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Biomedical subjects

F Rapp

Publications and source records attributed to F Rapp.

At least 73 records · Page 4Linked to original sources

Evidence for the association of cytomegalovirus with carcinoma of the prostate.

A human genital isolate of cytomegalovirus is shown to have transformed human embryonic lung cells in vitro. These cells produce tumors when injected into athymic nude mice. Two cell lines derived from tissue from human prostatic carcinoma have survived more than 20 passages in vitro and demonstrate cytomegalovirus-specific membrane antigen. Significant humoral antibody titers against cytomegalovirus have been demonstrated. Cell-mediated lymphocytotoxicity against these transformed cells has been demonstrated in patients with urinary tract tumors. This evidence indicates that an association between cytomegalovirus and human prostatic cancer may be more than coincidental.

Adenocarcinoma

Lymphocyte reactivity against virally transformed cells in patients with urologic cancer.

Lymphocytes from patients with urologic cancer were tested in microcytotoxicity assays against human cells transformed by cytomegalovirus. Human lymphocytes were significantly cytotoxic against the transformed cell line when compared to a normal human control cell line. Patients with prostatic carcinoma demonstrated greater target cell reduction than those with benign prostatic hyperplasia.

Adenocarcinoma

Variation in ability of measles virus plaque progeny to induce interferon.

Plaque progeny of three interferon (IF)-inducing strains of measles virus (Edmonston, Schwarz, and CC) were examined for ability to induce IF in BSC-1 cells. Only after passage in Vero cells did any of the Edmonston progeny induce IF. The vast majority of plaque progeny selected from the Schwarz strain induced IF, even though this virus was originally derived from the Edmonston strain. This property was retained even after serial plaque purification of the progeny. However, the Schwarz-derived CC strain consisted of a population generally unable to induce IF. Stocks grown from both Edmonston and CC plaques demonstrating the IF+ phenotype maintained this characteristic as a whole, but it was not a property that was inherited by all progeny in the stocks. Levels of IF induced were approximately the same for all strains, even though the proportion of inducing progeny varied markedly among them. These noninducing variants appeared to be normal, fully infectious measles virions. The results suggest that induction of IF by measles virus is at least partially under the genetic control of the virus.

Cell Line

Human cells transformed in vitro by human cytomegalovirus: tumorigenicity in athymic nude mice.

Athymic nude mice were inoculated with human embryo lung cells transformed in vitro by human cytomegalovirus (CMV). Of the inoculated animals, 62% developed tumors after an average latent period of 19 days. The tumors were composed of small, polygonal cells with large nulei and scanty cytoplasm embedded in an abundant collagenous matrix. The cells were poorly differentiated but may have been of epithelial origin. Adjacent structures were rarely invaded. CMV-related intracellular and membrane antigens were detected by indirect and anticomplement immunofluorescence techniques in cells cultured in vitro from the tumors.

Animals

Comparison of the polypeptides of several strains of human cytomegalovirus.

Analysis of purified human cytomegalovirus (CMV) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed 32 polypeptides with mol. wt. ranging from 13,500 to 235,000. Similar analysis of purified preparations of four strains of CMV showed a remarkable similarity in polypeptide composition. Results indicate that the four strains may be related.

Cell Line

Varicella-zoster virus-induced DNA polymerase.

Nuclear extracts of varicella-zoster virus (VZV)-infected human embryo lung (HEL) cells were found to contain DNA polymerase activity not present in uninfected HEL cells. This enzyme was designated the VZV-induced DNA polymerase. The VZV-induced polymerase was partially separated from the cellular alpha- and beta-polymerases by fractionation of the cells and by phosphocellulose chromatography. The separated enzymes were examined for the effect of added (NH4)2SO4, activity with synthetic templates, optimal pH, and the effect of phosphonoacetic acid. The VZV-induced DNA polymerase was distinct from cellular enzymes and had the properties of a typical herpesvirus-induced DNA polymerase.

Cell Nucleus

Complementation analysis of measles virus temperature-sensitive mutants.

Two sets of independently isolated measles virus temperature-sensitive mutants were quantitatively tested for complementation. Analysis of the nine possible combinations of representative mutants indicated that only one pair of mutants is noncomplementing. Thus, the measles virus mutants studied to date define five complementation groups.

Genetic Complementation Test

Differential effect of arabinofuranosylthymine of the replication of human herpesviruses.

The thymidine analog 1-beta-arabinofuranosylthymine (ara-T) has previously been found to selectively inhibit herpes simplex virus replication. At a relatively nontoxic conentration (50 microgram/ml), ara-T reduced herpes simplex virus yields by 4 to 5 log10. Ara-T was also effective in inhibiting the replication of varicellazoster virus (VZV) in vitro in human embryo fibroblasts, completely preventing VZV-specific cytopathic effects. The inhibition of VZV was reversible upon drug removal at 48 h after addition but was not reversible after 5 days of treatment. ara-T also reduced cell-free virus infectivity and the plaque-forming cell yield of VZV. Compared with the untreated controls, which demonstrated a 1-log10 increase over input plaque-forming cells at 24 h after infection, 50 microgram of ara-T per ml resulted in a 1-log10 decrease. In contrast to herpes simplex virus and VZV, cytomegalovirus replication was relatively resistant to ara-T. Neither cytopathic effects nor the incorporation of [3H]thymidine into acid-insoluble material in cytomegalovirus-infected cells was markedly affected. Analysis of the newly synthesized labeled DNA by CsCl buoyant density determinations indicated that the same relative proportions of cell and virus DNA were synthesized with or without added drug. Interpretation of these results with regard to virus-induced deoxypyrimidine kinase is discussed.

Arabinonucleosides

Temperature-sensitive mutants of human cytomegalovirus.

Eight temperature-sensitive mutants of human cytomegalovirus have been isolated after mutagenesis with nitrosoguanidine. Three of these mutants have been classified into three separate complementation groups and are capable of synthesizing virus DNA at the nonpermissive temperature (39.5 degrees C). Two others appear unable to synthesize virus DNA at the elevated temperature.

Cytomegalovirus

The effect of phosphonoacetic acid on the in vitro replication of varicella-zoster virus.

Phosphonoacetic acid (PAA) was found to inhibit in vitro varicella-zoster virus (VZV) replication. At 100 microng/ml, PAA blocked the development and spread of VZV cytopathology in both growing and contact-inhibited cultures. Formation of virus plaques by infected cells and cell-free virus was effectively blocked at concentrations as low as 25 microng/ml. The development of nuclear and cytoplasmic virus antigens was also inhibited by PAA. Inhibition by PAA suggests that VZV DNA replication, like that of other herpes-viruses, involves a virus-specific DNA polymerase.

Acetates

A novel approach to study the DNA of herpes zoster virus.

Herpes zoster virus DNA was isolated from infected human embryo lung cells because it is released into the "Hirt supernatant". The buoyant density of the virus DNA was found to be slightly higher than that of cellular DNA. The molecular weight of this DNA was estimated to be 92 x 10(6) daltons by cosedimentation with T4 DNA in neutral sucrose gradients. As with the DNA of other herpesviruses, the DNA of herpes zoster virus is fragmented when denatured under alkaline conditions and is therefore "alkali-labile". Studies of virus DNA using reassociation kinetics reveal that the kinetic complexity of the DNA correlates with the genome size as estimated by sucrose gradient sedimentation.

Centrifugation, Density Gradient

Measles virus meningoencephalitis. Immunofluorescence study of brains infected with virus mutants.

The localization of measles virus antigens in hamster brains inoculated with a temperature-sensitive mutant of measles virus r its revertant was studied by immunofluorescence. We found significantly less virus antigen in mutant-inoculated than in revertant-inoculated brains. In mutant-inoculated brains the virus antigens were very often found in the meninges. Possible mechanisms for the development of experimental hydrocephalus and meningoencephalitis are discussed.

Animals

The guinea pig as an animal model of diabetes mellitus.

Spontaneous diabetes mellitus, observed in a colony of guinea pigs, parallels in many ways the syndrome known as juvenile diabetes mellitus in man: elevated blood glucose levels; reproductive dysfunction in the female; degranulation and severe cytoplasmic vacuolation of beta cells, severe fatty degeneration of acinar cells, and hyperplasia of the islets of the pancreas; and a high frequency of abnormal pancreatic secretions. Islet-cell necrosis and insulinitis usually seen in viral infections was not observed. Microangiopathy, another characteristic of juvenile diabetes mellitus in man was demonstrated as a significant increase in the thickness of the basal membranes in peripheral capillaries. A glomerular lesion encountered in some of the diabetic guinea pigs was shown to be similar to the glomerular sclerosis seen in human diabetics. Although a definitive etiologic agent was not identified, the disease was clearly contagious in origin.

Animals