Shear Stiffness of 4 Common Intracranial Tumors Measured Using MR Elastography: Comparison with Intraoperative Consistency Grading.

BACKGROUND AND PURPOSE: The stiffness of intracranial tumors affects the outcome of tumor removal. We evaluated the stiffness of 4 common intracranial tumors by using MR elastography and tested whether MR elastography had the potential to discriminate firm tumors preoperatively. MATERIALS AND METHODS: Thirty-four patients with meningiomas, pituitary adenomas, vestibular schwannomas, and gliomas scheduled for resection were recruited for MR elastography. On the elastogram, the mean and the maximum shear stiffnesses were measured by placing an ROI on the tumor. Blinded to the MR elastography findings, surgeons conducted qualitative intraoperative assessment of tumor consistency by using a 5-point scale. Histopathologic diagnosis was confirmed by using the resected specimens. The mean and maximum shear stiffnesses were compared with histopathologic subtypes, and the intraoperative tumor consistency was graded by the surgeons. RESULTS: The mean and maximum shear stiffnesses were the following: 1.9 ± 0.8 kPa and 3.4 ± 1.5 kPa for meningiomas, 1.2 ± 0.3 kPa and 1.8 ± 0.5 kPa for pituitary adenomas, 2.0 ± 0.4 kPa and 2.7 ± 0.8 kPa for vestibular schwannomas, and 1.5 ± 0.2 kPa and 2.7 ± 0.8 kPa for gliomas. The mean and maximum shear stiffnesses for meningiomas were higher than those of pituitary adenomas (P < .05). The mean and maximum shear stiffnesses were significantly correlated with the surgeon's qualitative assessment of tumor consistency (P < .05). The maximum shear stiffness for 5 firm tumors was higher than that of nonfirm tumors (P < .05). CONCLUSIONS: MR elastography could evaluate intracranial tumors on the basis of their physical property of shear stiffness. MR elastography may be useful in discriminating firm tumors preoperatively.

Capturing drug responses by quantitative promoter activity profiling.

Quantitative analysis of cellular responses to drugs is of major interest in pharmaceutical research. Microarray technologies have been widely used for monitoring genome-wide expression changes. However, this approach has several limitations in terms of coverage of targeted RNAs, sensitivity, and quantitativeness, which are crucial for accurate monitoring of cellular responses. In this article, we report an application of genome-wide and quantitative profiling of cellular responses to drugs. We monitored promoter activities in MCF-7 cells by Cap Analysis of Gene Expression using a single-molecule sequencer. We identified a distinct set of promoters affected even by subtle inhibition of the Ras-ERK and phosphatidylinositol-3-kinase-Akt signal-transduction pathways. Furthermore, we succeeded in explaining the majority of promoter responses to inhibition of the upstream epidermal growth factor receptor kinase quantitatively based on the promoter profiles upon inhibition of the two individual downstream signaling pathways. Our results demonstrate unexplored utility of highly quantitative promoter activity profiling in drug research.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e77; doi:10.1038/psp.2013.53; published online 25 September 2013.

Persistence of ferroelectricity in BaTiO3 through the insulator-metal transition.

The ferroelectric BaTiO(3) is a band-gap insulator. Itinerant electrons can be introduced in this material by doping, for example, with oxygen vacancies. Above a critical electron concentration of n(c) approximately 1 x 10(20) cm(-3), BaTiO(3-delta) becomes metallic. This immediately raises a question: Does metallic BaTiO(3-delta) still retain ferroelectricity? One may expect itinerant electrons to destroy ferroelectricity as they screen the long-range Coulomb interactions. We followed the phase transitions in BaTiO(3-delta) as a function of n far into metallic phase. Although their stability range decreases with n, the low-symmetry phases in metallic BaTiO(3-delta) are still retained up to an estimated concentration of n* approximately 1.9 x 10(21) cm(-3). Moreover, it appears that the itinerant electrons partially stabilize the ferroelectric phases in metallic BaTiO(3-delta) by screening strong crystal field perturbations caused by oxygen vacancies.

A graph-based clustering method for a large set of sequences using a graph partitioning algorithm.

A graph-based clustering method is proposed to cluster protein sequences into families, which automatically improves clusters of the conventional single linkage clustering method. Our approach formulates sequence clustering problem as a kind of graph partitioning problem in a weighted linkage graph, which vertices correspond to sequences, edges correspond to higher similarities than given threshold and are weighted by their similarities. The effectiveness of our method is shown in comparison with InterPro families in all mouse proteins in SWISS-PROT. The result clusters match to InterPro families much better than the single linkage clustering method. 77% of proteins in InterPro families are classified into appropriate clusters.

Protein-losing enteropathy due to thrombophlebitis of the mesenteric vein: report of a case.

We report herein the case of a 70-year-old woman with enteropathy accompanied by protein loss, the cause of which was found to be thrombophlebitis of the mesenteric vein. The patient was admitted to our hospital for investigations to determine the cause of hypoproteinemia. She had suffered an episode of left abdominal pain with high fever and vomiting lasting 10 days, 8 months prior to her admission. She also had a 6-year history of uncontrolled diabetes. The alpha1-antitrypsin clearance was 85.7 ml/day, suggesting protein-losing enteropathy. A scintigraphy with 99m-technetium-human serum albumin disclosed protein leakage into the intestine. X-Rays and computed tomography showed a stenotic and thickened area of small intestine 50 cm in length. Thus, a laparotomy was performed to resect this part of the intestine which was found to have undergone past thrombophlebitic changes. Following the operation, the alpha1-antitrypsin clearance decreased to within the normal range and the patient gained 5 kg in weight.

[Macrophage colony-stimulating factor in patients with rheumatoid arthritis].

Macrophage colony-stimulating factor (M-CSF) is a cytokine involved in the development and proliferation of the monocyte/macrophage lineage cells. M-CSF has also been reported to participate in the induction of osteoclasts, and may be important in the destruction of bone and cartilage and the periarticular osteoporotic changes seen in patients with rheumatoid arthritis (RA). We developed a new ELISA technique to measure M-CSF levels in synovial fluid with high sensitivity and reproducibility. The mean M-CSF level in the synovial fluid of patients with RA was 1.38 +/- 0.56 ng/ml, and that of patients with osteoarthritis (OA) was 0.67 +/- 0.13 ng/ml. In contrast, serum levels of M-CSF in patients with RA and in normal controls were 1.32 +/- 0.50 ng/ml and 0.90 +/- 0.09 ng/ml, respectively. These differences were both statistically significant. Since serum M-CSF levels correlate with inflammatory signs obtained from examination of blood, they indicate the general condition of patients with RA. Synovial fluid M-CSF levels increase even in the early phase of RA and remain high despite drug therapy, which suggests that they reflect the condition of affected joints including joint spaces and inflamed synovia more directly than do the levels of serum M-CSF. Measurement of the M-CSF level in the synovial fluid may be useful in the diagnosis, clinical evaluation, and assessment of the effects of treatment in patients with RA.

[Surgical treatment for complete rupture of anterior papillary muscle after acute myocardial infarction].

A 64-year-old male patient with postinfarction complete anterior papillary muscle rupture and massive mitral regurgitation is presented. The diagnosis was suspected clinically and confirmed by transesophageal echocardiography. One week after the episode of acute myocardial infarction (AMI) the patient had a sudden onset of severe congestive heart failure with pulmonary edema and was transferred to our hospital. The patient underwent an emergency mitral valve replacement with a SJM29M prosthetic valve. Histological examination revealed an acute coagulation necrosis of the anterior papillary muscle without specific inflammatory change. To our knowledge this is the second case with successful surgery for a complete rupture of the anterior papillary muscle following AMI in Japan.

[Ogilvie's syndrome in pregnancy--a case report].

A 23-year-old female in the 28th week of pregnancy was admitted with an acute abdominal distension. The plain X-ray films showed a marked gaseous dilatation of the colon from the cecum to the splenic flexure. A tube colostomy was performed. Her postoperative course was uneventful and she improved progressively. Her pregnancy and delivery elapsed uneventfully there after. After the delivery she again complained of marked abdominal distension. The colonoscopic decompression in combination with the administration of Cisapride was successfully accomplished. Ogilvie's syndrome is characterized by an unobstructed colon which progresses to marked dilatation. When the colonic diameter becomes 12cm or more, surgical decompression should be recommended to avoid the hazard of spontaneous rupture. This is the first reported case of Ogilvie's syndrome in pregnancy in Japan.

Maturation, fertilization, and development of dog oocytes in vitro.

Preovulatory oocytes were collected from ovaries of beagle bitches that had received superovulatory treatment. They were cultured in a modified Krebs-Ringer bicarbonate solution containing 10% fetal calf serum and 30 mg/L gentamicin sulfate for up to 72 h. About 32% of oocytes reached metaphase II by 72 h of culture. When these in vitro-matured oocytes were inseminated with ejaculated beagle spermatozoa that had been preincubated for 4 h, sperm penetration of the zona pellucida started about 1 h after insemination, and both male and female pronuclei were seen in the ooplasm at 8 h after insemination. At 18-20 h after insemination, oocytes were transferred to Whitten's medium and cultured for 76-78 h. The first cleavage was observed at 48 h after insemination, and 15 of 45 oocytes developed to the 2-8-cell stage. These results demonstrate that in vitro-matured canine oocytes can be fertilized and develop to the 8-cell stage in vitro.

[Studies on the skin test of cefotiam and anti-cefotiam antibody].

Patients having previously not received cefotiam (CTM), a recently introduced cephem antibiotic, were subjected to skin tests with a 300 micrograms/ml solution of CTM in physiological saline before and after CTM therapy to detect sensitization with the drug. Anti-CTM antibody titration was carried out on sera from patients who showed a positive skin test and those who developed signs of hypersensitivity during CTM therapy. The results were as follows: Of 1,927 patients examined by skin test with CTM prior to initiation of CTM therapy, 31 patients (1.61%) showed positive reactions with formation of a wheal and erythema. There were 7 patients (0.36%) who proved negative in the skin test but developed mild symptoms of hypersensitivity in association with the skin test. The 847 patients negative on the CTM skin test were retested after a completion of CTM therapy, of whom 6 (0.71%) were found to have become positive showing formation of a wheal and erythema and 3 others (0.35%) showing a negative skin test developed mild adverse reactions associated with the skin test. Sixty-eight serum samples collected from the patients positive on the CTM skin test and those who developed manifestations of hypersensitivity following CTM therapy were examined for anti-CTM antibody by the Prausnitz-K ustner reaction, passive cutaneous anaphylaxis test and hemagglutination test. All proved negative in these tests. Of various background factors assessed, none was found to have causal relation to the skin reaction in any of the patients showing positive skin reactions to CTM.

Regression of rat mammary tumors by a potent luteinizing hormone-releasing hormone analogue (leuprolide) administered vaginally.

Potent luteinizing hormone-releasing hormone analogues are known to cause regression of hormone-dependent mammary tumors. We have observed that high and long-lasting serum levels of a potent luteinizing hormone-releasing hormone analogue [desglycyl10-(D-leucyl6) luteinizing hormone-releasing hormone ethylamide, leuprolide] resulted from vaginal administration which effectively caused down regulation in the pituitary by chronic treatment. Regression of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in Sprague-Dawley rats by consecutive daily vaginal administration of leuprolide was investigated. In untreated rats, 71% of tumors were growing at 8 weeks, whereas after i.p. injection of leuprolide (500 micrograms/kg) all tumors were regressing 2 weeks after commencement of treatment and 86.7% of tumors disappeared by 8 weeks. Vaginal administration of 100 micrograms/kg for 8 weeks produced regression in 80% of tumors and disappearance in 35%. The vaginal administration of a higher dose (500 to 5000 micrograms/kg) produced highly significant antitumor effects [regression in 82.2 +/- 4.0% (S.E.) and disappearance in 52.9 +/- 2.1%]. These results are consistent with the effects produced by ovariectomy. Whereas 13 and 7 new tumors appeared in untreated rats and those treated vaginally with leuprolide (100 micrograms/kg), respectively, only one or two tumors appeared in i.p. and vaginally (above 500 micrograms/kg) treated rats during treatment. Histological classification of the mammary tumors after treatment indicated therapeutic effects similar to those shown by tumor size determination. Thus, it was concluded that vaginal application of leuprolide at doses above 500 micrograms/kg might be a potentially useful method for antitumor therapy.

Preventive effect of a quinonyl derivative of N-acetylmuramyl dipeptide, QMDP-66, against adriamycin-induced ECG abnormalities in rats.

The effects on adriamycin cardiotoxicity of an immunoadjuvant, 2-[2-acetamido-2-deoxy-6-0-[10-(2,3-dimethoxy-5-methyl-1, 4-benzo-quinon-6-yl) decanoyl]-D-glucopyranos-3-0-yl]-D-propionyl-L-valyl D-isoglutamine methyl ester (QMDP-66), and a reference compound, ubiquinone-10, were studied in Wistar Kyoto (WKY) rats. Adriamycin, 1 mg/kg/day intra-peritoneally (i.p.) for 23 days, elicited cardiotoxicity, as judged by widening of the QRS complexes in ECGs. Electron microscopic examination of myocytes from the treated rats revealed many cytoplasmic vacuoles possibly originating from deranged endoplasmic reticula or mitochondria. In addition, the treatment significantly inhibited body weight gain, and decreased ventricular weight. QMDP-66 alone, 1 mg/kg/day i.p. for 23 days, had no effect on the parameters described above. When QMDP-66 (1 mg/kg/day, i.p.) or ubiquinone-10 (3 mg/kg/day, i.p.) was administered together with adriamycin, the widening of the QRS complexes was significantly depressed, and cytoplasmic vacuoles in myocytes were rarely observed. The QMDP-66 or ubiquinone-10 treatment, however, did not alleviate the decrease in body weight gain or ventricular weight due to adriamycin. Heart rate was not significantly changed by any of the treatments. These findings suggest that QMDP-66 is an effective antidote against adriamycin cardiotoxicity.

Delayed type hypersensitivity for penicillin in mice. I. Induction and characterization of delayed type hypersensitivity for penicillin in mice.

The delayed type hypersensitivity (DTH) for benzylpenicilloyl (BPO) group was observed in the footpad swelling reaction (FSR) in mice. Mice were subcutaneously immunized with 300 microgram of BPO-human serum albumin (HSA) conjugate and Freund's complete adjuvant and challenged into footpads with 25 microgram of BPO-bovine gamma globulin (BGG) conjugate 2 weeks after the immunization. The strongest FSR was observed 24 hours after the challenge. This FSR was typical DTH. Namely, the kinetics of FSR and the histological study showed the pattern of the DTH. Furthermore, the FSR could be transferred to normal syngenic mice by transfer of antigen-primed spleen cells and could not be transferred by anti-Thy-1,2-serum treated cells. The DTH for BPO was observed on day 4 after the immunization and reached the maximum on day 11 to 14. Thereafter, the DTH for BPO decreased gradually in proportion as the IgG antibodies for BPO were produced. C57BL/6 and C3H/He mice high responders, A/J mice moderate, and BALB/c and DBA/2 mice were low responders. Penicillins were broad cross-reactive in FSR and its desensitization test because the DTH for penicillins contained the common reactivity for the penicilloyl moiety. The DTH for BPO was suppressed by intravenous preadministration of HSA and this suppression was sensitive to cyclophosphamide.

Immunopathology of rhino mouse, an autosomal recessive mutant with murine lupus-like disease.

Detection of high incidence of antinuclear antibodies (ANA) was reported in young homozygous rhino mice employing formalinized chicken erythrocyte nuclei as substrate for indirect immunoflourescence (IF) assay. The titers of ANA heightened with increasing age, and attained to 1:1024 by the time mice reached 5 months of age. The occurrence of ANA was associated with development of splenic and hepatic fibrosis, glomerulonephritis and abnormalities of lymphoreticular tissue. The granular deposits of IgG and C3 detected by direct IF were initially found at the basement membrane of dermal-epidermal junction of rhino mice aged 2.5 months. These deposits distributed progressively in the fibrotic areas of spleen and liver, and renal glomerular tufts at 5 months of age. Dense deposits revealed by electron microscopy were found in the regions where IF of IgG and C3 was observed. Acid buffer eluates from liver and kidney contained IgG reactive with nuclear antigens. Importance of homozygous rhino gene was discussed in relation to development of autoimmune disorders of these mice.

Impaired antibody response against T-dependent antigens in rhino mice.

The antibody response in rhino mice, which carry a mutant gene hrrh, to thymus-dependent (TD) or thymus-independent (TI) antigens was compared with that of phenotypically normal littermates. The magnitude of antibody response to TD antigens in rhino mice decreased as they grew up, whereas the antibody response to TI antigens in rhino mice was indistinguishable from that of littermates. A transfer of thymus cells from littermates to rhino mice resulted in the partial restoration of the responsiveness to TD antigens. The experiments employing adoptive transfer of spleen cells from rhino mice to the irradiated normal mice suggested that the hyporesponsiveness of TD antigens of adult rhino mice was mainly due to the defect in the T helper cell activities rather than either the increase of the suppressor cells or defects in other cell types.

Ultrastructures of the normal surface of corneal epithelium of the heterozygous rhino mouse with special reference to so-called epithelial holes.

The surface structures of the corneal epithelium of the heterozygous rhino mouse were examined by transmission electron microscopy and scanning electron microscopy. The surface structures of the corneal epithelium were composed of microvilli, microplicae and epithelial holes. Microvilli and microplicae showed the same features as those described previously. However, some microvilli bent at the top of stalk and looked like microplicae by scanning electron microscopy. The structure of epithelial holes was different from that reported previously. Epithelial holes with elevated rim demonstrated by scanning electron microscopy were formed by a large fold or process of epithelial cells in the outermost layer. Microvilli were present on the process (margin) and floor of epithelial holes. Thus microvilli on the floor belong to the outermost layer, not to the second layer.