Molecular cytogenetic analysis of a nontumorigenic human breast epithelial cell line that eventually turns tumorigenic: Validation of an analytical approach combining karyotyping,comparative genomic hybridization,chromosome painting,and single-locus fluorescence in situ hybridization

The immortalized, nontumorigenic human breast epithelial cell line HMT-3522 has been used as a model for premalignant and, eventually, malignant development. During cultivation, the karyotype evolution was followed. At an early stage, a very long constant phase showed a near-diploid karyotype, with only five marker chromosomes. DNA from this phase was used for comparative genomic hybridization (CGH) analysis, confirming a previously known MYC amplification, and the integration sites were subsequently determined by single-locus fluorescence in situ hybridization (FISH). Furthermore, gains of 5q22-qter and 20q11-qter and deletion of most of chromosome 6 (6p23-qter) were detected by CGH. Because of uncertainty about some of the indicated changes, including a deletion of 1p35-pter, the CGH findings were investigated more closely by chromosome painting, leading to a revision of the karyotype: 45,XX,del(1)(p35),−6,dup(8)(pter→qter::qter→q24),der(12) t(6;12)(p23;p13),der(14)t(5;14)(q22;q32.3),der(17)t(8;17;20)(17pter→17q25::8qter→8q23::8q24→8qter::8q24→8qter::8q23→8q24.1::20q11→20qter). Some karyotypic changes were confirmed by CGH; others had to be revised; and, in the 1p35 region, classical cytogenetics seems superior to CGH. However, CGH revealed a karyotypically unsuspected dup(20q) that might be of special relevance to breast tumor initiation or progression. Our study confirms that CGH is supplementary to current technologies, e.g., karyotyping and Southern analysis, but cannot replace them. In addition, our cell line turned out to be an excellent model for comparison among the different methods. The results imply that future cytogenetic analyses of complex karyotypes should be based on a combination of karyotyping, CGH, and FISH. Genes Chromosom. Cancer 20:30–37, 1997. © 1997 Wiley-Liss, Inc.     

Measurement of gas absorption in a swelling polymeric material by a combined gravimetric-dynamic method

A new gravimetric-dynamic method is described allowing to measure simultaneously the amount of gas absorbed by a polymeric material and its change in volume due to absorption. The method determines a 3-dimensional change in size of the polymer sample. The sample can be of either dense, pulverous, or pellet-like shape. The method combines well known gravimetric measurements with a dynamic method where the inertia of mass is determined instead of its gravity. This leads to an additional information on the volume of the sample. The dynamic measurements can be performed either by slow oscillations of a rotational pendulum or by the relaxational motion of a floating rotator. Sample data of the mass absorbed (m) and volume (V) of the loaded sorbent are given for the system carbon dioxide/polycarbonate pellets at T = 293 K in the pressure range 0 < p < 6 MPa.     

Superconducting Properties and Electron Scattering Mechanisms in a Nb Film with a Single Weak-Link Excavated by Focused Ion Beam

Granularity is one of the main features restricting the maximum current which a superconductor can carry without losses, persisting as an important research topic when applications are concerned. To directly observe its effects on a typical thin superconducting specimen, we have modeled the simplest possible granular system by fabricating a single artificial weak-link in the center of a high-quality Nb film using the focused ion beam technique. Then, its microstructural, magnetic, and electric properties in both normal and superconducting states were studied. AC susceptibility, DC magnetization, and magneto-transport measurements reveal well-known granularity signatures and how they negatively affect superconductivity. Moreover, we also investigate the normal state electron scattering mechanisms in the Boltzmann theory framework. The results clearly demonstrate the effect of the milling technique, giving rise to an additional quadratic-in-temperature contribution to the usual cubic-in-temperature sd band scattering for the Nb film. Finally, by analyzing samples with varying density of incorporated defects, the emergence of the additional contribution is correlated to a decrease in their critical temperature, in agreement with recent theoretical results.     

Concomitant overexpression of the EGFR and erbB-2 genes in renal cell carcinoma (RCC) is correlated with dedifferentiation and metastasis

Gene amplification or structural alteration of different erbB genes exerts a transforming effect in a variety of human neoplasms. Overexpression of the EGF receptor is associated with tumor initiation and progression of renal cell carcinoma (RCC). However, the role of erbB-2 in these processes remains unknown. We investigated 34 renal cell carcinomas for gene amplification and expression of the EGFR and erbB-2 genes at the mRNA and protein level and their relationship to pathological and clinical parameters. No amplification of both genes has been observed. However, high expression of the EGF receptor protein and p185erbB2 was frequent in RCC and statistically significantly related to higher tumor grades. We could demonstrate a close correlation of p185erbB2 overexpression with high EGF receptor levels. Co-overexpression of both receptor types was significantly associated with metastatic disease. Our results suggest a synergistic involvement of both EGF receptor and p185erbB2 in the progression of RCC. © 1996 Wiley-Liss, Inc.     

Automated quality assessment of structural magnetic resonance images in children: Comparison with visual inspection and surface‐based reconstruction

Motion‐related artifacts are one of the major challenges associated with pediatric neuroimaging. Recent studies have shown a relationship between visual quality ratings of T₁ images and cortical reconstruction measures. Automated algorithms offer more precision in quantifying movement‐related artifacts compared to visual inspection. Thus, the goal of this study was to test three different automated quality assessment algorithms for structural MRI scans. The three algorithms included a Fourier‐, integral‐, and a gradient‐based approach which were run on raw T₁‐weighted imaging data collected from four different scanners. The four cohorts included a total of 6,662 MRI scans from two waves of the Generation R Study, the NIH NHGRI Study, and the GUSTO Study. Using receiver operating characteristics with visually inspected quality ratings of the T₁ images, the area under the curve (AUC) for the gradient algorithm, which performed better than either the integral or Fourier approaches, was 0.95, 0.88, and 0.82 for the Generation R, NHGRI, and GUSTO studies, respectively. For scans of poor initial quality, repeating the scan often resulted in a better quality second image. Finally, we found that even minor differences in automated quality measurements were associated with FreeSurfer derived measures of cortical thickness and surface area, even in scans that were rated as good quality. Our findings suggest that the inclusion of automated quality assessment measures can augment visual inspection and may find use as a covariate in analyses or to identify thresholds to exclude poor quality data.     

A population‐based and cross‐sectional study of the long‐term prognosis in multifocal motor neuropathy

A population‐based, cross‐sectional study of patients referred to the Danish hospital system between 1985 and 2006 was conducted to evaluate the long‐term outcome in Danish patients treated for multifocal motor neuropathy (MMN). Thirty‐four MMN patients were identified, three had died of unrelated diseases, 10 were excluded, one did not reply to study request and 20 were included. The median disease duration was 24 years (interquartile range: 18.5‐31.0). Compared to 24 healthy matched control subjects, the Rasch‐built Overall Disability Scale for Multifocal Motor Neuropathy was reduced by 9%, the Neuropathy Impairment Score showed a 3‐fold increase, the isokinetic strength was reduced by 29%, the grip strength by 56%, the Timed 25‐Foot Walk was prolonged by 13% and the EQ‐5D‐5 L‐Index value was impaired by 20%. The isokinetic strength was significantly more impaired at the wrist and ankle as compared to the elbow and knee, and one patient had lost ambulation because of instability at the ankle. Patients were considerably more fatigued and had substantially impaired hand dexterity, while mood, aerobic capacity, social adjustment, and working capacity were not affected. Regression analysis showed that lag‐time until start of initial therapy lead to impaired long‐term outcome without any effect of disease duration. Long‐term prognosis in treated MMN is characterized by moderate to severe impairment primarily affecting dexterity and stability at the ankle. Our observations support previous observations that the long‐term impairment in MMN might be improved following earlier start of therapy and that an effect of disease duration cannot be demonstrated.     

Comparison of outcomes between complete and incomplete congenital duodenal obstruction

BACKGROUND Congenital duodenal obstruction (CDO) can be complete (CCDO) or incomplete (ICDO). To date there is no outcome analysis available that compares both subtypes. AIM To quantify and compare the association between CCDO and ICDO with outcome parameters. METHODS We retrospectively reviewed all patients who underwent operative repair of CCDO or ICDO in our tertiary care institution between January 2004 and January 2017. The demographics, clinical presentation, preoperative diagnostics and postoperative outcomes of 50 patients were compared between CCDO (n = 27;atresia type 1-3, annular pancreas) and ICDO (n=23;annular pancreas, web, Ladd′s bands). RESULTS In total, 50 patients who underwent CDO repair were enrolled and followed for a median of 5.2 and 3.9 years (CCDO and ICDO, resp.). CCDO was associated with a significantly higher prenatal ultrasonographic detection rate (88% versus 4%;CCDO vs ICDO, P<0.01), lower gestational age at birth, lower age and weight at operation, higher rate of associated congenital heart disease (CHD), more extensive preoperative radiologic diagnostics, higher morbidity according to Clavien-Dindo classification and comprehensive complication index (all P≤0.01). The subgroup analysis of patients without CHD and prematurity showed a longer time from operation to the initiation of enteral feeds in the CCDO group (P<0.01). CONCLUSION CCDO and ICDO differ with regard to prenatal detection rate, gestational age, age and weight at operation, rate of associated CHD, preoperative diagnostics and morbidity. The degree of CDO in mature patients without CHD influences the postoperative initiation of enteral feeding.