PubMed Health⌕ Search

Biomedical subjects

J Salk

Publications and source records attributed to J Salk.

At least 37 records · Page 2Linked to original sources

Vaccinology of poliomyelitis.

Vaccinology requires not only an understanding of the fundamental properties of the immune system and specific immunogens, but also the application of basic knowledge to develop effective immunization programmes for particular social, political, and environmental conditions. Two problems exist in the use of oral, live poliovirus vaccine: the occurrence of vaccine-associated paralytic poliomyelitis and the uncertain antibody response in tropical climates. These difficulties can be overcome by the use of killed poliovirus vaccine formulated to be effective with a single dose. Application of basic principles can bring poliomyelitis fully under control in all parts of the world.

Administration, Oral↗

Serum demyelinating factors in multiple sclerosis.

Sera from 21 patients with multiple sclerosis were applied to myelinated spinal cord cultures and evaluated for demyelinating activity. Samples were collected at various times when patients were on or off therapy with myelin basic protein or prednisone or both, and at various stages of disease. Five of 31 serum samples from 17 patients exhibited demyelinating activity when tested in a 40% concentration in tissue culture nutrient medium. Four of the 10 serum samples taken from patients with active or remitting multiple sclerosis (2 samples from the same patient) were demyelinative; 1 of 21 sera collected during stationary periods of disease was positive. There was no correlation between serum demyelinating activity and the presence or absence of treatment. Sera positive for demyelinating activity failed to inhibit myelin formation in initially unmyelinated cerebellar cultures.

Animals↗

Antigen content of inactivated poliovirus vaccine for use in a one- or two-dose regimen.

The immunologic response to inactivated poliovirus vaccine following one and two doses has been studied in infants in developing and developed countries using vaccine prepared at the Rijks Instituut voor de Volksgezondheit, The Netherlands. Virus was grown in microcarrier cultures of monkey kidney cells, purified, concentrated, and inactivated with formalin. The vaccines used contained different quantities of D-antigen units for each of the three types. The data reveal that both antibody and immunologic memory (booster-type responsiveness) were induced in virtually all individuals following a single dose of a sufficient quantity of antigen. Immunologic memory was readily revealed by the booster-type response following a second dose given six months after the first. The degree of booster-type response to a second dose is linked primarily to the quantity of antigen used for primary immunization, and secondarily to the quantity of antigen used for the booster dose. The data base is presented for formulating the antigen content of an inactivated poliovirus vaccine that can be relied upon to be protective after the first dose when given alone or when incorporated with combinations of other antigens (diphtheria-per tussis-tetanus) that may require two or more doses.

Antibody Formation↗

Monkey kidney cell growth optimization and poliovirus propagation in microcarrier culture.

Three monkey kidney cells lines Vero, LLC-MK2 and CV-1 were grown in microcarrier cultures. The carrier support was DEAE-Sephadex gel beads at low anion exchange capacity prepared according to a protocol developed at the Massachusetts Institute of Technology. The growth rate of the cells and the final cell density in microcarrier culture was dependent on the concentration of the beads in culture and on the size of the initial cell inoculum. The efficiency of the microcarrier culture system was compared to that of stationary and roller bottle cultures. The microcarrier culture system was applied to the propagation of polioviruses in the three established monkey kidney cell lines and the yields were compared with those obtained in roller bottle and stationary cultures. The yield of the three types of polioviruses in the various cell lines and culture systems was similar. The use of the microcarrier culture system for anchorage-dependent cells together with the use of continuously propagating cell lines offer great advantage for large-scale cultivation of poliovirus for the preparation of killed poliovirus vaccines.

Animals↗

Detection and elimination of cellular nucleic acids in biologicals produced on continuous cell lines.

Experiments have been conducted to determine the extent to which currently available purification techniques can remove contaminating substrate cellular DNA from inactivated poliovirus vaccine produced on continuous cell lines rising highly [32P]-labeled, nick-translated cellular DNA added to poliovirus suspensions, we found that purification procedures were capable, in small-scale experiments, of reducing contaminating DNA by factors of 10(3) (DNAse treatment followed by gel filtration) and 10(3)-3X10(5) (ion exchange chromatography). Sequential application of these purification steps should reduce contaminating cellular DNA to acceptable levels. We also examined the potential usefulness of immobilized nucleic acid hybridization techniques for the routine direct testing of residual cellular nucleic acids in final production lots of inactivated poliovirus vaccine and other biologicals. A filter hybridization test, using [32P]-labeled, nick-translated cellular DNA as a probe, was capable of detecting 40 pg of homologous cellular DNA. Using probes of higher specific activity the assay should be sensitive enough for use in routine quality control.

Animals↗

Theoretical and practical considerations in the application of killed poliovirus vaccine for the control of paralytic poliomyelitis.

This paper contains a summary of the principles upon which the preparation and use of killed poliovirus vaccine (KPV) are based, as well as a summary of earlier and more recent work suggesting the feasibility of formulating a KPV preparation that would be fully and durably effective in a one- or two-dose regimen. The essential factor in the preparation of such a vaccine is the inclusion of a sufficient mass of the immunizing antigen, for each of the three antigenic types of poliovirus, to induce the formation of humoral antibody and/or immunologic memory after the first dose. The results of a series of studies carried out in West African and Scandinavian countries are summarized, which suggest that such a vaccine should contain 40, 8, and 32 D-antigen units for types I, II and III, respectively. If the D-antigen unit measurement is to be used as a guide to KPV standardization, the details of the method of manufacture are important; in this regard, the method of vaccine preparation used at the Rijks Instituut voor de Volksgezondheid should serve as a reference standard for the preparation of vaccines expected to produce the effects described.

Antibody Formation↗

Theoretical considerations and practical concerns regarding the use of continuous cell lines in the production of biologics.

The origin and history of continuous cell lines are discussed briefly in the context of their biological relationship to diploid and tumorigenic cells. The question of the potential tumorigenicity of continuous cell lines is examined from the points of view of the theoretical risks involved in the use of these cells for the production of biological products, and of practical approaches to risk assessment. Animal and in vitro tumorigenicity test systems are discussed, and published data on the transfer of tumorigenic properties by DNA are reviewed. Both animal and human experience with vaccines produced in tumor cells is discussed in relation to cancer risk. When the theoretical risks of using continuous cell lines as substrates to produce biological products are balanced against the available data, it would appear reasonable to proceed with the use of such cell lines for the development of biologics because the benefits of those products appear to exceed by far the potential risks associated with the use of these cell substrates.

Animals↗

Immunization against poliomyelitis: risk/benefit/cost in a changing context.

Benefit/risk factors in immunization against poliomyelitis are examined from the viewpoint of the relative risk and efficacy of killed and live poliovirus vaccines in the currently changing contexts of poliomyelitis prevalence in developed and developing countries. Risk factors include virus of vaccine origin gaining access to the CNS, and failure of the vaccine to immunize. Data are presented to illustrate the degree to which the respective risks occur in developed and developing countries. The ultimate elimination of risk by eradication of wild and vaccine virus from the population is discussed.

Adolescent↗

Temperature distribution in tissue during laser irradiation.

During irradiation with an Ar+-and Kr+-laser the temperature rise in living and dead tissue was measured in various depths. The contribution of the blood flow to the heat transport during irradiation was found to be small. The influence of the different depths of penetration and backscattering at the blue-green Ar+-and the red Kr+-radiation was investigated. The measurements compared with theory show reasonable agreement for an one-dimensional model below 100 degrees C. The results are discussed with respect to laser application in medicine.

Animals↗

A laser-endoscope with direct beam coupling.

An optical element for direct laser-beam coupling into the observation optic of a rigid endoscope was developed. Using this coupling element every suitable endoscope can be modified into a laser endoscope which can be used for laser surgery e.g. in ENT and urology. The requirements for the endoscope and the optical coupling element are discussed.

Endoscopes↗

Killed poliovirus antigen titration in humans.

To establish the antigen content of a killed poliovirus vaccine sufficiently potent to induce immunity with one or two doses and to establish a reference standard vaccine which has been tested under field conditions, a titration was carried out in infants to determine the amount of each of the three antigenic types of poliovirus vaccine required to induce seroconversion with a single dose. It has been observed that over a critical range of antigen concentration there is an essentially linear relationship between antibody response and quantity of antigen administered. More than 90 percent of the groups studied had detectable antibody after receiving single injections of 80, 8 and 64 D-antigen units of Types I, II and III, respectively. Four-fold less antigen for each of the three types was less effective. The implications of these findings for an efficient immunization procedure are discussed.

Antibodies, Viral↗