Human papillomavirus infection of the cervix: the atypical condyloma

We report on 162 cases of human papillomavirus (HPV) infection of the cervix seen in a two-year period in which the cell sample showed such marked atypia that errors of interpretation could easily have been made. These atypical condylomata are difficult to diagnose cytologically as well as histologically because they mimic dysplasia or carcinoma in situ and, on smears, even invasive squamous carcinoma. HPV particles associated with fibrillar material were found within nuclei of these lesions; their nature was further proved by the immunoperoxidase test. This new form of HPV infection of the cervix showed a 9.1% rate of progression to more advanced cervical lesions. The cytologic finding of atypical condylomata is an indication for colposcopy, confirmative biopsy and appropriate treatment.     

Evidence for a Polymorphism in Gametic Segregation Using a Malate Dehydrogenase Locus in the Tetraploid Treefrog HYLA VERSICOLOR

Artificial cross combinations of tetraploid Hyla versicolor were analyzed electrophoretically using a polymorphic malate dehydrogenase locus (MDH-1) to determine the mechanism of chromosome segregation. Models for differentiating between disomic and tetrasomic inheritance are presented and tested. In some crosses progeny genotypes fit a disomic mode of segregation. In other crosses there is only evidence for a tetrasomic mode of segregation. Additional crosses produced genotypic ratios which conformed to either a disomic or tetrasomic mode of segregation. The same type of inheritance was demonstrated for any individual when used in multiple cross combinations. These results suggest that there exists in H. versicolor a polymorphism with respect to segregation of gametes, resulting from differences in chromosome pairings during meiosis I.     

Enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity: selective radioassay, properties, and regional distribution in human brain

Abstract: The compound [³H-Tyr¹,D-Ala²,Lcu-OH⁵]enkephalin has been synthesised as a potentially selective substrate for enkephalin dipeptidyl carboxypcptidase ( enkephalinase ) activity in brain. lncubations in the presence of homogenates and particulate fractions from rodent and human brain result in the formation of [³H]Tyr-D-Ala-Gly, which can be conveniently isolated by polystyrene bead column chromatography. The enzyme activity responsible for the hydrolysis of the Gly³-Phe⁴ amide bond of this substrate displays close resemblance to that hydrolysing the natural enkephalins at the same level. In addition, enkephalinase activity characterised in postmortem human brain is closely similar to that in rodent brain, with regard to optimal pH and apparent affinities of various substrates and inhibitors, including the potent compound thiorphan. Enkephalinase activity is distributed in a highly heterogeneous fashion among regions of human brain, the highest levels being found in globus pallidus and pars reticulata of the substantia nigra. This distribution is poorly correlated with that of opiate receptor binding sites but displays some resemblance to that of reported Met5-enkephalin levels.     

Phosphorylation patterns of tumour antigens in cells lytically infected or transformed by simian virus 40.

The phosphorylation sites of simian virus 40 (SV40) large tumor (T) antigens have been analyzed by partial proteolysis peptide mapping and phosphoamino acid analysis of the resulting products. At least four sites were found to be phosphorylated. An amino-terminal part of the molecule contained both phosphoserine and phosphothreonine. One phosphothreonine residue was located in the proline-rich carboxy-terminal end of the molecule, either at position 701 or at position 708. The mutant dl 1265, which is defective in adenovirus helper function, lacked this phosphorylation site. In addition, the carboxy-terminal part of the molecule contained phosphoserine at a more central position. T-antigen-associated proteins of SV40-transformed cell (nonviral T; 51,000 to 55,000 daltons) also contained multiple phosphorylation sites involving at least two serine residues in mouse antigens and an additional threonine residue in rat, human, and monkey antigens. The latter residue and at least one phosphoserine residue were located near one terminus of the human NVT molecule. We did not find any evidence for phosphorylation of tyrosine residues in any of the multiple species of either large T or nonviral T molecules. Several forms of large T antigens were extracted from both SV40-transformed and SV40-infected permissive and nonpermissive cells, and their phosphorylation patterns were compared. No evidence was found for a different phosphorylation pattern of T antigen in transformed cells.     

H-Y antigen in X,i(Xq) gonadal dysgenesis: Evidence of X-linked genes in testicular differentiation

Summary Three years ago, we detected H-Y antigen in the white blood cells of a phenotypic female with several of the stigmata of Turner's syndrome, and the mosaic karyotype: 45,X/46,X,i(Xq). We surmised at the time that the isochromosome, i(Xq), may have contained occult Y-chromosome-derived material. We have now confirmed the presence of H-Y in this patient and we have obtained evidence for the presence of H-Y in four of five other similar patients, all of whom are notable for carrying at least a single cell line with the karyotype 46,X,i(Xq). Although we cannot categorically exclude the presence of Y-chromosomal genes in the cells of these patients, there is no cytogenetic evidence of structural rearrangement involving the Y in any of the cases. Expression of H-Y antigen in association with i(Xq) thus implies that H-Y structural genes are X-situated, or alternatively that they are autosomal and X-regulated. It would follow that the H-Y⁺ cellular phenotype per se is not a valid marker for the Y-chromosome, and that H-Y genes that have been mapped to the pericentric region of the Y may be regulatory.     

Effects of Hoechst 33258 on condensation patterns of hetero- and euchromatin in mitotic and interphase nuclei of Drosophila nasuta

Embryonic and third instar larval brain cells of D. nasuta were cultured in vitro in the presence of Hoechst 33258 (H) and H + 5-bromodeoxyuridine (BUdR) for periods varying from 2 to 24 h at 24 °C. Air-dried chromosome preparations were made with and without hypotonic pretreatment and stained with Giemsa. Metaphase chromosomes from H-treated (2 h) embryonic preparations show typical inhibition of condensation of the A-T-rich heterochromatin as in mouse. Presence of BUdR with H causes inhibition of condensation in fewer embryonic metaphase cells, but in the affected metaphases the degree of inhibition is more severe. In larval brains, however, even a 24 h H or H + BUdR treatment does not cause any significant inhibition of heterochromatin condensation. It is suggested that the differences in H effect on metaphase chromosomes of embryos and larval brains is related to differences in chromosome organization in the two cell types. Exposure of H-treated embryonic as well as larval brain cells to a hypotonic salt solution prior to fixation causes a ‘supercondensation’ of the heterochromatic chromocentre in most interphase nuclei. Presence of BUdR along with H reduces the frequency of cells showing such ‘supercondensed’ chromocentre. The euchromatin region in H-treated interphase nuclei is, on the other hand, slightly more diffuse than in control nuclei. Apparently, H-binding to DNA affects the nucleoprotein organization in hetero- and euchromatic regions of interphase nuclei in specific ways.     

Cotugnia digonopora: Transport of leucine

The uptake of leucine through the tegument of Cotugnia digonopora, a cestode found in the fowl intestine, occurs by a process of active transport. The K_t of transport is 0.87 mM and the V_max is 0.223 μmol/min/g. Uptake of the amino acid is competitively inhibited by valine (K_t = 1.30 mM). Potassium cyanide and 2,4-dinitrophenol do not completely block the entry of leucine into the parasite.     

Complement-dependent induction of DNA synthesis and proliferation of human diploid fibroblasts

The effects of fresh human serum (FHS) and heat-inactivated human serum (HHS) on the DNA synthesis and proliferation of human diploid fibroblasts were assessed. FHS activated significantly more quiescent fibroblasts to undergo DNA synthesis and proliferation than did HHS. The stimulatory effect occurred consistently over a serum concentration range of 0.1–10%. Using bromodeoxyuridine selective killing techniques, it was shown that this FHS stimulatory effect was on a specific subpopulation of fibroblasts unresponsive to HHS. The involvement of the complement system, and specifically of C1, was shown by the inability of Clq-depleted FHS to support enhanced DNA synthesis whereas Clq-depleted serum reconstituted with purified Clq was effective. Purified Clq did not restore activity when added to heated serum, nor was it mitogenic when tested in basal medium without serum. The addition of purified Clq to fresh serum inhibited the enhancement of DNA synthesis, and at Clq concentrations of 4γ/ml and greater, the fresh serum effects were abrogated. Thus, it appears that binding of the assembled C1 complex to the fibroblast surface was required for FHS-mediated enhancement of fibroblast proliferation, with Clq subcomponent serving as the recognition site. The results from several experiments indicated that antibody was not required for the complement-dependent fibroblast activation. FHS was not cytotoxic, and autologous serum was as effective as allogeneic sera. A 20-fold molar excess of Fab' from pooled human IgG did not alter the FHS effects. FHS from which IgG was more than 99% depleted was still effective. These results suggested an antibody-independent role for complement in the activation of a subpopulation of human diploid fibroblasts.