SEARCH · PubMed Health

Results for “Serial Passage”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed2001

Phenotypic resistance of Staphylococcus aureus, selected Enterobacteriaceae, and Pseudomonas aeruginosa after single and multiple in vitro exposures to ciprofloxacin, levofloxacin, and trovafloxacin.

The phenotypic resistance of selected organisms to ciprofloxacin, levofloxacin, and trovafloxacin was defined as a MIC of > or =4 microg/ml. The dynamics of resistance were studied after single and sequential drug exposures: clinical isolates of methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa were utilized. After a single 48-h exposure of a large inoculum to four times the initial MIC for the organism, the frequency of selection of resistant mutants of MSSA was greater for trovafloxacin than levofloxacin (P = 0.008); for E. cloacae, the frequency was highest for ciprofloxacin and lowest for levofloxacin and trovafloxacin; for S. marcescens, the frequency was highest for trovafloxacin and lowest for ciprofloxacin (P = 0.003). The results of serial passage experiments were analyzed both by the Kaplan-Meier product-limited method as well as by analysis of variance of mean inhibitory values. By both methods, MSSA and MRSA expressed mutants resistant to ciprofloxacin after fewer passages than were required for either levofloxacin or trovafloxacin. For the aerobic gram-negative bacilli, two general patterns emerged. Mutants resistant to trovafloxacin appeared sooner and reached higher mean MICs than did mutants resistant to levofloxacin or ciprofloxacin. Mutants resistant to ciprofloxacin appeared later and reached mean MICs lower than the MICs of the other two drugs studied. Even though individual strain variation occurred, the mean MICs were reproduced when the serial passage experiment was repeated using an identical panel of E. coli isolates. In summary, the dynamic selection of fluoroquinolone-resistant bacteria can be demonstrated in experiments that employ serial passage of bacteria in vitro.

Anti-Infective Agents↗

PubMed1993

Spontaneous evolution of cytoplasmic lectin binding and nuclear size and deoxyribonucleic acid content in human colorectal cancers grafted onto nude mice.

BACKGROUND: The development of certain biologic characteristics in human colorectal tumor xenografted onto nude mice are described with respect to their precocious passages, i.e., passaging below 10 onto athymic mice. EXPERIMENTAL DESIGN: The biologic characteristic monitoring involved the determination of modifications occurring in cytoplasmic lectin binding and spontaneous development in nuclear size and DNA content. The lectin immunohistochemistry included the characterization of staining modifications in the glandular parts of the colorectal xenografts of wheat germ, Dolichos biflorus, peanut, Solanum tuberosum and Ulex europaeus I agglutinins. The nuclear modifications were monitored by means of the digital cell image analyses of Feulge-stained nuclei. RESULTS: The results show that although the xenografted human colorectal lines may be relatively stable according to their macroscopic growth over serial passaging, certain of their microscopic characteristics develop markedly. Three lectins, i.e., wheat germ agglutinin, Solanum tuberosum, and Ulex europaeus I, showed a glandular binding which remained relatively stable over serial passaging, whereas the peanut binding exhibited some variations and the DBA binding progressively disappeared. These cytoplasmic modifications occurring over time were less pronounced than those that occurred with respect to nuclear measurements, i.e., size and DNA content. CONCLUSIONS: Nuclear DNA content heterogeneity as revealed by DNA histogram typing rather than by DNA index assessments increased markedly in the colorectal xenografts over their serial passaging on nude mice.

Animals↗

PubMed1980

Preferential replication of a class of host-substituted defective simian virus 40 variants at low temperature.

The host-substituted variant termed CVP8/1/P2 (EcoRI res) was first isolated several years ago after serial passage of simian virus 40 strain 777 on BSC-1 cells at 37 degrees C. When BSC-1 are coinfected with wild-type simian virus 40 strain 777 and variant CVP8/1/P2 (EcoRI res), the variant rapidly becomes the dominant species produced, often representing as much as 80% of the total DNA I synthesized after infection. We present evidence that the replicative advantage of the variant was increased when the infection was carried out at 33 rather than 37 degrees C. Also described are nine new and independent serial passage experiments carried out at 33 degrees C with several purified wild-type virus stocks, including strain 776, and both BSC-1 and primary African green monkey kidney cells. In each series variants related to CVPs/1/P2 (EcoRI res) were detected in the progeny viral genomes after four serial passages. Hybridization data suggest that at least some of these variant DNA I molecules contain simian virus 40 DNA sequences, monkey alpha-component DNA sequences (highly repetitive), and the infrequently reiterated monkey DNA sequences found in CVP8/1/P2 (EcoRI res), all covalently linked as in CPV8/1/P2 (EcoRI res). It appears that this type of variant emerges with some frequency during infection and is then preferentially replicated at 33 degrees C, thereby becoming readily detectable in passaged stocks. A variety of control experiments indicated that the repeated emergence of similar, if not identical, variants is unlikely to be the result of inadvertent cross-contamination or the presence of detectable amounts of the variant in the plaque-purified viral stocks.

Animals↗

PubMed1986

Complementation between SV40 and RFV defectives and acquisition of SV40 origins by late RFV genomes.

EL SV40 and RFV are variants of SV40 and BKV which contain bipartite or dual genomes. One molecule contains all the early viral sequences (E-SV40, E-RFV) and the other all the late viral sequences (L-SV40, L-RFV). Early and late genomes complement one another during productive infection. Experiments were designed to determine if E-genomes of one virus could complement L-genomes of another virus. If complementation did occur, intermolecular recombination events which lead to a more efficient infection or an altered host range might occur, and the sequences involved could than be identified. Two combinations were generated by direct transfection of BSC-1 green monkey cells. E-RFV and L-SV40 DNA complementation resulted in hybrid virus growth and cell killing. The hybrid demonstrated a narrow host range. Following serial passage, some E-RFV genomes contained SV40 origin region sequences but these recombinants did not overgrow prototype E-RFV genomes, even after many virus passages. In addition, no significant alterations in host range could be detected. Complementation between E-SV40 and L-RFV yielded a virus with a relatively wider host range. Virus growth and cell killing appeared very slowly at first. However, with each passage of E-SV40/L-RFV, cell killing occurred progressively more rapidly, until passage 7 when it became extensive in 7 days rather than 6-8 weeks. Infected cells contained 10-20 times more E-SV40 than L-RFV DNA during the first passage. However, by passage 7, both genomes were equally represented. During serial passage, L-RFV DNA acquired SV40 sequences from around the origin and the terminus of replication, such that recombinant (r) L-RFV genomes contained three SV40 origins [corrected] (including the 72-bp repeat) and 2 termini, and prototype L-RFV DNA was lost. E-SV40/rL-RFV demonstrated an altered host range propagating in some cell lines which did not support E-SV40/L-RFV growth. Both the host range change and the increased growth of rL-RFV genomes were shown to be at least partly caused by the acquisition of the SV40 sequences.

Animals↗

PubMed2006

Preparation and evaluation of Vero-cell infectious bursal disease vaccine in Pakistan.

The present work was carried out to develop an effective vaccine to control infectious bursal disease (IBD). The very virulent infectious bursal disease virus (vvIBDV) was adapted to grow in Vero-cell line after three serial passages. The virus was then attenuated by further serial passages and pathogenicity of different passages was determined in broiler chicks free from antibodies against IBDV. The ninth passage virus was completely attenuated, as it was non-pathogenic to chicks. The birds inoculated with ninth passage virus had bursa to body weight ratio comparable to un-inoculated control and zero mean lesion score. This ninth passage virus was evaluated as live attenuated Vero-cell adapted vaccine. A commercial live cell culture origin vaccine (IBD-VAC, Korea) was used for comparison. Experimental trials were conducted in 3-week-old broiler chicks. Clinical signs, gross and histopathological lesions and bursa to body weight ratio were all comparable to un-vaccinated control group in case of live attenuated Vero-cell vaccine (group A). High virus-neutralizing antibody titres were also found at 7, 14, and 21 days post-vaccination in group A. On challenge, 100% protection was achieved in group A and 65% in case of commercial vaccine (group B) in terms of bursal lesions. All the birds in control group showed sever bursal lesions post-challenge. The study indicated newly developed infectious bursal disease vaccine was found to be safe and immunogenic.

Animals↗

PubMed2004

Selection of resistance of telithromycin against Haemophilus influenzae, Moraxella catarrhalis and streptococci in comparison with macrolides.

OBJECTIVE: The in vitro abilities of telithromycin, azithromycin and clarithromycin to select for resistance were compared by testing isolates of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and beta-haemolytic streptococci. METHODS: Five strains each of beta-lactamase-positive and beta-lactamase-negative H. influenzae, beta-lactamase-positive and beta-lactamase-negative M. catarrhalis, S. pneumoniae, beta-haemolytic group A, group C and group G streptococci and three strains of beta-lactamase-negative ampicillin-resistant H. influenzae were evaluated. Development of resistance was determined by multi-step and single-step methodologies. For multi-step studies, MIC values were determined after five serial passages on antibiotic-gradient plates and after 10 serial passages on antibiotic-free plates. Acquisition of resistance was defined as an increase of >/=4-fold from the starting MIC. In single-step studies, the rate of spontaneous mutations was calculated after a passage on plates containing antibiotics at concentrations equal to the highest NCCLS breakpoints. RESULTS: Azithromycin, clarithromycin and telithromycin gave a >/=4-fold increase in 20, 20 and 10 streptococcus strains, in 4, 5 and 0 H. influenzae strains and in 2, 7 and 4 M. catarrhalis strains, respectively. After 10 passages on antibiotic-free plates, 21/26 strains for azithromycin, 22/32 for clarithromycin and 1/14 for telithromycin maintained high MIC values. In single-step studies, the frequency of mutations was <10(-10) for H. influenzae and M. catarrhalis for telithromycin, azithromycin and clarithromycin. Telithromycin induced mutations at a lower rate than azithromycin and clarithromycin in streptococcal strains. CONCLUSION: Telithromycin showed a very limited ability to select for resistance in respiratory pathogens compared with azithromycin and clarithromycin.

Anti-Bacterial Agents↗

PubMed2004

Osteogenic potential of rat mesenchymal stem cells after several passages.

Osteogenic potential of serially passaged rat bone marrow derived mesenchymal stem cells (BMCs) was evaluated for clinical feasibility. Osteogenic differentiation in vitro was evaluated by means of the concentration and mRNA expression of alkaline phosphatase and osteocalcin. For in vivo osteogenesis, BMCs in various degrees of differentiation were implanted into the athymic mice. Although elevated levels of osteogenic markers were prominent in the less passaged BMCs continuously cultured with osteogenic supplements (OS group), they decreased with passaging. Similar to the in vitro experiments, abundant bone and cartilage formations inside the membrane were observed in the P0 through P2 cells of the OS group. In the P3 cells, however, the chambers were filled with fibrous tissues showing the failure of osteogenesis. Establishment of the culture conditions that permit the rapid expansion of BMCs while retaining their potential for differentiation will be required for future clinical applications.

Alkaline Phosphatase↗

PubMed1994

Change in phenotype of tick-borne encephalitis virus following passage in Ixodes ricinus ticks and associated amino acid substitution in the envelope protein.

Serial passage of an uncloned tick-borne encephalitis virus (strain 4387 isolated from the liver and lungs of a bank vole) in Ixodes ricinus ticks, was accompanied by gradual reduction in virulence of the virus, as indicated by transmission of virus by infected ticks feeding on laboratory mice. After the 7th serial passage in ticks (strain 4387/7), 95% of mice survived the bite of infected ticks. The surviving infected mice showed either no or only low viraemia although virus could be isolated from the brains of some mice 14 and 30 days after commencement of tick feeding, implying that the tick passaged virus might have established a persistent infection in the mice. Tests for haemagglutinating capacity were positive with TBE strain 4387 but strain 4387/7 exhibited no haemagglutinating activity over a wide pH range, suggesting that phenotypic changes, resulting from selection, had affected the site on the viral envelope protein that binds red blood cell receptors. Sequencing of the envelope protein gene of the virulent TBE strain 4387 showed 3 amino acid codon differences from western European TBE virus strain Neudorfl, which is also virulent for mice. The attenuated virus 4387/7, had an amino acid substitution that was different from 4387 and Neudorfl TBE virus (amino acid 84, E to K) and a second substitution different from 4387 but identical to Neudorfl virus (amino acid 319, I to T). Thus, the phenotypic change from virulence to attenuation was associated with a single amino acid codon change in the viral envelope gene of TBE virus. It is recognised, however, that amino acid substitutions in other parts of the viral genome have not been ruled out.

Amino Acid Sequence↗

PubMed2000

Accelerated replicative senescence of medial smooth muscle cells derived from abdominal aortic aneurysms compared to the adjacent inferior mesenteric artery.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are associated with aging and atherosclerosis. AAAs arise through a degenerative process characterized in part by depletion of medial smooth muscle cells (SMC), suggesting that generalized aging and SMC senescence represent potential mechanisms contributing to aneurysmal degeneration. It is not yet known whether SMC from AAA tissue exhibit a difference in proliferative capacity compared to SMC from nonaneurysmal vessels or to what extent such differences might be due to aging alone or other patient-specific factors. MATERIALS AND METHODS: Aneurysm wall tissues were obtained from 15 patients undergoing AAA repair. In each case, a segment of the adjacent (nonaneurysmal) inferior mesenteric artery (IMA) from the same patient was used as a control. Paired AAA- and IMA-derived SMC strains were obtained by explant techniques and their proliferative capacities were compared during serial passage in culture. RESULTS: Sustainable SMC cultures were established from all IMA explants but from only 9 of 15 AAAs (P < 0.05). The interval required to achieve primary explant growth was longer for AAAs than IMAs (16.4 +/- 2 vs 6.4 +/- 1 days; P < 0.001), but it was unrelated to patient age, gender, or aneurysm size. AAA-derived SMC appeared larger and rounder than the corresponding IMA-derived SMC, even after repeated passage in culture, and their maximal proliferation was reduced by 44.2 +/- 8% (n = 5 pairs, P < 0.05). Serum-stimulated [(3)H]thymidine uptake in AAA-derived SMC was also reduced by 54.9 +/- 7% (n = 5 pairs, P < 0.01), but flow cytometry revealed no differences in SMC viability, apoptosis, or necrosis. While IMA-derived SMC continued to proliferate beyond passage 20 during serial subculture, all AAA-derived SMC developed replicative senescence by passage 12. CONCLUSIONS: AAA-derived SMC exhibit a distinct morphologic appearance in culture, a diminished proliferative capacity compared to SMC from the adjacent IMA, and a limited in vitro life span. These differences reflect an intrinsic alteration in SMC growth capacity independent of age alone. Tissue-specific processes leading to accelerated replicative senescence may therefore contribute to the selective medial SMC depletion observed in AAAs.

Aged↗

PubMed2002

Growth and molecular evolution of vesicular stomatitis serotype New Jersey in cells derived from its natural insect-host: evidence for natural adaptation.

In this study we evaluated the growth and molecular evolution of a natural isolate of VSV-NJ (89GAS) from sand flies in cells derived from sand flies (LL5), mosquitoes (C6/36) or hamsters (BHK21). Two VSV-NJ natural isolates of mammalian origin were used for comparison. For each virus we measured: (i) ability to grow in one-step growth curve or after serial passage on each cell type; (ii) ability to induce persistent infection, and (iii) genetic stability of the glycoprotein gene (G) after serial passage in each cell type. Sand fly virus 89GAS grew to higher titers in insect cells compared with viruses of mammalian origin and showed increasing titers with each passage only in C6/36 cells. All viruses established productive persistent infections in both mosquito and sand fly cells but only LL5 cells yielded sustained high virus titers for periods of up to 81 days. Analyses of the consensus sequences of the G gene from each virus after 0, 10 or up to 25 passages in each cell line showed nucleotide substitution rates between 1.39 x l0(-4) and 6.95 x l0(-5). The majority of these changes were non-synonymous, suggesting positive selection. We did not detect increased nucleotide substitution rates on the G gene of 89GAS after passage in cell lines of mosquito or mammalian origin, nor in viruses of mammalian origin after passage in insect cells. This indicates that although VSV G is positively selected in vitro by the insect cell environment, this does not fully explain VSV natural adaptation. This is the first evidence of naturally occurring adaptation of VSV to cells derived from its natural host.

Adaptation, Physiological↗

PubMed1963

INFLUENCE OF TISSUE CULTURE PASSAGE ON VIRULENCE OF FOOT-AND-MOUTH DISEASE VIRUS FOR MOTHER MICE.

Campbell, Charles H. (Plum Island Animal Disease Laboratory, Greenport, N.Y.). Influence of tissue culture passage on virulence of foot-and-mouth disease virus for mother mice. J. Bacteriol. 86:593-597. 1963.-Foot-and-mouth disease virus serially passaged in bovine cell cultures was more lethal for mother mice than the parent virus from infected steers. In tests with virus from several pools of bovine tongue tissue, only 0 to 20% of the mice died. Serial passage of such virus in primary calf-kidney cell cultures progressively increased the lethality of the virus. By the eighth passage, after which no further appreciable increase was observed, the mortality was 60%. As the lethal capability of this virus population increased, the average time required for it to produce death decreased.

Animals↗

PubMed1979

DNA of human cytomegalovirus: size heterogeneity and defectiveness resulting from serial undiluted passage.

The majority of DNA molecules associated with plaque-purified, low-multiplicity-passaged human cytomegalovirus (Towne strain) had a molecular weight of approximately 150 x 10(6) and a molecular complexity of approximately 140 x 10(6). Serial high-multiplicity passage resulted in the production of defective cytomegalovirions. An accumulation of smaller DNA molecules packaged into virions was directly correlated with a decrease in infectivity and an increase in the particle-to-PFU ratio. The majority of defective DNA molecules had a molecular weight of approximately 100 x 10(6). In addition, there were some viral DNA molecules of approximately 60 x 10(6). Restriction enzyme analysis of defective cytomegalovirus DNA detected unique DNA fragments, suggesting a specific alteration in the nucleotide sequence. Some reasons for the generation of defective cytomegalovirus DNA are discussed.

Base Sequence↗

PubMed1966

Host influence on the characteristics of Venezuelan equine encephalomyelitis virus.

Heydrick, Fred P. (Fort Detrick, Frederick, Md.), Ralph F. Wachter, and Henry J. Hearn, Jr. Host influence on the characteristics of Venezuelan equine encephalomyelitis virus. J. Bacteriol. 91:2343-2348. 1966.-Alterations in plaque size, virulence, and lipid content of Venezuelan equine encephalomyelitis (VEE) virus were examined for possible interrelationships among these properties during 10 serial passages in embryonated eggs, suckling mice, chick embryo fibroblasts, and L cells. The chick embryo host maintained the same large-plaque and virulence properties of the virus through 10 passages as seen in the original seed. Passage of virus in either L cells or chick fibroblasts rapidly produced populations that were, in the main, intermediate with respect to plaque size and virulence. Passage of virus in suckling mouse brain yielded populations that were intermediate with respect to plaque size only. The nature of the lipid of the virus, in terms of the ratio of petroleum ether-soluble to -insoluble lipid, changed after only one passage in all systems except in chick embryos. Nine additional serial passages failed to enhance these changes in viral lipid, suggesting that the decrease in the large-plaque and virulence properties was not directly associated with changes in lipid content.

Animals↗

PubMed1983

Morphological transformation in vitro of normal human fibroblasts by chrysotile.

Pathologic response of tissue to asbestos in vivo gives rise to fibromatoma, granuloma and mesothelioma. We are attempting to develop a model system in vitro using human cells in order to investigate the possible mechanisms responsible for these pathologies. Within the first 12 hr of exposure to chrysotile, the fibroblasts showed distinctive morphological changes. Cells appeared elongated with occasional vacuolated nuclei and granular cytoplasm. Cells showed no other obvious morphological changes by light microscopy and were serially passaged at confluence. The cells with vacuolated nuclei were successfully serially passaged. Binucleated cells were first observed 48 hr after passaging. As time in culture increased (3 days to 2 weeks) many cells lost their distinctive bipolar properties and developed "stress striations" and multiple vacuoles in the cytoplasm. Multinucleated giant cells (2-11 nuclei/cell) with lobate nucleoli became more numerous. With increasing passages, the confluent cell density decreased and cell size increased. Cells usually had condensed nucleoli and had lost all control of directional growth. Preliminary indications suggest that these in vitro morphological transformations are due--at least in part--to a lack of control over cytokinesis.

Asbestos↗

PubMed1986

Immediate ascites conversion of mammary tumors induced in NYLR/Nya mice by 7,12-dimethylbenz-[a] anthracene and urethane feeding and by forced breeding.

Intragastric feeding of dimethylbenz-[a]anthracene in corn oil together with urethane in the drinking water and forced breeding were successful in rapidly inducing (2-4 months) mammary tumors (adenoacanthomas) in inbred NYLR/Nya mice, which have a low incidence of spontaneous breast tumors and of other tumors. The tumors could be quickly and permanently transformed to an ascites form by intraperitoneal inoculation of enzyme-dissociated cells and subsequent serial passage of free cells. Only 10 (3 in some cases) serial passages were required, thus conveniently providing multiple isogeneic carcinoma cell lines in this strain of mice. Some tumor cell lines proliferated strongly in the abdominal cavity even on the first passage.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1986

Observations on mouse-infective stocks of Cowdria ruminantium: attempts to demonstrate antigenic changes of the Kwanyanga stock in mice.

Starting from a stabilate of caprine blood infected with the Kwanyanga stock of Cowdria ruminantium, eight serial passages were made in groups of mice, and eight parallel serial passages in goats. Cross-immunity tests in goats and mice failed to demonstrate any difference between stabilates made after the eighth passage. The Kwanyanga stock was of exceptionally low virulence for Dutch goats.

Animals↗

PubMed1980

Variability in derivative strains of Bordetella pertussis.

Bordetella pertussis strain UT25 was isolated on Bordet-Gengou(B-G) agar from a child with whooping cough in 1977. Derivative strains were isolated from UT25 by serial passages on Trypticase Soy Agar (TSA) containing blood,followed by serial passages on plain TSA. At passage 69, UT25 was subcultured in parallel on TSA and B-G. For experiments, strains were grown in defined liquid medium, adjusted to a standard turbidity, and tested in parallel. Tests were performed to detect changes in immunogenicity, production of dermonecrotic toxin, histamine sensitizing ability, serologic properties, infectivity for mice by the intranasl route, production of adenylate cyclase, patterns of outer membrane proteins. Notable changes occurred in the properties of UT25 at passage 16, just when stable growth on blood-fresh medium was established. After 5 additional passages on TSA, however, the strain resembled the original isolate. At about passage 45, biological activity began to decline, and by passage 60 most biological activities were sharply diminished or undetectable. No recovery of biological activity was observed during a further 15 passages on TSA. Strains derived from the sixty-ninth passage of UT25, after passage on B-G for 5 subcultures, showed partial recovery of biological activity. Ten additional subcultures on B-G yielded strains which showed even higher biological activity. Fluorescent antibody staining confirmed that all strains studied were B. pertussis, and maintained reactive surface antigen(s), in spite of loss of agglutinability in specific antiserum.

Adenylyl Cyclases↗

PubMed1993

Dilute passage promotes expression of genetic and phenotypic variants of human immunodeficiency virus type 1 in cell culture.

We have studied the extent of genetic and phenotypic diversification of human immunodeficiency virus type 1 (HIV-1) upon 15 serial passages of clonal viral populations in MT-4 cell cultures. Several genetic and phenotypic modifications previously noted during evolution of HIV-1 in infected humans were also observed upon passages of the virus in cell culture. Notably, the transition from non-syncytium-inducing to syncytium-inducing phenotype (previously observed during disease progression) and fixation of amino acid substitutions at the main antigenic loop V3 of gp120 were observed in the course of replication of the virus in MT-4 cell cultures in the absence of immune selection. Interestingly, most genetic and phenotypic alterations occurred upon passage of the virus at a low multiplicity of infection (0.001 infectious particles per cell) rather than at a higher multiplicity of infection (0.1 infectious particles per cell). The degree of genetic diversification attained by HIV-1, estimated by the RNase A mismatch cleavage method and by nucleotide sequencing, is of about 0.03% of genomic sites mutated after 15 serial passages. This value is not significantly different from previous estimates for foot-and-mouth disease virus when subjected to a similar process and analysis. We conclude that several genetic and phenotypic modifications of HIV-1 previously observed in vivo occur also in the constant environment provided by a cell culture system. Dilute passage promotes in a highly significant way the expression of deviant HIV-1 genomes.

Acquired Immunodeficiency Syndrome↗