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Biomedical subjects

B L Padgett

Publications and source records attributed to B L Padgett.

At least 37 records · Page 2Linked to original sources
PubMed1980

Experimental glioma in primates: a computed tomography model.

Owl and squirrel monkeys inoculated intracerebrally with human polyomavirus obtained from the brain of patient with progressive multifocal leukoencephalopathy developed cerebral gliomas. Among these tumors, three out of five were detected and accurately localized by contrast enhanced computed tomography (CT) when the animals were still clinically normal. Various CT features of these tumors corresponded to specific pathologic changes, such as histologic type and presence of hemorrhage and necrosis. Also, tumor progression was clearly demonstrated in repeat scans of one animal. The CT sensitivity and the capability of distinguishing various pathologic features are encouraging. It appears that a much needed, suitable model of experimental cerebral tumors in primates is now available for CT studies.

Animals↗
PubMed1980

Rapid detection and identification of JC virus and BK virus in human urine by using immunofluorescence microscopy.

An indirect immunofluorescence method was developed and used to detect urinary excretion of abnormal transitional cells infected with JC virus (JCV) or BK virus (BKV). This method was compared with urinary cytology, electron microscopy, viral culture, and viral serology in groups of immunosuppressed renal transplant recipients and normal controls. The indirect immunofluorescence method detected and identified JCV excretion in four persons, BKV excretion in one person, and both JCV and BKV excretion in eight others. Viral antigen was identified only in the nuclei of cytologically abnormal cells. Of these 13 persons, 8 also had polyoma virions detected in the urine by electron microscopy. With repeated study of sequential urine samples, 30% of transplant recipients and 6% of normal controls were positive by one or more microscopy methods. Serological results confirmed a high incidence of both JCV and BKV multiplication in the immunosuppressed patients. However, serology did not correlate directly with urinary virological findings. Urinary cytology and the indirect immunofluorescence method were rapid and sensitive methods for detecting and identifying urinary excretion of JCV and BKV.

Adult↗
PubMed1980

Integration pattern of human JC virus sequences in two clones of a cell line established from a JC virus-induced hamster brain tumor.

The physical state of the JC virus (JCV) genome was studied in two clonal cell lines (clones 2 and 7) derived from a tissue culture cell line (HJC-15) established from a hamster brain tumor induced by JCV. Saturation-hybridization and reassociation kinetic analyses, using in vitro (32)P-labeled JCV DNA, indicated that clone 7 and 2 cells contain 9 to 10 and 4 to 5 copies per cell, respectively, of all or most of the viral genome. Both cell DNAs were analyzed by using the Southern blotting procedure with three restriction endonucleases: XhoI, which does not cleave JCV DNA; EcoRI, which cleaves once; and HindIII, which cleaves three times. With each DNA, a variety of JCV-specific DNA fragments were detected. The following conclusions are possible: (i) JCV DNA is integrated into cell DNA in both clonal lines; (ii) both clonal lines contain multiple copies of the viral genome integrated in a tandem head-to-tail orientation; (iii) neither clonal line contains detectable free-form I, II, or III JCV DNA; (iv) each clonal line contains multiple independent sites of JCV DNA integration; and (v) most or all of the sites of integration on the cellular or the viral genome, or both, are different in clone 7 DNA than in clone 2 DNA. Thus, although both clone 7 and clone 2 cells were established from the HJC-15 tumor cell line, they differ in the copy number and integration pattern of JCV DNA.

Animals↗
PubMed1980

Progressive multifocal leukoencephalopathy (PML): in vitro cell-mediated immune responses to mitogens and JC virus.

Cell-mediated immunity was studied by in vitro tests in seven patients with progressive multifocal leukoencephalopathy (PML). Lymphocyte proliferation in response to mitogenic stimulation was reduced to a variable degree in all patients, indicating a general impairment of cell-mediated immune responsiveness, although mitogen-induced production of the lymphokine migration inhibitory factor (LIF) was normal in most cases. Cell-mediated immunity to JC virus (JCV) was assessed by LIF production in response to JCV antigen. In the six PML patients tested, LIF production with JCV antigen was absent despite the presence of antibody to JCV in serum. This contrasted with positive LIF production in seropositive normal individuals and patients and patients with other diseases. These results provide the first in vitro evidence of a depressed cell-mediated immune response to JCV in patients with PML, and support the hypothesis that PML is accompanied by a selective marked deficiency in cellular response to this virus in association with a general depression of cell-mediated immunity of variable severity.

Adult↗
PubMed1980

Human polyomavirus infections with JC virus and BK virus in renal transplant patients.

Infection with the human polyomaviruses JC virus and BK virus was studied in 61 immunosuppressed renal transplant patients. Urine cytologic studies, indirect immunofluorescence microscopy, electron microscopy, and serologic studies were used to assess viral activity. Patients records were abstracted for events associated with polyomavirus infections. Polyomavirus excretion in urine was detected in 12 of 61 patients (20%). Eleven excreted JC virus and nine, BK virus. Fourfold hemagglutination-inhibition antibody titer rises occurred in 25 of 61 patients (41%). The serologic data suggested that most JC virus infections were primary, whereas most BK virus infections resulted from virus reactivation. During this 2-year study, 32 of 61 patients (52%) had evidence of active viral replication. Urinary tract excretion was associated with drug-requiring diabetes mellitus (P = 0.001), arterial occlusive disease (P = 0.03), and ureteral stricture with loss of renal function (P = 0.02). Antibody increases to BK virus were associated with a rising seurum creatinine (P = 0.02) and need for transplant biopsy (P = 0.02). Polyomavirus replication was therefore associated with an increased frequency of transplant related complications.

Adolescent↗
PubMed1979

Restriction endonuclease cleavage map of the DNA of JC virus.

A physical map of the sites cleaved by the following restriction endonucleases was derived for the DNA of JC virus, a human polyomavirus: EcoRI, HpaI, and PstI (one site each); HindII (four sites); and HindIII (three sites). By agarose gel electrophoresis of fragmented DNA, the size of full-length DNA of JC virus was estimated to be 5,125 +/- 105 base pairs (98 +/- 2% of the length of simian virus 40 DNA).

DNA Restriction Enzymes↗
PubMed1979

Infectivity of the DNA from four isolates of JC virus.

The infectivity of JC virus DNA was demonstrated in its most permissive cell culture, primary human fetal glial cells. The amount of infectivity observed in these heterogeneous cultures varied considerably between batches of cells. Contrary to results obtained with the papovaviruses simian virus 40 and BK virus, the calcium technique (F. L. Graham and A. J. van der Eb, Virology 52:456--467, 1973) was found to be more efficient at promoting JC virus DNA infectivity than the DEAE-dextran method (J. H. McCutchan and J. S. Pagano, J. Natl. Cancer Inst. 41:351--357, 1968): maximum infectivity titers of 4 x 10-(4) and 6 x 10(3) fluorescent cell units per microgram of DNA, respectively. These values represent an approximate recovery of infectivity from virus of between 0.02 and 0.14%. Comparisons of infectivity of DNAs obtained from four isolates of JC virus and which differed in their degrees of heterogeneity did not reveal significant differences. The JC virus DNA was not infectious in primary human fetal lung and kidney cells.

Antigens, Viral↗
PubMed1978

Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus).

Owl monkeys were inoculated intracerebrally, subcutaneously, and intravenously with JC, BK, or SV40 virus. Two of four adult owl monkeys inoculated with JC virus, a human polyomavirus, developed brain tumors at 16 and 25 months after inoculation, respectively. A grade 3 to grade 4 astrocytoma (resembling a human glioblastoma multiforme) was found in the left cerebral hemisphere and brainstem of one monkey. The second monkey developed a malignant tumor in the left cerebral hemisphere containing both glial and neuronal cell types. Impression smears prepared from unfixed tissue of this tumor showed cells that contained polyomavirus T antigen. Virion antigens were not detected. Tumor cells cultured in vitro also contained T antigen but were negative for virion antigen. Infectious virus was not isolated from extracts of this tumor.

Antibodies, Viral↗
PubMed1978

Induction of peripheral neuroblastomas in Syrian hamsters after injection as neonates with JC virus, a human polyoma virus.

Neuroblastomas developed in 10 of 31 Syrian hamsters inoculated intraocularly with JC virus, a human polyoma virus. The latent period was 6 to 11 months. Primary tumors occurred in the abdominal cavity, pelvis, mediastinum, and neck region. The origin of one tumor from the adrenal gland was demonstrated. Metastases were seen in the liver, bone marrow, and lymph nodes. Two neuroblastomas arising in this experiment were transplanted serially in weanling hamsters, and a tissue culture cell line was established from one of the transplanted tumors. T-antigen was detected in three of five primary tumors tested and in the transplanted tumors. Antibody against T-antigen was demonstrated in sera from five of six animals with neuroblastomas. Neuroblastomas also developed after combined s.c. and i.p. injection of JC virus.

Animals↗
PubMed1977

Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy.

Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-density lesions seen by computerized tomography. One of the patients was observed to excrete abnormal epithelial cells into the urine. These cells contained papovaviruslike particles, and JC virus was cultured from the urine sediment. The relative number of these abnormal cells declined during Ara-A treatment. Both patients died shortly after the conclusion of therapy without a change in the progression of the central nervous system disease. Systemic administration of Ara-A did not offer significant clinical benefit in the treatment of these 2 advanced cases of PML.

Aged↗
PubMed1977

Modification of hydroxyindole-O-methyltransferase activity in experimental pineocytomas induced in hamsters by a human papovavirus (JC).

Hydroxyindole-O-methyltransferase (HIOMT) (HIOMT) activity was studied and compared in 7 pineal tumors (pineocytomas) induced in vivo in Syrian hamsters after postnatal inoculation with strains of human papovavirus (JC). Levels of tumor HIOMT activity were correlated with degree of cytologic differentiation of the pineocytes of each neoplasm, as judged from electrom micrographs. The relative capacities of the HIOMT in the tumors to methylate three related substrates gave similar ratios in the individual tumors and were not different from those of HIOMT in normal hamster pineal glands.

Acetylserotonin O-Methyltransferase↗
PubMed1977

JC virus, a human polyomavirus associated with progressive multifocal leukoencephalopathy: additional biological characteristics and antigenic relationships.

JC virus, a human polyomavirus, failed to grow or produce cytopathic effects in any of a variety of cells tested other than primary human fetal glial (PHFG) cells. Cells tested included other primary human cells and glial cells from other animals. Only a rare cell in inoculated insusceptible human cell cultures produced T or virion antigen. In PHFG cell cultures JC virus produced subtle cytopathic effects, and the majority of progeny remained cell associated. Only a few cells in the heterogenous PHFG cell cultures contained T antigen at 24 h postinoculation, and virion antigen was not detected until 48 h postinoculation. The infectivity of JC virus was resistant to inactivation by ether and by heating at 50 degrees C for 1 h. A three-way minor antigenic relationship was demonstrated among the virion antigens of JC virus, BK virus, and simian virus 40 by neurtralization and/or hemagglutination inhibition tests. Serological evidence is presented for the existence of JC virus as a distinct entity before the use of simian virus 40-contaminated poliovirus vaccines and for the nonexistence of an animal reservoir for JC virus infection.

Animals↗
PubMed1977

Specificity of the Tumor-specific transplantation antigen induced by JC virus, a human polyomavirus.

The specificity of the tumor-specific transplantation antigen (TSTA) induced by JC virus was investigated by cross protection tests in weanling hamsters. Hamsters immunized with JC virus, BK virus, or SV40 were challenged 5 weeks later with known numbers of JC virus- or SV40-induced hamster tumor cells. Both the JC virus-immune and the SV40-immune hamsters showed resistance to challenge with homologous but not heterologous tumor cells, and the BK virus-immune hamsters were not resistant to either heterologous tumor cell. The TSTA induced by JC virus did not cross-react with that induced by SV40.

Animals↗
PubMed1977

Differential neurooncogenicity of strains of JC virus, a human polyoma virus, in newborn Syrian hamsters.

The neurooncogenicity recently isolated strains of the human polyoma virus, JC virus, was determined by intracerebral inoculation of newborn Syrian golden hamsters. All three strains produced malignant brain tumors in a majority of inoculated animals during a 6.5-month observation period. The results obtained with the MAD-2 strain, 19 of 20 animals with cerebellar medulloblastomas and 0 of 20 animals with pineal gland tumors, were quite similar to those observed previously with the prototypic strain of JC virus, MAD-1. Inoculation of the MAD-4 strain, however, resulted in 10 of 22 animals with pineal gland tumors and only 10 of 22 animals with tumors in the cerebellum. The MAD-3 strain was neurooncogenic, but too few animals lived to be weaned to provide significant additional information. The basis for the apparent predilection of the MAD-4 strain for the pineal gland is unknown. Two hamsters in the experiment developed extracranial neuroblastomas.

Abdominal Neoplasms↗
PubMed1976

JC Papovavirus in progressive multifocal leukoencephalopathy.

Brain tissue from seven patients with progressive multifocal leukoencephalopathy was tested for the presence of papovaviruses. JC virus, ahuman papovavirus, was identified in all seven cases. Virus was isolated in tissue culture from extracts from each of four patients and was detected by immunofluorescence in sections from the other three. The new osolates were indistinguishable from the prototypical JC strain serologically and in all biological characteristics examined. Thus JC virus has, to date, been associated with 20 cases of progressive multifocal leukoencephalopathy.

Adult↗
PubMed1976

Comparison of JC and BK human papovaviruses with simian virus 40: DNA homology studies.

Studies were performed to ascertain the relationship of human papovavirus JC to BK virus and to simian virus 40 (SV40) by further restriction endonuclease analysis and by DNA-DNA competition hybridization on membrane filters. Form I DNA extracted from two new isolates from cases of progressive multifocal leukoencephalopathy of human papovaviruses that were JC-like in their antigenic properties were found to yield restriction endonuclease fragmentation patterns similar to those of prototypic JC virus DNA and different from those of BK or SV40. Form I DNA preparations of JC and BK viruses were found to be related to each other and to SV40 DNA to a similar extent, with JC and BK virus DNAs containing sequences homologous to both early and late regions of the SV40 genome. The relatedness in each comparison was less than 50%, and heterologous hybrids between either JC or BK and SV40 DNAs were found to be less stable than homologous SV40-SV40 hybrids in high concentrations of formamide, suggesting substantial mismatch within homologous regions, to the extent of 15 to 30%. The new JC-like isolates were also studied in competition hybridization reactions with SV40 DNA and yielded results similar to those obtained with JC virus.

BK Virus↗