Thoracic splenosis

Thoracic splenosis is a rare pathologic entity resulting from seeding of splenic tissue in the pleural cavity after thoracoabdominal trauma. A 45-year-old man with a history of splenectomy secondary to abdominal trauma presented with a left lung mass and an inconclusive tissue diagnosis after needle biopsy. Thoracic splenosis was not suspected preoperatively, considered on an intraoperative frozen section, and established on permanent pathologic biopsy specimens obtained during thoracotomy. A history of thoracoabdominal trauma, combined with radiologic and radionuclide imaging studies, may establish the diagnosis without thoracotomy.     

Epidermal growth factor receptor and c-erbB-2 oncoproteins in tissue and tumor effusion cells of histopathologically different ovarian neoplasms

In order to explore a possible association between psychiatric symptoms and eye movements, 32 patients with schizophrenia were examined using an eye mark recorder in combination with the Positive and Negative Syndrome Scale, and were compared with 32 controls. Four types of figures were presented to the subjects: geometrical figures, drawings, story drawings, and sentences. Mean eye fixation time was significantly longer and mean eye scanning length was significantly shorter for the patients than for controls, not only in response to the geometric figures, but also in response to the story drawings. Eye fixation time and scanning velocity were positively correlated with degrees of thought disturbance. The number of eye fixations, eye fixation time and scanning velocity were negatively correlated with degree of depressive tendency.     

Comparative genomic hybridization and its application to Wilms' tumorigenesis

Eighty sporadic Wilms' tumor samples were analyzed by comparative genomic hybridization (CGH) to identify chromosomal regions involved in the etiology of the disease. Twenty percent of the samples showed chromosomal gains or losses. The majority of chromosomal gains and losses were similar to those identified through molecular and cytogenetic studies. Gains were observed on chromosomes 1q, 7q, 8, and 12, whereas losses were found on chromosomes 1p, 4p, 4q, 7p, 16q, 18q, 21q, and 22q. Other genetic aberrations identified in this study included deletions of chromosomes 5p and 15q, as well as gains of discrete loci on chromosomes 3p and 3q. These latter regions have not been previously implicated in Wilms' tumorigenesis and may contain novel genes relevant to the development and/or progression of this disease.     

Cerebral hypoxia during cardiopulmonary bypass: a magnetic resonance imaging study

BACKGROUND: Neurocognitive deficits after open heart operations have been correlated to jugular venous oxygen desaturation on rewarming from hypothermic cardiopulmonary bypass (CPB). Using a porcine model, we looked for evidence of cerebral hypoxia by magnetic resonance imaging during CPB. Brain oxygenation was assessed by T2*-weighted imaging, based on the blood oxygenation level-dependent effect (decreased T2*-weighted signal intensity with increased tissue concentrations of deoxyhemoglobin). METHODS: Pigs were placed on normothermic CPB, then cooled to 28 degrees C for 2 hours of hypothermic CPB, then rewarmed to baseline temperature. T2*-weighted, imaging was undertaken before CPB, during normothermic CPB, at 30-minute intervals during hypothermic CPB, after rewarming, and then 15 minutes after death. Imaging was with a Bruker 7.0 Tesla, 40-cm bore magnetic resonance scanner with actively shielded gradient coils. Regions of interest from the magnetic resonance images were analyzed to identify parenchymal hypoxia and correlated with jugular venous oxygen saturation. Post-hoc fuzzy clustering analysis was used to examine spatially distributed regions of interest whose pixels followed similar time courses. Attention was paid to pixels showing decreased T2* signal intensity over time. RESULTS: T2* signal intensity decreased with rewarming and in five of seven experiments correlated with the decrease in jugular venous oxygen saturation. T2* imaging with fuzzy clustering analysis revealed two diffusely distributed pixel groups during CPB. One large group of pixels (50% +/- 13% of total pixel count) showed increased T2* signal intensity (well-oxygenated tissue) during hypothermia, with decreased intensity on rewarming. Changes in a second group of pixels (34% +/- 8% of total pixel count) showed a progressive decrease in T2* signal intensity, independent of temperature, suggestive of increased brain hypoxia during CPB. CONCLUSIONS: Decreased T2* signal intensity in a diffuse spatial distribution indicates that a large proportion of cerebral parenchyma is hypoxic (evidenced by an increased proportion of tissue deoxyhemoglobin) during CPB in this porcine model. Neuronal damage secondary to parenchymal hypoxia may explain the postoperative neuropsychological dysfunction after cardiac operations.     

Low-level resistance to camptothecin in a human small-cell lung cancer cell line without reduction in DNA topoisomerase I or drug-induced cleavable complex formation

To study the evolution of camptothecin (CPT) resistance, we have established two small-cell lung cancer cell lines with low (3.2-fold, NYH/CAM15) and high (18-fold, NYH/CAM50) resistance to CPT by stepwise drug exposure. NYH/CAM50 cells had reduced topoisomerase I (topo I) content and activity, and consequently CPT-induced DNA single strand breaks (SSBs) were reduced, as measured by alkaline elution. In contrast, NYH/CAM15 cells had identical topo I content and activity as compared with wild-type (wt) cells. CPT-mediated SSBs and the rate of their reversal after drug removal were also equal in wt and NYH/CAM15 cells, as were doubling time, the fraction of cells in S-phase and DNA synthesis rate in response to CPT. As the conversion of DNA SSBs to DNA double strand breaks (DSBs) is thought to represent a critical event leading to cell death, we measured DNA DSBs by neutral elution. In contrast to DNA SSBs, CPT induced fewer DNA DSBs in NYH/CAM15 than in wt cells. DNA flow cytometry showed that, in CPT-treated cells, the G1 phase was emptied as cells accumulated in late S- and G2M phase. A Spearman rank correlation showed that depletion of G1 and accumulation in late S and G2M correlated to CPT sensitivity in these three cell lines. In conclusion, acquired resistance to CPT can occur without a reduction in either topo I enzyme or CPT-induced cleavable complex formation, while a decrease in the level of CPT-induced DNA DSBs may be of major importance in the early stages of CPT resistance.     

Overview of the Second International Workshop to define swine cluster of differentiation (CD) antigens

The aim of the Second International Swine Cluster of Differentiation (CD) Workshop, supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS), was to standardize the assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte differentiation antigens and to define new antibody clusters. At the summary meeting of the workshop in July, 1995, revisions in the existing nomenclature for Swine CD were approved, so that the rules are now in accord with those for human and ruminant CD. Swine CD numbers will now be given to clusters of mAb to swine orthologues of human CD molecules when homology is proven by (1) suitable tissue distribution and lymphoid cell subset expression, (2) appropriate molecular mass of the antigen recognized by the mAbs, and (3) reactivity of mAbs with the cloned swine gene products, or cross-reactivity of the mAb on the human gene products. In some cases, this reactivity would not be fully proven, mainly due to the lack of cloned gene products; for these CD antigens, the respective clusters will be assigned by the prefix 'w' which will lead to 'wCD' antigens. As a result of the Second International Swine CD Workshop the assignment of 16 mAb to existing CD groups (CD2a, CD4a, CD5a, wCD6, wCD8, CD14, CD18a, wCD21, wCD25) was confirmed, and 2 mAb to existing swine workshop clusters (SWC). More importantly, for the work on the porcine immune system, was the definition of 5 new swine CD antigens, namely CD3 (recognized by 6 new mAb and 3 epitopes), CD16 (1 new mAb), wCD29 (2 mAb), CD45RA (3 mAb) and CD45RC (1 new mAb). Finally, the demarcation of two new SWC molecules in swine, SWC8 (2 mAb) and SWC9 (2 mAb) was confirmed.     

Estimation of dominance variance in purebred Yorkshire swine

We used 179,485 Yorkshire reproductive and 239,354 Yorkshire growth records to estimate additive and dominance variances by Method Fraktur R. Estimates were obtained for number born alive (NBA), 21-d litter weight (LWT), days to 104.5 kg (DAYS), and backfat at 104.5 kg (BF). The single-trait models for NBA and LWT included the fixed effects of contemporary group and regression on inbreeding percentage and the random effects mate within contemporary group, animal permanent environment, animal additive, and parental dominance. The single-trait models for DAYS and BF included the fixed effects of contemporary group, sex, and regression on inbreeding percentage and the random effects litter of birth, dam permanent environment, animal additive, and parental dominance. Final estimates were obtained from six samples for each trait. Regression coefficients for 10% inbreeding were found to be -.23 for NBA, -.52 kg for LWT, 2.1 d for DAYS, and 0 mm for BF. Estimates of additive and dominance variances expressed as a percentage of phenotypic variances were, respectively, 8.8 +/- .5 and 2.2 +/- .7 for NBA, 8.1 +/- 1.1 and 6.3 +/- .9 for LWT, 33.2 +/- .4 and 10.3 +/- 1.5 for DAYS, and 43.6 +/- .9 and 4.8 +/- .7 for BF. The ratio of dominance to additive variances ranged from .78 to .11.     

Different MRF4 knockout alleles differentially disrupt Myf-5 expression: cis-regulatory interactions at the MRF4/Myf-5 locus

Three different null alleles of the myogenic bHLH gene MRF4/herculin/Myf-6 were created recently. The three alleles were similar in design but were surprisingly different in the intensity of their phenotypes, which ranged from complete viability of homozygotes to complete lethality. One possible explanation for these differences is that each mutation altered expression from the nearby Myf-5 gene to a different extent. This possibility was first raised by the observation that the most severe MRF4 knockout allele expresses no Myf-5 RNA and is a developmental phenocopy of the Myf-5 null mutation. Furthermore, initial studies of the two weaker alleles had shown that their differences in viability correlate with the intensity of rib skeletal defects, and the most extreme version of this rib defect is the hallmark phenotype of Myf-5 null animals. In the present study we tested this hypothesis for the two milder MRF4 alleles. By analyzing compound heterozygous animals carrying either the intermediate or the weakest MRF4 knockout allele on one chromosome 10 and a Myf-5 knockout allele on the other chromosome, we found that both of these MRF4 alleles apparently downregulate Myf-5 expression by a cis-acting mechanism. Compound heterozygotes showed increased mortality of the normally viable MRF4 allele, together with intensified rib defects for both MRF4 alleles and increased deficits in myotomal Myf-5 expression. The allele-specific gradation in phenotypes also suggested that rib morphogenesis is profoundly sensitive to quantitative differences in Myf-5 function if Myf-5 products drop below hemizygous levels. The mechanistic basis for cis interactions at the MRF4/Myf-5 locus was further examined by fusing a DNA segment containing the entire MRF4 structural gene, including all sequences deleted in the three MRF knockout alleles, with a basal promoter and a lacZ reporter. Transgenic embryos showed specific LacZ expression in myotomes in a pattern that closely resembles the expression of Myf-5 RNA. cis-acting interactions between Myf-5 and MRF4 may therefore play a significant role in regulating expression of these genes in the early myotomes of wildtype embryos.