Genome-wide examination of myoblast cell cycle withdrawal during differentiation.

Skeletal and cardiac myocytes cease division within weeks of birth. Although skeletal muscle retains limited capacity for regeneration through recruitment of satellite cells, resident populations of adult myocardial stem cells have not been identified. Because cell cycle withdrawal accompanies myocyte differentiation, we hypothesized that C2C12 cells, a mouse myoblast cell line previously used to characterize myocyte differentiation, also would provide a model for studying cell cycle withdrawal during differentiation. C2C12 cells were differentiated in culture medium containing horse serum and harvested at various time points to characterize the expression profiles of known cell cycle and myogenic regulatory factors by immunoblot analysis. BrdU incorporation decreased dramatically in confluent cultures 48 hr after addition of horse serum, as cells started to form myotubes. This finding was preceded by up-regulation of MyoD, followed by myogenin, and activation of Bcl-2. Cyclin D1 was expressed in proliferating cultures and became undetectable in cultures containing 40% fused myotubes, as levels of p21(WAF1/Cip1) increased and alpha-actin became detectable. Because C2C12 myoblasts withdraw from the cell cycle during myocyte differentiation following a course that recapitulates this process in vivo, we performed a genome-wide screen to identify other gene products involved in this process. Using microarrays containing approximately 10,000 minimally redundant mouse sequences that map to the UniGene database of the National Center for Biotechnology Information, we compared gene expression profiles between proliferating, differentiating, and differentiated C2C12 cells and verified candidate genes demonstrating differential expression by RT-PCR. Cluster analysis of differentially expressed genes revealed groups of gene products involved in cell cycle withdrawal, muscle differentiation, and apoptosis. In addition, we identified several genes, including DDAH2 and Ly-6A, whose expression specifically was up-regulated during cell cycle withdrawal coincident with early myoblast differentiation.     

Diagnostic efficiency of carcinoembryonic antigen and CA125 in the cytological evaluation of effusions.

In our previous study, the combination of the concentrations of carcinoembryonic antigen (CEA) and CA125 and the findings from cytological examination in 189 benign and malignant pleural and peritoneal effusions was useful in the diagnosis/classification of malignant effusions. Sensitivity of CEA (level, greater than 5 ng/mL) was 68%; specificity was 99% for the diagnosis of malignant effusions secondary to carcinoma of the lung, breast, gastrointestinal tract, and mucinous carcinoma of the ovary. Sensitivity of CA125 (level, greater than 5000 U/mL) was 85%; specificity was 96% for the diagnosis of malignant effusions in carcinoma of the ovary, fallopian tube, and endometrium. We now expanded the study to include 840 pleural and peritoneal effusions (benign, n = 520; malignant, n = 320) and analyzed the data by the statistical method of Rudolph and colleagues. Based on new cutoff values, ie, CEA level at 6.3 ng/mL and CA125 level at 3652 U/mL, the sensitivities for detection of malignant effusions secondary to carcinomas of the lung, breast, and gastrointestinal tract and mucinous carcinoma of the ovary varied between 75% and 100%; specificity was 98%. Sensitivity of CA125 for detection of malignant effusions from müllerian epithelial carcinoma was 71%; specificity was 99%. The elevated CEA fluid level alone helped to diagnose malignant effusions of the gastrointestinal tract in 54%, breast in 19%, and lung in 16%. The high CA125 fluid level was predictive of müllerian epithelial carcinoma. Adjunctive use of CEA and CA125 levels in fluid enhances the sensitivity of cytological diagnosis and may be predictive of the primary site in patients who present with carcinoma of an unknown primary source.     

Female phenotype and multiple abnormalities in sibs with a Y chromosome and partial X chromosome duplication: H--Y antigen and Xg blood group findings.

A mentally retarded female child with multiple congenital abnormalities had an abnormal X chromosome and a Y chromosome; the karyotype was interpreted as 46,dup(X)(p21 leads to pter)Y. Prenatal chromosome studies in a later pregnancy indicated the same chromosomal abnormality in the fetus. The fetus and proband had normal female genitalia and ovarian tissue. H--Y antigen was virtually absent in both sibs, a finding consistent with the view that testis-determining genes of the Y chromosome may be suppressed by regulatory elements of the X. The abnormal X chromosome was present in the mother, the maternal grandmother, and a female sib: all were phenotypically normal and showed the karyotype 46,Xdup(X)(p21 leads to pter) with non-random inactivation of the abnormal X. Anomalous segregation of the Xga allele suggests that the Xg locus was involved in the inactivation process or that crossing-over at meiosis occurred.     

A limiting factor in the "normalization" of schizophrenic orienting response dysfunction

Forty schizophrenic patients, 40 non-schizophrenic patients, and 40 normal subjects were given 60 each alternating 1000- and 2000-Hz, 1-second tones at 60 dB. Half of each sample, the Press Group (PG), had to press a pedal to the high (low) target tone, ignoring the nontarget tone. The other half, the Nonpress Groups (NPGs), were given no reason to attend. Skin conductance response (SCR), finger pulse volume (FPV), and electroencephalographic (EEG) activity were recorded. NPG schizophrenic subjects were more often nonresponsive in both SCR and FPV than other samples, but less often responsive in EEG only when a 20 percent criterion of alpha blockade was used. Schizophrenic subjects showed greater consistency of OR nonresponsiveness in SCR and FPV, and nonsignificantly greater consistency in criterion alpha block, pointing to a deficit in orienting response (OR) rather than in peripheral response. When the targeted signal was given, schizophrenic subjects showed the same response as other groups in all systems. This was not due to an indiscriminate increase in reactivity, since response increase centered on the targeted signal itself in all groups. As the target signal was repeated, autonomic OR in schizophrenics declined sharply so that they again became underresponsive. Thus, OR "normalization" achieved by targeting significant signals is restricted to relatively early responsiveness. The rapid decline in autonomic OR may help explain differences in schizophrenic subjects between P300 and autonomic ORs to significant stimuli. Schizophrenic subjects were no different from controls in bilateral SCR or FPV asymmetry, but displayed less frequent criterion alpha blockade and reduced background alpha power in the left hemisphere. Each system showed a different pattern of bilateral asymmetry, reflecting complex, not well understood relations among these responses. This was further emphasized by the fact that skin conductance level (SCL) incremented over trials in PG subjects, reflecting sustained activation, while EEG background showed an increase in slower wave power, consistent with reports of increased drowsiness. The only drug effect seen was a lowering of SCL. Neuroleptics were associated with a flexible inhibitory control of SCL, permitting normal-like increment when circumstances required. Depressed patients' data suggested they might show heightened OR nonresponsiveness to innocuous stimuli which might not be subject to "normalization" by manipulation of stimulus significance; hence OR deficit might still differentiate schizophrenic from depressive patients.     

胰腺多房性潴留性囊肿1例

0　引言　胰腺多房性潴留性囊肿极为罕见,我科收治1例,报道如下.1　病例报告　患者,男,29岁,因发现右上腹包块11d入院,缘于11d前无明显诱因感右上腹痛,仅局限于右上腹部,无肩背部放散痛,伴间歇性发热,体温最高达38.3℃,经抗炎,对症治疗无效.并逐渐可触及右上腹有一肿块,在当地医院行穿刺检查为脓血性液体.镜检发现炎性细胞,B超示:胆囊窝下方及右肾内侧及腹腔动脉,下腔静脉外前方可见异常区,大小约9.1cm×6.6cm×7.6cm,边界清楚,形态不规则,内呈蜂窝状,可见多个大小不等的液性暗区,CT示:右上腹部上腔静脉前方6.0cm×9.0cm肿块和周围组织粘…     

Genetic and transgenic approaches to dissecting muscle development and contractility using the Drosophila model system

Both genetic and transgenic analyses of Drosophila melanogaster, the common fruit fly, are providing important insights into the mechanisms of muscle cell determination and development, myofibril assembly, and muscle contraction. This model system affords tremendous advantages such as ease of isolating mutants defective in these processes, determining the identity of affected genes, and analyzing protein function by transformation with in vitro mutagenized versions of such genes. These approaches have identified a series of proteins that are critical to mesoderm and muscle determination, many of which are likely to serve similar roles in vertebrates. The effects of mutating structural protein genes upon myofibril assembly and function in Drosophila help to define the differential roles of contractile protein isoforms and the importance of proper protein stoichiometry for physiologic function. These studies may also provide insight into the role of structural proteins in vertebrate contractility.     

IMPACTED RIGHT UPPER CENTRAL INCISOR AND TRANSPOSITION OF TWO OTHER ANTERIOR TEETH ON THE SAME SIDE (A Case Report)

A young boy presented with an uncommon finding of impaction of upper right central incisor and transposition of canine and lateral incisor on the same side. Esthetic management of his cosmetic problem which included fixed appliance therapy followed by light cure restorations is discussed.KEY WORDS: Impaction, Transposition