Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.

Loss of the cell adhesion molecule E-cadherin has been observed in a variety of human carcinomas, and germline E-cadherin mutations have been found in several familial cases of diffuse gastric cancer. We sought to determine the prevalence and nature of E-cadherin alterations in "sporadic" gastric carcinomas. We performed comprehensive sequencing of the coding region, loss of heterozygosity (LOH) analysis, and immunohistochemical protein expression determination on 40 sporadic gastric adenocarcinomas. In total, 7 of 25 diffuse-type cancers harbored genetic alterations in the E-cadherin gene. Novel mutations predicted to significantly compromise protein function were found within 4 of these cancers, 2 of which harbored alterations resulting in biallelic inactivation of the gene product. Three diffuse cancers failed to amplify Exon 8 of E-cadherin, suggesting the presence of a homozygous abnormality. Notably, one germline E-cadherin mutation was also identified within these "sporadic" diffuse cancers. Significant gene mutations were not found in the 14 intestinal-type or histologically mixed cancer. Immunohistochemistry revealed aberrant or negative protein expression in seven diffuse-type tumors, four of which correlated with the genetic alterations. Both diffuse and intestinal-type tumors exhibited low rates of LOH, suggesting that allelic loss at the locus is not a common mechanism for E-cadherin inactivation during gastric tumorigenesis. Our observations suggest that inactivation of the E-cadherin gene occurs only in a subset of diffuse-type gastric cancers, as the majority of cases did not contain genetic alterations or identifiable protein abnormalities. Germline E-cadherin alterations, although rare, may underlie some diffuse gastric cancer cases that have important biologic and practical implications     

Modification of surface composition of Actinomyces viscosus T14V and T14AV.

The morphology and serology of Actinomyces viscosus T14V and T14AV were compared. When grown in supplemented tryptic soy broth, the virulent strain (T14V) possessed an extensive network of cell surface fibrils. In this medium, the avirulent strain (T14AV) possessed a microcapsule, absent on strain T14V, and a comparatively small number of surface fibrils. Mild acid extraction (Lancefield procedure) solubilized common antigenic components on both strains as well as components detectable only in the virulent strain T14V (virulence-associated antigens 1 and 2). When grown in Socransky chemically defined medium or Carlsson complex medium, the avirulent strain possessed increased amounts of surface fibrils and virulence-associated antigens. Whole cells and extracts of avirulent cells grown in Socransky medium absorbed antibodies to virulence-associated antigens with approximately the same efficiency as did whole cells and extracts of strain T14V, suggesting antigenic similarity between the two cell types. The results strongly support the hypothesis that observable differences between A. viscosus strains T14V and T14AV represent quantitative, rather than qualitative, differences in particular cell surface components. In addition, the magnitude of these differences can be modified by changing growth conditions.     

Cephalometric analyses and flow-volume loops in obstructive sleep apnea patients

Fifteen patients with obstructive sleep apnea syndrome (OSAS) and 10 controls were studied. Polygraphic monitoring during sleep confirmed the presence or absence of OSAS. Ten OSAS patients and five controls had cephalometric analysis and 12 OSAS patients and five controls had a flow-volume loop study during wakefulness. Seven OSAS patients were submitted to both analyses. Flow-volume loops were unable to detect extrathoracic airway obstruction in six out of 12 OSAS patients. One control was found with positive results. Six out of seven subjects with positive flow-volume loops were overweight (greater than or equal to 30% ideal weight). Cephalograms were very useful in demonstrating mandibular deficiencies in OSAS patients. The length of the soft palate and the position of the hyoid bone, together with the measurement of the posterior airway space, are criteria of great interest in OSAS patients. Cephalometric analysis is recommended in all OSAS patients scheduled for surgical procedure. None of these tests, however, whether alone or in combination, is capable of identifying all cases of OSAS.     

Blood Pressure and Heart Rate Changes Accompanying Classical Eyeblink Conditioning In The Rabbit (Oryctolagus Cuniculus)

In two experiments employing 38 rabbits differential classical conditioning of heart rate, blood pressure, and corneoretinal potential (CRP) response were examined using l-sec and 4-sec interstimulus intervals ISI respectively. The conditioned response consisted of HK decelerations and DP depressor responses early in conditioning. However, many, but not all, animals revealed pressor responses and HR accelerations after the CRP discrimination was acquired. Significant correlations were also obtained between BP pressor responses, HR accelerations, and the frequency of CRP CRs. These results were discussed within the context of the orienting and defense reflexes.     

Pedigree study of familial Alzheimer disease

Twenty-one families with familial Alzheimer disease were ascertained in a dementia clinic and assessed by multiple family interviews. Eight autopsies were reviewed. The age of onset varied from 25 to 85. Seven pedigrees showed evidence of 3 generation transmission. Paternal age of the founders of 4 lines which could be assessed was higher than controls.     

Selective vulnerability of unmyelinated fiber Schwann cells in nerves exposed to local anesthetics

When peripheral nerves of experimental rats are exposed to local anesthetics, distinctive and reproducible pathologic changes occur involving the perineurial sheath and endoneurial contents. Application of intermediate strength concentrations of the local anesthetics, 2-chloroprocaine, lidocaine, etidocaine, and intermediate or high concentrations of procaine to the surface of rat sciatic nerves resulted in the following changes. By 48 hours, the perineurial sheath exposed to the drug was disrupted and became permeable to granulocytes which infiltrated the subjacent endoneurium in conjunction with edema formation in the endoneurial interstitium. Application of 10% procaine to exposed nerve resulted in extensive demyelination. The most striking pathologic change occurring with either intermediate or high doses was accumulation of lipid droplets in Schwann cells, a phenomenon that occurred often in myelin-producing Schwann cells but much less frequently in unmyelinated fiber Schwann Cells. Lipid accumulation appears to be one of several reactive changes that affect Schwann cells of myelinated fibers and is dose-dependent. On the other hand, while reactive changes were infrequently seen in unmyelinated fiber Schwann cells, these cells appeared more susceptible to injury as shown by electron microscopy. Injury to Schwann cells by local anesthetics is temporary because these cells can replicate quickly. Autoradiographic studies of thymidine incorporation 1 week after procaine administration to the sciatic nerve showed intense proliferation of Schwann cells, but no such activity in controls. These findings support the view that their neurotoxic properties may account in some part for the function of local anesthetics, that Schwann cells of small unmyelinated fibers are more vulnerable to these agents than those of myelinated fibers, and that destruction of their supporting cells is followed by vigorous mitotic activity in the endoneurium.