Incidence and diagnostic significance of minor pathologic changes in the adult pancreas at autopsy: a systematic study of 112 autopsies in patients without known pancreatic disease

In 112 unselected autopsies of adult patients without known pancreatic disease (except adult-onset diabetes mellitus), the pancreas was examined to establish the incidence and degree of such minor pancreatic lesions as lipomatosis, fibrosis, alterations of ducts and ductal epithelium, inflammatory infiltrates, focal necrosis, acinar dilation, and vascular changes. Each lesion was then tested for statistically significant correlations with the age of the patient and a number of clinical conditions, including cholelithiasis, adult-onset diabetes mellitus, adiposity, generalized severe atherosclerosis, chronic alcoholism, severe bacterial infection prior to death, and generalized malignant tumor. This was done in the hope of finding associated or predisposing factors for the pancreatic lesions. The results show, in addition to the unexpectedly high incidence of the various pancreatic lesions, a clear increase of lipomatosis, fibrosis, and both ductal and ductal epithelial alterations with increasing age; these conditions were accompanied by a steady decrease in the mean weight of the gland, starting at the age of about 40 years, except in cases of advanced lipomatosis. The latter condition was associated with adult-onset diabetes mellitus. Severe generalized atherosclerosis was correlated with lipomatosis and fibrosis, but the two latter conditions were found together only rarely. Acute (terminal) lesions, including focal necrosis and acinar dilation, were associated with severe bacterial disease prior to death. Other statistically significant correlations were rare, indicating the lack of specificity of these minor pancreatic lesions rather than offering a clue as to their pathogenesis. The diagnostic significance and the relations of these lesions to clinically relevant chronic pancreatitis are discussed briefly.     

Defective viral RNAs in Aedes albopictus C6/36 cells persistently infected with Semliki Forest virus

A persistent infection of Semliki Forest virus (SFV) has been established in Aedes albopictus C6/36 cells. Only a small number of cells survived the initial infection with this RNA virus and gave rise to a persistently infected culture which produced continuously small amounts of infectious virus. To investigate whether defective viral RNA is involved in establishing and maintaining a persistent infection, the intracellular viral RNA was analyzed early and late after infection by blot hybridizations. Several defective viral RNAs were detected with a common sequence corresponding to the 3′ end of the viral genome during and after the establishment of the persistent infection. These defective viral RNAs resemble the defective interfering RNAs in vertebrate cells generated during serial undiluted passages of standard SFV. The defective viral RNAs are rarely released from cells as virions. The rapid generation of defective viral RNAs may be important for the establishment of a persistent infection in mosquito cells.     

Morphogenesis and possible precursor lesions of invasive carcinoma of the papilla of Vater: epithelial dysplasia and adenoma

Surgical specimens from 58 invasive carcinomas of the papilla of Vater were studied histomorphologically. Tubular or villous adenomas, adenomatous residues, and microadenomas were found in the vicinity of the carcinomas in 91.4 per cent of the cases; moderate or severe epithelial dysplasia in adenomatous structures or in surface and ductal epithelium was present in 81 per cent of the cases. The results of the present histomorphologic study support the hypothesis that invasive carcinomas arise from pre-existing mucosal lesions, such as adenoma or dysplasia.     

Immunocytochemical demonstration of β-lipotropin in mouse pituitary cells and neurons cultured in vitro

Specific antiserum directed against human β-lipotropin was used to demonstrate the presence of β-lipotropin immunoreactivity in dissociated cell cultures of mouse pituitary, hypothalamus, spinal cord and dorsal root ganglia.A large population of pituitary cells and hypothalamic neurons were positive for β-lipotropin immunoreactivity, while only 10–20% of the neurons from spinal cord and dorsal root ganglia were stained. The specificity of the β-lipotropin immunoreaction was confirmed by blocking the reaction by prior absorption of the antiserum with added β-lipotropin.     

Senescence in vitro and ionising radiations—the human diploid fibroblast model

The influence of ionising radiations on ageing is still controversial. Since Hayflick established the concept that diploid cells have finite lifespan in vitro, human diploid fibroblast (HDF) cultures have been recognised as a potent experimental model for cytogerontological investigations. In this study HDF cultures in phase II were exposed to acute irradiation with either X-rays on fast neutrons. The replicative potentials and labelling indices with [³H]thymidine were measured post irradiation until the cultures ceased growth in phase III. Cell mortality was measured by cloning. The apparent loss in replicative potential of irradiated mass cultures was wholly attributable to the loss of viable clonogenic cells. The current concept of precocious clonal senescence in vitro as a late effect of irradiation in clonogenic survivors is not supported by the present experiments. Instead, our results suggest that exposure to a single dose of ionising radiations either causes total replicative incapacitation (killing) of HDF cells and their progeny early after irradiation or leaves their replicative potentials unperturbed.     

The effect of denervation of Merkel cells in cats

The morphology of Merkel cells in sinus hair follicles of the upper lip (vibrissae with a circular blood sinus), and in touch domes of the glabrous skin of the nose, was investigated in cats up to 12 weeks after resection of the infraorbital nerve. Even 12 weeks after denervation there was neither an ultrastructural alteration of Merkel cells nor a reduction of their number in sinus hair follicles. Also in touch domes the Merkel cells did not disappear.     

Suppression of reaginic antibody formation in guinea pigs by anti-idiotypic antibodies

Syngeneic immunization of strain 2 and strain 13 guinea pigs with purified antibodies against benzyl-penicilloyl bovine IgG (BPO-BGG) produces anti-idiotypic antibodies which specifically inhibit antigen-induced T cell proliferation in vitro. In sensitized guinea pigs, passive administration (either intravenously or subcutaneously in complete Freund's adjuvant [CFA] of these anti-idiotypic antibodies has a reversible suppressive effect on IgG and IgM responses. In addition, preimmunization with idiotypes effects a long-term and specific suppression of the production of homocytotropic antibodies against a hapten-protein conjugate (BPO-BGG). The suppression of the homocytotropic antibody response in already sensitized outbred guinea pigs was attempted by immunization with autologous serum, autologous antibodies, or autologous lymphoid cells. With all immunization procedures used so far, no significant suppressive effects could be demonstrated. The significance of these findings, in terms of the practical potential of autoanti-idiotypic immunization for the management of allergic diseases, is briefly discussed.     

Bacteriophage interference in Streptococcus pyogenes. I. Characterization of prophage--host systems interfering with the virulent phage A25.

K56-derived group A streptococcal strains permissive for the virulent phage A25 were lysogenized by bacteriophages isolated from a wide variety of serologically different Streptococcus pyogenes strains and examined for their ability to support the growth of A25. Of 25 artificial lysogens, 5 interfered with A25 as revealed by determining adsorption, efficiency of plating, yielder frequency, and relative burst size of the superinfecting phage. These interfering strains showed normal adsorption and penetration of A25 but could not replicate A25 DNA. Injected phage DNA was neither extensively broken down, cleaved to low molecular weight fragments, nor nicked, indicating the absence of phage restriction. Whereas one of the interfering prophages was unable to prevent its host from being killed by A25 infection, the remaining interfering lysogens continued to synthesize bacterial DNA and survived A25 infection. This observation, together with the finding that the various prophages mediated different degrees of interference and further evidence presented in an accompanying paper, suggests that we encountered at least three different interference mechanisms.     

Bacteriophage interference in Streptococcus pyogenes. II. A25 mutants resistant to prophage-medicated interference.

On the basis of the host ranges of the interference-resistant A25 mutants h1 and h2, which recombine with high frequency, five group A streptococcal strains carrying prophages interfering with wild-type A25 can be subdivided into three groups, a classification which is consistent with that made previously on a different basis [Behnke, D., and Malke, H. (1978) Virology85, 118–128]. Mixed infection of appropriate lysogens with the two A25 mutants does not result in either rescue of the inhibited phage or suppression of the resistant one, suggesting that A25 does not form diffusible products which are involved in the interference process. Mutation h2 causing resistance to interference mediated by prophages P6240, P13234mo, and R58/14820 increases the sensitivity of A25 to P5004 interference and suppresses h1, which when present alone renders A25 resistant to the latter mechanism. Since A25h2 is still inhibited on an interference-deficient P5004-lysogenic strain which supports growth of A25, it is possible that P5004 determines two distinct interference mechanisms, one acting on A25 and the other on A25h2. Prophage-mediated interference and classical phage restriction/ modification are found to act side by side in strain 5004, the natural host of P5004.     

9-beta-D-Arabinofuranosyladenine as a tool to study herpes simplex virus DNA replication in vitro.

9-β-d-Arabinofuranosyladenine (araAdo) strongly suppresses herpes simplex virus (HSV) DNA synthesis in intact cell systems. After incubation with araAdo, two HSV-DNA fractions can be isolated by neutral isopycnic CsCl density gradient centrifugation, a light fraction with a buoyant density of 1.726 g/cm³, and a heavy fraction with a density of 1.738 g/cm³. After recentrifugation in neutral CsCl gradients, the light and heavy fractions are detected at a density of 1.729 and 1.741, respectively. Analysis of the two HSV-DNA fractions by hydroxylapatite chromatography and by digestion with nuclease S₁ revealed that the light fraction consists predominantly of native DNA and the heavy fraction of denatured DNA. AraAdo is incorporated into HSV-DNA and has been shown to be present in terminal positions at the 3′-hydroxyl position. The HSV-DNA pieces, containing incorporated araAdo, are of low molecular weight (less than 2.6 × 10⁶) and are not assembled to higher molecular weight aggregates.     

Microglandular adenosis of the female mammary gland: study of a case with ultrastructural observations

A case of microglandular adenosis of the breast in a 75-year-old woman is presented, with emphasis on the ultrastructural features. While the tumor was histologically similar to those reported previously in the literature, certain microscopic aspects suggested malignant change. Ultrastructurally, the characteristic findings were villus interdigitation between epithelial cells, thick basement membranes around individual tubules, and abundant apical lysosomal granules.     

Cortical potential correlates of selective attention in multidimensional scaling

Cortical evoked potentials were recorded from the vertex of subjects performing a similarity rating task. Proximity data were analysed according to INDSCAL (Carroll and Chang, 1970). Brain activity was averaged separately for different stimulus attributes and different stages of the judgement process. The amplitudes of the two positive deflections of the averaged evoked potential, peaking around 160 and 330 msec after stimulus onset respectively, were systematically influenced by two factors: The weight, which the evoking attribute received in the overall dissimilarity judgement, and the position of the evoking attribute in the stimulus train. The results support the hypothesis that differences in the perception of similarity are due to differences in attentional set. Reference is made to the ‘additive-difference model’ of scaling behaviour (Tversky and Krantz, 1970) and Broadbent's (1970) distinction between stimulus set and response set attention.     

Variation of DNA polymerase and RNA polymerase activities in cells infected with herpes simplex virus type 1.

Infection of rabbit kidney cells with herpes simplex virus (HSV) leads to pronounced alterations of the different species of DNA-dependent DNA and DNA-dependent RNA polymerases. The activity of distinct polymerase species was determined; it was ruled out first that deoxyribonucleases or ribonucleases had an influence on these determinations and second that the activities of isoenzymes modified the evaluation of the activity of a distinct enzyme species. The three different DNA-dependent DNA polymerases (form a and β and HSV-induced enzyme) were separated by velocity sedimentation through sucrose density gradients and were asscyayed using activated DNA as template. DNA polymerase a and HSV polymerase were resolved by different assay conditions. The cellular polymerase a decreases by 80% 10 hr after infection with HSV, while the cellular polymerase β shows a slight increase during this period. The activity of HSV-induced DNA polymerase at the beginning of infection is virtually zero; it increases to a maximum 8 hr postinfection. The activity of DNA-dependent RNA polymerase I declines dramatically, by 68%, after infection with HSV while the alterations of the activities of RNA polymerases II and III are less pronounced.     

Changes in conformation and charge paralleling proteolytic activation of Newcastle disease virus glycoproteins

The hemagglutinin-neuraminidase and the fusion glycoprotein of strains Italien and Ulster of Newcastle disease virus were isolated by isoelectric focusing after solubilization with n-octylglucoside or other nondenaturing detergents. The isoelectric points of the glycoproteins varied depending on the virus strain; host-specific variations were not observed. When the precursor F₀ of the fusion protein of strain Ulster was converted by proteolytic cleavage into the complex F_{1, 2}, there was a shift in the isoelectric point from pH 6.3 to pH 5.0. When the precursor HN₀ of the same strain was cleaved to HN, its isoelectric point (pH 5.6) did not change. A shift from a more basic to a more acidic pH was also observed, when the isoelectric points of F₀ and F_{1, 2} were analyzed under denaturing conditions. These observations are compatible with the concept that F₁ and F₂ are linked in the precursor by a basic intervening sequence that is eliminated in the cleavage reaction. Circular dichroism spectra of the isolated glycoproteins have been determined. The spectra obtained from glycoprotein F_{1, 2} of strain Italien and of strain Ulster were similar, but there were strain-specific differences with glycoprotein HN. With the hemagglutinin-neuraminidase and the fusion protein of strain Ulster, precursors and cleavage products showed different spectra. This indicates that proteolytic activation of both glycoproteins is paralleled by a conformational change.     

Establishment and characterization of a human glioblastoma cell line with a stable karyotype and nullisomy 13

A permanent cell line (HeRo) with a stable karyotype (80-84,XXYY) and with defined numerical and structural chromosome aberrations was established from a human glioblastoma, a highly malignant brain tumor. Transformation of these cells with SV40 led to a second permanent cell line (HeRo-SV) with a reduced, but also stable, karyotype (72-74,XXYY). The morphological appearance of the glioblastoma line was similar to the main component of the original tumor tissue. The transformed cells differed from their counterparts in accelerated growth, enhanced growth in soft agar, reduced growth conditions, expression of SV40 T antigen, and altered epitheloid morphology. Both cell lines have been grown in continuous culture for more than 2 years. The stability of both the biologic properties and the karyotypic changes induced by SV40 is quite remarkable. Both lines show a nullisomy 13.