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Biomedical subjects

S Jablonska

Publications and source records attributed to S Jablonska.

At least 199 records · Page 11Linked to original sources

Introduction of cloned human papillomavirus genomes into mouse cells and expression at the RNA level.

The entire DNA genomes of five different human papillomaviruses (HPVs) were cloned into the BamHI site of pBR322 (HPV-1a, HPV-3, HPV-4, and HPV-9) or the EcoRI site of pBR325 (HPV-2), using as starting materials virus preparations isolated from papillomas of individual patients. Under stringent hybridization conditions (Tm-28 degrees), the five cloned HPVs exhibited less than 10% homology with one another. To establish model cell systems that may be useful for the identification of HPV genes and HPV gene products, mouse thymidine kinase negative (tk-) cells were cotransformed to the tk+ phenotype with the herpesvirus thymidine kinase gene and each of the five HPV cloned DNAs (either as intact recombinants or excised HPV DNA without removal of pBR). In most tk+ cell clones, a complex pattern of multiple high molecular weight inserts of HPV DNA were present in high copy number. Most of the HPV DNA sequences in the cotransformed cells were not present as unit-length episomal viral DNA. Analyses of the integration pattern (DNA blot) and RNA expression (RNA blot) of several HPV-1a and HPV-3 transformed cell lines suggest that some copies of the viral genome are integrated in a similar manner in different cell lines leading to the expression of identical viral RNA-containing species. Two of the cell lines transformed by the intact HPV-1a/pBR322 recombinant synthesized substantial amounts of four discrete viral polyadenylated cytoplasmic RNA species of 1.9, 3.2, 3.8, and 4.5 kb. Two cell lines transformed by the intact HPV-3/pBR322 recombinant synthesized 4-5 polyadenylated cytoplasmic viral RNA species ranging from 0.8 to 4.6 kb. The analysis shows that each viral RNA species appears to be a hybrid RNA molecule containing both HPV and pBR322 sequences. Based on these findings and the molecular organization of the HPV-1a genome (O. Danos, M. Katinka, and M. Yaniv (1982). EMBO J. 1, 231-237), it is possible that transcription of each of the HPV-1a RNA species is initiated using the HPV early promoter and terminated in pBR322.

Animals↗

Etretinate in severe psoriasis. Results of double-blind study and maintenance therapy in pustular psoriasis.

A randomized double-blind study was performed in forty patients with severe psoriasis. Etretinate, in contrast to placebo, clearly reduced the psoriatic area and severity index score, and this difference was statistically significant from week 2. The results in psoriasis vulgaris were satisfactory in only three of ten patients; however moderate improvement was noticed in four of ten patients. In pustular psoriasis of von Zumbusch type, the drug produced moderate improvement to complete clearing in all four of the treated patients and was regarded as the first-choice therapy in all of them. In erythrodermic psoriasis satisfactory results were obtained in four of six patients. In three of the five patients with psoriatic arthropathy there was a marked improvement of arthralgia. Laboratory investigations did not show significant abnormalities with the exception of an increase of alanine transaminase (ALT; SGPT) in about 20% of the patients. Ten patients with pustular psoriasis (four of them included in the double-blind trial) on long-term, i.e., maintenance, therapy remained free of lesions up to this writing for 3 years. Triglyceride levels were not elevated.

Clinical Trials as Topic↗

In vivo mobilization of polymorphonuclear leukocytes in psoriasis: relationship to clinical parameters and serum inhibitory factors.

Mean migration of polymorphonuclear leukocytes (PMNL) toward autologous and homologous control sera, evaluated by quantitative skin window chamber technique, was only slightly reduced in 60 patients with psoriasis as compared to 27 normal controls (p less than 0.1). A significant decrease in cell migration was found (1) in patients with actively spreading lesions, (2) in patients with extensive lesions involving more than 40-60% of the skin surface, (3) in the first 2 months of relapse, and (4) 5-6 months after onset of new lesions. However, PMNL migration was increased when psoriatic lesions lasted 3-4 months. Seventy-one percent of psoriatic sera exerted a suppressive effect on the psoriatic and normal PMNL migration. The inhibitors were found predominantly in patients with stationary and long-standing lesions. Some of the psoriatic sera had a stimulatory effect on the chemotaxis of psoriatic PMNL. These sera originated from those patients with active spreading lesions in the first 2 months of relapse. These data indicate that neutrophil migration is abnormal in the course of psoriasis and that it could be modified by different proportions of both inhibitors and stimulators of chemotaxis.

Cell Movement↗

Human papillomaviruses associated with epidermodysplasia verruciformis. II. Molecular cloning and biochemical characterization of human papillomavirus 3a, 8, 10, and 12 genomes.

The DNAs of four human papillomaviruses (HPVs) that were found in the benign lesions of three patients suffering from epidermodysplasia verruciformis have been characterized. The flat wart-like lesions and the macular lesions of patient 1 contained two viruses, HPV-3a and HPV-8, respectively, whose genomes had previously been only partially characterized. The flat wart-like lesions of patient 2 and the macular lesions of patient 3 each contained a virus previously considered as belonging to types 3 and 5, respectively. These viruses are shown in the present study to be different from all of the HPV types so far characterized; they have tentatively been named HPV-10 and HPV-12. The HPV-3a, HPV-8, and HPV-12 DNAs and the two SalI fragments of HPV-10 DNA (94.1 and 5.9% of the genome length) were cloned in Escherichia coli after having been inserted in plasmid pBR322. The cloned HPV genomes have similar sizes (about 7,700 base pairs), but their guanine-plus-cytosine contents differ from 41.8% for HPV-12 DNA to 45.5% for HPV-3a DNA. The study of the sensitivity of the four HPV DNAs to 14 restriction endonucleases permitted the construction of cleavage maps. Evidence for conserved restriction sites was found only for the HPV-3a and HPV-10 genomes since 5 of the 21 restriction sites localized in the HPV-3a DNA seem to be present also in the HPV-10 DNA. Hybridization experiments, performed in liquid phase at saturation, showed a 35% sequence homology between HPV-3a and HPV-10 DNAs, 17 to 29% sequence homology among HPV-5, HPV-8, and HPV-12 DNAs, almost no sequence homology between the HPV-3a or HPV-10 DNA and the other HPV DNAs, and a weak homology between HPV-9 DNA and HPV-8 or HPV-12 DNA. Blot hybridization experiments showed no sequence homology between the HPV-3a, HPV-8, and HPV-12 DNAs and the DNAs of the HPVs associated with skin warts (HPV-1a, HPV-2, HPV-4, and HPV-7) or with mucocutaneous and mucous membrane lesions (HPV-6b and HPV-11a, respectively). One exception was a weak sequence homology between the HPV-2 prototype and HPV-3a or HPV-10 DNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Composition↗

Studies in immunodermatology. XI. Demonstration of allospecificity of stratum corneum antibodies and antigens by indirect immunofluorescence.

The presence of allospecificities of stratum corneum (SC) antibodies was suggested by the observation that 5 normal human sera tested by indirect immunofluorescence (IF) on 5 unrelated normal human skins yielded variable titers on some skin specimens. Titers of SC antibodies of normal sera absorbed with ground callus collected from one donor in IF tests on 5 unrelated normal human skin specimens provided further evidence that allospecific SC antibodies are present in human sera and that SC antigens in different human skins are not identical. Since SC antibodies in human sera do not give significantly different titers on autologous skin substrates as compared to homologous ones, they behave both like auto- and alloantibodies.

Antibody Specificity↗

Studies in immunodermatology. IX. Effect of organic solvents and enzymes on the reactivity of stratum corneum antigens.

Explants of normal skin fail to react in direct immunofluorescence tests with stratum corneum antibodies. However, upon stripping with cellophane tape, the horny layer of such explants react in tissue culture. Swabbing of skin explants with ether and chloroform converts stratum corneum antigen (SCAg) from a nonreactive to a reactive form. Treatment with methanol, acetone or phosphate-buffered saline failed to bring about such a conversion. Treatment of skin explants with hyaluronidase and phosphilipase A converst SCAg of at least some skin explants to a reactive form. Treatment with trypsin, chymotrypsin and plasmin abolished the reactivity of SCAg upon prolonged incubation. However, upon short incubation with plasmin, SCAg was converted to a reactive form.

Antigens↗

Studies in immunodermatology. X. Detection of glycoprotein- and carbohydrate-type stratum corneum antigens by immunofluorescence: conversion effects of enzymes and trauma.

Normal human sera contain stratum corneum (SC) antibodies to two biochemically distinct antigens of normal skin as demonstrated by indirect immunofluorescence (IF) staining with selectively absorbed sera. Absorption of normal human sera with ground callus removed the SC antibodies reactive with the horny layer of normal skin but did not affect the SC antibody titers on cut edges of trypsin-digested callus or lesions of monkey skin induced by scratching. Conversely, absorption of the same sera with a carbohydrate-type SC antigen reduced SC antibody titers on the cut edges of trypsin-digested callus and on lesions of monkey skin induced by scratching but did not alter titers of SC antibodies on normal skin sections.

Animals↗

Biochemical characterization of two types of human papillomaviruses associated with epidermodysplasia verruciformis.

The DNAs of the human papillomaviruses (HPVs) associated with the benign lesions of two patients suffering from epidermodysplasia verruciformis (patients JD and JK) were analyzed by using 12 restriction endonucleases. None of the restriction endonucleases were one-cut enzymes for the HPV DNA obtained from patient JD, referred to as the prototypical HPV-5, whereas five of them were one-cut enzymes for the DNA of the major virus found in patient JK, referred to as HPV-9. The molecular cloning of the two fragments resulting from the cleavage of HPV-5 DNA by endonuclease HindIII and of the single fragment obtained after treatment of HPV-9 DNA with endonuclease BamHI was performed in Escherichia coli after the fragments were inserted in plasmid pBR322. A cleavage map of the two cloned genomes was constructed. Little sequence homology (4 to 5%) was detected between HPV-5 and HPV-9 DNAs by DNA-DNA hybridization experiments in liquid phase at saturation; this homology was reproducibly higher than that (2 to 3%) detected under the same conditions between these DNAs and HPV-1a DNA. In addition, blot hybridization experiments performed under stringent conditions showed no or little sequence homology between the DNAs of HPV-5 and HPV-9 and those of HPV prototypes of types 1, 2, 3, 4, and 7 associated with skin warts. These results confirm that HPV-5 and HPV-9 are two distinct HPV types.

Animals↗

Stripping of the stratum corneum in patients with psoriasis: production of prepinpoint papules and psoriatic lesions.

In patients with psoriasis, partial stripping of the stratum corneum induced minute erythematous and edematous, nonscaling papules six hours to seven days later. These "prepinpoint papules" PPPs) comparable to spontaneous PPPs, which we described earlier, appeared in 75 of 159 patients with active psoriasis but in none of 27 controls; 73% to 91% of these PPPs, depending on the activity of the disease, transformed into pinpoint papules. Histological and histochemical examinations of the PPPs showed infiltrates containing numerous polymorphonuclear leukocytes around the vessels and penetrating into the epidermis, partly destroying it. The earliest change in the epidermis was thinning of the granular layer without other features of psoriasis. Immunoglobulin G and complement deposits on stratum corneum (SC) antigen sites were found in the PPPs initially in about one third, and later in two thirds of the papules, whereas they were present in virtually all of the psoriatic pinpoint papules. Papules induced by stripping, similar to spontaneous PPPs, play a central role in the etiology of at least some forms of psoriasis. Polymorphonuclear leukocyte infiltrates and SC antibody binding are key features of the conversion of PPP to pinpoint psoriatic lesions.

Complement C3↗

Identification of papillomaviruses in butchers' warts.

We have studied the papillomaviruses found in the hand warts of 60 butchers, most of them from 2 distant slaughterhouses. Warts differing in morphology and location were studied separately. The viruses were identified by molecular hybridization, restriction enzyme analysis and immunofluorescence. Four known human papillomaviruses (HPV-1, HPV-2, HPV-3, HPV-4) were detected and one hitherto unknown papillomavirus was identified in 9 butchers. The DNA of the latter virus did not anneal with any of the RNAs complementary to either HPV-1 to HPV-5 or bovine papillomavirus type 1 (BPV-1) DNAs, and showed a Hind II + III restriction enzyme cleavage pattern distinct from those of known HPVs and BPVs. This virus showed distinct antigenic properties, as shown by immunofluorescence, using HPV-1, -2, -3, -5, and BPV-1 antisera. It may represent a new type of human papillomavirus (HPV-7) or a yet unidentified animal papillomavirus. In addition, 6 butchers were found to be infected with a papillomavirus, distinct from the known skin HPVs and from BPV-1, which could not be characterized by restriction enzyme analysis. Eleven butchers were found to be infected by 2 viruses. A characteristic histological pattern was found to be associated with the different papillomaviruses.

Bovine papillomavirus 1↗