, we demonstrate that dendritic cells could be expanded from the bone marrow of -/- mice and littermate controls. Bone marrow from -/- mice also gave rise to LC after transfer into lethally irradiated recipients. Thus, the LC defect in TGFbeta1 null mice does not result from an absolute deficiency in bone marrow precursors, and paracrine TGFbeta1 production is sufficient for LC development. Several approaches were used to assess the suitability of -/- skin for LC localization. A survey revealed that although a number of cytokine mRNAs were expressed de novo, mRNAs encoding proinflammatory cytokines known to mobilize LC from epidermis (IL-1 and TNFalpha) were not strikingly overrepresented in -/- skin. In addition, bone marrow-derived LC populated full-thickness TGFbeta1 null skin after engraftment onto BALB/c nu/nu recipients. Finally, the skin of transgenic mice expressing a truncated loricrin promoter-driven dominant-negative TGFbeta type II receptor contained normal numbers of LC. Because TGFbeta1 signaling in these mice is disrupted only in keratinocytes and the keratinocyte hyperproliferative component of the TGFbeta1 -/- phenotype is reproduced, these results strongly suggest that the LC defect in TGFbeta1 null mice is not due to an epidermal abnormality but reflects a requirement of murine LC (or their precursors) for TGFbeta1.

Chemically induced forestomach papillomas in transgenic mice carry mutant human c-Ha-ras transgenes.

Forestomach papillomas and skin papillomas were induced very efficiently by a single dose administration of the chemical carcinogen methylnitrosourea (MNU) in transgenic mice (rasH2 line) carrying human hybrid c-Ha-ras genes, which encode the prototype p21 gene product. The incidence of forestomach papillomas was dose dependent; when 50 mg/kg of MNU were administered i.p., all of the transgenic mice (56 of 56) developed forestomach papillomas within 12 weeks after administration, whereas 5 and 0.5 mg/kg of MNU induced papillomas in 2 of 19 and 1 of 19 mice, respectively. Nine of 56 transgenic mice (16%) also developed skin papillomas at sites wounded by bites or scratches. Only 1 of 77 nontransgenic littermates developed forestomach papillomas after administration of 50 mg/kg of MNU, and no skin papillomas appeared within 12 weeks after MNU administration. The transgenes (integrated copy number, 5-6) in the tumors developed in 55 of 56 affected transgenic mice (98%) contained at least 1 copy of the transgene that was activated by somatic point mutation at the 12th codon, from GGC (Gly) to GAC (Asp). Because somatic point mutations at the 12th or 61st codon of transgenes have never been detected in normal tissues of transgenic mice thus far examined, these mutational activations of transgenes are tumor-specific events. RNA expression of these activated transgenes was also detected. From these results, it is suggested that somatic mutational activation of the human c-Ha-ras transgene plays a causative role in the occurrence of forestomach and skin papillomas induced by MNU administration in these transgenic mice. This transgenic mouse provides a unique screening system for chemicals that induce or suppress papillomagenesis.

Most tumors in transgenic mice with human c-Ha-ras gene contained somatically activated transgenes.

Two independent transgenic mouse lines carrying human hybrid c-Ha-ras genes with their own promoter region encoding prototype products, were established. In these lines, about 50% of transgenic offspring had tumors within 18 months. The tumors developed in restricted tissues and about 60% of affected mice had angiosarcomas. The transgenes were expressed both in the tumors and in all normal tissues. However, somatic mutational activation was detected only in the transgenes of the tumors. The point mutation at the 61st codon, from CAG(Gln) to CTG(Leu), was detected in all angiosarcomas (22/22), some lung adenocarcinomas (3/11) and Harderian gland adenocarcinomas (4/7) in both lines. The other point mutation at the 12th codon from GGC(Gly) to GTC(Val) was detected in two of the four skin papillomas. No mutations on these codons were detected in normal tissues of transgenic mice. Nontransgenic littermates had no tumors at all. From these results, it was strongly suggested that the mouse tumors do not develop only by the expression of the transgenes, and that definite somatic point mutation of the human c-Ha-ras transgenes in certain cell types may be a causative event in tumorigenesis in these transgenic mice.

Pneumonia in HIV-infected patients: a case-control survey of factors involved in risk and prevention.

OBJECTIVE: To assess the factors that increase or decrease the risk of pneumonia with particular attention to immunization with pneumococcal and influenza vaccines in a group of HIV-infected persons. DESIGN: A retrospective, case-control study based on information entered into a standard database and the medical record. SETTING: Patients attending a referral clinic specializing in AIDS/HIV care at a public hospital. PATIENTS: Among over 2000 subjects entered into a database in 8 years, 127 incidents of pneumonia were identified from the record. These cases were matched with 127 CD4 cell count matched, concurrent controls. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The principal hypothesis was that chart review would find a decreased frequency of pneumococcal immunization in the pneumonia cases compared with matched controls. RESULTS: Pneumococcal immunization was associated with a reduction of the risk of pneumonia by nearly 70%. The effect was seen even when immunization was given with a CD4 cell count of less than 100/mm3. Injection drug users and African-Americans had a twofold increased risk of pneumonia. CONCLUSION: The study provides data to support the current recommendation for pneumococcal immunization of all HIV-infected persons. Although this conclusion could lead to renewed enthusiasm for increasing pneumococcal immunization rates in HIV-infected persons, it must be recognized that the study is observational and ascertainment bias cannot be excluded.

Migration of Thy-1+ dendritic epidermal cells (Thy-1+DEC): Ly48 and TNF-alpha are responsible for the migration of Thy-1+DEC to the epidermis.

Thy-1+ dendritic epidermal cells (Thy-1+DEC) are mainly T cells that express T-cell receptor gamma and delta chains with limited diversity of gamma delta, mainly gamma 3 delta 1; such gamma 3 delta 1 TCR-bearing Thy-1+DEC originate from day 16 fetal thymic cells. To understand the migratory capability of Thy-1+DEC, we developed an in vitro model, using skin organ culture. First, emigration of Thy-1+DEC from the epidermis was examined. Ear skin from C3H/He mice was separated into two parts and incubated for 3 d with dermal side down. Thy-1+DEC emigrated from the epidermis into the dermis and then migrated out of the skin into the culture medium. Next, immigration of Thy-1+DEC into the epidermis was examined. Thy-1+DEC were depleted in vivo by daily application of clobetazole propionate solution topically onto the ears of C3H/He mice. Seven days later, ear skin was harvested, separated, and cultured with the dermal side up with syngeneic epidermal cell suspensions with a migration chamber for 3 d. It was found that 1) Thy-1+DEC immigrated into the Thy-1+DEC depleted epidermis as well as into untreated epidermis, and 2) the migratory capability of Thy-1+DEC was directly proved by a biolabeling technique with PKH-26. Blocking studies with various antibodies revealed that leukosialin (S11 monoclonal antibodies) and TNF alpha were important for Thy-1+DEC migration. Thus, Thy-1+DEC retain the potential for migration in vitro, and leukosialin and TNF alpha are partially responsible for the migration of Thy-1+DEC into the epidermis.

Selective upregulation of fibroblast Fas ligand expression, and prolongation of Fas/Fas ligand-mediated skin allograft survival, by retinoic acid: the skin as a retinoide-inducible immune privilege site.

Fas/Fas ligand-mediated lymphocyte apoptosis has been implicated in the suppression of immune responses and may cause immune privilege. Human corneas exhibit immune privilege and can be transplanted across allogeneic barriers without immunosuppressive therapy, perhaps, because corneal keratinocytes express Fas ligand. To characterize Fas and Fas ligand expression in skin, we examined expression by murine keratinocytes, dermal fibroblasts, melanocytes, and human umbilical endothelial cells. We also studied the regulation of Fas and Fas ligand in skin cells by retinoic acid, vitamin D3, and dexamethasone as well as various cytokines. Among the molecules and cells tested, retinoic acid selectively upregulated the expression of Fas ligand molecule by fibroblasts. Retinoic acid-induced Fas ligand+ fibroblasts killed Fas+ target cells, and this killing was blocked by anti-Fas ligand antibody. The function of Fas ligand on dermal fibroblasts in vivo was tested in a cutaneous allograft system. Histoincompatible BALB/C mouse (H-2d) donor skin was grafted on to allogeneic C57BL/6 mice (H-2b). Daily local injection of retinoic acid blocked inflammation and extended graft survival for more than 10 d. Injection of retinoic acid into Fas ligand mutated gld/gld donor skin did not prevent leukocyte infiltration into the allograft or prolong graft survival. These experiments indicate that, in skin, retinoic acid selectively increases Fas ligand expression by fibroblasts and that retinoic acid has potent Fas/Fas ligand-dependent immunosuppressive activity.

Identification and characterization of novel dermal Thy-1 antigen-bearing dendritic cells in murine skin.

Using immunofluorescence on dermal sheets of mouse ear, we identified novel Thy-1+ dermal dendritic cells in murine skin. These cells are resistant to topical corticosteroid treatment. The number of these dermal Thy-1+ dendritic cells is not altered with aging of the mice or with 3 d of culture. Dermal Thy-1+ dendritic cells have melanosomes in their cytoplasm; hence, phagocytic activity is likely to be present. Double immunofluorescence revealed that most of these dermal Thy-1+ dendritic cells express CD45. Furthermore, conventional immunofluorescence and confocal laser scanning microscopic findings showed that most of these Thy-1+ dermal dendritic cells express gamma delta and V gamma 3 T-cell receptors. The relationship between these dermal Thy-1+ dendritic cells and dendritic epidermal T cells is discussed.

Conjugation of recombinant reverse transcriptase of HIV-1 to beta-D-galactosidase from Escherichia coli for ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) of anti-HIV-1 IgG.

Recombinant reverse transcriptase (RT) of HIV-1 was conjugated to beta-D-galactosidase from Escherichia coli in three different ways. Maleimide groups were introduced into beta-D-galactosidase molecules using N,N'-o-phenylenedimaleimide in the absence (method I) or presence (method II) of N-ethylmaleimide or into beta-D-galactosidase molecules, which had been treated with excess of 4,4'-dithiodipyridine to block thiol groups, using N-succinimidyl-6-maleimidohexanoate (method III). Subsequently, the maleimide groups were reacted with thiol groups introduced into recombinant RT molecules using N-succinimidyl-S-acetylmercaptoacetate. The conjugates were tested by a sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay). The immune complex consisting of 2,4-dinitrophenyl-bovine serum albumin-recombinant RT conjugate, anti-HIV-1 IgG and recombinant RT-beta-D-galactosidase conjugate was captured by polystyrene beads coated with (anti-2,4-dinitrophenyl group) IgG, eluted with N epsilon-2,4-dinitrophenyl-L-lysine and transferred to polystyrene beads with (anti-human IgG gamma chain) IgG. The conjugate prepared by method III, which showed the least polymerization, the least loss of the specific enzyme activity and the lowest nonspecific binding, improved the sensitivity of the enzyme immunoassay for anti-HIV-1 IgG approximately 30-fold compared with RT-horseradish peroxidase conjugate.

Involvement of dopamine D2 receptor-mediated functions in the modulation of morphine-induced antinociception in diabetic mouse.

The effects of the dopamine agonists and antagonists on morphine-induced antinociception in diabetic mice were studied. The antinociceptive effect of morphine (5 mg/kg, s.c.) in diabetic mice was significantly less than that in non-diabetic mice. The antinociceptive effect of morphine in diabetic mice, but not that in non-diabetic mice, was significantly enhanced following pretreatment with sulpiride, a selective dopamine D2 antagonist, (30 mg/kg, s.c.). Pretreatment with quinpirole, a selective dopamine D2 agonist, (100 nmol, i.c.v.), markedly increased the antinociceptive effect of morphine in diabetic mice, but not in non-diabetic mice. There was no significant difference in the antinociceptive effect of morphine (5 mg/kg, s.c.) between the quinpirole-treated diabetic mice and saline-treated non-diabetic mice. A higher dose of quinpirole (300 nmol, i.c.v.) had no significant effect on morphine-induced antinociception in diabetic mice. On the other hand, the antinociceptive effect of morphine was significantly reduced by pretreatment with quinpirole (300 nmol, i.c.v.) in non-diabetic mice. Quinpirole (100 and 300 nmol, i.c.v.) dose-dependently increased total locomotor activity in non-diabetic mice. In contrast, a lower dose of quinpirole (100 nmol, i.c.v.) significantly reduced spontaneous locomotor activity in diabetic mice, while a higher dose of quinpirole had no significant effect on the spontaneous locomotor activity. The dopamine turnover ratio in the limbic forebrain and midbrain in diabetic mice were significantly greater than those in non-diabetic mice. When mice were pretreated with quinpirole (100 and 300 nmol, i.c.v), this enhanced dopamine turnover ratio was not observed in either the limbic forebrain or the midbrain of diabetic mice. These findings suggest that the attenuation of morphine-induced antinociception and dopamine D2 receptor-mediated function in diabetic mice may somehow be related.

Expression of facilitative glucose transporter 1 mRNA in colon cancer was not regulated by k-ras.

The expression of facilitative glucose transporter isoforms in colon adenocarcinoma and the possible role of k-ras in inducing GLUT (glucose transporter) mRNA were studied. RT-PCR demonstrated GLUT2 and GLUT3 expression in 100% of the ten normal colon mucosa samples but detected no GLUT1 mRNA. By contrast, GLUT1 mRNA was detected in all 20 (100%) colon cancer samples examined. GLUT4 mRNA was not detected in either normal mucosa or colon cancer tissues. Semiquantitative PCR demonstrated equal amounts of GLUT2 and GLUT3 mRNA in both normal mucosa and colon cancer samples. A point mutation in codon 12 of k-ras was detected in only six of the 20 (30%) colon cancer samples. Thus, a major difference between normal colon epithelia and colon cancer was the acquisition of GLUT1 expression, which was unlikely to have been induced by a point mutation in codon 12 of k-ras.

Use of the recombinant chimera proteins, LacZ-Env and Gag-Env, for immunological studies on HIV-1 infection.

To use Env proteins as antigens for detection of the human immunodeficiency virus type-1 (HIV-1) antibodies, we attempted to overexpress the Env proteins in Escherichia coli. To study the epitopes in the Env proteins recognized by the sera of HIV carriers, various regions of the proviral DNA encoding the Env region were fused to the 3' end of the lacZ gene. The immunoblotting analysis of the LacZ-Env(512-611) and LacZ-Env(721-826) proteins with the 41 positive sera revealed that the former and the latter immunologically reacted with 100 and 78% of the sera, respectively. To avoid rare false-positive reactions due to the LacZ moiety of the fusion protein, we attempted to express the Env(512-611) alone or Gag-Env(512-611) under the control of bacteriophage T7 promoter. Although we could express only a low level of the Env(512-611) peptide in E. coli, we succeeded in producing large amounts of the Gag(121-406)-Env(512-611) and Gag(308-406)-Env(512-611) proteins as chimeric proteins. Both of these chimera proteins strongly reacted with the 41 positive sera. We purified these proteins and analyzed the immunological reactivity by dot blot with the 60 positive sera and the 84 normal sera. As little as 20 ng of the dotted proteins was enough for the reaction with the positive sera, whereas as much as 320 ng of them did not show false-positive reactions with the normal sera. We obtained highly purified Gag-Env proteins with highly specific seroreactivity, which should be useful for diagnosis and prognosis.

Migration of Langerhans cells in an in vitro organ culture system: IL-6 and TNF-alpha are partially responsible for migration into the epidermis.

Although it is well established that epidermal Langerhans cells (LC) originate from bone marrow, little is known about the mechanism of this migration into the epidermis from bone marrow. In order to clarify the mechanism of this migration, we constructed an in vitro model. LC were depleted by daily topical application of clobetazole propionate (CP) solution onto the ear of Balb/c mice. Seven days later, ear skin was cut off, separated and co-cultured dermal-side-up with syngeneic (Balb/c), semisyngeneic ((C3H x Balb/c)F1), or allogeneic (C3H) epidermal cells (EC) for 3 days. We found (1) that a marked migration of donor LC into the recipient epidermis was observed in the LC-depleted skin, (2) that only syngeneic LC actively migrated into the recipient epidermis; however, the migration of semisyngeneic and allogeneic LC was detected at very low levels, (3) that the migratory capacity of donor LC was directly proved by a biolabeling technique using donor EC labeled with PKH-26, and (4) that anti-IL-6 and anti-TNF-alpha antibodies inhibited the migration of donor LC into the recipient epidermis. These data demonstrate that the resident LC have the potential to traffic through the dermis into the epidermis in a highly syngeneic-specific fashion, and that IL-6 and TNF-alpha are partially responsible for promoting this migration.

Age effect on expression of myosin heavy and light chain isoforms in suspended rat soleus muscle.

This study was designed to test the hypothesis that myosin heavy (MHC) and light chain (MLC) plasticity resulting from hindlimb suspension (HS) is an age-dependent process. By using an electrophoretic technique, the distribution of MHC and MLC isoforms was quantitatively evaluated in the soleus muscles from 3- or 12-wk-old rats after 1-3 wk of HS treatment was maintained. In normal 12- and 15-wk-old rats, the soleus muscles contained a predominance of MHCI ( approximately 94%) with small amounts of MHCIIa, but not MHCIId or MHCIIb. The suspended muscles of adult rats were characterized by the appearance of MHCIIb and MHCIId, the latter reaching approximately 6% after 3 wk of HS treatment. In contrast to changes in MHC, HS did not induce a transition in the MLC pattern in the soleus muscles from adult rats. Compared with adult rats, in juveniles HS had a much more pronounced effect on the shift toward faster MHC and MLC isoform expression. The soleus muscles of 6-wk-old rats after 3 wk of HS were composed of 37.0% MHCI, 19.1% MHCIIa, 23.7% MHCIId, and 20.2% MHCIIb. Changes in MLC isoforms consisted of an increase in MLC1f and MLC2f concomitant with a decrease in MLC2s. These results indicate the existence of a differential effect of HS on MHC and MLC transitions that appears to be age dependent. They also suggest that the suspended soleus muscles from young rats may acquire the intrinsic contractile properties that are intermediate between those in the normal soleus and typical fast-twitch skeletal muscles.

Differentiation between glycoprotein III gene-deleted vaccine and wild-type strains of pseudorabies virus by polymerase chain reaction (PCR).

One of the attenuated and genetically recombinant modified-live viral (MLV) vaccine strains currently used contains a deletion in its glycoprotein III (gIII) gene, while prototypic wild-type pseudorabies (WT-PR) viruses contain an intact gIII gene. A polymerase chain reaction (PCR) system differentiating, based on this difference, between the vaccine virus and prototypic WT-PR viruses was investigated. This PCR system utilized two consecutive stages. Primers for the first-stage PCR were designed so as to amplify of DNA fragments lengths in respect to the vaccine and WT-PR viruses. The second-stage PCR amplification for improving the sensitivity and specificity and for confirming of the sites deleted from the first-stage PCR products produced an all-or-none result: internal DNA fragments were derived from only WT-PR viruses but not from the vaccine virus. These PCR-amplified fragment length polymorphisms clearly distinguished the vaccine virus from WT-PR viruses. The vaccine and WT-PR viruses in mixtures were each identified in this PCR system. This PCR system may permit rapid and sensitive detection of PR viral gIII gene, analysis of the genotype of PR virus isolates, and also examination of the isolates for purity and identity.

Effects of simvastatin on serum lipids and atherosclerosis in WHHL rabbits.

Watanabe heritable hyperlipidemic rabbits aged three months (young group) or 10 months (adult group) received 10 mg/kg of simvastatin daily for 24 weeks. Serum levels of total cholesterol, triglycerides, and beta-lipoproteins were reduced significantly in the treated animals but not in untreated controls. The decreases were greater in the young than in the adult animals. Levels of high-density lipoprotein cholesterol were not affected by treatment. At 24 weeks, the extent of atheromatous lesions on the thoracic-abdominal aorta was lower in the treated animals than in the controls, but the difference was significant only in the young animals. The results indicate that simvastatin would be effective in the treatment of atherosclerosis.