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D Salk

Publications and source records attributed to D Salk.

48 records · Page 3Linked to original sources
PubMed1981

Evidence of clonal attenuation, clonal succession, and clonal expansion in mass cultures of aging Werner's syndrome skin fibroblasts.

Skin fibroblast-like (FL) cells from patients with Werner's syndrome (adult progeria) demonstrate multiple, stable, structural chromosome rearrangements (variegated translocation mosaicism) which can be used to identify cytogenetically marked clones of cells within a mass culture. We have cytogenetically followed eight FL cell strains (from two patients) throughout their entire in vitro replicative lifespans, and we show a correlation between the expansion and attenuation of individual clones and the growth of the mass cultures. One strain, which was aged several times, demonstrated a generally reproducible pattern of clonal succession but, surprisingly, also demonstrated, in two parallel derivative cultures, the late emergence of two relatively rapidly growing clones that had not been observed in the parental culture. These observations suggest that clonal succession and clonal attenuation occur in mass cultures, as had been predicted on the basis of dilute-plating cloning experiments. Our results may have implications for models of in vitro cellular senescence. In addition, there are interesting parallels with the tissue hyperplasia associated with in vivo aging, and this observation is compatible with the suggestion that skin FL cells in vitro provide a model for hyperplasia in vivo.

Cell Cycle↗
PubMed1981

Herd effect and virus eradication with use of killed poliovirus vaccine.

Use of killed poliovirus vaccine reliably provides protection against paralysis in individuals and can reduce the transmission of poliovirus in communities to the point of eradication. In some countries improved hygienic conditions have blocked the fecal-oral spread of poliovirus as indicated by a shift in the age distribution and the occurrence of epidemic outbreaks of poliomyelitis. In these countries pharyngeal spread is the principal means of poliovirus transmission, and it is effectively blocked by use of killed poliovirus vaccine. In countries where poliomyelitis is endemic the fecal-oral route of spread may play a more significant role; it remains to be seen if there will be an epidemiologic effect from the reduction in fecal virus excretion that is associated with high levels of serum antibody induced by potent killed poliovirus vaccine. Nevertheless, killed poliovirus vaccine will prevent paralysis in individuals in countries where poliomyelitis is endemic, and it can prevent the disease from becoming epidemic as hygienic conditions improve.

Adolescent↗
PubMed1980

Effects of chromosome constitution on growth and longevity of human skin fibroblast cultures.

Employing standardized cell-culture methods, 10 euploid and 22 constitutionally aneuploid human skin fibroblast strains were assessed in triplicate for total growth potential, growth rates, population-doubling times, and cloning. In addition, longitudinal growth rate studies were carried out with otherwise isogenic 45,X and 47,XXX clonal cultures derived from a mosaic parental strain. Growth rates and longevities were cell-strain specific and highly reproducible among sister cultures of a given strain. There was no systematic correlation between chromosome constitution and any of the measured growth parameters. Trisomic as well as monosomic strains showed the same degree of variability with respect to these parameters as did euploid cultures. In particular, 4 trisomy 21 strains were not unusually short-lived, nor were clones with the 47,XXX constitution compared to those with 45,X karyotypes. We therefore conclude that the cumulative number of in vitro doublings preceding senescence of fibroblast-like cells cultured from skin does not differ significantly among cultures derived from humans who have a normal karyotype, trisomy 13, 18, or 21, the 45,X constitution, or various combinations of extra X and Y chromosomes.

Aneuploidy↗
PubMed1979

Cellular aging in Werner's syndrome: a unique phenotype?

Werner's syndrome is commonly regarded as a model for the study of premature aging. There are, however, a variety of clinical and pathologic anatomical features that clearly distinguish it from aging in normal individuals. In this paper we report on in vitro cytogenetic and cell fusion studies that indicate cultured fibroblast-like cells derived from Werner patients differ from cells of normal donors. Despite these discordances with "natural" aging, however, Werner's syndrome, like several other "segmental progeroid syndromes," may prove useful for the investigation of selected aspects of the aging process and of age-related diseases.

Adult↗
PubMed1977

Control of influenza and poliomyelitis with killed virus vaccines.

The requirements for inducing immunity against an infectious disease are outlined, and the application of these requirements to the development of effective vaccines (vaccinology) is discussed. Influenza and poliomyelitis are examined from this viewpoint, and data are presented that demonstrate the effectiveness of killed virus vaccines against these diseases. A comparison between live and killed poliovirus vaccines suggests the desirability of returning to the use of a killed virus vaccine for the eradication of polio. The natural history of influenza and experience with vaccination suggest that influenza might be brought under effective control by routine immunization in childhood with a polyvalent killed virus vaccine potentiated by an immunologic adjuvant.

Adjuvants, Immunologic↗
PubMed1977

Long-term changes in the perception of comfortable mandibular occlusal positions.

The aim of this study was to disclose, whether use of a screw jack device to set the distance between the jaws, would contribute towards a stabilization of the magnitude and position of a comfortable zone of mandibular positions or even eliminate it. Thirteen subjects participated in each of fifteen experimental sessions distributed over a 3-week period. Throughout the investigation the zone prevailed at an average width of 1-3 mm. The gap shrank 0-08 mm on average per experimental session. Although this latter value was found to be significant statistically, it can hardly be of clinical importance, considering the time needed for a total contraction of 0-8 mm to develop.

Aged↗
PubMedDate not supplied

Age-related increase in methylation of ribosomal genes and inactivation of chromosome-specific rRNA gene clusters in mouse.

An age-related increase in DNA methylation of the multicopy 18S and 28S ribosomal RNA genes was found in CBA/Ca mice beginning between 6 and 18 months of age at the 5' end of these genes in liver, brain and spleen. The highest level of age-associated hypermethylation was mapped to the proximal 5' spacer domain. Silver staining of actively transcribing ribosomal genes in metaphase chromosomes from stimulated spleen cells provided cytological evidence that these mice have 3 rRNA cistrons located on chromosomes 15, 16, and 18. The ribosomal gene cluster located on chromosome 16 was preferentially inactivated in older animals. Exposure of spleen cells from older individuals to 5-azacytidine appeared to both reactivate ribosomal gene clusters and reduce rRNA gene methylation.

Aging↗
PubMedDate not supplied

Eradication of poliomyelitis in the United States. I. Live virus vaccine-associated and wild poliovirus disease.

The patterns of incidence of poliovirus disease in the United States are analyzed. A category of live poliovirus vaccine-associated paralysis is defined that includes those cases associated with vaccine virus but with no known history of exposure to the vaccine (indirect community contact). Domestically arising wild poliovirus disease has essentially been eradicated from the United States, whereas the incidence of vaccine-associated disease has been constant at approximately nine cases per year. The age distribution of vaccine-associated disease reflects patterns ofuse of the vaccine rather than intrinsic differences in susceptibility believed to be associated with age. Eighty-eight percent of vaccine-associated cases of poliomyelitis occur in individuals with a normal immune system.

Disease Outbreaks↗
PubMedDate not supplied

Eradication of poliomyelitis in the United States. II. Experience with killed poliovirus vaccine.

Killed poliovirus vaccine was the only poliomyelitis vaccine available in the United States from 1954 to 1962. During that time, the incidence of poliomyelitis among non-vaccinated individuals decreased by 90%, an indication that the circulation of wild poliovirus had been reduced ("herd effect"). The rate of decline of wild poliovirus disease, which resulted from use of killed vaccine, did not change after oral, live poliovirus vaccine was introduced in 1962. Neither mass immunization campaigns nor use of an orally administered vaccine has increased rates of poliomyelitis immunization. Outbreaks of poliomyelitis can occur in susceptible subgroups in otherwise well vaccinated populations; therefore, the degree of population protection is best evaluated in terms of the number of susceptible individuals and their opportunities for contact with each other rather than in terms of the percentage of the total population vaccinated. Eradication of poliomyelitis and elimination of poliovirus from large populations are possible with use of killed poliovirus vaccine.

Age Factors↗
PubMedDate not supplied

Eradication of poliomyelitis in the United States. III. Poliovaccines--practical considerations.

Practical considerations for the choice of poliomyelitis vaccine in the United States are discussed. Both killed and live poliovirus vaccines protect against paralysis. They provide equivalent duration of immunity in individuals, equivalent protection against spread of poliovirus in communities, and equally rapid protection during epidemic outbreaks of poliomyelitis. The principal differences between these vaccines are the transmission of live vaccine viruses from recipieits to their contacts and the occurrence of occasional cases of paralytic poliomyelitis associated with use of live poliovirus vaccine. Risks and benefits of "spreading immunity" by person-to-person transmission of live vaccine viruses are presented. Suggestions for reducing the incidence of live virus vaccine-associated disease are discussed. The level of protection against poliomyelitis that has been achieved in the general population of the United States has resulted in the virtual eradication of disease due to wild polioviruses. Routine use of killed poliovirus vaccine may eradicate all domestically arising poliomyelitis, both vaccine-associated and wild poliovirus disease, and may eliminate poliovirus from the United States.

Age Factors↗
PubMedDate not supplied

Use of killed poliovirus vaccine in a routine immunization program in West Africa.

Combined diphtheria-tetanus-pertussis (DTP)-killed poliovirus vaccine was used (along with bacille Calmette-Guérin, measles, yellow fever, and smallpox vaccines) in a routine immunization program in a rural area of Senegal. A control group in a neighboring region received DTP vaccine without poliovirus vaccine. All immunizations were given at two sessions six months apart by a small mobile health team led by a nurse. Six months after the second dose of DTP-polio vaccine, 97.4%, 97.7%, and 90% of subjects two to eight months old at the start had detectable antibody to poliovirus types 1, 2, and 3, respectively. In the control group, 50%, 38%, and 80% of such subjects had antibody to poliovirus types 1, 2, and 3, respectively, acquired by natural infection during the study year. An average of 3.9 cases of paralytic poliomyelitis (range, one to 13) were observed annually at one dispensary in the test region from 1966 through 1979. From 1980 through 1982, since the immunization program has been in effect, only one case has been observed (in a nonimmunized child).

Africa, Western↗