MR of the cerebral operculum: abnormal opercular formation in infants and children.

PURPOSETo evaluate abnormalities of the cerebral operculum in infants and children and to propose the embryogenic basis of abnormal opercular formation as determined from MR imaging findings.METHODSEighty-six infants and children who had abnormally wide interopercular distances and/or distorted opercular topography seen on MR images were studied retrospectively. Clinically, patients presented with tonal abnormalities, macrocephaly, microcephaly, seizures, developmental delay, cerebral palsy, or facial dysmorphism. The abnormal opercula were compared with developing opercula at different stages of gestation.RESULTSAmong the 86 infants and children, two categories of opercular abnormalities were identified: an underdeveloped operculum (n = 64) and a malformed operculum (n = 22). The malformed operculum was further classified into three subtypes: nonformation of the operculum with lissencephaly (n = 1, 1%), abnormal opercular formation with pachygyria (n = 11, 13%), and nonformation or abnormal formation of the operculum without pachygyria or lissencephaly (n = 10, 12%). Two subtypes of the underdeveloped operculum were identified: an open operculum without a normal insula (n = 6, 7%) and an open operculum with a normal insula (n = 58, 67%). The five subtypes of abnormal opercular configuration showed a range of maturity that was comparable to the developing operculum at different ages.CONCLUSIONOpercular anomalies appear to follow sequentially predetermined normal steps in development. Arrest in opercular development or malformation may occur after an initial insult. MR imaging is the method of choice by which to identify these abnormalities.     

Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)

Inactivated severe acute respiratory syndrome-associated coronavirus (SARS-CoV) has been tested as a candidate vaccine against the re-emergence of SARS. In order to understand the efficacy and safety of this approach, it is important to know the antibody specificities generated with inactivated SARS-CoV. In the current study, a panel of twelve monoclonal antibodies (mAbs) was established by immunizing Balb/c mice with the inactivated BJ01 strain of SARS-CoV isolated from the lung tissue of a SARS-infected Chinese patient. These mAbs could recognize SARS-CoV-infected cells by immunofluorescence analysis (IFA). Seven of them were mapped to the specific segments of recombinant spike (S) protein: six on S1 subunit (aa 12-798) and one on S2 subunit (aa 797-1192). High neutralizing titers against SARS-CoV were detected with two mAbs (1A5 and 2C5) targeting at a subdomain of S protein (aa 310-535), consistent with the previous report that this segment of S protein contains the major neutralizing domain. Some of these S-specific mAbs were able to recognize cleaved products of S protein in SARS-CoV-infected Vero E6 cells. None of the remaining five mAbs could recognize either of the recombinant S, N, M, or E antigens by ELISA. This study demonstrated that the inactivated SARS-CoV was able to preserve the immunogenicity of S protein including its major neutralizing domain. The relative ease with which these mAbs were generated against SARS-CoV virions further supports that subunit vaccination with S constructs may also be able to protect animals and perhaps humans. It is somewhat unexpected that no N-specific mAbs were identified albeit anti-N IgG was easily identified in SARS-CoV-infected patients. The availability of this panel of mAbs also provided potentially useful agents with applications in therapy, diagnosis, and basic research of SARS-CoV.     

Evidence for object permanence in the smooth-pursuit eye movements of monkeys

We recorded the smooth-pursuit eye movements of monkeys in response to targets that were extinguished (blinked) for 200 ms in mid-trajectory. Eye velocity declined considerably during the target blinks, even when the blinks were completely predictable in time and space. Eye velocity declined whether blinks were presented during steady-state pursuit of a constant-velocity target, during initiation of pursuit before target velocity was reached, or during eye accelerations induced by a change in target velocity. When a physical occluder covered the trajectory of the target during blinks, creating the impression that the target moved behind it, the decline in eye velocity was reduced or abolished. If the target was occluded once the eye had reached target velocity, pursuit was only slightly poorer than normal, uninterrupted pursuit. In contrast, if the target was occluded during the initiation of pursuit, while the eye was accelerating toward target velocity, pursuit during occlusion was very different from normal pursuit. Eye velocity remained relatively stable during target occlusion, showing much less acceleration than normal pursuit and much less of a decline than was produced by a target blink. Anticipatory or predictive eye acceleration was typically observed just prior to the reappearance of the target. Computer simulations show that these results are best understood by assuming that a mechanism of eye-velocity memory remains engaged during target occlusion but is disengaged during target blinks.     

The significance of small erythrocytes.

Small erythrocytes (mean corpuscular volume less than 80 mu-3 by the Coulter Model S) were found in 222 (2.75%) of 8,086 consecutive patients admitted to a large suburban general hospital. Forty-five (20.3%) of these 222 patients had laboratory findings consistent with thalassemia. Seventy-six (31.2%) were found to be iron deficient. Patients whose hemoglobin values were below 9.0 Gm. per 100 ml. were more likely to be iron deficient. The hemoglobin A2 values were significantly lower in iron-deficient than in non-iron-deficient patients. Although the mean corpuscular volume is much lower and the erythrocyte count is higher in thalassemia than in iron deficiency, hematologic values obtainable from the Counlter S (such as MCV, erythrocyte count, and hemoglobin) alone are not valuable in differentiating thalassemia from iron deficiency.     

Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas

Large congenital melanocytic nevi (CMN) are at an increased risk of developing melanoma. Several forms of secondary proliferations can arise in congenital nevi on rare occasions. Although some of these closely resemble melanoma both clinically and histologically, metastasis is rare. We used comparative genomic hybridization to analyze chromosomal aberrations in different types of proliferations arising in CMN and compared them to typical congenital nevi, clear-cut melanomas arising in congenital nevi, as well as primary cutaneous melanomas that were not associated with a CMN. Cases of CMN and CMN with secondary proliferations were assigned to six groups according to the predominant histological pattern: group I, bland congenital nevi (n = 6); group II, congenital nevi with foci of increased cellularity (n = 4); group III, CMN with a proliferation simulating superficial spreading melanoma in situ (n = 3); group IV, CMN with a proliferation simulating nodular melanoma (n = 9); group V, proliferating neurocristic hamartoma (n = 1); and group VI, melanoma arising in congenital nevus (n = 6). No aberrations were found in groups I to III, whereas seven of nine cases of group IV, and one of one case of group V, showed aberrations. In group IV six of seven cases with aberrations (86%) showed numerical aberrations of whole chromosomes exclusively. This pattern differed significantly from the findings in melanoma that arose within CMN (n = 6), group VI, or independent of CMN (n = 122) in which only 5% showed numerical changes only. The single case in group V showed aberrations similar to melanoma. The finding of frequent numerical chromosomal aberrations in atypical nodular proliferations arising in CMN identifies these as clonal neoplasms with a genomic instability consistent with a mitotic spindle checkpoint defect. This difference compared to the aberration pattern found in melanoma might explain their more benign clinical behavior and may be of diagnostic value in ambiguous cases.     

ST2作为Th2细胞亚群标志以及其与支气管哮喘的关系的研究

各自主要分泌IFN γ和IL 4的Th1和Th2亚群 ,与临床疾病的关系十分密切。如何从表面标志上加以区分是一项迫切需要解决的问题。ST2是近年来提出的Th2细胞的稳定标志物。本工作在体外成功地诱导人脐带血T细胞向Th1或Th2分化的基础上 ,应用逆转录PCR分析了ST2mRNA的表达特点。证实ST2在人Th2细胞上的选择性表达。为了探索ST2、Th2与支气管哮喘的关系 ,本工作进一步检测了正常人和支气管哮喘患者外周血单个核细胞中 β actin、ST2以及IFN γ和IL 4的mRNA水平。结果显示 :支气管哮喘患者ST2mRNA水平升高 ,IL 4水平也明显升高 ,但IFN γ无变化。这提示ST2作为Th2细胞的标志物 ,有可能成为Th2极化性疾病如哮喘发病机制研究的一个参考性标志 ,至于ST2是否有可能作为治疗的靶分子 ,有待进一步探讨     

Myosin light chain kinase modulates hypotonicity-induced Ca2+ entry and Cl– channel activity in human cervical cancer cells

Hypotonicity-induced Ca2+ entry is a critical signal for the normal regulatory volume decrease in human cervical cancer cells. The aim of this study was to explore the role of myosin light chain kinase (MLCK) in the regulation of hypotonicity-induced Ca2+ signalling and Cl- channel activity. Blockade of MLCK activity by MLCK(11-19) amide, a substrate-specific peptide inhibitor, markedly attenuated hypotonicity-induced Ca2+ entry. A similar result was obtained with ML-7, a synthetic naphthalenesulphonyl derivative that inhibits the binding of ATP to MLCK. More than 85% of the activity of the volume-regulated Cl- channel was suppressed when intracellular Ca2+ was buffered to near zero in the absence of extracellular Ca2+, suggesting that hypotonicity-induced Ca2+ signalling is important for the activation of the volume-regulated Cl- channel. Intracellular dialysis with MLCK(11-19) amide or ML-7 concentration-dependently reduced the amplitude and rate of activation of the volume-regulated Cl- channel. Swelling-activated taurine transport was also inhibited concentration dependently by ML-7 and MLCK(11-19) amide with IC(50) values of 6.4 and 2.0 microM, respectively. Hypotonicity induced MLC phosphorylation which was mediated totally by MLCK and depended on Ca2+ entry. However, phosphorylated MLC per se was not involved critically in the regulation of Ca2+ entry and activation of volume-sensitive organic osmolyte/anion channels (VSOAC). We propose that MLCK has a novel function in regulating the activation of VSOAC by mediating Ca2+ entry in response to hypotonicity. This function of MLCK on Ca2+ signalling does not correlate with MLC phosphorylation.     

Evaluation of RGS4 as a candidate gene for schizophrenia.

Several studies have suggested that the regulator of G-protein signaling 4 (RGS4) may be a positional and functional candidate gene for schizophrenia. Three single nucleotide polymorphisms (SNP) located at the promoter region (SNP4 and SNP7) and the intron 1 (SNP18) of RGS4 have been verified in different ethnic groups. Positive results have been reported in these SNPs with different numbers of SNP combinatory haplotypes. In this study, these three SNP markers were genotyped in 218 schizophrenia pedigrees of Taiwan (864 individuals) for association analysis. Among these three SNPs, neither SNP4, SNP7, SNP18 has shown significant association with schizophrenia in single locus association analysis, nor any compositions of the three SNP haplotypes has shown significantly associations with the DSM-IV diagnosed schizophrenia. Our results fail to support the RGS4 as a candidate gene for schizophrenia when evaluated from these three SNP markers.