Diagnostic capability of feature-tracking cardiovascular magnetic resonance to detect infarcted segments: a comparison with tagged magnetic resonance and wall thickening analysis.

AIM: To examine the diagnostic capabilities of feature-tracking cardiovascular magnetic resonance (FT-CMR), tagged cine magnetic resonance (MR), and wall thickening (WT) analyses to detect infarcted segments in patients with established myocardial infarction (MI). MATERIALS AND METHODS: Twenty patients with established MI were selected retrospectively and the peak endocardial circumferential strain (CS) was quantified based on the 16-segment model. According to CMR with late gadolinium enhancement, segments were categorised as transmural MI, subendocardial MI, and no MI. RESULTS: A total of 320 segments (62 transmural MI, 50 subendocardial MI, and 208 no MI) were analysed. Peak endocardial CS was significantly lower for transmural MI compared with subendocardial MI (p<0.05) and no MI (p<0.001). Cut-off values of -11.2% for CS by FTCMR, -10.9% for CS by tagged MR, and 23.8% for %WT, differentiated between infarcted and non-infarcted segments with a sensitivity of 72%, 71%, and 56%; specificity of 71%, 75%, and 67%; accuracy of 72%, 73%, and 63%; positive predictive value of 57%, 60%, and 48%; negative predictive value of 83%, 83%, and 74%; and an area-under-the-curve of 0.77, 0.79, and 0.64, respectively. CONCLUSIONS: FT-CMR was diagnostically superior to %WT, and could differentiate between subendocardial and transmural MI. Unlike tagged MR, FT-CMR did not require the acquisition of additional sequences.

Antimicrobial properties and mechanism of volatile isoamyl acetate, a main flavour component of Japanese sake (Ginjo-shu).

AIMS: To evaluate the antimicrobial properties of the main Ginjo-flavour components of sake, volatile isoamyl acetate and isoamyl alcohol. METHODS AND RESULTS: Volatile isoamyl acetate and isoamyl alcohol both inhibited growth of the five yeast and 10 bacterial test strains. The minimum inhibitory dose and minimum bactericidal (fungicidal) dose of isoamyl acetate were higher than those of isoamyl alcohol. Escherichia coli and Acetobacter aceti were markedly sensitive to isoamyl acetate and isoamyl alcohol. In E. coli exposed to isoamyl acetate for 5 h, changes in expression were noted in proteins involved in sugar metabolism (MalE, MglB, TalB and PtsI), tricarboxylic acid cycle (AceA, Pfl and AcnB) and protein synthesis (EF-Tu, EF-G, and GlyS). Expression of acid and alcohol stress-response proteins was altered in E. coli exposed to isoamyl acetate. Esterase activity was detected in E. coli, suggesting that isoamyl acetate was hydrolyzed to acetic acid and isoamyl alcohol. Acetic acid and isoamyl alcohol damaged E. coli cell membranes and inactivated membrane proteins, impairing respiration. CONCLUSIONS: Volatile isoamyl acetate and isoamyl alcohol were effective in inactivating various micro-organisms, and antimicrobial mechanism of volatile isoamyl acetate against E. coli was clarified based on proteome analysis. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the first report to examine the antimicrobial mechanism of volatile organic compound using proteome analysis combining two-dimensional difference gel electrophoresis with peptide mass fingerprinting.

Evaluation of the human papillomavirus mRNA test for the detection of cervical lesions in Japan.

AIMS: For the screening of cervical abnormalities, human papillomavirus (HPV) DNA testing is widely used along with Papanicolaou (Pap) testing. Although the sensitivity of the HPV DNA testing is good, its specificity is relatively low. In the present study, the authors evaluated the use of the Gen-Probe APTIMA HPV Assay for the detection of HPV mRNA and compared it with HPV DNA testing. MATERIALS AND METHODS: Liquid cervical Pap specimens collected from 410 women were assessed using the APTIMA test, the Qiagen Hybrid Capture 2 HPV DNA (HC2) Test, and the AMPLICOR HPV Test. RESULTS: The sensitivity and specificity for the detection of high-risk HPV were 85.6% and 99.2% for the APTIMA test, 94.1% and 98.4% for the HC2 test, and 90.2% and 95.7% for the AMPLICOR test, respectively. As the severity of the cervical lesion progressed, the positive rate of the three tests indicated a similar increase. The clinical sensitivity and specificity for the detection of squamous intraepithelial lesion (SIL) were 91.2% and 84.2% for the APTIMA test, 94.5% and 80.4% for the HC2 test, and 87.9% and 78.2% for the AMPLICOR test, respectively. CONCLUSION: The APTIMA is sensitive and specific for the detection of high-risk HPV. In the specimens with SIL, the APTIMA test is more specific than the HC2 and the AMPLICOR tests. This indicates that the APTIMA test may improve patient management and reduce the cost of screening.

Sarcoidal granulomas in the spleen associated with multiple carcinomas.

Sarcoid reactions are relatively rare manifestations of epithelioid cell granulomas associated with malignancy; they are especially found in the lymph nodes draining malignant tumors, but rarely found in other organs. We present a case of a 60-year-old female with sarcoid reactions in the spleen identified during the consecutive diagnosis and management of ovarian, breast, and thyroid carcinomas during a period of about 2 years. The symptoms and laboratory data suggestive of systemic sarcoidosis were absent except for a slight mediastinal lymphadenopathy detected only by a computed tomographic scan. The splenic granulomas were accompanied by dendritic cells of mature and immature types, the latter being different from the reported nodal counterparts. To our knowledge, this is the first reported case of splenic sarcoid reactions associated with multiple cancers, and the first reported immunohistochemical detection of dendritic cells in splenic granuloma.

Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.

Direct-puncture approach to the extraconal portion of the superior ophthalmic vein for carotid cavernous fistulae.

INTRODUCTION: The transvenous approach via the superior ophthalmic vein (SOV) is an available approach for carotid cavernous fistula (CCF), especially in the event that there is no other suitable approach route to the fistula. Surgical exposure of the peripheral roots of the SOV is commonly used; however, often, the SOV is often not accessible because of anatomical problems and/or complications. In this paper, we present and discuss our original direct-puncture approach to the extraconal portion of the SOV. METHODS: An attempt on three patients with traumatic CCF failed with the transarterial approach and the conventional venous approach via the inferior petrosal sinus; therefore, the patients were treated with the direct-puncture approach to the extraconal portion of the SOV using two-dimensional digital subtraction angiography with local anesthesia. RESULTS: All cases that had tortuous and partially stenotic division of the SOV were treated successfully with this approach and without complications. CONCLUSION: This approach will become an alternate approach, especially when the peripheral roots of the SOV are focally narrowed and tortuous, making it impossible to insert a catheter.

Multiple (18)F-FDG, PET-CT for postoperative monitoring of breast cancer patients.

BACKGROUND: Positron emission tomography (PET)-computed tomography (CT) may be useful in the post-treatment follow-up of breast cancer patients. PURPOSE: To assess the usefulness of (18)F-fluorodeoxyglucose (FDG) PET-CT (PET-CT) for postoperative monitoring of breast cancer patients. MATERIAL AND METHODS: One hundred twenty-nine PET-CT studies performed on 55 female postoperative breast cancer patients (median age 56 years, range 36-86 years) were analyzed. The median interval between the PET-CT studies was 6 months (range 1-15 months). In order to determine the usefulness of serial PET-CT examinations in the postoperative follow-up of breast cancer patients, the PET-CT findings were compared with the physical findings, findings obtained by other imaging modalities, and the (18)F-FDG-PET (PET) findings. RESULTS: The PET findings were negative in 4 metastatic bone lesions with a positive bone scan. The PET findings were also negative in 6 of 9 osteogenic bone metastases and one of 64 osteolytic bone lesions. There were 5 cases with false-positive of PET, which were determined to be areas of soft-tissue hyperactivity. All false-positive/-negative findings were corrected by the addition of CT. CONCLUSION: The results of this study lend support to the clinical role of PET-CT in the postoperative follow-up/monitoring of breast cancer patients.

[Surgical removal of native aortic valve thrombosis associated with acute myocardial infarction and protein C deficiency; report of a case].

Native aortic valve thrombosis is an uncommon event. We describe the case of a 76-year-old man who suffered acute myocardial infarction associated with native aortic valve thrombosis diagnosed by cardiac catheterization. Since the thrombus was localized on the right coronary cusp and occluded right coronary artery, rescue revascularization was performed using perfusion catheter, which was continuously engaged to the right coronary artery. Operation was immediately performed under cardiopulmonary bypass. After incision of ascending aorta, thrombus was removed easily and aortic valve was preserved without degenerative change. Histological study showed a typical thrombus without any specific findings. He had a good clinical course and discharged 9 days after the operation. He had no history of heart valve disease, left heart catheterization or bacterial endocarditis. Since laboratory data showed 41% in protein C antigen and 32% of protein C activity, he was diagnosed of protein C deficiency. Our report emphasize that this thrombus formation may be caused by protein C deficiency.

Ciliated craniopharyngioma may arise from Rathke cleft cyst.

OBJECTIVE: The histogenesis of craniopharyngioma is not fully understood. We encountered a ciliated craniopharyngioma, the details of which may shed light on the histogeny of craniopharyngioma in general. PATIENT: A 74-year-old man presented with visual disturbance. Computed tomography showed an intra-suprasellar cyst including a solid tumor. Transsphenoidal surgery was performed. During surgery, the cyst was found to contain mucoid milky-white fluid and a solid tumor 1 cm in diameter. Histologically, the tumor was shown to be a papillary type craniopharyngioma with foci of ciliated columnar epithelial cells. Ciliated craniopharyngioma was diagnosed. CONCLUSION: Our findings in this case together with findings in other reported cases suggest that the basal cells of Rathke cleft cyst transform to papillary type craniopharyngioma after squamous metaplasia, explaining the presence of the cilia and goblet cells.

Expression and mutation of SMAD4 in poorly differentiated carcinoma and signet-ring cell carcinoma of the colorectum.

Poorly differentiated adenocarcinoma (Por) and signet-ring cell carcinoma (Sig) are rare but highly malignant types of colorectal cancer. To explore their genetic backgrounds we investigated TGF-beta type II receptor (TGF-beta RII) and SMAD4 in the TGF-beta signaling pathway, and to identify their mutator phenotype we examined microsatellite instability (MSI) status. Loss of SMAD4 expression was significantly more frequent in Por (12 of 38; 31%) and Sig (4 of 5; 80%) tumors than in well (Well) and moderately differentiated (Mod) carcinomas (p = 0.04, 0.003, respectively). Mutation of the SMAD4 gene was detected in 2 of 26 Por tumors. MSI was positive in 14 of the 38 Por tumors and in 1 of the 5 Sig tumors, but in none of the Well or Mod tumors examined. We also found mutation of TGF-beta RII, a putative target of MSI, in 10 of 35 Por tumors (28.6%), but in none of 3 Sig tumors. As a whole, about 50% of the Por tumors and 80% of the Sig tumors showed abnormalities of either TGF-beta RII or SMAD4 expression. This suggests that disruption of the TGF-beta signaling pathway may play a central role in the pathogenesis of Por and Sig tumors of the colorectum.

Association of thalamic hyperactivity with treatment-resistant depression and poor response in early treatment for major depression: a resting-state fMRI study using fractional amplitude of low-frequency fluctuations.

Despite novel antidepressant development, 10-30% of patients with major depressive disorder (MDD) have antidepressant treatment-resistant depression (TRD). Although new therapies are needed, lack of knowledge regarding the neural mechanisms underlying TRD hinders development of new therapeutic options. We aimed to identify brain regions in which spontaneous neural activity is not only altered in TRD but also associated with early treatment resistance in MDD. Sixteen patients with TRD, 16 patients with early-phase non-TRD and 26 healthy control (HC) subjects underwent resting-state functional magnetic resonance imaging. To identify brain region differences in spontaneous neural activity between patients with and without TRD, we assessed fractional amplitude of low-frequency fluctuations (fALFF). We also calculated correlations between the percent change in the Hamilton Rating Scale for Depression (HRSD17) scores and fALFF values in brain regions with differing activity for patients with and without TRD. Patients with TRD had increased right-thalamic fALFF values compared with patients without TRD. The percent change in HRSD17 scores negatively correlated with fALFF values in patients with non-TRD. In addition, patients with TRD showed increased fALFF values in the right inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and vermis, compared with patients with non-TRD and HC subjects. Our results show that spontaneous activity in the right thalamus correlates with antidepressant treatment response. We also demonstrate that spontaneous activity in the right IFG, IPL and vermis may be specifically implicated in the neural pathophysiology of TRD.

Clinically unidentified dissection of vertebral artery as a cause of cerebellar infarction.

BACKGROUND AND PURPOSE: Dissection of vertebral arteries has been reported in association with minor neck movements without signs of trauma on the surface of the neck. In addition, injury of a vertebral artery can cause brain infarctions. However, few cases have been reported in which fatal brain infarction was due to nonocclusive, clinically undetected, traumatic thrombus formation in a vertebral artery. CASE DESCRIPTION: A 62-year-old man was hit by a car, and a right cerebellar infarction was found the day after the accident. The cause of the infarction could not be detected by angiography. Although the patient recovered favorably after surgical removal of the right lateral hemisphere of the cerebellum, he died suddenly 2 weeks after the accident. An autopsy and a microscopic study revealed pulmonary thromboembolism and organizing traumatic lesions of the right vertebral artery without occlusion or noteworthy stenosis of the artery. CONCLUSIONS: We concluded that the patient sustained traumatic lesions of the right vertebral artery during the traffic accident 2 weeks before death and that his cerebellar infarction was due to a thrombus resulting from these traumatic lesions.

Serum from patients with autoimmune diseases induces in vitro production of disease-associated antibodies by peripheral blood mononuclear cells from normal subjects.

Antibodies present in serum of patients with rheumatoid arthritis (RA), autoimmune thyroid diseases, and myasthenia gravis are preferentially cytotoxic to suppressor T lymphocytes from normal subjects induced by Concanavalin A. The aim of this study was to determine whether the lymphocytotoxic antibodies found in patients with these diseases also react with regulatory T cells to facilitate production of the autoantibodies responsible for each disease. Peripheral blood mononuclear cells (PBMC) from normal subjects were treated with serum from patients and complement. After washing, residual viable cells were cultured with pokeweed mitogen for 7 days. Immunoglobulin M rheumatoid factor and antihuman thyroglobulin antibody (anti-hTgAb) in the culture supernatants were measured by RIA. Anti-hTgAb was produced in culture supernatants of PBMC treated with serum samples from patients with autoimmune thyroid diseases, whereas serum samples from patients with RA, myasthemia gravis, or normal subjects did not stimulate production of detectable anti-hTgAb. In contrast, Immunoglobulin M rheumatoid factor was produced by normal PBMC treated only with serum from patients with RA. When normal T cells treated with serum were cultured with autologous untreated non-T cells in the presence of pokeweed mitogen, autoantibodies also were produced. Furthermore, the production of anti-hTgAb was suppressed by adding untreated T cells to the mixture of treated T cells and untreated non-T cells. These results suggest that lymphocytotoxic antibodies found in patients with autoimmune disorders may cause disease-associated suppressor T cell dysfunction.

Class II major histocompatibility complex antigen expression and cellular interactions in thyroid glands of Graves' disease.

Class II major histocompatibility complex (MHC) antigens have been demonstrated on the surface of thyroid epithelial cells (thyrocytes) from patients with autoimmune thyroid disease. The present study was designed to investigate how the expression of class II MHC antigens is involved in autoimmune processes in Graves' disease by studying cellular interactions among thyrocytes, lymphocytes within thyroid glands (TG), and peripheral blood (PB) lymphocytes. Thyrocytes were prepared by collagenase digestion, and T or non-T cells were separated by E-rosette formation. Thyrocytes were cocultured in the presence or absence of interferon-gamma, and the expression of HLA-DR antigens on cultured thyrocytes was examined by an indirect immunofluorescence method using monoclonal anti-HLA-DR antibody and monoclonal anti-HLA-DQ antibody. The cellular interactions were assessed as the proliferative response of T cells to autologous stimulators, such as thyrocytes or lymphocytes. Expression of HLA-DR antigens on thyrocytes after culture for 18 h in the absence of interferon-gamma was found in two thirds of the patients with Graves' disease studied (n = 18). Interferon-gamma induced and maintained the expression of HLA-DR antigens on thyrocytes. The percentages of HLA-DR+T cells were significantly higher among TG-T cells than among PB-T cells [32.6 +/- 12.4% (+/- SD) vs. 12.2 +/-5.0%; n = 18; P less than 0.01]. Thyrocytes from Graves' patients induced proliferation of both autologous PB-T cells and TG-T cells, and TG-T cells stimulated proliferation of autologous PB-T cells. In conclusion, interferon-gamma induces HLA-DR antigen expression on thyrocytes from patients with Graves' disease, and these cells induce proliferation of autologous T cells, which may, in turn, act on thyrocytes to perpetuate the process.

Monoclonal antihuman thyroglobulin antibodies.

Six murine hybridomas secreting monoclonal antihuman thyroglobulin (Tg) antibodies (TAK 1-6) were established by cell fusion techniques. Solid phase RIA was employed to detect the anti-Tg antibody in culture supernatants of hybridomas. The characteristics of these monoclonal antibodies were analyzed by radioimmune blocking assay using rat Tg, human glycoproteins, thyroid hormones, and various preparations of Tg obtained from patients with thyroid disease as inhibitors. In the same system, competitive inhibition studies between 125I-labeled and unlabeled monoclonal antibodies were carried out to determine whether these antibodies recognized the same antigenic determinant. TAK 2 and 3 reacted with human Tg specifically and had equal binding activity using various preparations of human Tg. The other four monoclonal antibodies (TAK 1, 4, 5, and 6) cross-reacted with xenogeneic Tg (rat Tg) and their affinity for human Tg increased as the iodine content of Tg increased. Tg binding to TAK 1 and 4 was inhibited by T4, whereas Tg binding to TAK 5 and 6 was not inhibited by any thyroid hormone or their precursors. In conclusion, we prepared six monoclonal antihuman Tg antibodies. One group is specific for human Tg and recognizes the framework structure unmodified by iodination; the second group reacts with iodination-related epitopes other than iodoamino acids, and the third group recognizes determinants consisting of T4. These monoclonal antibodies provide important probes to detect the polymorphism of human Tg.

Tumorigenicity of EBNA2-transfected cells.

The Epstein-Barr virus nuclear antigen 2 (EBNA2) gene is thought to be important for transformation by Epstein-Barr virus (EBV), but the mechanism of this transformation is little understood. Here, to examine the transforming ability of EBNA2, we transfected a rat fibroblast cell line F2408 with a recombinant EBNA2 expression plasmid and examined cell morphology, colony formation in soft agar, and tumorigenicity in nude mice. The morphology of transfected clones was similar to those of untransfected cells, but two of seven clones grew in soft agar, and four clones of seven clones reproducibly formed tumors in nude mice. These four clones showed EBNA2 expression, but non-tumorigenic clones did not. These results indicate that the expression of EBNA2 is correlated with tumorigenicity.

Multiple, unique, and common p53 mutations in a thorotrast recipient with four primary cancers.

Four primary cancers found at autopsy of a patient who received the thorium-based contrast agent Thorotrast 50 years ago and who was healthy up until a few months before his death from liver failure were analyzed for p53 mutations. The data suggest that the chronic alpha-irradiation may be a large causative factor. Multiple mutations were found in all the cancer tissues: two foci of a cholangiocellular carcinoma, a tubular adenocarcinoma of the stomach, a squamous cell carcinoma of the lung, and an adenocarcinoma of Vater's ampulla. The total number of point mutations detected were 13. Moreover, homozygous aberrations were detected in a large area of normal small intestine and noncancer liver tissues suggesting that nontumor cells which harbored p53 abnormalities gained a survival advantage and clonally expanded.

Mechanism of inhibitory effect of dextran sulfate and heparin on human T-cell lymphotropic virus type I (HTLV-I)-induced syncytium formation in vitro: role of cell-to-cell contact.

Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with target cells. These two compounds almost completely blocked syncytium formation in the early phase of the reaction at a concentration of 125 micrograms/ml, but dextran, as a control, did not inhibit it at concentrations up to 625 micrograms/ml. 50% inhibition of syncytium formation was detected at a concentration of 2 micrograms/ml of dextran sulfate 5000, 3 micrograms/ml of dextran sulfate 8000 and 8 micrograms/ml of heparin. The binding of radiolabeled HTLV-I-infected cells (HCT-1) to the target cells was inhibited by addition of dextran sulfate and heparin, and the inhibitory effects were concentration-dependent. No marked changes were detected in the expression of adhesion molecules on the virus-infected cells and target cells, and in the expression of envelope proteins on the virus-infected cells after exposing them to the polyanionic compounds. These results suggest that the blocking of cell-to-cell contact by polyanionic compounds, probably independent of surface adhesion molecules, is important for their inhibitory effect on HTLV-I-induced syncytium formation.

Purification and characterization of glutaredoxin (thioltransferase) from rice (Oryza sativa L.).

We purified and characterized glutaredoxin (thioltransferase), which catalyzes thiol/disulfide exchange reaction, for the first time in plants. The purification procedure employed an immunoabsorbent, antiglutaredoxin-Sepharose. Glutaredoxin was purified about 2,200-fold from rice bran and it appeared to be homogeneous on SDS-PAGE. MALDI-TOF mass spectrometry revealed that the protein has a molecular mass of 11,097.9 Da. Rice glutaredoxin consists of 105 amino acid residues, containing the tetrapeptide -Cys-Phe-Pro (Tyr)-Cys-, which constitutes the active site of Escherichia coli and mammalian glutaredoxins. Inactivation assay also indicated that cysteine residues are responsible for enzyme activity. Kinetic analyses revealed that the enzyme did not exhibit normal Michaelis-Menten kinetics. The enzyme has an optimum pH of about 8.7 with 2-hydroxyethyl disulfide as a substrate. In addition, rice glutaredoxin has dehydroascorbate reductase activity, like mammalian glutaredoxin.

Purification, molecular cloning, and genomic organization of human brain long-chain acyl-CoA hydrolase.

An acyl-CoA hydrolase, referred to as hBACH, was purified from human brain cytosol. The enzyme had a molecular mass of 100 kDa and 43-kDa subunits, and was highly active with long-chain acyl-CoAs, e.g. a maximal velocity of 295 micromol/min/mg and K(m) of 6.4 microM for palmitoyl-CoA. Acyl-CoAs with carbon chain lengths of C(8-18) were also good substrates. In human brain cytosol, 85% of palmitoyl-CoA hydrolase activity was titrated by an anti-BACH antibody, which accounted for over 75% of the enzyme activity found in the brain tissue. The cDNA isolated for hBACH, when expressed in Escherichia coli, directed the expression of palmitoyl-CoA hydrolase activity and a 44-kDa protein immunoreactive to the anti-BACH antibody, which in turn neutralized the hydrolase activity. The hBACH cDNA encoded a 338-amino acid sequence which was 95% identical to that of a rat homolog. The hBACH gene spanned about 130 kb and comprised 9 exons, and was mapped to 1p36.2 on the cytogenetic ideogram. These findings indicate that the long-chain acyl-CoA hydrolase present in the brain is well conserved between man and the rat, suggesting a conserved role for this enzyme in the mammalian brain, and enabling genetic studies on the functional analysis of acyl-CoA hydrolase.