Inchworm sign of endometrial cancer on diffusion-weighted MRI: radiology-pathology correlation.

AIM: To perform radiology-pathology correlation of the inchworm sign on diffusion-weighted imaging (DWI) in patients with endometrial cancer. MATERIALS AND METHODS: Consecutive patients (345) with histopathologically proven endometrial cancer who underwent preoperative magnetic resonance imaging (MRI), including DWI images, and hysterectomy were included in the present study. The inchworm sign was defined as a hypointense stalk between hyperintense endometrial cancer and hypointense myometrium on DWI images. A genitourinary pathologist reviewed the resected specimen at the site of the inchworm sign. RESULTS: The inchworm sign on DWI images was observed in 32 (9.3%) patients. On T2-weighted images, areas of hypointense stalk on DWI images showed hypointensity in 31 (97%) patients and hyperintensity in one (3%). Among them, the depth of myometrial invasion at histopathology was superficial (<50% myometrial invasion) in 28 (87.5%) patients and deep (≥50% myometrial invasion) in four (12.5%). As a result of histopathological investigation, the hypointense stalk of the inchworm sign was mainly composed of various degrees of stromal proliferation, including smooth muscle cells and metaplastic fibromuscular stroma, with or without intervening endometrial cancer. CONCLUSION: The inchworm sign of endometrial cancer on DWI images usually indicated superficial myometrial invasion and was caused by a stalk composed of stromal proliferation with or without intervening endometrial cancer.

Extending coherence time of macro-scale diamond magnetometer by dynamical decoupling with coplanar waveguide resonator.

Ultimate sensitivity for quantum magnetometry using nitrogen-vacancy (NV) centers in a diamond is limited by a number of NV centers and coherence time. Microwave irradiation with a high and homogeneous power density for a large detection volume is necessary to achieve a highly sensitive magnetometer. Here, we demonstrate a microwave resonator to enhance the power density of the microwave field and an optical system with a detection volume of 1.4 × 10-3 mm3. The strong microwave field enables us to achieve 48 ns Rabi oscillation which is sufficiently faster than the phase relaxation time of NV centers. This system combined with a decoupling pulse sequence, XY16, extends the spin coherence time (T 2) up to 27 times longer than that with a spin echo method. Consequently, we obtained an AC magnetic field sensitivity of 10.8 pt/ Hz using the dynamical decoupling pulse sequence.

Dysregulation of BMI1 and microRNA-16 collaborate to enhance an anti-apoptotic potential in the side population of refractory mantle cell lymphoma.

The proto-oncogene BMI1 and its product, Bmi1, is overexpressed in various types of tumors, particularly in aggressive tumors and tumors resistant to conventional chemotherapy. BMI1/Bmi1 is also crucially involved in cancer-initiating cell maintenance, and is recurrently upregulated in mantle cell lymphoma (MCL), especially aggressive variants. Recently, side population (SP) cells were shown to exhibit tumor-initiating characteristics in various types of tumors. In this study, we show that recurrent MCL cases significantly exhibit upregulation of BMI1/Bmi1. We further demonstrate that clonogenic MCL SP shows such tumor-initiating characteristics as high tumorigenicity and self-renewal capability, and that BMI1 was upregulated in the SP from recurrent MCL cases and MCL cell lines. On screening for upstream regulators of BMI1, we found that expression of microRNA-16 (miR-16) was downregulated in MCL SP cells by regulating Bmi1 in the SPs, leading to reductions in tumor size following lymphoma xenografts. Moreover, to investigate downstream targets of BMI1 in MCL, we performed cross-linking/chromatin immunoprecipitation assay against MCL cell lines and demonstrated that Bmi1 directly regulated pro-apoptotic genes such as BCL2L11/Bim and PMAIP1/Noxa, leading to enhance anti-apoptotic potential of MCL. Finally, we found that a proteasome inhibitor bortezomib, which has been recently used for relapsed MCL, effectively induced apoptosis among MCL cells while reducing expression of Bmi1 and increasing miR-16 in MCL SP. These results suggest that upregulation of BMI1 and downregulation of miR-16 in MCL SP has a key role in the disease's progression by reducing MCL cell apoptosis. Our results provide important new insight into the pathogenesis of MCL and strongly suggest that targeting BMI1/Bmi1 might be an effective approach to treating MCL, particularly refractory and recurrent cases.

Gene cloning and characterization of the protein encoded by the Neospora caninum bradyzoite-specific antigen gene BAG1.

Neospora caninum is an Apicomplexan parasite that causes repeated abortion and stillbirth in cattle. The aim of this study was to clone the gene encoding the N. caninum orthologue (NcBAG1) of the Toxoplasma gondii bradyzoite-specific protein TgBAG1 and characterize its expression pattern in the parasite. Isolation of the full-length 684-bp gene revealed that it shared 78.3% sequence similarity with TgBAG1. NcBAG1 encodes a predicted protein of 227 amino acids with 80.3% similarity to TgBAG1. A putative signal peptide sequence and an invariant GVL motif characteristic of small heat-shock proteins were identified in the predicted N. caninum amino acid sequence. We expressed the NcBAG1 gene as a recombinant glutathione S-transferase fusion protein (rNcBAG1) in Escherichia coli and used the purified 60 kDa protein to obtain a monoclonal antibody (Mab). rNcBAG1 reacted to Mabs specific for NcBAG1 and TgBAG1. No reaction between the NcBAG1 Mab and N. caninum tachyzoites was observed. Although the predicted molecular mass of NcBAG1 is 25 kDa, Western blot analysis of parasite lysates using the NcBAG1 Mab revealed a cross-reactive protein of approximately 30 kDa. Additionally, immunofluorescence assays using the tachyzoite-specific Mab for NcSAG1 and the bradyzoite-specific Mab for TgBAG1 or NcSAG4 revealed NcBAG1-specific expression in bradyzoites in cultures exposed to sodium nitroprusside, a reagent that increases the frequency of bradyzoites. Interestingly, the NcBAG1 protein was identified in the cytoplasm of the bradyzoite-stage parasites. This preliminary analysis of the NcBAG1 gene will assist investigations into the role of this protein in N. caninum .

Epidermotropic CD8+ cytotoxic T-cell lymphoma exhibiting a transition from the indolent to the aggressive phase, accompanied by emergence of CD7+ cells and formation of neutrophilic pustules.

A 47-year-old-man presented with rashes on his trunk and limbs, and a diagnosis of parapsoriasis was made. Ten years later, the rashes had progressed gradually to form plaques and tumours. Gene rearrangement studies revealed monoclonality of the T-cell receptor ß-chain (TCR-Jß)1 gene, and results of flow cytometry and immunohistochemical examination confirmed a diagnosis of epidermotropic CD8+ cytotoxic T-cell lymphoma. The clinical course of the disease remained indolent for some time, but about 2 years later, neutrophilic pustules formed on the surface of the skin lesions, and tumours developed in the patient's testes. Using flow cytometry, emergence of CD7+ cells was found. The patient died the following year of respiratory failure due to brain herniation. On postmortem examination, CD8+ tumour cells were found in the brain. This case demonstrates an unusually protracted indolent phase in a patient with cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma; its transition into the aggressive phase was accompanied by emergence of CD7+ cells and formation of neutrophilic pustules.

Involvement of brown adipose tissue in subcutaneous fat necrosis of the newborn.

BACKGROUND: Subcutaneous fat necrosis (SCFN) of the newborn is a rare condition that manifests within days after birth. The interscapular region, axillae and shoulders are the most commonly affected sites, corresponding to anatomic sites of brown adipose tissue (BAT) in newborns. OBJECTIVE: We postulated a specific involvement of BAT in SCFN and searched for brown adipocytes at affected sites. METHODS: Biopsy specimens were immunostained with antibodies against uncoupling protein 1 (UCP-1) and examined by electron microscopy. We also examined BAT by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and computed tomography (PET-CT) scanning. RESULTS: A few cells in biopsy specimens from two patients bound antibodies against UCP-1, and brown adipocytes were detected at several stages of degeneration. PET-CT scans revealed lower uptake of (18)F-FDG at major sites of SCFN. CONCLUSION: SCFN and BAT can be found at the same sites, suggesting a pathophysiological connection.

Obesity induced changes to plasma adiponectin concentration and cholesterol lipoprotein composition profile in cats.

Feline obesity generally results in aberrations to plasma metabolite levels, such as lipid concentrations and lipoprotein composition. This study sought to investigate the resultant effect of obesity on cholesterol lipoprotein composition and circulating adiponectin concentrations in cats. Plasma glucose, lipids (triglyceride, cholesterol and free fatty acid), insulin and adiponectin concentrations, and cholesterol lipoprotein composition were measured and compared between body condition score (BCS) determined normal healthy control and obese cats. Although the obese group demonstrated higher levels of plasma cholesterol, glucose, and triglycerides, as compared to healthy controls, the difference was insignificant thus indicating that the BCS determined obese cats may have been overweight and not morbidly obese. Plasma insulin levels were significantly higher (25-30%) versus healthy control animals thereby possibly hinting at the ensuing emergence of obesity induced insulin resistance. However, the BCS determined obese cat demonstrated a significant reduction (p<0.05) in plasma adiponectin concentration and a significant increase (p<0.05) in LDL-cholesterol % as compared to age matched healthy control animals. This would indicate that changes in plasma adiponectin concentration and cholesterol lipoprotein composition may be good early indicators of obesity in cats.

Exacerbation of acetazolamide-responsive sodium channel myotonia by uterotonic agents.

The symptoms of myotonia can worsen during pregnancy and tocolysis with ritodrine has been associated with rhabdomyolysis. We describe a patient with myotonia who developed hypertonus immediately following the administration of uterotonic agents. A 24-year-old, G2P1 at 31 weeks of gestation with a history of acetazolamide-responsive myotonia presented with premature rupture of membranes. During cesarean delivery she experienced significant hypertonus of the upper limbs, shoulders, fingers, and mouth immediately after intravenous administration of oxytocin 5 IU and methylergometrine maleate 0.2mg. The mechanism underlying increased muscle tone in response to these drugs remains unclear. Anesthesiologists should be especially attentive to the administration of uterotonic drugs during the management of pregnant myotonia patients.

Cerebral oxygenation in the beach chair position before and during general anesthesia.

AIM: Ischemic brain damage related to the beach chair position is a matter of concern. The current study was designed to evaluate whether the beach chair position before and during general anesthesia differentially induces changes in cerebral oxygenation as determined by near-infrared spectroscopy (NIRS) in surgical patients. METHODS: We evaluated brain tissue oxygen index (TOI) values using the NIRS monitor NIRO-200TM in the beach chair position the day before and during general anesthesia. Thirty patients with normal preoperative TOI values undergoing shoulder surgery were enrolled. The initial TOI measurement in the supine position after 10 min rest or 10 min after tracheal intubation was followed by measurements after 5 min each in the 30-degree and subsequently 60-degree head-up tilt positions. During general anesthesia, patients were mechanically ventilated to obtain normocapnia under inhalation of 1.5% sevoflurane in 50% oxygen. Mean blood pressure (MAP) was measured non-invasively in the arm at heart level and was maintained above 60 mmHg with phenylephrine. RESULTS: Preoperative TOI values and preoperative MAP were within the normal range in the study population. MAP decreased upon anesthesia but did not further change when the patient was placed in the 30- and 60-degree head-up tilt positions. Heart rate also decreased upon anesthesia. However, TOI values did not change with induction of general anesthesia or placement of the patients in the beach chair position. CONCLUSION: Under general anesthesia, the beach chair position does not alter cerebral oxygenation in patients showing normal preoperative cerebral TOI values.

Hypertriglyceridemia with increased plasma insulin concentrations in cats.

Metabolite, insulin and adiponectin concentrations and LDH, AST and ALT activities were measured in plasma of 142 client-owned cats (1-13years old, 16 breeds) to set up a new criterion of hypertriglyceridemia (hyper-TG) with increased plasma insulin concentrations for early diagnosis of lipid metabolism abnormality including obesity. 25 cats with over 165mg/dl of plasma triglyceride (TG) concentrations were decided as hyper-TG with increased plasma insulin concentrations, and prevalence of hyper-TG was 16.7% in young (1-6years old) and 18.3% in old (>7years old) cats examined. In the hyper-TG cats, their plasma TG concentrations increased to 6.6-7.4-fold of the values of control cats with 35-50mg/dl of plasma TG and their plasma cholesterol, FFA and insulin concentrations and LDH and ALT activities increased significantly, whereas their plasma adiponectin concentrations decreased significantly compared to those in the control cats. Hyper-TG cats with significantly increased body weights and plasma insulin and decreased plasma adiponectin seemed to be in early stage of obesity accompanying increased plasma insulin concentrations. Increased TG, insulin, LDH and ALT and decreased adiponectin values in plasma seemed to be key factors for diagnosis of lipid metabolism abnormality at early stage in cats.

Leiomyoma and rhabdomyoma of the vagina . Vaginal myoma.

Vaginal fibromyomas (leiomyomas and rhabdomyomas) are rare; approximately 300 cases have been reported in the literature. They usually present as a mass per vaginum or dyspareunia or pressure symptoms on the urinary tract. However, they sometimes have an unusual presentation that is largely responsible for the relative difficulty in preoperative diagnosis. Preoperative imaging and careful examination may help to rule out malignancy. Recurrence occurs infrequently but the practical approach entails immediate careful excision. Surgical excision through the vaginal route has been the traditional approach, but abdominoperineal route may be necessary for huge tumours.

Monosomy and trisomy of 15q24-qter with cleft lip and palate.

Chromosome 15 aberrations clinically present as facial dysmorphisms such as a prominent nose, low-set ears, micrognathia and a short neck; a cleft lip and palate have not been reported. This is the first reported case of de-novo terminal deletion at 15q24 with a cleft lip and palate and low-set ears. The baby boy had a complete cleft lip and palate on the left side and incomplete cleft lip and palate on the right. A chromosomal study revealed partial monosomy and trisomy of the long arm of chromosome 15, with a karyotype of 46,XY,add(15)(24q) de novo. Surgery for lip plasty was performed at 6 months old and for palate plasty at 1 year and 9 months. Both operations were uneventful, although preoperative and postoperative examinations showed high creatinine phosphokinase values. At 3 years old, mild mental retardation was observed, but his physical development was normal.

Mechanism of the ropivacaine-induced increase in intracellular Ca2+ concentration in rat aortic smooth muscle.

BACKGROUND: Ropivacaine is a long-acting local anesthetic with low cardiac toxicity that induces vasoconstriction in vitro and in vivo. Vascular smooth muscle tone is regulated by changes in both intracellular Ca(2+) concentration ([Ca(2+)](i)) and myofilament Ca(2+) sensitivity. Therefore, the aim of this study was to examine the mechanism underlying the increase in [Ca(2+)](i) in ropivacaine-induced vascular contraction. METHODS: Ropivacaine-induced contractile responses and changes in [Ca(2+)](i) were examined using an isometric force transducer and a fluorometer, respectively. RESULTS: Ropivacaine induced a biphasic, concentration-dependent change in [Ca(2+)](i) and contractile response in rat aortic smooth muscles: an increase in [Ca(2+)](i) occurred at lower ropivacaine concentrations (3 x 10(-5) to 3 x 10(-4) M) and a decrease was observed at higher concentrations (10(-3) to 3 x 10(-3) M). Contraction and the [Ca(2+)](i) increase induced by ropivacaine were attenuated significantly by a voltage-dependent Ca(2+) channel antagonist, an inositol 1,4,5-triphosphate receptor antagonist and Ca(2+)-free solution (P < 0.01, n = 6). CONCLUSION: Ropivacaine-induced contraction of rat aortic smooth muscle is, in part, regulated by Ca(2+) influx from the extracellular space and Ca(2+) release from the sarcoplasmic reticulum.