Investigation of clinical utility of contrast-enhanced MRI in the diagnosis of ectopic pregnancy.

AIM: To investigate whether contrast-enhanced (CE)-magnetic resonance imaging (MRI) improves identification of implantation site of ectopic pregnancy. MATERIALS AND METHODS: This retrospective study enrolled 63 patients in whom implantation sites had been confirmed at histopathology. Two expert radiologists for gynaecological imaging and two inexpert radiologists independently reviewed non-CE MRI and a combination of non-CE and CE-MRI (non-CE+CE-MRI), then determined implantation site with a confidence level. The following MRI features were also evaluated: extrauterine gestational sac (GS)-like structure (shape, signal intensities at T1-weighted imaging [WI], T2WI, and diffusion-weighted imaging [DWI], presence of the three rings appearance, and distinct low intensity areas at T2WI, presence of tree or dot-like components, degree of contrast enhancement), fallopian tube (dilatation, dilatation with haematoma, degree of contrast enhancement, enhanced components within the tube), and ascites. These findings were compared for non-CE and non-CE+CE-MRI data, and for expert and inexpert groups. RESULTS: The expert group identified implantation sites correctly in 58/63 (92%) cases for non-CE and non-CE+CE-MRI. In the inexpert group, the correct identification was improved from 54/63 (86%) using non-CE MRI to 58/63 (92%) using non-CE+CE-MRI, but was not significant (p=0.29). In comparison between non-CE and non-CE+CE-MRI, dilation of the fallopian tubes was observed more frequently (p=0.004) and the confidence level was elevated significantly in the non-CE+CE-MRI (p<0.0001) in the inexpert group. Intergroup comparison revealed that confidence level was significantly higher in the expert group than in the inexpert group using non-CE MRI (p<0.0001), although the difference was not significant at non-CE+CE MRI (p=0.49). CONCLUSION: CE-MRI did not significantly improve correct identification of ectopic pregnancy implantation sites, although the addition of contrast enhancement did enable inexpert radiologists to diagnose confidently.

Influence of radiologic expertise in detecting lung tumors on chest radiographs.

PURPOSE: To analyze the influence of radiologic expertise in detecting lung tumors on chest radiographs. MATERIALS AND METHODS: We retrieved posteroanterior chest radiographs and CT examination obtained from 283 patients with solitary primary malignant lung tumors who underwent surgical resection. There were 176 men and 107 women with a mean age of 67.0±9.1 (SD) years (range: 33-88 years). Thirteen first-year post-graduate (PGY-1) trainees and nine pulmonary specialists (three radiologists, three thoracic surgeons, and three pulmonologists) interpreted the chest radiographs. Detection rates among trainees and specialists were compared using Student t test. RESULTS: The total numbers of detected tumors ranged from 103 (36.4%) to 136 (48.1%) with a mean of 127.9±9.1 (45.2±3.2%) in the trainee group, and 137 (48.4%) to 182 (64.3%) with a mean of 161.6±13.1 (57.1±4.6%) in the specialist group; the intergroup difference was statistically significant (P<0.001). Significant intergroup detectability differences of >10% were noted for tumors in the peripheral zone with (i) ground glass opacity (GGO) ratio ≥10% and <70% and any size, or (ii) GGO ratio <10% and size ≤2cm; and for tumors hidden by the mediastinum, heart, or diaphragm with (i) GGO ratio ≥10% and <30% and size >3cm, or (ii) GGO ratio <10% and size >2cm. CONCLUSION: Our study demonstrates significant differences in lung tumor detectability on chest radiographs between PGY-1 trainees and pulmonary specialists according to tumor size, extent of GGO, and tumor location.

Fe-oxide concretions formed by interacting carbonate and acidic waters on Earth and Mars.

Spherical Fe-oxide concretions on Earth, especially in Utah, USA, have been investigated as an analog of hematite spherules found in Meridiani Planum on Mars to support interpretations of water-rock interactions in early Mars. Although several formation mechanisms have been proposed for the Fe-oxide concretions on Earth, it is still unclear whether these mechanisms are viable because a precise formation process and precursor of the concretions are missing. This paper presents evidence that Fe-oxide concretions in Utah and newly found Fe-oxide concretions in Mongolia had spherical calcite concretions as precursors. Different formation stages of calcite and Fe-oxide concretions observed, both in Utah and Mongolia, indicate that calcite concretions initially formed within eolian sandstone strata and were dissolved by infiltrating Fe-rich acidic waters to form spherical FeO(OH) crusts due to pH buffering. The similarity between these Fe-oxide concretions on Earth and the hematite spherule occurrences in Meridiani Planum, combined with evidence of acid sulfate water influences on Mars, suggest that the hematite spherules also formed from dissolution of preexisting carbonate spherules possibly formed under a dense carbon dioxide early martian atmosphere.

Arthroscopic decompression with indigo carmine for treating paralabral cysts in the shoulder.

Paralabral cysts in the shoulder are a relatively rare pathology. It is sometimes difficult to detect the location of a paralabral cyst in the shoulder using arthroscopy, and it can be difficult to confirm sufficient decompression by arthroscopy. We describe the case of a 64-year-old woman who underwent arthroscopic decompression for a paralabral cyst in the shoulder. Indigo carmine was injected into the cyst under ultrasonography guidance just before the operation. The leakage point of indigo carmine was detected using arthroscopy. Arthroscopic decompression was performed until the indigo carmine was completely discharged. Her shoulder pain, limited range of motion, and muscle weakness during abduction and external rotation improved postoperatively. Magnetic resonance imaging confirmed the disappearance of the cyst. Arthroscopic decompression using an ultrasonography-guided injection of indigo carmine is a useful treatment for a paralabral cyst in the shoulder.

STAT3 integrates cooperative Ras and TGF-ß signals that induce Snail expression.

The epithelial-mesenchymal transition (EMT) is a crucial morphological event that occurs during the progression of epithelial tumors. EMT can be induced by transforming growth factor ß (TGF-ß) in certain kinds of cancer cells through the induction of Snail, a key regulator of EMT. We have previously found that TGF-ß remarkably induces Snail expression in cooperation with Ras signals; however, the underlying mechanism of this synergism has not yet been determined. Here, we demonstrate that signal transducer and activator of transcription 3 (STAT3) acts as a mediator that synergizes TGF-ß and Ras signals. The overexpression of STAT3 enhanced Snail induction, whereas siRNA-mediated knockdown of STAT3 inhibited it. The STAT3-YF mutant, which has Tyr 705 substituted with Phe, did not enhance Snail induction. Several STAT3 mutants lacking transcriptional activity also failed to enhance it; however, the putative STAT3-binding elements in the Snail promoter regions were not required for STAT3-mediated Snail induction. Protein inhibitor of activated STAT3 (PIAS3) inhibited the enhanced Snail promoter activity induced by TGF-ß and Ras. The interaction between PIAS3 and STAT3 was reduced by TGF-ß in cells harboring oncogenic Ras, whereas TGF-ß promoted the binding of PIAS3 to Smad3, a crucial mediator of TGF-ß signaling. Therefore, these findings suggest that STAT3 enhances Snail induction when it is dissociated from PIAS3 by TGF-ß in cooperation with Ras signals.

Lung Transplantation for Lymphangioleiomyomatosis in a Single Japanese Institute, With a Focus on Late-onset Complications.

BACKGROUND: Although late-onset complications are important factors related to inadequate outcomes of lung transplantation (LTx), little is known about them. The results of LTx for lymphangioleiomyomatosis (LAM) patients, which is a large cohort of LTx recipients in Japan, especially with late-onset complications, are reported. METHODS: Thirteen consecutive LTx cases with LAM at our institute were evaluated, and those with late-onset complications were identified. RESULTS: The 5-year survival rate was 69.2%. There were 4 cases with late-onset complications. Case 1: A 35-year-old woman who underwent right single LTx and sustained uncontrollable massive chylous ascites. She underwent placement of a peritoneal-venous shunt, and the ascites was controlled. Unfortunately, she died of small cell cervical cancer (SCCC) 43 months after the LTx. Case 2: A 50-year-old woman who underwent left single LTx had pneumothorax of the native lung 16 months after the LTx. She underwent operative repair of the right lung with a polyglycolic acid (PGA) sheet. She had no recurrence of pneumothorax 1 year after the operation. Case 3: A 33-year-old woman, who underwent left single LTx, had recurrence of LAM in the transplanted lung 2 years after the LTx. She was started on sirolimus. Case 4: A 47-year-old woman, who underwent right single LTx, developed repeated high fevers. She developed an acute abdomen, and swollen subcutaneous lymph nodes were found. After lymph node biopsy, she was diagnosed as having post-transplant lymphoproliferative disorder, and she died 8 months after the LTx. CONCLUSION: It is hoped that these reports and the knowledge gained from them help improve the outcomes of LTx recipients.

Carnosol Is a Potent Lung Protective Agent: Experimental Study on Mice.

INTRODUCTION: Oxidative stress has been implicated in various disease states and ischemia/reperfusion injury is a direct consequence of oxidative stress in lung transplantation. Because the success rate of organ transplantation in which ischemia/reperfusion is inevitable is highly influenced by oxidative stress, development of strategies to control oxidative stress would be beneficial. Here we identified natural compounds to reduce oxidative stresses in isolated mouse lungs. METHODS: We screened compounds associated with antioxidative stress in 200 plant extracts by monitoring the activities of nuclear factor erythroid 2-related factor 2 (NRF2). Compounds found to ameliorate antioxidative stress were enriched and mice were administered the extract orally every day for 1 week. Then, the lungs were isolated and cultured in the culture medium at 37 °C. Lung damage was monitored by lactate dehydrogenase (LDH) released in the culture medium. Arterial (left ventricle) blood gas levels were also monitored after hilar clamping. RESULTS: We found that Callicarpa longissima extract was rich in NRF2 activators. The responsible compounds were carnosic acid and its oxidative product, carnosol. Carnosol induced heme-oxygenase 1 (HO-1) expression, which is downstream of NRF2, more efficiently than carnosic acid. CONCLUSIONS: Lungs from mice treated with C longissima extract were less damaged than those from control mice and accompanied by HO-1 induction. These results suggest that carnosol is a candidate compound to increase the success rate of lung transplantation.

How does pain induce negative emotion? Role of the bed nucleus of the stria terminalis in pain-induced place aversion.

Pain consists of sensory-discriminative and negative-affective components. Neuronal mechanisms for the sensory component of pain have been investigated extensively. On the other hand, neuronal mechanisms for the affective component of pain remain to be investigated. Recent behavioral studies have revealed the brain regions and neuronal mechanisms involved in the affective component of pain. Glutamatergic transmission within the anterior cingulate cortex and basolateral amygdaloid nucleus plays a critical role in pain-induced aversion. Noradrenaline and corticotropin-releasing factor (CRF) within the ventral and dorsolateral parts of the bed nucleus of the stria terminalis (BNST), respectively, play important roles in paininduced aversion. Electrophysiological studies have revealed that both noradrenaline and CRF activate type II BNST neurons, which may inhibit the BNST output neurons. A recent histochemical study showed that most VTA-projecting BNST output neurons are GABAergic neurons, which preferentially make synaptic contact with VTA GABAergic neurons. Therefore, activation of VTA-projecting BNST output neurons should increase the neuronal excitability of VTA dopaminergic (DAergic) neurons through increased inhibitory input to VTA GABAergic neurons, which negatively regulate VTA DAergic neurons. Pain-induced release of noradrenaline and CRF within the BNST may activate type II BNST neurons, which could suppress VTA-projecting BNST output neurons, thereby attenuating the excitatory influence to the VTA DAergic neurons. Recent optogenetic studies suggest that the suppression of VTA DAergic neurons is sufficient to induce place aversion. Pain-induced place aversion may be due to the suppression of VTA DAergic neurons via the processing of nociceptive information within the BNST.

Reduction en masse of inguinal hernia: MDCT findings of two cases.

Reduction en masse of inguinal hernia is an extremely rare complication arising from manual reduction of a hernia. The hernial content remaining in the hernia sac returns above the inguinal canal but remains in the abdominal wall. Accurate preoperative diagnosis of reduction en masse of inguinal hernia is challenging because the hernia appears to be reduced upon physical examination. We experienced two cases of reduction en masse. In both cases, multidetector row computed tomography revealed a closed loop obstruction near the inguinal fossa. In addition, we observed a continuous tract of the hernia sac to the inguinal canal and prominent peritoneal thickening suggestive of the hernia sac.

Results of surveillance bronchoscopy after cadaveric lung transplantation: a Japanese single-institution study.

BACKGROUND: The prevention and early detection of post-transplantation rejection and infection are key clinical points to achieve long-term survival after lung transplantation. Although surveillance bronchoscopy (SB) is performed in many transplantation centers, it is still controversial because of its undefined clinical significance and its possible complications. We evaluated the clinical utility of SB after cadaveric lung transplantation in Japan, where bilateral transplantation is officially limited to patients medically requiring bilateral grafts. PATIENTS AND METHODS: Twenty-eight patients who underwent cadaveric lung transplantation followed by SB were retrospectively analyzed with reference to the results of bronchoscopy. SB is routinely performed at 1, 2, 3, 6, and 12 months after lung transplantation and annually thereafter. Clinically indicated bronchoscopy (CIB) is considered in patients with suspected rejection or airway infection, and for follow-up examination after treatment for acute rejection. RESULTS: There were 206 bronchoscopies, including 189 SBs and 17 CIBs, performed in 28 patients who underwent cadaveric lung transplantation between 2000 and 2013 at Osaka University Hospital. Among SBs, 92 (49%) showed positive results of transbronchial lung biopsy (TBLB) or bronchoalveolar lavage (BAL), and intervention was applied following 34 SBs (18%). Among CIBs, 8 (47%) showed positive results of TBLB or BAL, with intervention performed in 3 patients (18%). A2-3 and B2R findings according to the revised International Society for Heart and Lung Transplantation (ISHLT) rejection score and airway infection/colonization were frequently observed within a year following lung transplantation. Cytomegalovirus infection was found in 7 SBs (6%) by TBLB only within 2 months after transplantation. Regarding complications, moderate bleeding occurred in 21 (11%), pneumothorax in 2 (1%), prolonged hypoxemia in 1 (0.5%), and pneumonia in 1 (0.5%) among the 189 SBs. CONCLUSION: SB frequently detects rejection and airway infection or colonization with minimum complications, especially within 12 months after cadaveric lung transplantation.

Japanese strategies to maximize heart and lung availabilities: experience from 100 consecutive brain-dead donors.

OBJECTIVE: Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies have been established to maximize heart and lung transplantations (HTs and LTs, respectively). We reviewed 100 consecutive brain-dead donors to evaluate our strategies to identify and manage heart and lung donors. METHODS: We retrospectively reviewed all 100 consecutive brain-dead donors procured since the law was issued in 1997. There were 56 mens and the overall mean donor age was 43.5 years. The causes of death were cerebrovascular disease (n = 62), head trauma (n = 20), and asphyxia (n = 16): Since November 2002, special transplant management doctors were sent to donor hospitals to assess cardiac and lung functions, seeking to identify transplant opportunities. They stabilized donor hemodynamics and lung function by administering antidiuretic hormone intravenously and performing bronchofibroscopy for pulmonary toilet. RESULTS: Seventy-nine HTs, 1 heart-lung transplantations, and 78 LTs (46 single and 32 bilateral) were performed. By applying these strategies organs per donor were increased from 4.5 to 6.8. Among heart donors, 61/80 were marginal: high inotrope requirement (n = 29), cardiopulmonary resuscitation (n = 28), and/or >55 years old (n = 20). None of the 80 HT recipients died of primary graft failure (PGF). Patient survival rate at 10 years after HT was 95.4%. Among lung donors, 48/65 were marginal: pneumonia (n = 41), chest trauma (n = 4), and >55 years old (n = 9). Only 2/78 LT recipients died of PGF. Patient survival rate at 3 years after LT was 72.2%. After inducing frequent pulmonary toilet, lung procurement and patient survival rates increased significantly after LT. CONCLUSIONS: Although the number of cases was still small, the availability of organs has been greater and the outcomes of HT/LT acceptable.

Donor evaluation and management system (medical consultant system) in Japan: experience from 200 consecutive brain-dead organ donation.

PURPOSE: As the donor shortage is extremely severe in Japan because of a strict Organ Transplantation Act, special strategies must be established to maximize organ transplant opportunities. The purpose of this study was to evaluate our strategies to identify and manage 200 consecutive brain-dead organ donors. METHODS AND MATERIALS: We retrospectively reviewed the 200 donors procured since the Organ Transplantation Act was issued in 1997, including 118 males, a mean overall age of 45.1 years and cause of death being cerebrovascular disease (n = 119), head trauma (n = 37), and asphyxia (n = 44). DONOR EVALUATION AND MANAGEMENT SYSTEM: Since November in 2002, special transplant management doctors ("medical consultants") were sent to donor hospitals to assess organ function and identify transplantable organs. They also provided intensive care to stabilize hemodynamics and improve cardiac and lung functions by administering antidiuretic hormone intravenously and providing bronchofiberscopic pulmonary toilet. RESULTS: We obtained 146 heart, 1 heart-lung, and 154 lung (87 single and 67 bilateral), 175 liver (28 splitted liver), 142 pancreas (114 pancreas-kidney), 253 kidney and 12 small bowel grafts. Organs procured from 1 donor increased from 4.5 to 6.8 after applying these strategies. CONCLUSIONS: Although the number of cases was still small, the availability of organs and outcomes of transplantation have been acceptable.

Small Indian mongooses and masked palm civets serve as new reservoirs of Bartonella henselae and potential sources of infection for humans.

The prevalence and genetic properties of Bartonella species were investigated in small Indian mongooses and masked palm civets in Japan. Bartonella henselae, the causative agent of cat-scratch disease (CSD) was isolated from 15.9% (10/63) of the mongooses and 2.0% (1/50) of the masked palm civets, respectively. The bacteraemic level ranged from 3.0 × 10(1) to 8.9 × 10(3) CFU/mL in mongooses and was 7.0 × 10(3) CFU/mL in the masked palm civet. Multispacer typing (MST) analysis based on nine intergenic spacers resulted in the detection of five MST genotypes (MSTs 8, 14, 37, 58 and 59) for the isolates, which grouped in lineage 1 with MST genotypes of isolates from all CSD patients and most of the cats in Japan. It was also found that MST14 from the mongoose strains was the predominant genotype of cat and human strains. This is the first report on the isolation of B. henselae from small Indian mongooses and masked palm civets. The data obtained in the present study suggest that these animals serve as new reservoirs for B. henselae, and may play a role as potential sources of human infection.

Peritoneovenous shunt for chylous ascites after lung transplantation for lymphangioleiomyomatosis.

A 37-year-old woman with lymphangioleiomyomatosis (LAM) who underwent right single-lung transplantation from a cadaveric donor developed persistent chylous ascites. Despite use of diuretics and sirolimus to reduce ascites-associated symptoms and to prevent gastroesophageal reflex triggered by increased abdominal pressure, the ascites were refractory, and periodic paracenteses were required. With placement of a peritoneovenous shunt (Denver shunt), the patient's abdominal circumference decreased, and her symptoms abated. Thus, placement of a peritoneovenous shunt can be an effective management strategy for refractory chylous ascites in patients with LAM, even after lung transplantation.

Immunology mini-review: the basics of T(H)17 and interleukin-6 in transplantation.

The outcomes of organ transplantation are determined by graft rejection, the mechanisms of which are some of the most important areas of study in the transplantation field. The main cause of rejection is the immunologic response of the recipient toward the transplanted organ. The immunologic responses are regulated by T-cell subsets, especially helper T-cells, which have been characterized as T(H)1 or T(H)2 cells according to their profiles of cytokines production. A unique subset of recently identified lymphocytes, the regulatory T cells (T(reg)s), seem to play a role in tolerance. The recently identified T(H)17 cells are a subset of effector-helper lymphocytes that specifically secrete interleukin (IL) 17. Interestingly, T(H)17 and T(reg) both develop from naïve T cells on stimulation by transforming growth factor ß. The difference is only the existence of IL-6, a proinflammatory cytokine. T(H)17 clears pathogens that are not adequately handled by T(H)1 and T(H)2 elements, as well as contributing to autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory diseases. Autoimmune diseases are caused by reactions to self-antigens. T(H)17 (or IL-17) and IL-6 are also thought to be involved in rejection after organ transplantation. We examined the contributions of T(H)17 and IL-6 in bronchiolitis obliterans (BO), the histologic finding in chronic rejection of lung transplantations. Earlier studies have reported that T(H)17 and IL-6 contribute not only to chronic rejection of lung transplantations, but also to the rejection of other solid organs, e.g., heart, liver, and kidney. In addition, prospective avenues of research on T(H)17 and IL-6 in transplantation have emerged from the perspectives of recent studies.

Less maintenance immunosuppression in lung transplantation following hematopoietic stem cell transplantation from the same living donor.

Living-donor lobar lung transplantation (LDLLT) is one of the final options for saving patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). We retrospectively investigated 19 patients who had undergone LDLLT after HSCT in Japan. Eight patients underwent LDLLT after HSCT in which one of the donors was the same living donor as in HSCT (SD group), while 11 received LDLLT from relatives who were not the HSCT donors (non-SD group). In the SD group, three patients underwent single LDLLT. The 5-year survival rate was 100% and 58% in the SD and non-SD groups, respectively. In the SD group, postoperative immunosuppression was significantly lower than in the non-SD group. Two patients died of infection and one died of post-transplant lymphoproliferative disease (PTLD) in the non-SD group, while only one patient died of PTLD 7 years after LDLLT in the SD group. Hematologic malignancy relapsed in two patients in the non-SD group. For the three single LDLLTs in the SD group, immunosuppression was carefully tapered. In our study, LDLLT involving the same donor as for HSCT appeared to have advantages related to lower immunosuppression compared to LDLLT from relatives who were not the HSCT donors.

Low incidence of cardiovascular events in Japanese patients with Type 2 diabetes in primary care settings: a prospective cohort study (JDDM 20).

AIMS: To investigate whether a reduced incidence of cardiovascular disease in Type 2 diabetes can be achieved in a newly recruited cohort following the recently advanced concept of multifactorial treatment and followed in primary care settings as compared with earlier cohorts. METHODS: A prospective study was performed in primary care settings at multiple clinics nationwide in the Japan Diabetes Clinical Data Management (JDDM) study group. Subjects were 2984 patients with Type 2 diabetes without prevalent cardiovascular disease. The main outcome measure was the first event of non-fatal or fatal coronary heart disease, ischaemic stroke or peripheral artery disease, and the incidence was compared with other representative cohorts. RESULTS: There were 90 cardiovascular events over 10,827 person-years of follow-up with a dropout rate of 6%. The incidences (per 1000 person-years, 95% confidence interval) of composite, coronary heart disease, ischaemic stroke and peripheral artery disease in the JDDM study were 8.3 (6.6-10.0), 4.4 (3.2-5.6), 3.1 (2.1-4.2), and 0.7 (0.2-1.2), respectively. Each incidence was lowest in the JDDM study compared with other cohorts (P < 0.01 vs. each cohort). In the JDDM study, significant variables predictive of the occurrence of a cardiovascular event were age, duration of diabetes, HbA(1c), HDL cholesterol and urinary albumin. CONCLUSION: The novel finding of low cardiovascular disease occurrence in this study may be conferred by the feasibility at primary care settings for providing patients with Type 2 diabetes with favourable control of blood glucose, blood pressure and lipids, coupled with unique ethnicity/country factors.

Redox and metal-regulated oligomeric state for human porphobilinogen synthase activation.

The oligomeric state of human porphobilinogen synthase (PBGS) [EC.4.2.1.24] is homooctamer, which consists of conformationally heterogenous subunits in the tertiary structure under air-saturated conditions. When PBGS is activated by reducing agent with zinc ion, a reservoir zinc ion coordinated by Cys(223) is transferred in the active center to be coordinated by Cys(122), Cys(124), and Cys(132) (Sawada et al. in J Biol Inorg Chem 10:199-207, 2005). The latter zinc ion serves as an electrophilic catalysis. In this study, we investigated a conformational change associated with the PBGS activation by reducing agent and zinc ion using analytical ultracentrifugation, negative staining electron microscopy, native PAGE, and enzyme activity staining. The results are in good agreement with our notion that the main component of PBGS is octamer with a few percent of hexamer and that the octamer changes spatial subunit arrangement upon reduction and further addition of zinc ion, accompanying decrease in f/f (0). It is concluded that redox-regulated PBGS activation via cleavage of disulfide bonds among Cys(122), Cys(124), and Cys(132) and coordination with zinc ion is closely linked to change in the oligomeric state.