Three 4-monosubstituted butyrolactones from a regulatory gene mutant of Streptomyces rochei 7434AN4.

Extensive metabolite analysis of Streptomyces rochei 7434AN4 was performed to discover uncharacterized secondary metabolites. A mutant strain of S. rochei, in which two regulatory genes srrC (a tetR-type repressor) and srrY (SARP-type activator) were inactivated, accumulated three 4-monosubstituted γ-butyrolactones YT02-A, YT02-B, and KH01-A, which were not detected in the parent strain. Their structures were identified as 4,10-dihydroxy-10-methyldodecan-4-olide, 4,10-dihydroxy-10-methylundecan-4-olide, and 4-hydroxy-11-oxo-10-methyldodecan-4-olide. A structural comparison indicated that the three butanolides and the signaling molecules, termed S. rochei butenolides (SRBs), could share common C12 or C13 fatty acids for their biosynthesis intermediates, however, these three butanolides did not induce antibiotic production even at 50 µM concentration (1000-folds of the minimum antibiotic-inducing concentration of SRBs) in S. rochei.

Rapid growth of a mature mediastinal teratoma in a middle-aged woman: A case report.

A mediastinal mass was incidentally detected in a 42-year-old Japanese woman during a routine medical checkup. Computed tomography revealed a 7-cm, well-circumscribed multilocular cystic mass consistent with a mature cystic teratoma; however, no solid or cystic lesion had been detected at a voluntary complete medical checkup 1.5 years earlier. An anterior mediastinal tumor resection was performed, and the histopathological findings were compatible those of a mature teratoma. Although the mechanisms that underlie rapid growth of all tridermic components in a mature teratoma remain unclear, it is presumed that the mechanisms involve hemorrhage, rupture, inflammation caused by pancreatic enzymes, and estrogen hormone activity. We presented a rare case of a rapid formation of a mediastinal teratoma, which revealed that a mediastinal teratoma with all tridermic components could develop in a relatively short period.

Retrograde transvenous lymphatic embolization for postoperative chylous ascites: A report of three cases and literature review.

Percutaneous transabdominal lymphangiography and embolization have been reported as useful approaches for intractable chylothorax or chylous ascites. However, they are often difficult to perform after extensive lymph node dissection because disruption of the antegrade lymphatic flow makes leaks identification difficult. When the leakage point cannot be identified or percutaneous transabdominal lymphangiography and embolization fail, a retrograde transvenous approach to the thoracic duct can be used instead. We report 3 cases of refractory chylous ascites after retroperitoneal operation or extensive lymph node dissection that was addressed by retrograde transvenous lymphatic embolization. In one case, a combination of retrograde transvenous lymphatic embolization, transcatheter sclerotherapy, and transcatheter embolization was used. These findings suggest that retrograde transvenous lymphatic embolization appears to be feasible and efficient for postoperative chylous ascites.

Desmoplastic ameloblastoma of the jaw: CT and MR imaging findings.

OBJECTIVES: Desmoplastic ameloblastoma (DA) is one of the rare pathological variants of ameloblastoma. The purpose of this study is to investigate CT and MR imaging findings of DA. METHODS: We retrospectively evaluated six DA cases that were gathered from four different hospitals and confirmed histopathologically with resected specimens. Two radiologists who specialized in head and neck imaging retrospectively interpreted and reviewed pretreatment CT and MR imaging findings. RESULTS: On CT, all DAs presented with well-defined border and low internal attenuation. Regarding locularity, five cases showed honeycomb-like lesions and one showed a unilocular lesion. Bone expansions were seen in all patients and located on the labial side in four cases. On MR imaging, all DAs showed well-defined borders and solid moderately low signal intensities with small cystic high signal intensities on T2-weighted images and intermediate signal intensity on T1-weighted images. Five DAs showed linear low signal intensity on T1- and T2-weighted images. Gd-DTPA-enhanced MR imaging was performed in three cases, and all cases showed moderate enhancement. Dynamic-enhanced MR imaging was performed in two of them, and persistent enhancement was detected. CONCLUSION: Our findings strongly suggest that MR imaging should also be consulted, particularly for honeycomb-like lesions with well-defined margins, bone expansion and anterior location on radiographs or CT. Additionally, findings by MR imaging such as solid low-signal-intensity, hyperintense cystic foci and persistent enhancement pattern will suggest the diagnosis of DA.

Cylindrical Inversion Pulse for the Reduction of Cardiac Motion Artifacts in Contrast-enhanced Breast MRI.

We proposed a simple technique for reduction of cardiac-related motion artifacts on contrast-enhanced images in the breast by using cylindrical regional-suppression technique (CREST) that can directly suppress the heart signals. The purpose of this study was to select the optimal scan parameters and to evaluate the feasibility in the breast. We demonstrated that the optimized CREST could dramatically reduce the cardiac-related flow artifacts without any penalty to the acquisition time, signal-to-noise ratio and contrast-enhanced lesion-to-parenchyma contrast.

Hyperecho PROPELLER-MRI: Application to rapid high-resolution motion-insensitive T2 -weighted black-blood imaging of the carotid arterial vessel wall and plaque.

PURPOSE: To demonstrate the usefulness of hyperecho and PROPELLER (HEP) for carotid arterial vessel wall imaging by using a quantitative comparison with conventional methods. PROPELLER is a motion-insensitive turbo spin-echo (TSE) sequence and has recently been utilized in magnetic resonance (MR) plaque imaging instead of double inversion recovery TSE (DIR-TSE). Wider blade-width, higher k-space density, and an improved blood suppression effect result in better image quality. In this study we introduce a new combination of HEP. MATERIALS AND METHODS: A total of 17 subjects were examined on a 3.0T system. We conducted quantitative comparisons for signal-to-noise ratio (SNR), contrast-to-noise-ratio, and image sharpness among HEP, DIR-TSE, and conventional PROPELLER (c-PROPELLER). Subsequently, images obtained with DIR-TSE, c-PROPELLER, and HEP were visually evaluated using a three-point scale by two board-certified radiologists. RESULTS: HEP showed high SNR similar to c-PROPELLER, good T2 contrast approximating DIR-TSE, and better blood suppression compared with the other two methods (P < 0.05). The image sharpness of HEP (2.55 ± 0.53) was higher than that of DIR-TSE (1.89 ± 0.33) and the absence of ghost or streak artifacts in HEP (2.89 ± 0.33) was better than that in both other methods (2.22 ± 0.83 for DIR-TSE and 2.00 ± 0.50 for c-PROPELLER) (P < 0.05). Furthermore, the degree of blood suppression, particularly in cases of slow or turbulent flow close to the atherosclerotic plaque, was identical for HEP (2.80 ± 0.45) and DIR-TSE (2.80 ± 0.45) but was significantly better than for c-PROPELLER (1.60 ± 0.55) (P < 0.05). CONCLUSION: This study demonstrates the usefulness of HEP in the carotid arteries. HEP can provide higher-resolution T2 -weighted black-blood imaging without flow- and/or motion-related artifacts, compared to conventional techniques. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:515-524.

Volume isotropic simultaneous interleaved black- and bright-blood imaging: a novel sequence for contrast-enhanced screening of brain metastasis.

We introduced and optimized a novel sequence of fast (about 4 min), volumetric, high resolution, simultaneous bright- and black-blood imaging with sufficient T1 contrast between enhanced metastasis and surrounding brain parenchyma for their differentiation. This proposed sequence can be used for 3-dimensional volumetric T1-weighted bright- and black-blood imaging in contrast-enhanced studies and may be promising for detecting small brain metastases by improving differentiation between blood vessels and small brain metastases.

Improvement of T1 contrast in whole-brain black-blood imaging using motion-sensitized driven-equilibrium prepared 3D turbo spin echo (3D MSDE-TSE).

We demonstrated a new scheme for performing the T1-enhanced whole-brain black-blood imaging pulse sequence using motion-sensitized driven-equilibrium prepared 3-dimensional (3D) turbo spin echo (MSDE-TSE) with anti-driven-equilibrium post pulse. The use of an anti-driven-equilibrium pulse considerably improved the T1 contrast of MSDE-TSE black-blood images. This sequence can be used for whole-brain 3D volumetric T1-weighted black-blood imaging and may improve the accuracy of anatomical localization for certain brain lesions.

Simple method for whole-brain volumetric T(1)-weighted turbo spin-echo imaging.

We propose a simple scheme of 3D turbo spin echo (TSE) with low-refocusing flip angles (RFAs) for obtaining sufficient T1-weighted contrast. The low RFA can easily lead spins into a pseudo-steady-state (PSS) condition, but a preparation scheme is required for smooth transition into static PSS. For obtaining T1 contrast, PSS preparation is the most important factor, and therefore we focused on the PSS preparation. To optimize the T1 contrast in the proposed sequence, we compared the following parameters: RFAs of 90° and 30°, and a PSS preparation scheme of "90° + α/2" and asymptotic preparation. Subsequently, to demonstrate the quality of the proposed sequence, we compared the image quality regarding conventional 3D TSE and 2D spin echo (SE). A combination of an RFA of 30° and the "90° + α/2" preparation scheme showed the highest T1 contrast. The optimized sequence provided higher contrast and sharper images compared to 3D TSE, and it showed contrast and a signal-to-noise ratio similar to those of 2D SE.

Whole-brain black-blood imaging with magnetization-transfer prepared spin echo-like contrast: a novel sequence for contrast-enhanced brain metastasis screening at 3T.

In contrast-enhanced (CE) brain metastasis screening, coexistence of enhanced blood vessel suppression and higher tumor-to-parenchyma contrast may improve radiologists' performances in detecting brain metastases compared with conventional sequences. In this study, we propose a new scheme, allowing both suppression of blood signals and improvement of tumor-to-parenchyma contrast, using motion-sensitized driven equilibrium prepared 3D low-refocusing flip-angle turbo spin echo (TSE) ("magnetization transfer prepared spin echo"-like contrast volume examination: MATLVE) for brain metastasis screening at 3.0 T, and we compare MATLVE to conventional three-dimensional (3D)-gradient recalled echo (GRE) and 3D-TSE sequences. With the use of MATLVE, the signal intensity of CE blood decreased substantially. Furthermore, the contrast ratio of tumor-to-white matter was significantly higher than in either conventional 3D-GRE or 3D-TSE. MATLVE can be used for 3D volumetric post-CE black-blood imaging, and it may be effective in detecting small brain metastases by selectively enhancing tumor signals while suppressing blood signals.

Vessel-selective, non-contrast enhanced, time-resolved MR angiography with vessel-selective arterial spin labeling technique (CINEMA-SELECT) in intracranial arteries.

We demonstrate the feasibility of the vessel-selective, non-contrast, time-resolved magnetic resonance angiography (MRA) technique, "contrast inherent inflow enhanced multi-phase angiography combining vessel-selective arterial spin labeling technique (CINEMA-SELECT)". This sequence consists of two major techniques: pulsed star labeling of arterial regions (PULSAR) and Look-Locker sampling. We hypothesize that this technique allows selective labeling of single intracranial arteries, consisting of high-resolution four-dimensional data with a wide coverage of the brain. In this study, a new vessel-selective, time-resolved angiographic technique is demonstrated that can produce individual angiograms non-invasively by labeling the principal arterial vessels proximal to the circle of Willis. Clear vessel delineation is achieved, and the separation of the three vessels is evident in healthy volunteers. This technique could play an important role in the assessment of the structure and hemodynamics of intracranial arteries without the use of contrast agents.

Head and neck contrast-enhanced CT for identification of internal carotid artery stenosis progression on the affected side after treatment for oral squamous cell carcinoma.

OBJECTIVES: To determine the incidence of progressive internal carotid artery (ICA) stenosis by head and neck contrast-enhanced computed tomography (CT) in 82 patients who underwent surgery, chemotherapy, or combination therapy for oral squamous cell carcinoma (OSCC). METHODS: The study included 82 patients who underwent head and neck contrast-enhanced CT after surgery alone or combined surgery and chemotherapy for OSCC at the Department of Oral and Maxillofacial Surgery of Ichikawa General Hospital, Tokyo Dental College, or Tokyo Dental College Oral Cancer Center between December 2002 and March 2010. RESULTS: Comparison with previously obtained head and neck contrast-enhanced CT images revealed progressive arterial stenosis of the ICA in five patients with a mean age of 62.0 years. All five patients were male, and their OSCC sites were the tongue in two, the floor of the mouth in two, and the mandibular gingiva in one. Tumor resection and neck dissection were performed for four patients and tumor resection alone for one patient. Four patients underwent chemotherapy. ICA stenosis occurred on the same side as the tumor in all five patients. CONCLUSIONS: The results of this study suggest that, given the possibility of post-treatment vascular events, attention must be paid to subsequent changes in the ICA over time. The results also indicate the usefulness of head and neck contrast-enhanced CT in identifying such problems.

What can be identified by three-phase bone scintigraphy in patients with chronic osteomyelitis of the mandible?

OBJECTIVE: Three-phase bone scintigraphy has been used for the diagnosis of osteomyelitis in some regions of the body. However, its utility in patients with chronic osteomyelitis of the mandible (COM) has been reported only occasionally and the significance has not been fully examined. The aim of this study was to investigate what can be identified from each phase of the three-phase bone scintigraphy in patients with COM. METHODS: Three-phase bone scintigraphy using (99m)Tc-labeled phosphonates was performed [96 s (phase 1), 5 min (phase 2) and 3 h (phase 3)] in 15 patients with COM. An increase in accumulation was regarded as a positive result in visual analysis. We investigated the positive ratio of each phase, including in the classification of the disease type, serum white blood cell count, C-reactive protein value and morbidity period. We also calculated the uptake ratio relative to the contralateral side using mean and maximum counts of the region of interest in semiquantitative analysis and investigated the correlation between the uptake ratios of each phase. RESULTS: The positive ratio of phases 2 and 3 was 100% and higher than that of phase 1 (33.3%, p = 0.0001). Almost all patients with a positive result in phase 1 had the osteolytic type (5/6). The extent of increased uptake on phase 3 images was similar to that of phase 2 images. The uptake ratio of phase 2 correlated with that of phase 3 (mean: r = 0.88, p < 0.0001, max: r = 0.78, p = 0.0006), but was not as high as that of phase 3. CONCLUSIONS: The phase 1 results reflect hyperemia and have a strong potential to diagnose the disease type. Phase 3 alone is sufficient to diagnose the disease and the extent of lesion in patients with highly suspected COM.

Extensive mutational analysis of modular-iterative mixed polyketide biosynthesis of lankacidin in Streptomyces rochei.

Extensive mutations of lankacidin synthase genes were carried out to analyze the modular-iterative mixed polyketide biosynthesis of lankacidin. Three ketoreductase domains (lkcC-KR, lkcF-KR1, and lkcF-KR2) were inactivated by in-frame deletion and site-directed mutagenesis of their active sites. The mutants ceased or diminished lankacidin production, indicating that the three KR domains are functional in lankacidin biosynthesis. However, all of the KR mutants failed to accumulate the expected unreduced metabolites. Mutational analysis of two tandemly aligned acyl carrier protein domains (lkcC-ACP1 and lkcC-ACP2) revealed that either ACP is sufficient for lankacidin production. Disruption and complementation experiments on three unique genes/domain (lkcD for acyltransferase, lkcB for dehydratase, and lkcC-MT for a C-methyltransferase domain) suggested that their gene products function iteratively during lankacidin biosynthesis.

Analysis of modular-iterative mixed biosynthesis of lankacidin by heterologous expression and gene fusion.

Lankacidin is a unique 17-membered macrocyclic antibiotic different from usual even-membered macrolides. Based on the gene organization of the lankacidin biosynthetic cluster coded on the linear plasmid pSLA2-L in Streptomyces rochei, we previously proposed a hypothesis of modular-iterative mixed polyketide biosynthesis for lankacidin. Two experimental evidences in this paper further strengthened this hypothesis. Heterologous expression of the lankacidin cluster (lkcA-lkcO) in Streptomyces lividans resulted in lankacidinol A production, indicating that the gene cluster is sufficient for the synthesis of the lankacidin skeleton. In addition, a gene fusant of lkcF and lkcG produced lankacidin at a similar level to the parent strain, suggesting that an iterative function of the LkcF protein is unlikely. These results are consistent with the hypothesis that LkcC is used four times and LkcA, LkcF and LkcG are used modularly to accomplish eight condensation reactions leading to the lankacidin skeleton.

Analysis of the loading and hydroxylation steps in lankamycin biosynthesis in Streptomyces rochei.

The biosynthetic gene cluster of lankamycin (LM), a 14-member macrolide antibiotic, is encoded on the 210-kb linear plasmid pSLA2-L in Streptomyces rochei 7434AN4. LM contains a 3-hydroxy-2-butyl group at the C-13 position, which is different from an ethyl group in erythromycin. The following two possibilities could be considered for the origin of this starter moiety of LM biosynthesis: (i) an extra module exists in the biosynthetic gene cluster and loads an additional acetate molecule, or (ii) 3-hydroxy-2-butyrate or its equivalent is loaded and incorporated as a starter. The former possibility was eliminated by the complete sequencing of pSLA2-L, which showed no extra module. On the other hand, the latter was confirmed by incorporation of deuterium in [3-(2)H]dl-isoleucine into the C-14 position of LM. The timing of hydroxylation reactions at the C-15 and C-8 positions of LM was studied by constructing disruptants of two P450 hydroxylase genes, lkmF (orf26) and lkmK (orf37). The lkmF disruptant produced 8-deoxylankamycin, while the lkmK disruptant produced both 15-deoxylankamycin and 8,15-dideoxylankamycin. These results clearly showed that LkmF is a C-8 hydroxylase and LkmK is a C-15 hydroxylase in LM biosynthesis and in addition suggested the order of hydroxylation steps; namely, hydroxylation may occur at first at C-15 by LkmK and then at C-8 by LkmF.