Following the Interstellar History of Carbon: From the Interiors of Stars to the Surfaces of Planets.

The chemical history of carbon is traced from its origin in stellar nucleosynthesis to its delivery to planet surfaces. The molecular carriers of this element are examined at each stage in the cycling of interstellar organic material and their eventual incorporation into solar system bodies. The connection between the various interstellar carbon reservoirs is also examined. Carbon has two stellar sources: supernova explosions and mass loss from evolved stars. In the latter case, the carbon is dredged up from the interior and then ejected into a circumstellar envelope, where a rich and unusual C-based chemistry occurs. This molecular material is eventually released into the general interstellar medium through planetary nebulae. It is first incorporated into diffuse clouds, where carbon is found in polyatomic molecules such as H2CO, HCN, HNC, c-C3H2, and even C60+. These objects then collapse into dense clouds, the sites of star and planet formation. Such clouds foster an active organic chemistry, producing compounds with a wide range of functional groups with both gas-phase and surface mechanisms. As stars and planets form, the chemical composition is altered by increasing stellar radiation, as well as possibly by reactions in the presolar nebula. Some molecular, carbon-rich material remains pristine, however, encapsulated in comets, meteorites, and interplanetary dust particles, and is delivered to planet surfaces. Key Words: Carbon isotopes-Prebiotic evolution-Interstellar molecules-Comets-Meteorites. Astrobiology 16, 997-1012.

Optimizing production of in vivo-matured oocytes from superstimulated Holstein cows for in vitro production of embryos using X-sorted sperm.

The present study aimed to establish an efficient system for the production of female embryos from dairy cows by in vitro fertilization (IVF) using X-sorted sperm and in vivo-matured oocytes collected by ovum pick up (OPU). Nonlactating Holstein cows (n = 36) were administered a controlled intravaginal progesterone-releasing (controlled internal drug release) device (d 0), underwent dominant follicle ablation (DFA) or ovulation by administration of 100 µg of GnRH on d 5, and were superstimulated with FSH and PGF2α, following standard procedures. Controlled internal drug release devices were removed on the evening of d 8 or on the morning of d 9, depending on the experiment. For LH surge induction, 200 µg of GnRH was administered on the morning of d 10 (0 h). In experiment 1, the peak (48.1%) of ovulating follicles was detected at 29 to 32 h after GnRH injection (0 h), and the range in the timing of the initiation of ovulation was less by timing from GnRH administration (30.0 ± 2.8h) rather than by timing the onset of estrus (32.7 ± 4.7h). Only 0.9% of total ovulated follicles were recorded before 26 h after GnRH injection. Therefore, OPU was carried out at 26 h and IVF occurred at 30 h after GnRH in experiments 2 and 3. In experiment 2, 83.3 ± 10.8% of oocytes with expanded cumulus cells had extruded the first polar body at 30 h after GnRH injection. The aim of experiment 3 was to compare the effect of either DFA or GnRH-induced LH surge before superstimulation on the efficiency of embryo production by IVF following superstimulation. Progesterone concentrations from d 10 to 12 in the DFA group were lower than those in the GnRH group. A greater proportion of recovered oocytes with expanded cumulus cells from ≥ 8-mm follicles was observed in the DFA group than in the GnRH group (95.9 and 77.4%, respectively). Blastocyst rates in the DFA and GnRH groups (58.0 and 52.8%, respectively) did not differ from those of oocytes collected from nonstimulated OPU and matured in vitro (49.9%). However, the proportion of high-quality blastocysts was higher in the DFA group compared with the GnRH group (54.9 vs. 21.5%). Our results demonstrate that high rates of good-quality blastocysts can be produced by IVF with X-sorted frozen sperm using in vivo-matured oocytes collected by OPU from cows after DFA and superstimulation combined with ovulation induction.

Culture of bovine embryos in polyester mesh sections: the effect of pore size and oxygen tension on in vitro development.

The purpose of this study was to assess the feasibility of polyester mesh culture for the in vitro production of bovine embryos, as polyester mesh is an alternative way for tracking individual embryos throughout culture using time-lapse cinematography (TLC). Bovine embryos were isolated during in vitro culture using sections of three different polyethylene terephthalate (PET) mesh products. In vitro matured and fertilized bovine oocytes were cultured in the 217 × 217, 230 × 230 or 238 × 238-µm openings of PET mesh sections or in simple micro-drops (control) for 7 days under either 20% or 5% O(2) tensions. No difference in embryo developmental rates was found between the culture groups in terms of cleavage, blastocyst formation and blastocyst expansion irrespective of O(2) tension. In contrast, under 20% O(2) tension, blastocysts that developed in PET mesh with 217 × 217-µm opening had significantly higher numbers of total and trophectoderm (TE) cells than control embryos; however, the numbers and proportions of inner cell mass (ICM) cells did not differ. Under 5% O(2) tension, no difference was found among the culture groups in the numbers of total, ICM and TE cells in embryos. All three PET mesh products investigated in this study were proven to be effective to prevent embryo movement. The results demonstrate that bovine embryos can be cultured in PET mesh sections without negative side-effects and suggest that embryo distance determined by the mesh affects embryo quality at atmospheric oxygen tension. Polyethylene terephthalate mesh with 217 × 217-µm openings was found to be the most suitable for further application in TLC.

The entry of manganese ions into the brain is accelerated by the activation of N-methyl-D-aspartate receptors.

Manganese-enhanced magnetic resonance imaging (MEMRI) is receiving increased interest as a valuable tool for monitoring the physiological functions in the animal brain based on the ability of manganese ions to mimic calcium ions entering to excitable cells. Here the possibility that in vivo MEMRI can detect the entry of manganese ions (Mn2+) in the brain of rats behaving without intended stimulation is tested. This hypothesis was a result of the unexpected observation that Mn2+-dependent signal enhancement was dramatically suppressed in ketamine-anesthetized rats compared with other anesthetics, such as urethane, pentobarbital and isoflurane. The effects of noncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonists, ketamine and MK-801, on MEMRI for MnCl2 injected rats were examined. Treatment with MK-801 suppressed the signal enhancement more effectively than with ketamine. NMDAR agonists, glutamate (100 mg/kg) and N-methyl-d-aspartate (NMDA) (35 mg/kg), enhanced the signal intensities on MEMRI, and this signal enhancement was completely antagonized by MK-801. The systemic administration of the competitive NMDAR antagonist, D-2-amino-5-phosphono-pentanoate (D-AP5), which does not cross the blood-brain barrier (BBB), showed no effects on the signal enhancement induced by NMDA and glutamate. A selective AMPA receptor (AMPAR) antagonist, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), did not block the signal enhancement. These data indicated that the Mn2+-dependent signal enhancement took place as a result of the activation of glutamatergic neurons through NMDAR, but not through AMPAR in the brain.

Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic syndrome impair AML1- and p53-mediated transcription.

The AML1 transcription factor complex is the most frequent target of leukemia-associated chromosomal translocations. Homeodomain-interacting protein kinase 2 (HIPK2) is a part of the AML1 complex and activates AML1-mediated transcription. However, chromosomal translocations and mutations of HIPK2 have not been reported. In the current study, we screened mutations of the HIPK2 gene in 50 cases of acute myeloid leukemia (AML) and in 80 cases of myelodysplastic syndrome (MDS). Results indicated there were two missense mutations (R868W and N958I) in the speckle-retention signal (SRS) domain of HIPK2. Subcellular localization analyses indicated that the two mutants were largely localized to nuclear regions with conical or ring shapes, and were somewhat diffused in the nucleus, in contrast to the wild type, which were mainly localized in nuclear speckles. The mutations impaired the overlapping localization of AML1 and HIPK2. The mutants showed decreased activities and a dominant-negative function over wild-type protein in AML1- and p53-dependent transcription. These findings suggest that dysfunction of HIPK2 may play a role in the pathogenesis of leukemia.

Inhibitory effects of an anti-rheumatic agent T-614 on immunoglobulin production by cultured B cells and rheumatoid synovial tissues engrafted into SCID mice.

OBJECTIVE: To clarify the pharmacological action of an anti-rheumatic agent T-614, we investigated its effects on immunoglobulin (Ig) production by cultured B cells and Ig secretion from synovial tissues of patients with rheumatoid arthritis (RA) using SCID mice engrafted with human RA tissue (SCID-HuRAg). METHODS: Murine B cells were prepared from mouse spleen by a T-cell depletion method. The cells were cultured with lipopolysaccharide (LPS) and/or interleukin 4 (IL-4) in the absence or presence of T-614. Human B cells were isolated from peripheral blood of healthy donors and the Ig production was induced by co-culture with autologous T cells and anti-CD3 antibody. SCID-HuRAg was prepared according to our previous method. T-614 was orally administered to the mice once daily for 4 weeks starting on the fourth week after the implantation. Then, peripheral blood was obtained and the implanted tissues were removed. Igs in the culture media or the sera were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: In murine B-cell cultures, T-614 significantly decreased not only the IgM production stimulated with LPS but IgG1 production induced by LPS and IL-4. Regarding human B cells stimulated with T cells, it also inhibited IgM and IgG production. In SCID-HuRAg mice, high concentrations of polyclonal human IgG were detectable in the sera of all mice. A significant decrease in the IgG level was observed in the T-614-treated group compared with the control group. CONCLUSIONS: We showed that T-614 inhibited Ig production by the cultured B cells and also decreased the high level of human IgG observed in SCID-HuRAg mice. These results may support its effect on plasma Ig in RA patients and provide insights into the mechanisms of its anti-rheumatic effect.

An anti-rheumatic agent T-614 inhibits NF-kappaB activation in LPS- and TNF-alpha-stimulated THP-1 cells without interfering with IkappaBalpha degradation.

OBJECTIVE: Compound T-614, a member of the methanesulfoanilide class of anti-inflammatory agents, shows potent anti-arthritic activity in animal models of rheumatoid arthritis. The aim of the present investigation was to characterize the anti-arthritic activity of T-614 in terms of regulation of the nuclear transcription factor NF-kappaB, which is associated with expression of many immune and inflammatory genes. MATERIALS AND METHODS: THP-1 cells (human monocytic leukemia cell line) were used throughout this in vitro study, and lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-alpha were employed for activation of the cells. Cytokine production was assayed by enzyme-linked immunosorbent assay (ELISA). The mRNA levels were determined by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. Assessment of the NF-kappaB DNA binding activity was performed by an electrophoretic mobility shift assay (EMSA) using a digoxigenin (DIG)-labeled double-stranded oligonucleotide containing kappaB-binding site. Degradation kinetics of the cytosolic NF-kappaB inhibitor a (IkappaBalpha) were studied by Western blot analysis. RESULTS: T-614 inhibited LPS-stimulated production of TNF-alpha, interleukin (IL)-6, and IL-8 in a concentration-dependent manner with decreasing mRNA levels (IL-6 and IL-8). EMSA study showed that T-614 prevented TNF-alpha as well as LPS-stimulated activation of NF-kappaB, and Western blot analysis proved that T-614 did not affect degradation of IkappaBalpha protein. CONCLUSIONS: These results suggest that the inhibitory effect of T-614 on the production of TNF-alpha, IL-6 and IL-8 in LPS-stimulated THP-1 cells may involve transcriptional regulation through suppression of NF-kappaB activation without interfering with IkappaBalpha degradation.

Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein.

The AML1-CBF beta transcription factor complex is the most frequent target of specific chromosome translocations in human leukemia. The MOZ gene, which encodes a histone acetyltransferase (HAT), is also involved in some leukemia-associated translocations. We report here that MOZ is part of the AML1 complex and strongly stimulates AML1-mediated transcription. The stimulation of AML1-mediated transcription is independent of the inherent HAT activity of MOZ. Rather, a potent transactivation domain within MOZ appears to be essential for stimulation of AML1-mediated transcription. MOZ, as well as CBP and MOZ-CBP, can acetylate AML1 in vitro. The amount of AML1-MOZ complex increases during the differentiation of M1 myeloid cells into monocytes/macrophages, suggesting that the AML1-MOZ complex might play a role in cell differentiation. On the other hand, the MOZ-CBP fusion protein, which is created by the t(8;16) translocation associated with acute monocytic leukemia, inhibits AML1-mediated transcription and differentiation of M1 cells. These results suggest that MOZ-CBP might induce leukemia by antagonizing the function of the AML1 complex.

Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8;22)(p11;q13) chromosome translocation.

Histone acetyltransferase p300 functions as a transcriptional co-activator which interacts with a number of transcription factors. Monocytic leukemia zinc finger protein (MOZ) has histone acetyltransferase activity. We report the fusion of the MOZ gene to the p300 gene in acute myeloid leukemia with translocation t(8;22)(p11;q13). FISH and Southern blot analyses showed the rearrangement of the MOZ and p300 genes. We determined the genomic structure of the p300 and the MOZ genes and the breakpoints of the translocation. Analysis of fusion transcripts indicated that the zinc finger and acetyltransferase domains of MOZ are fused to a largely intact p300. These results suggest that MOZ-p300, which has two acetyltransferase domains, could be involved in leukemogenesis through aberrant regulation of histone acetylation.

Regional wall stress predicts ventricular remodeling after anteroseptal myocardial infarction in the Healing and Early Afterload Reducing Trial (HEART): an echocardiography-based structural analysis.

BACKGROUND: Increased left ventricular (LV) wall stress after myocardial infarction (MI) has been implicated in LV remodeling. However, the relationship between LV wall stress and LV remodeling is incompletely defined. METHOD: We prospectively studied the relationship between regional wall stress and LV remodeling by application of the finite element method to end-systolic LV models from patients enrolled in the Healing and Early Afterload Reducing Therapy (HEART) Trial. Individual LV models were constructed from orthogonal apical echocardiographic views obtained at day 14 after anteroseptal MI in 64 patients. Of these, 31 patients received low-dose (0.625 mg) ramipril and 33 patients received full-dose (10 mg) ramipril. LV wall stress was calculated by the finite element method and correlated with change in LV volume from day 14 to day 90 after MI. RESULTS: Among all patients, increases in apical regional wall stress were associated with LV volume changes (P -trend =.015). The relationship between apical regional wall stress and change in LV volume was strongest in the low-dose ramipril group (r = 0.53, P =.002) and remained significant after adjustment for end-diastolic volume, infarct size, ejection fraction, and systolic blood pressure yet was attenuated in the full-dose ramipril group. CONCLUSIONS: Apical regional wall stress is an independent predictor of subsequent LV remodeling after MI. The relationship between increased apical wall stress and LV dilatation appears to be attenuated by full-dose angiotensin-converting enzyme inhibition.

Inhibitory effect of T-614 on tumor necrosis factor-alpha induced cytokine production and nuclear factor-kappaB activation in cultured human synovial cells.

OBJECTIVE: To investigate the mechanism of the immunosuppressive effect of T-614 [N-(3-formylamino-4-oxo-6-phenoxy-4H-chromen-7-yl)methanesulfonamide], a new antirheumatic drug whose clinical efficacy has been determined for the treatment of patients with rheumatoid arthritis (RA). METHODS: RA synovial fibroblast-like cells were cultured with tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml) in the presence or absence of T-614. After incubation, cytokine production was measured by ELISA. Expression of interleukin 6 (IL-6) and IL-8 mRNA was examined by real-time quantitative reverse transcriptase-polymerase chain reaction analysis and TNF-alpha induced nuclear factor-kappaB (NF-kappaB) activation was observed using immunostaining with an antibody against NF-kappaB p65. RESULTS: T-614 suppressed TNF-alpha induced production of IL-6, IL-8, and monocyte chemoattractant protein 1, and also reduced the accumulation of IL-6 and IL-8 mRNA in a concentration dependent manner. T-614 interfered with the TNF-alpha induced translocation of NF-kappaB to the nucleus from the cytoplasm. CONCLUSION: Inhibition of NF-kappaB activation and transcription of proinflammatory cytokines by T-614 contributes to its clinical antirheumatic effect.

Effect of acupuncture-like stimulation on cortical cerebral blood flow in anesthetized rats.

The effect of acupuncture-like stimulation of various areas (cheek, forepaw, upper arm, chest, back, lower leg, hindpaw, perineum) on cortical cerebral blood flow (CBF) was examined in anesthetized rats. An acupuncture needle (diameter, 340 microm) was inserted into the skin and underlying muscles at a depth of about 5 mm and twisted to the right and left once a second for 1 min. CBF of the cortex was measured using a laser Doppler flowmeter. Stimulation of the cheek, forepaw, upper arm and hindpaw produced significant increases in CBF, but stimulation of the chest, back, lower leg and perineum did not produce significant responses. Stimulation of the cheek, forepaw, and hindpaw produced an increase in mean arterial pressure (MAP), while stimulation of the back produced a decrease in MAP. Stimulation of the upper arm, chest, lower leg and perineum did not produce a significant MAP response. After spinal transection at the 1st to 2nd thoracic level, the blood pressure response to stimulation of the cheek and forepaw was suppressed, whereas an increase in CBF still took place. The increase in CBF induced by forepaw stimulation was abolished by severance of the somatic nerves at the brachial plexus. Forepaw stimulation enhanced the activity of the radial, ulnar and median nerves. Furthermore, in the present study, passing of an electric current through acupuncture needles showed that excitation of group III (Adelta) and group IV (C) afferent fibers in the somatic nerve was capable of producing an increase in CBF, whereas excitation of group I (Aalpha) and group II (Abeta) fibers was ineffective. The increase in CBF induced by forepaw stimulation was almost abolished by intravenous administration of muscarinic and nicotinic cholinergic blocking agents (atropine 5 mg/kg and mecamylamine 20 mg/kg), and by bilateral lesions in the nucleus basalis of Meynert. Acupuncture-like stimulation of a forepaw increased acetylcholine release in the cerebral cortex. We concluded that the increase in CBF, independent of systemic blood pressure, elicited by acupuncture stimulation is a reflex response in which the afferent nerve pathway is composed of somatic group III and IV afferent nerves, and efferent nerve pathway includes intrinsic cholinergic vasodilators originating in the nucleus basalis of Meynert.

Detection of hepatocellular carcinoma and its metastases with various pulse sequences using superparamagnetic iron oxide (SHU-555-A).

BACKGROUND: To identify the most useful combinations of various pre- and postcontrast magnetic resonance (MR) image sequences in detecting hepatocellular carcinoma (HCC) and its intrahepatic metastases before and after injection of SHU-555-A. METHODS: Thirty-eight lesions in 16 patients were evaluated before and after administration of SHU-555-A by using fast spin echo (FSE), gradient echo (GRE), and echo planar (EP) imaging sequences using a 1.5-Tesla superconducting MR system. The signal intensity ratio (SIR) and contrast-to-noise ratio (CNR) of the lesions, signal-to-noise ratios, and other parameters were calculated. RESULTS: Tumors were better detected after injection of SHU-555-A on all pulse sequences except on out-of-phase T1-weighted (T1W)-GRE sequences. Tumor detectability was higher for precontrast EP imaging and T2*-weighted (T2*W)-GRE sequences, whereas detectability at postcontrast was higher for T2*W-GRE, proton-density-weighted-FSE, and in-phase T1W-GRE sequences. The SIR and CNR at precontrast were highest for EP imaging, and those at postcontrast were highest for T2*W-GRE. CONCLUSION: SHU-555-A will increase the detectability of HCC and its liver metastases. T1W- and T2*W-GRE sequences would be the sequences of choice.

A 2-Mb sequence-ready contig map and a novel immunoglobulin superfamily gene IGSF4 in the LOH region of chromosome 11q23.2.

Human chromosome 11q23.2 has been proposed to contain a tumor suppressor gene(s) whose deletion has been associated with cancer of the lung and breast and with neuroblastoma. To analyze the genomic structure and to isolate a candidate tumor suppressor gene from this region, we constructed a 2-Mb sequence-ready contig map using bacteriophage P1 (P1), bacterial artificial chromosome (BAC), and P1-derived artificial chromosome (PAC). The map comprises a contig of 24 overlapping P1, BAC, and PAC clones. To isolate gene fragments from the region, we performed direct cDNA library screening, exon trapping, EST mapping, and genomic sequencing using the P1, BAC, and PAC clones. Sequence analysis of 5 clones, which spans 23% (458,738 bp) of the region, and extensive gene scanning along the entire region revealed that the region is extraordinarily scarce in genes, but we identified one ubiquitously expressed novel gene and one testis-specific gene fragment. The novel gene, which we call IGSF4 (immunoglobulin superfamily 4), is transcribed into a 1.6- or 4.4-kb RNA encoding a 442-amino-acid protein. It shares strong homology with mouse IGSF-B12 and cell adhesion molecules NCAM1 and NCAM2 within their Ig-like C2-type domains. The IGSF4 gene, a novel gene that is shown to be located in the common loss of heterozygosity region, possesses a number of interesting features and may be good candidate for a tumor suppressor gene.

Occurrence of free D-amino acids and aspartate racemases in hyperthermophilic archaea.

The occurrence of free D-amino acids and aspartate racemases in several hyperthermophilic archaea was investigated. Aspartic acid in all the hyperthermophilic archaea was highly racemized. The ratio of D-aspartic acid to total aspartic acid was in the range of 43.0 to 49.1%. The crude extracts of the hyperthermophiles exhibited aspartate racemase activity at 70 degrees C, and aspartate racemase homologous genes in them were identified by PCR. D-Enantiomers of other amino acids (alanine, leucine, phenylalanine, and lysine) in Thermococcus strains were also detected. Some of them might be by-products of aspartate racemase. It is proven that D-amino acids are produced in some hyperthermophilic archaea, although their function is unknown.

Involvement of PITPnm, a mammalian homologue of Drosophila rdgB, in phosphoinositide synthesis on Golgi membranes.

Phosphatidylinositol transfer protein (PITP) is involved in phospholipase C-mediated signaling and membrane trafficking. We previously reported cloning and characterization of a gene encoding for membrane-bound PITP, named PITPnm, that is a mammalian homologue of the Drosophila retinal degeneration B (rdgB) gene (Aikawa, Y., Hara, H., and Watanabe, T. (1997) Biochem. Biophys. Res. Commun. 236, 559-564). Here we report the subcellular localization of PITPnm protein and provide evidence for its involvement in phosphatidylinositol 4-phosphate (PtdIns 4-P) synthesis. PITPnm is an integral membrane protein that largely localized in close association with membranes of Golgi vacuoles and the endoplasmic reticulum (ER). The amino terminus region of PITPnm was exposed to cytoplasmic side. Interaction with various phosphoinositides was observed in the amino terminus region spanning from 196 amino acids to 257 amino acids of PITPnm. At the amino terminus regions of 1-372 amino acids, PITPnm formed a complex with type III PtdIns 4-kinase. The transmembrane and carboxyl-terminal portions (residues 418-1242) functioned to retain the PITPnm in the Golgi vacuole. These results suggest that PITPnm plays a role in phosphoinositide synthesis on the Golgi vacuoles and possibly in the PtdIns signaling pathway in mammalian cells.

Assessment of regional left ventricular wall stress after myocardial infarction by echocardiography-based structural analysis.

OBJECTIVES: The objective of this study was to determine the distribution of regional left ventricular (LV) wall stress after myocardial infarction (MI). BACKGROUND: After a large MI, structural changes occur in the heart that ultimately may lead to alterations in LV size and shape, a process generally referred to as ventricular remodeling. Regional variation in myocardial wall stress may be responsible for initiation of physiologic and cellular changes that result in myocardial hypertrophy, dilatation, and remodeling after MI. Simplified geometric analytic methods of estimating global LV wall stress cannot determine regional variation such as that occurring after MI. METHODS AND RESULTS: To assess regional LV wall stress after MI, we applied the finite element method to patient-specific end-systolic LV models generated from echocardiographic imaging. After validation by comparison with analytic solutions of LV wall stress in idealized ventricles, LV models were constructed from rotated orthogonal apical images from 13 normal volunteers, 16 patients with recent (<4 days) anterior MI, and 7 patients with recent infero-posterior MI. The mean Von Mises stress was calculated for the entire LV and for 5 separate regions of the LV. Von Mises LV wall stress was increased globally in patients with anterior MI (211 +/- 46 kdyne/cm2; P < .002) or infero-posterior MI (175 +/- 23 kdyne/cm2; P = .04) compared with normal patients (144 +/- 57 kdyne/cm2). Global wall stress correlated directly with ejection fraction (P < .0001) and inversely with wall motion index (P < .004) in patients with anterior MI. Wall stress in the apical regions was increased by a factor of 2.3 in patients with anterior MI (P < .0001), whereas other regions did not differ from normal patients. There were no individual regions that were significantly different from normal in patients with infero-posterior MI. CONCLUSIONS: Anterior MI is associated with an increase in apical end-systolic wall stress compared with normal and infero-posterior MI. This may be an important stimulus for LV remodeling after anterior MI.

A quadricuspid aortic valve diagnosed by transesophageal echocardiography: report of a case.

A quadricuspid aortic valve is a very rare anomaly which may cause aortic regurgitation in adulthood. We describe herein the case of a 54-year-old man with aortic regurgitation in whom a quadricuspid aortic valve was diagnosed, not through transthoracic investigation, but by transesophageal echocardiography (TEE). TEE also indicated that the right coronary ostium was located in a lower position. Subsequent aortic valve replacement was successfully performed, at which time the diagnosis was confirmed. Thus, TEE played an important role in identifying the anatomy of the aortic valve and the location of the coronary ostium.

A new anti-rheumatic drug, T-614, effectively suppresses the development of autoimmune encephalomyelitis.

In the present study, we examined the therapeutic effects of T-614 (3-formylamino-7-methylsulfonylaminoxy-4H-1-benzopyran-4-one), a new anti-rheumatic drug, on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). T-614 dose-dependently suppressed the development of active EAE induced in Lewis rats by immunization with myelin basic protein (MBP) when administered for 2 weeks starting on the day of immunization (day 0 to 14). Amelioration of clinical signs was also obtained by the treatment at the effector phase (day 7 to 14) of the disease. Furthermore, T-614 treatment of recipient rats that had received MBP-sensitized lymphoid cells resulted in suppression of the clinical severity of EAE. Immunohistological examination revealed that the number of TCR alpha beta-expressing T cells and the extent of MHC class II expression in the spinal cord of rats treated with T-614 was markedly reduced. In vitro study using MBP-specific T cells showed that the addition of T-614 inhibited the proliferative responses of T cells and the production of pro-inflammatory cytokines such as IFN-gamma, IL-6 and TNF produced by T and accessory cells. Taken together, these findings imply that T-614 suppresses the development of EAE by inhibiting the proliferation of autoreactive T cells and pro-inflammatory cytokine production not only by T cells but also by macrophages/microglia. This may be attributable to the result that T-614 is more effective at the effector phase rather than the induction phase. Thus, this drug has a potential value for the treatment of various T cell-mediated autoimmune diseases including multiple sclerosis (MS) as well as rheumatoid arthritis.