[Posterior mediastinal hemangioma with extramedullary haematopoieisis].

We report a very rare coexistence of posterior mediastinal hemangioma with extramedullary haematopoieisis. A 69-year-old woman was detected to have an abnormal mass on the chest radiograph during a routine medical examination. No disorders were found by hematologic exams before and after surgery. Chest computed tomography (CT) revealed a well circumscribed posterior mediastinal tumor measured 32×11 mm in diameter, located on paravertebral space. The most likely diagnosis was a benign neurogenic tumor and we were planning to remove this tumor by video-assisted thoracic surgery (VATS) via a right transthoracic approach. Thoracoscopic finding revealed that this tumor was brownish and soft, such as hemangioma. Initially, incisional biopsy was done to obtain definitive diagnosis. Since intraoperative microscopic examination of the biopsy specimen revealed extramedullary haematopoieisis, we obtained another larger samples and finished the operation. Interestingly, the postoperative final histological diagnosis was mediastinal hemangioma with extramedullary haematopoieis.

Impact of intraperitoneal chemotherapy after gastrectomy with positive cytological findings in peritoneal washings.

BACKGROUND: There is no standard treatment available for gastric cancer patients whose sole 'non-curative factor' is positivecytological findings in peritoneal washings (CFPW). The aim of this study was to examine the safety, pharmacokinetics and efficacy for free intraperitoneal cancer cells of intraperitoneal chemotherapy with paclitaxel after gastrectomy with en bloc D2 lymph node dissection in cases of gastric cancer with positive CFPW. METHODS: Ten patients with gastric cancer who underwent gastrectomy and systemic lymphadenectomy with D2 dissection, without any other non-curative factors besides positive CFPW, were treated with early postoperative intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complications were measured using NCI-CTC version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatographic assay. RESULTS: Grade 3/4 toxic effects included anemia (20%) and neutropenia (10%) that required no treatment. Operative complications were, for example, superficial surgical site infections (10%) that were treated with antibiotics. No viable cancer cells were observed in the intra-abdominal fluid 24 h after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve ratio was 2,003.3:1. CONCLUSION: Intraperitoneal chemotherapy with paclitaxel is a safe and effective treatment modality for free intraperitoneal cancer cells.

Dietary supplementation with fructooligosaccharides attenuates airway inflammation related to house dust mite allergen in mice.

Fructooligosaccharides (FOS) are prebiotic supplements that can enhance immunological responses in the host to activate mucosal immunity, probably through regulation of gastrointestinal microflora. An area that has not been investigated, however, is the therapeutic potential of prebiotics on allergic airway diseases. The purpose of this study is to evaluate the effects of dietary supplementation with FOS on a murine model of allergic airway inflammation induced by the house dust mite allergen Dermatophagoides farinae (Der f). Male C3H/HeN mice were intratracheally administered with Der f and were fed a diet containing 0% or 2.5% FOS ad libitum. Supplementation with FOS alleviated mite allergen-related airway inflammation characterized by eosinophilic inflammation and goblet cell hyperplasia, which was evidenced by cytological and histological examinations. In addition, the FOS-supplemented diet reduced the serum allergen-specific IgG1 level as compared with a control diet in the presence of the mite allergen. Moreover, FOS tended to suppress the expression of IL-5 and eotaxin in the lungs, which is enhanced by mite allergen. These results suggest that dietary supplementation with FOS can prevent/improve allergic airway inflammation induced by the mite allergen. This effect can be at least partially associated with the inhibition of allergen-specific Ig production and probably with that of IL-5 and eotaxin expression.

Expression of Tumour Endothelial Marker 8 in Canine Mammary Gland Tumour Cells.

The aim of this study was to investigate the expression of tumour endothelial marker 8 (TEM8) in canine mammary gland tumours (MGTs) by immunohistochemistry and to evaluate the association between tumour cell TEM8 expression and tumour histological features, histological grades and expression of luminal and basal/myoepithelial cell markers. TEM8 expression was detected in >60 % of neoplastic epithelial cells in all simple adenomas (n = 25), simple carcinomas (n = 43) and invasive micropapillary carcinomas (n = 5) studied. Six of the 18 solid carcinomas studied showed TEM8 expression in >60% of carcinoma cells present in solid structures and in 12 of the 18 solid carcinomas, <30% of the luminal structure-forming carcinoma cells showed TEM8 expression. TEM8 expression in the neoplastic cells was not associated with histological malignancy in canine MGTs. TEM8+ tumour cells frequently showed the luminal-like phenotype cytokeratin (CK)19+/p63-/α-smooth muscle actin (SMA)-, while most TEM8- tumour cells exhibited the basal-like phenotype CK19-/p63+/αSMA-. These findings indicate that TEM8 may be involved in maintaining the characteristics of luminal cells in canine MGTs and that TEM8 would be useful in identifying the type of neoplastic epithelial cell in MGTs.

Cacao liquor proanthocyanidins inhibit lung injury induced by diesel exhaust particles.

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEPs), which generate reactive oxygen species, may be involved in the recent increase in the prevalence of lung diseases. Cacao liquor proanthocyanidins (CPs) are naturally occurring polyphenols with antioxidative activities. We carried out a study in mice to investigate the effects of dietary supplementation of CPs on lung injury induced by intratracheal administration of DEPs (500 microg/body). Dietary supplementation with 1.0 percent CPs inhibited DEP-induced lung injury, characterized by neutrophil sequestration and edema. Immunohistochemical analyses showed that CPs prevented enhanced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 caused by DEPs in the lung injury. Numerous adducts of nitrotyrosine, N-(hexanonyl) lysine, 4-hydroxy-2-nonenal, and 8-OHdG were also observed immunohistochemically in the lungs of mice treated with DEPs. However, these indicators of oxidative stress were barely visible in mice pretreated with CP supplementation. In addition, the level of thiobarbituric acid reactive substances in the lung was decreased by CP supplementation in the presence of DEPs. These results suggest that CPs inhibit DEP-induced lung injury by reducing oxidative stress, in association with a reduction in the expression of adhesion molecules.

Isolation and analysis of bacteria associated with spores of Gigaspora margarita.

AIMS: The aim of this work was to observe bacteria associated with the spores of Gigaspora margarita, an arbuscular mycorrhizal fungus (AMF). METHODS AND RESULTS: First, a direct analysis of DNA from sterilized spores indicated the bacteria belonging to the genus Janthinobacterium. In the second assay, two bacterial strains were isolated by osmosis from protoplasts, which were derived from spores by using two particular enzymes: lysing enzymes and yatalase. After isolation, cultivation and identification by their DNA as performed in the first experiment, the species with the closest relation were Janthinobacterium lividum (KCIGM01) and Paenibacillus polymyxa (KCIGM04) isolated with lysing enzymes and yatalase respectively. Morphologically, J. lividum was Gram negative and oval, while P. polymyxa was also oval, but Gram positive. Both strains had antagonistic effects to the pathogenic fungi Rosellimia necatrix, Pythium ultimum, Fusarium oxysporum and Rhizoctonia solani. In particular, J. lividum was much stronger in this role. However, in phosphorus (P) solubilization P. polymyxa functioned better than J. lividum. CONCLUSIONS: This experiment had revealed two new bacteria species (P. polymyxa and J. lividum), associated with AMF spores, which functioned to suppress diseases and to solubilize P. SIGNIFICANCE AND IMPACT OF THE STUDY: AMF spores could be a useful source for bacterial antagonists to soil-borne diseases and P solubilization.

Facial-zygomatic triangle: a relationship between the extracranial portion of facial nerve and the zygomatic arch.

BACKGROUND: This study was conducted to clarify the relationships between the extracranial portion of the facial nerve (EFN) and the zygomatic arch (ZA). METHOD: Four cadaveric heads (8 parotid regions), examined under 3-40x magnification, were dissected from lateral to medial to expose the EFN. FINDINGS: In a vertical plane just anterior to the tragus, the distance from the superior edge of the ZA to the facial nerve (FN) is, on average, 26.88 mm. The FN then courses superiorly and anteriorly, crossing the ZA 18.65 mm anterior to the tragus on average. Thus, three points can be used to depict a triangle: A, at the level of the anterior border of the tragus, just above the superior edge of the ZA; B, 26 mm below A; and C, 18 mm anterior to A. This so called facial-zygomatic triangle represents the area where surgical dissection can be performed with no risk of damaging the FN. Thus, the closer one stays to the tragus, the lesser the risk of damaging the FN below the ZA. If the incision is carried out on a vertical plane closer to the tragus, the skin can be safely cut up to 2 cm below the ZA. CONCLUSION: The facial-zygomatic triangle is a very useful superficial landmark to avoid FN damage when working below the ZA.

The effects of microbial materials adhered to Asian sand dust on allergic lung inflammation.

Asian sand dust (ASD) containing microbiological materials, sulfate (SO(4)(2)), and nitrate (NO(3)(-) ) derived from air pollutants in East China, reportedly cause adverse respiratory health effects. ASD aggravates ovalbumin (OVA)-associated experimental lung eosinophilia. In this study, the toxic materials adsorbed onto ASD were excluded by heat treatment at 360 degrees C for 30 min. The effects of nonheated ASD or heated ASD (H-ASD) toward the allergic lung inflammation were compared in murine lungs. ICR mice were administered intratracheally with normal saline (control), H-ASD, ASD, OVA, OVA + H-ASD, and OVA + ASD, four times at 2-week intervals. ASD only increased neutrophils in bronchoalveolar lavage fluids (BALFs) along with pro-inflammatory mediators, such as keratinocyte chemoattractant (KC). H-ASD and ASD enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. The two ASDs synergistically increased interleukin-5 (IL-5), monocyte chemotactic protein-3 (MCP-3), and eotaxin, which were associated with OVA, in BALF. The enhancing effects were much greater in ASD than in H-ASD. The two ASDs induced the adjuvant effects to specific IgE and IgG1 production by OVA. In the in vitro study using RAW264.7 cells, ASD increased the expression of Toll-like receptor 2 (TLR 2) mRNA but not TLR4 mRNA. H-ASD caused no expression of either TLR mRNA. These results suggest that the aggravated lung eosinophilia by ASD may be due to activation of Th2-associated immune response via the activation of TLR2 by microbial components adhered to ASD.

Band-gap engineering of metal oxides for dye-sensitized solar cells.

Mixed oxides Ti(1-x)Zr(x)O2 with 0 < x < or = 0.2 were synthesized by means of thermal hydrolysis for use in dye-sensitized solar cells. The lattice parameter d is observed to increase linearly with Zr content x. The band gap of the mixed oxides was measured to increase by up to 0.2 eV. The respective shift of the conduction band edge leads to an increase of the open circuit voltage (V(OC)) by up to 0.1 V. Among others, temperature-dependent measurements of V(OC) clearly identify the correlation between band edge shift and change in V(OC).

[Surgical treatment for adrenal metastasis from lung cancer].

Several long-term survivors after surgical resection for a solitary adrenal metastasis from non-small cell lung cancer (NSCLC) have been reported in case reports and case series with a small number of patients. We have experienced 6 cases of patients who had adrenalectomy (ADR) for a metastasis from NSCLC. The median survival time (MST) after ADR was 24 months, and there was only 1 case of 3-year survivor. To elucidate the surgical indication and the prognostic factors of patients with a solitary adrenal metastasis from NSCLC, we analyzed 104 patients including our 6 patients who had ADR for a metastasis from NSCLC. The MST after ADR and 5-year survival were 24 months and 31%, respectively. Univariate and multivariate analysis demonstrated that lymph node metastasis at the surgery for primary lung cancer was the only significant and independent predictor of poor survival in patients after ADR. The results suggest that aggressive surgical treatment of a solitary adrenal metastasis from NSCLC may be effective when a patient have N0 disease.

Denervation-Associated Change in the Palatinus and Levator Veli Palatini Muscles of Dogs with Elongated Soft Palate.

Muscle lesions and decreased numbers of peripheral nerve branches have been reported in the soft palates of dogs presenting with brachycephalic airway obstruction syndrome (BAOS). Myosin adenosine triphosphatase staining was employed to investigate whether muscle lesions in the elongated soft palate (ESP) of dogs with BAOS reflect the presence of denervation. Soft palates were collected from nine brachycephalic dogs during surgical intervention for BAOS and from five healthy beagle dogs as controls. In the control soft palates, myofibres with relatively uniform diameters and a random mosaic pattern of type I and II myofibres were observed in the palatinus muscle (PM), while almost all of the myofibres in the levator veli palatini muscle (LVPM) were of type II. In the ESPs, small group atrophy, large group atrophy and angular-shaped atrophy were observed in myofibres of the PM and rarely in the LVPM. Fibre type grouping and an increase in type IIC myofibres were found only in the PM. Morphometric analysis of ESPs revealed a significant increase in the number of type I and II myofibres in the PM showing atrophy or hypertrophy compared with controls. A significant increase in atrophic type II myofibres was found in the LVPM of affected dogs. Myopathy consistent with denervation was observed in the PM, but rarely in the LVPM, of ESP specimens. The results suggest that the myopathy seen in dogs with ESP may partly reflect atrophy of myofibres resulting from damage to peripheral nerve branches, with subsequent reinnervation of myofibres.

The complete amino acid sequence of growth hormone of the bullfrog (Rana catesbeiana).

The primary structure of growth hormone (GH) isolated from the adenohypophysis of the bullfrogs (Rana catesbeiana) was determined. The hormone was reduced, carboxymethylated and subsequently cleaved with cyanogen bromide. Intact bullfrog GH was also digested with lysyl endopeptidase and trypsin. The resulting fragments were separated by reverse-phase high-performance liquid chromatography and subjected to sequence analysis using an automated gas-liquid sequencer employing the Edman method. Bullfrog GH was found to consist of 190 amino acid residues. The amino acid sequence determined is in accord with that deduced from bullfrog GH cDNA by Pan and Chang (1988) except for nine residues at positions 43-48, 73, 80 and 87. Sequence comparisons revealed that bullfrog GH is more similar to tetrapod GHs (e.g., 69% homology with sea turtle GH, 66% with chicken GH and 61% with ovine GH) than to GHs of teleosts (e.g., 35% homology with chum salmon GH and 33% with bonito GH) except for eel (52% identity). Bullfrog GH and prolactin exhibit a sequence homology of 25%.

The complete amino acid sequence of growth hormone from sturgeon (Acipencer guldenstadti).

The complete amino acid sequence of growth hormone (GH) from a chondrostean species, the sturgeon (Acipencer gludenstaditi), has been determined. Two variants of GH, termed GH I and GH II, were isolated from the pituitary by alkaline extraction, gel filtration on a Sephadex G-100 column, and reversed-phase high-performance liquid chromatography (rpHPLC) on a TSK gel ODS-120T column. The purified proteins were confirmed to be GHs by immunoblotting using bovine and chum salmon GH antisera. For determining of the primary structures, these GHs were digested with lysyl endopeptidase and cleaved with cyanogen bromide. The resulting fragments were separated by rpHPLC and subjected to sequence analysis on an automated gas-phase sequencer employing an Edman method. Both GHs consist of 190 amino acid residues, and contain two disulfide linkages at positions 52-163 and 180-188. The GHs differ from each other at only three positions. Sequence comparison with GHs from other vertebrates revealed that sturgeon GHs have greater sequence homology with tetrapod GHs (63-76%) than with teleost GHs (42-63%).

Solution conformations and aggregational properties of synthetic amyloid beta-peptides of Alzheimer's disease. Analysis of circular dichroism spectra.

The A4 or beta-peptide (39 to 43 amino acid residues) is the principal proteinaceous component of amyloid deposits in Alzheimer's disease. Using circular dichroism (c.d.), we have studied the secondary structures and aggregational properties in solution of 4 synthetic amyloid beta-peptides: beta-(1-28), beta-(1-39), beta-(1-42) and beta-(29-42). The natural components of cerebrovascular deposits and extracellular amyloid plaques are beta-(1-39) and beta-(1-42), while beta-(1-28) and beta-(29-42) are unnatural fragments. The beta-(1-28), beta-(1-39) and beta-(1-42) peptides adopt mixtures of beta-sheet, alpha-helix and random coil structures, with the relative proportions of each secondary structure being strongly dependent upon the solution conditions. In aqueous solution, beta-sheet structure is favored for the beta-(1-39) and beta-(1-42) peptides, while in aqueous solution containing trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP), alpha-helical structure is favored for all 3 peptides. The alpha-helical structure unfolds with increasing temperature and is favored at pH 1 to 4 and pH 7 to 10; the beta-sheet conformation is temperature insensitive and is favored at pH 4 to 7. Peptide concentration studies showed that the beta-sheet conformation is oligomeric (intermolecular), whereas the alpha-helical conformation is monomeric (intramolecular). The rate of aggregation to the oligomeric beta-sheet structure (alpha-helix----random coil----beta-sheet) is also dependent upon the solution conditions such as the pH and peptide concentration; maximum beta-sheet formation occurs at pH 5.4. These results suggest that beta-peptide is not an intrinsically insoluble peptide. Thus, solution abnormalities, together with localized high peptide concentrations, which may occur in Alzheimer's disease, may contribute to the formation of amyloid plaques. The hydrophobic beta-(29-42) peptide adopts exclusively an intermolecular beta-sheet conformation in aqueous solution despite changes in temperature or pH. Therefore, this segment may be the first region of the beta-peptide to aggregate and may direct the folding of the complete beta-peptide to produce the beta-pleated sheet structure found in amyloid deposits. Differences between the solution conformations of the beta-(1-39) and beta-(1-42) peptides suggests that the last 3 C-terminal amino acids are crucial to amyloid deposition.

Parathyroid hormone-related peptide is a potent tumor angiogenic factor.

Rat pituitary malignant tumor cells; mGH3, show hypervascularization in in vivo xenografts and overexpress parathyroid hormone-related peptide (PTHrP) compared to original GH3 cells. To elucidate whether PTHrP is involved in tumor-derived angiogenesis, we examined the effect of PTHrP on vascular endothelial cells both in vitro and in vivo. Results of in vivo diffusion chamber assay showed a clear hypervascularization on the outer surface of diffusion chambers containing mGH3 tumor cell implants but not in those containing GH3 cells. Co-incubation with antisense PTHrP oligonucleotide (10 microM), but not sense or mismatched PTHrP oligonucleotide, suppressed hypervascularization in diffusion chambers. To further examine the role of PTHrP on endothelial cell function, PTHrP(1-34) was added at various concentrations to cultured bovine endothelial cells (BAECs) harvested from the aorta. PTHrP(1-34) did not alter the proliferation or migration of endothelial cells, but rather dose-dependently increased capillary formation by endothelial cells on the collagen gel matrix. Furthermore, 0.1 mM of 8-bromo-cAMP caused a similar increase in tube formation, which was dose-dependently inhibited by H89, a protein kinase A inhibitor. Our results indicate for the first time that PTHrP is a potential paracrine factor acting via the PKA pathway to enhance angiogenesis through capillary tube formation by endothelial cells in malignant pituitary tumors.

A new natriuretic peptide isolated from cardiac atria of trout, Oncorhynchus mykiss.

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are two cardiac natriuretic peptides (NPs) found in tetrapods from amphibians to mammals, whereas ANP and ventricular NP (VNP) have been identified in eel hearts. Because VNP has also been found in the rainbow trout ventricle, we attempted to isolate NP from trout cardiac atria in order to determine whether ANP and VNP are common cardiac NPs in teleosts. In the present experiments, we isolated VNP and a novel atrial NP consisting of 29 amino acid residues from the atria. This new trout NP exhibited similar sequence identity to mammalian ANP and BNP (50-60%). Its homology to eel ANP was low (52%) compared with high homology of trout and eel VNP (78%). Based on yield, the content of this new NP in trout atria may be even smaller than that of VNP. The new trout atrial NP exhibited low relaxant activity in the chick rectum (only 1/10 of that of trout VNP), and extremely low vasorelaxant activity in the rat aortic strip (only 1/400 of that of human ANP). However, the new trout NP was equipotent with trout VNP and human ANP in relaxing trout epibranchial artery. Based on the sequence similarity with other NPs and on atrial content, the new NP isolated from trout atria cannot yet be assigned to a known member of the NP family.

Presynaptic modification of neuromuscular transmission by antiacetylcholine receptor antibody: myasthenic serum and monoclonal antibody produced by transformed lymphocytes.

When myasthenic serum or a monoclonal antiacetylcholine receptor (anti-AChR) antibody produced by human transformed lymphocytes and transferable to an animal was applied to rat diaphragms in vitro, presynaptic facilitation was demonstrated by changes in ACh quantal content of endplate potentials. The results correlated with ability of the antibody to block binding of alpha-bungarotoxin to AChR, but not with titers of anti-AChR antibody by immunoprecipitation assay and AChR degradation rate. Antibody to the receptor site near the ACh-binding site may act presynaptically to compensate for the postsynaptic failure in myasthenia gravis.

A single and novel natriuretic peptide is expressed in the heart and brain of the most primitive vertebrate, the hagfish (Eptatretus burgeri).

In teleost fish and tetrapods, the natriuretic peptide (NP) family consists of ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and VNP (ventricular natriuretic peptide) that are secreted from the heart, and C-type natriuretic peptide (CNP) that is found in the brain. However, CNP is the only NP identified in the heart and brain of elasmobranchs, suggesting that it is the ancestral type of the NP family and that ANP, BNP and VNP appeared later in the vertebrate phylogeny. To delineate more clearly the molecular evolution of this hormone family, we determined the sequence of NP molecule(s) in evolutionarily the oldest vertebrate group, the cyclostomes. We have cloned a novel NP cDNA from the heart and brain of hagfish, Eptatretus burgeri, using the RACE method and degenerate primers that amplify all known types of NP cDNAs. The novel NP, named EbuNP after the scientific name of this hagfish, appears to be the only NP in the heart and brain, as no other NP cDNAs were amplified even after specific removal of the cloned EbuNP mRNA from the mRNA pool, except for a minor alternatively spliced EbuNP cDNA with a truncated 3'-untranslated sequence. The EbuNP was equally similar to known NPs but was not considered to be a CNP because of the presence of a C-terminal tail sequence. The EbuNP gene was abundantly expressed in the cardiac atrium, ventricle, portal heart and brain but scarcely in the intestine; no expression was observed in the gill and kidney. Mass spectrometry of affinity-purified EbuNP in plasma, heart and brain revealed a 68 amino acid peptide circulating in the blood and stored in the heart, which is cleaved at the typical cleavage signal of a processing enzyme, furin, as observed in mammalian BNP. The C-terminal Gly residue was used for amidation as is the case in eel ANP. The immunoreactive EbuNP was not detected in the brain, suggesting the presence of a different processing form in the brain. These results show that the molecular evolution of the NP family in vertebrates is more complex than previously thought.

Generation of neutralizing antibody to the reverse transcriptase of human immunodeficiency virus type 1 by immunizing of mice with an infectious vaccinia virus recombinant.

Antibodies inhibiting the reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) were found to be generated in the serum of mice repeatedly infected with a vaccinia virus recombinant, WRRT, expressing the enzyme. A monoclonal antibody (mAb), 7C4, which specifically and almost completely inhibits the RNA-dependent DNA polymerase activity of HIV-1 RT was produced from a mouse repeatedly immunized with WRRT. 7C4 seems to be specific for HIV-1 among retroviruses: 7C4 inhibited RT activity of three strains of HIV-1 (IIIB, Bru, and IMS-1) but not of two strains of HIV-2 (GH-1 and LAV-2) or two strains of SIV (MAC and MND). The immunoglobulin isotype of three out of four mAbs produced from spleen cells of the immunized mouse were IgG2a. This immunization method that avoids protein denaturation may preferentially induce a T helper type-1 immune response and increase the chances of producing the only occasionally obtainable mAb capable of recognizing a conformational epitope and completely inhibiting enzyme activity.

Effects of a novel antihyperlipidemic agent, S-2E, on the blood lipid abnormalities in homozygous WHHL rabbits.

To improve mixed hyperlipidemia in the low-density lipoprotein (LDL) receptor-deficient state, suppression of very-low-density lipoprotein (VLDL) particle production may be an important approach. We previously reported that S-2E, (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl] methoxybenzoic acid, suppressed VLDL particle production by inhibiting the biosynthesis of both sterol and fatty acids in the liver. We therefore examined whether S-2E lowered the blood cholesterol and triglyceride (TG) levels simultaneously in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, which correspond to human familial hypercholesterolemia. S-2E given orally at doses of 30 to 300 mg/kg significantly lowered serum total cholesterol (TC) levels at 1 week as well as TG at 2 weeks, and the lowering of TC and TG levels by S-2E reached a maximum at 3 to 4 weeks. In contrast, oral administration of pravastatin at doses of 10 to 100 mg/kg resulted in a significant suppression of TC levels (100 mg/kg) but not TG levels. Further analysis of the TC content in fractionated serum of control and S-2E-treated animals showed that suppression of TC level by S-2E is attributable to a decrease in the proportions of VLDL, intermediate-density lipoprotein (IDL), and LDL. It is, therefore, reasonable to assume that S-2E may be useful to improve the blood lipid abnormalities in the LDL receptor-deficient state.