Overexpression of the myc target gene Mina53 in advanced renal cell carcinoma

The myc target gene Mina53 was reported to be overexpressed in esophageal cancer with a poor prognosis. The purpose of the present study was to examined Mina53 expression and its relationship to clinicopathological parameters in human renal cell carcinoma (RCC). Mina53 and Ki-67 expression was examined on immunohistochemistry for 64 surgically resected RCC and non-cancerous tissue. In addition, the relationship between Mina53 expression and clinicopathological prognostic factors of RCC such as age, stage, microvenous invasion (MVI), histological subtype, Ki-67 labeling index (LI), and prognosis, was examined. Mina53 was expressed in the nuclei of tumor cells and tubular nuclei of normal renal tissue. The expression level of Mina53 was significantly higher in patients with poor prognostic factors (stage IV, MVI-positive, and sarcomatoid RCC, and high Ki-67 LI). The prognosis of high Mina53-expressing tumors was significantly poorer than that of non-Mina53-high tumors (P < 0.0001). In conclusion, Mina53 is overexpressed in RCC tissue from patients with poor prognostic factors, suggesting that Mina53 overexpression is one of the factors for poor prognosis in RCC.     

PRINS Analysis of the Telomeric Sequence in Seven Lemurs

We examined the chromosomal localization of the telomeric sequence, (TTAGGG)_n, in seven species of the lemurs and one greater galago, as an outgroup, using the primed in-situ labeling (PRINS) technique. As expected, the telomeric sequence was identified at both ends of all chromosomes of the eight prosimians. However, six species showed a signal at some pericentromeric regions involving constitutive heterochromatin as well. The pericentromeric region of chromosome 1 of Verreaux's sifaka (Propithecus verreauxi verreauxi) was labeled with a large and intense signal. The range of the signal considerably exceeded the area of DAPI positive heterochromatin. On the other hand, in the five lemurs, a large signal was detected also in the short arm of acrocentric chromosomes. Acquisition of the large block of the telomeric sequence into the acrocentric short arm might be interpretable in terms of the tandem growth of the heterochromatic short arm and the reciprocal translocation between heterochromatic short arms involving the telomeric sequence. Subsequently, it was postulated that meta- or submetacentric chromosomes possessing the telomeric sequence at the pericentromeric region could be formed by centric fusion between such acrocentric chromosomes.     

Utility of bedside artificial pancreas for postoperative glycemic control in cardiac surgery

Journal of Artificial Organs - Perioperative hyperglycemia, hypoglycemia, and high glycemic variability are independent risk factors for mortality in critically ill patients. After cardiac surgery,...     

Effect of Diesel Exhaust Particles on House Dust Mite–Induced Airway Eosinophilic Inflammation and Remodeling in Mice

Recent research has focused on the effects of ambient particulate pollution and much evidence has indicated that particulate pollution is associated with the onset of asthma and allergy; however, the effect of diesel exhaust particles (DEP) on the development of allergen-induced airway remodeling has not been fully investigated in vivo. In the present study, we examined the effects of DEP on Dermatophagoides farinae allergens (Der f)–induced asthma-like phenotypes in mice. Mice were administered i.t. 8 times with Der f. DEP were injected i.t. with Der f 4 times throughout the experiment or twice at the sensitization period. In both cases, DEP aggravated Der f–induced increases in airway responsiveness to acetylcholine, the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF), serum Der f–specific IgG1 levels, Th2 cytokines and transforming growth factor-β 1 levels in BALF, and amount of hydroxyproline in the right lungs. Furthermore, goblet cell hyperplasia and subepithelial fibrosis were also markedly aggravated. These findings indicate that DEP can potentiate airway remodeling induced by repeated allergen challenge as well as Th2-drived airway hyperresponsiveness, eosinophilic inflammation, and IgG1 production and that DEP can exhibit adjuvant activity for airway remodeling, probably due to the enhancement of allergen sensitization and/or of Th2 polarizing pathways.     

Lung carcinoma: diffusion-weighted mr imaging--preliminary evaluation with apparent diffusion coefficient

PURPOSE: To prospectively evaluate diffusion-weighted (DW) magnetic resonance (MR) imaging with a split acquisition of fast spin-echo signals for diffusion imaging (SPLICE) sequence for tissue characterization of lung carcinomas by using apparent diffusion coefficients (ADCs). Materials and METHODS: An institutional review board approved this study; informed consent was obtained from patients. Thirty patients (nine women, 21 men; mean age, 68.0 years) with lung carcinoma underwent DW MR imaging with the SPLICE sequence. ADC of each lung carcinoma was calculated from DW MR images obtained with low and high b values. ADCs of lung carcinomas were statistically compared among histologic types. Nine surgically excised lung carcinomas were evaluated for correlation between ADCs and tumor cellularities. Analysis of variance was used to determine changes in ADCs and histologic lung carcinoma types. Spearman rank correlation was calculated between ADCs and tumor cellularities. RESULTS: ADCs for lung carcinomas were 1.63 x 10(-3) mm(2)/sec +/- 0.5 (mean +/- standard deviation) for squamous cell carcinoma, 2.12 x 10(-3) mm(2)/sec +/- 0.6 for adenocarcinoma, 1.30 x 10(-3) mm(2)/sec +/- 0.4 for large-cell carcinoma, and 2.09 x 10(-3) mm(2)/sec +/- 0.3 for small-cell carcinoma. ADC of adenocarcinoma was significantly higher than that of squamous cell carcinoma and large-cell carcinoma (P < .05). ADCs were 1.59 x 10(-3) mm(2)/sec +/- 0.5 and 1.70 x 10(-3) mm(2)/sec +/- 0.4 for moderately and poorly differentiated squamous cell carcinoma, respectively. ADCs were 2.52 x 10(-3) mm(2)/sec +/- 0.4 and 1.44 x 10(-3) mm(2)/sec +/- 0.3 for well- and poorly differentiated adenocarcinoma, respectively. ADC of well-differentiated adenocarcinoma was significantly higher than that of moderately and poorly differentiated squamous cell carcinoma and poorly differentiated adenocarcinoma (P < .05). With the Spearman rank test, ADCs of lung carcinomas correlated well with tumor cellularities (Spearman coefficient, -0.75; P < .02). CONCLUSION: ADCs of lung carcinomas overlap, but ADCs of well-differentiated adenocarcinoma appear to be higher than those of other histologic lung carcinoma types.     

New methods of control against postoperative methicillin-resistantStaphylococcus aureus infection

The incidence of postoperative infections caused by methicillin-resistantStaphylococcus aureus (MRSA) in Japan has been increasing dramatically. In March 1990, we assigned special doctors in infection control (infection control doctor, ICD), and defined comprehensive controls against MRSA infection. A total of 3 536 cases of digestive tract surgery performed at our department were studied during the period between September 1987 and August 1997. We changed the use of antibiotics to prevent postoperative infection. Cefazolin (CEZ) was employed for surgery of the upper digestive tract, including esophagus, stomach, duodenum, and gallbladder. Cefotiam (CTM) was employed for surgery of the lower digestive tract, liver, and pancreas. In esophageal resection, the tracheal tube was extracted during the early postoperative period, and for cervical esophagogastroanastomosis, the autosuture was changed to layer-to-layer anastomosis. We have achieved successful control of postoperative MRSA infection, the incidence having decreased to 0.3% (9/2703). In conclusion, our methods of control against postoperative MRSA infection implies that comprehensive measures of prevention, including the reviewed specification and usage of antibiotics and operation management, have been well implemented. This value is the lowest and the first of any domestic hospital or institute in Japan, suggesting a continued and significant decrease.     

Inter- and/or Intra-organ distribution of mitochondrial C3303T or A3243G mutation in mitochondrial cytopathy

Fatal infantile mitochondrial cytopathy associated with a C3303T mutation in the mitochondrial tRNA(Leu(UuR)) gene has been reported clinically, biochemically and genetically. Here we have analyzed the percentage of this mutation in various autopsied tissues, and also in single muscle fibers using a micromanupulator, to evaluate the correlation between the pathology and heteroplasmic condition using polymerase chain reaction/restriction fragment length polymorphism. A 5-month-old Japanese girl was admitted to our hospital showing generalized muscle weakness, hepatomegaly, and cardiomegaly with lactic acidosis, and died at 6 months of age. Skeletal muscle showed severe degenerating myopathy found to be full of ragged-red fibers (RRFs), an increased number of lipid droplets, and severe cytochrome c oxidase (COX) deficiency. Microscopically hepatocytes showed massive accumulation in lipid droplets, and the heart muscle showed a network pattern suggesting metabolic cardiomyopathy. The activities of respiratory chain enzyme complex I and complex IV in the skeletal muscle were significantly decreased to 23.4% and 5.0%, respectively, of the control value. The percentage of C3303T mutation in the patient tissues were variable, and ranged from 25% in the pancreas to 99% in the spinal cord. By single fiber analysis, the percentages of C3303T mutation in RRFs with COX negative (group 1; 42.4+/-7.0) and with COX positive (group 2; 58.2+/-5.8) were significantly higher than in non RRFs with normal COX staining (group 3; 10.7+/-6.3) (both P>0.001). Our patient showed a fatal infantile form of encephalopathy, myopathy and cardiomyopathy associated with widely distributed C3303T mutation in all of somatic cells.     

Fractional anisotropy values detect pyramidal tract involvement in multiple system atrophy

OBJECTIVE: Pathological studies have shown remarkable pyramidal tract involvement in multiple system atrophy (MSA), while clinical pyramidal signs are relatively rare. We investigated the fractional anisotropy (FA) values to assess the degree of pyramidal tract involvement in MSA, in comparison with amyotrophic lateral sclerosis (ALS) and controls. Furthermore, we compared FA values between MSA patients with or without clinical pyramidal signs and controls, and between MSA patients with or without positive conventional MRI findings and controls. METHODS: We evaluated FA values in the internal capsule, corona radiate and whole pyramidal tract using visualized tractography of 65 subjects (20 probable MSA patients, 28 age-matched ALS patients, and 17 age-matched healthy controls) using a 3.0T magnetic resonance system. RESULTS: The FA values in the internal capsule, corona radiate, and whole pyramidal tract were significantly lower in MSA patients than in controls and were at a level similar to those of ALS patients. In addition, low FA values were prominent in MSA patients, even in those with short duration of illness, lacking precentral gyrus hyperintensity in FLAIR images, and without pyramidal signs. CONCLUSION: FA values could identify pyramidal tract degeneration even in patients with early phase MSA and those without clinical pyramidal signs or abnormal MRI findings. More extensive degeneration of the pyramidal tract occurs in MSA than so far believed.     

Estrogen induces neurite outgrowth via Rho family GTPases in neuroblastoma cells

Estrogen (E2) has direct in vivo and in vitro effects, such as inducing neurite outgrowth, on neurons. We investigated the morphological changes and intracellular signaling pathway induced by E2 in neuroblastoma (SH-SY5Y) cells. The effect of medroxyprogesterone acetate (MPA) or progesterone (P4) on the E2-induced neurite outgrowth was also examined using SH-SY5Y cells. Neurite outgrowth was induced by E2 in association with the phosphorylation of Akt, and these effects of E2 were abolished by MPA but not by P4. Progesterone receptor antagonist RU486 blocked the inhibitory effects of MPA. Estrogen receptor antagonist ICI 182,780 and phosphatidylinositol 3-kinase inhibitor LY294002 inhibited the E2-induced neurite outgrowth. Because the Rho family of small GTPases has been shown to be involved in the regulation of neurite outgrowth, we examined the cross-talk among Rac1, Cdc42 and RhoA in the E2-induced neurite outgrowth. E2 immediately increased the Rac1 and Cdc42 activity and decreased the RhoA activity. E2-induced neurite outgrowth was attenuated in cells expressing dominant-negative mutants for Rac1 or Cdc42. These results suggest that regulation of Rho family GTPase activity by E2 is important for the neurite outgrowth in neuroblastoma cells, and that MPA may have an antagonistic effect against E2.