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PubMed2005

Multiplex detection of Ehrlichia and Anaplasma species pathogens in peripheral blood by real-time reverse transcriptase-polymerase chain reaction.

Tick-borne infections are responsible for many emerging diseases in humans and several vertebrates. These include human infections with Anaplasma phagocytophilum, Ehrlichia chaffeensis, and Ehrlichia ewingii. Because single or co-infections can result from tick bites, the availability of a rapid, multiplex molecular test will be valuable for timely diagnosis and treatment. Here, we describe a multiplex molecular test that can detect single or co-infections with up to five Ehrlichia and Anaplasma species. The test protocol includes the magnetic capture-based purification of 16S ribosomal RNA, its enrichment, and specific-pathogen(s) detection by real-time reverse transcriptase-polymerase chain reaction. We also report a unique cloning strategy to develop positive controls in the absence of a pathogen's genomic DNA. The test was assessed by examining blood samples from dogs suspected to be positive for ehrlichiosis. The dog was chosen as the model system because it is susceptible to acquire infections with up to five pathogens of the genera Ehrlichia and Anaplasma. The test identified single infections in the canine host with E. chaffeensis, E. canis, E. ewingii, A. phagocytophilum, and A. platys and co-infection with E. canis and A. platys. The multipathogen detection and novel positive control development procedures described here will be valuable in monitoring infections in people, other vertebrates, and ticks.

Anaplasma↗

PubMed2006

A genome-wide search for quantitative trait loci contributing to variation in seasonal pollen reactivity.

BACKGROUND: Asthma and atopy represent complex traits for which genetic predisposition has been demonstrated. Pollen sensitivity, whether seasonal or chronic, appears to be a major contributor to the asthmatic phenotype. OBJECTIVE: Regions of the genome contributing to skin test reactivity to 5 seasonal allergens are to be identified in a genome-wide scan. These regions may be distinct from those contributing to risk for asthma and/or atopy. METHODS: In the Collaborative Study on the Genetics of Asthma, 4 sites collected 287 families with 2 or more members with asthma. Reactivity to individual pollens were determined on all family members. A genome scan was performed at 9-centiMorgan intervals, and skin test reactivity to 5 seasonal allergens was the focus of nonparametric genetic linkage analysis. RESULTS: Chromosomal regions that exhibited suggestive linkage (logarithm of the odds >1.18; P < .01) to seasonal pollen reactivity were identified on chromosomes 13q34, 20p12, and 21q21. Evidence of ethnic differences in linkage to seasonal allergens was demonstrated, with support for linkage in African American subjects on chromosomes 8, 10, and 12, in European American subjects on chromosomes 14, 19, 20, and 22, and in Hispanics on chromosome 21. In all families, evidence for linkage of skin test reactivity for Betula, Lolium, and Artemisia was strongest in a region on chromosome 21 that contained the candidate gene, A Disintegrin And Metalloprotease domain 33 (ADAM33). CONCLUSION: These results suggest both substantial genetic overlap and extensive heterogeneity in the genetic basis for the allergic response to seasonal allergens.

Adolescent↗

PubMed1994

Effect of foscarnet induction treatment on quantitation of human cytomegalovirus (HCMV) DNA in peripheral blood polymorphonuclear leukocytes and aqueous humor of AIDS patients with HCMV retinitis. The Italian Foscarnet Study Group.

The aim of this study was to investigate peripheral blood polymorphonuclear leukocytes and, whenever possible, aqueous humor from 65 AIDS patients with ophthalmoscopically diagnosed human cytomegalovirus (HCMV) retinitis to determine (i) whether patients consistently carry viral DNA and (ii) to what extent foscarnet induction treatment decreases viral DNA levels. HCMV DNA was quantified by PCR using densitometric analysis of hybridization products obtained from external standards and a standard curve from which the number of genome equivalents of test samples, normalized by using an internal amplification control, was interpolated. Results showed that 56 of 65 patients (86.1%) were positive for HCMV DNA prior to induction treatment. Of 41 of the 56 patients (73.2%) whose blood had become DNA negative after induction, only 5 had a high viral load (> 5,000 genome equivalents per 2 x 10(5) polymorphonuclear leukocytes) prior to induction, whereas as many as 13 of the 15 (26.8%) patients remaining DNA positive after induction had a high viral load prior to induction. Finally, of the nine patients (13.8%) with DNA-negative blood prior to induction treatment, three were shifted to foscarnet from ganciclovir, while six were erroneously enrolled in the study. Pre- and postinduction aqueous humor samples were obtained from 12 patients; all of these were DNA positive prior to induction, whereas after induction, 4 became negative, 6 showed a marked decrease in viral DNA, and 2 had nearly stable low DNA levels. In conclusion, PCR is a valuable tool for etiologic diagnosis and monitoring of HCMV retinitis treatment in AIDS patients. HCMV DNA is consistently present in the blood and aqueous humor of all patients with HCMV retinitis. Foscarnet induction treatment is highly effective in suppressing or reducing DNA levels in both blood leukocytes and aqueous humor.

AIDS-Related Opportunistic Infections↗

PubMed2001

Specificities of eleven different DNA methyltransferases of Helicobacter pylori strain 26695.

Methyltransferases (MTases) of procaryotes affect general cellular processes such as mismatch repair, regulation of transcription, replication, and transposition, and in some cases may be essential for viability. As components of restriction-modification systems, they contribute to bacterial genetic diversity. The genome of Helicobacter pylori strain 26695 contains 25 open reading frames encoding putative DNA MTases. To assess which MTase genes are active, strain 26695 genomic DNA was tested for cleavage by 147 restriction endonucleases; 24 were found that did not cleave this DNA. The specificities of 11 expressed MTases and the genes encoding them were identified from this restriction data, combined with the known sensitivities of restriction endonucleases to specific DNA modification, homology searches, gene cloning and genomic mapping of the methylated bases m(4)C, m(5)C, and m(6)A.

Cloning, Molecular↗

PubMed1998

Genomic DNA sequence, promoter expression, and chromosomal mapping of rat muscle carnitine palmitoyltransferase I.

Carnitine palmitoyltransferase I (CPT-I) is a key enzyme involved in the regulation of fatty acid oxidation. CPT-IA and CPT-IB are isoforms of carnitine palmitoyltransferase I, of which CPT-IA is expressed in liver, kidney, fibroblasts, and heart and CPT-IB is expressed in skeletal muscle, heart, brown and white adipocytes, and testes. Although the genomic DNA sequence of human CPT-IB is available, the transcription start site and upstream regulatory sequences are not known. For rat CPT-IB, only the cDNA sequence has been published. We have cloned the entire rat CPT-IB gene from a Lambda fix II rat kidney genomic library. The genomic structure contains 19 exons, with the transcription start site for CPT-IB located in a short first exon, which is a 13-bp extension to the previously published cDNA 5' sequence. The coding sequence is identical with the rat muscle cDNA. The rat CPT-IB gene contains 18 introns and 19 exons, the latter 18 exons showing 85% homology to the human CPT-IB cDNA. CPT-IB maps to rat chromosome 7 at band q34. A putative promoter region was identified to within 391 bp of the transcription start site. The muscle specificity of the 5' flanking region was verified by comparison of luciferase expression to that of beta-galactosidase in cardiac myocytes and in HepG2 cells.

Animals↗

PubMed2000

Replication of lengthened Moloney murine leukemia virus genomes is impaired at multiple stages.

It has been assumed that RNA packaging constraints limit the size of retroviral genomes. This notion of a retroviral "headful" was tested by examining the ability of Moloney murine leukemia virus genomes lengthened by 4, 8, or 11 kb to participate in a single replication cycle. Overall, replication of these lengthened genomes was 5- to 10-fold less efficient than that of native-length genomes. When RNA expression and virion formation, RNA packaging, and early stages of replication were compared, long genomes were found to complete each step less efficiently than did normal-length genomes. To test whether short RNAs might facilitate the packaging of lengthy RNAs by heterodimerization, some experiments involved coexpression of a short packageable RNA. However, enhancement of neither long vector RNA packaging nor long vector DNA synthesis was observed in the presence of the short RNA. Most of the proviruses templated by 12 and 16 kb vectors appeared to be full length. Most products of a 19. 2-kb vector contained deletions, but some integrated proviruses were around twice the native genome length. These results demonstrate that lengthy retroviral genomes can be packaged and that genome length is not strictly limited at any individual replication step. These observations also suggest that the lengthy read-through RNAs postulated to be intermediates in retroviral transduction can be packaged directly without further processing.

3T3 Cells↗

PubMed2026

First-line drug-resistant tuberculosis among children under 15 years in Ethiopia: insights from phenotypic and whole-genome sequencing approaches.

BACKGROUND: Childhood drug-resistant tuberculosis is often underdiagnosed and inadequately characterized due to the paucibacillary nature of the disease. This study aimed to assess resistance to first-line anti-tuberculosis drugs in children using phenotypic drug susceptibility testing and whole-genome sequencing. METHODS: A retrospective-prospective study was conducted on culture-confirmed childhood tuberculosis cases in Ethiopia (2017–2023). Phenotypic drug susceptibility testing was performed on 110 Mycobacterium tuberculosis complex isolates. Whole-genome sequencing was completed for 85 of these isolates, which were analyzed using the TB-Profiler and MTBSeq pipelines. We assessed the sensitivity, specificity, predictive values, and kappa agreement of whole-genome sequencing compared with phenotypic drug susceptibility testing. RESULTS: Phenotypic resistance to at least one first-line anti-TB drug was observed in 26/110 (23.6%) of the examined isolates, with isoniazid resistance being the most frequent, 23/110 (20.9%), followed by rifampicin resistance, 18/110 (16.4%). TB-Profiler showed almost perfect agreement with phenotypic drug susceptibility testing for rifampicin (sensitivity 94.4%, kappa = 0.96) and isoniazid (sensitivity 91.3%, kappa = 0.91), whereas MTBSeq showed slightly lower performance. Both pipelines demonstrated moderate to weak agreement with phenotypic drug susceptibility testing for detecting resistance to ethambutol, pyrazinamide, and streptomycin. The most frequently observed resistance mutations among phenotypically resistant isolates were rpoB (Ser450Leu), katG (S315Thr), embB (Met306Ile), and pncA (C-11 A > G) for rifampicin, isoniazid, ethambutol, and pyrazinamide, respectively. Discrepancies between genotypic and phenotypic drug susceptibility testing were observed across all first-line anti-TB drug-resistant isolates, particularly for ethambutol and pyrazinamide. CONCLUSION: We found a high prevalence of isoniazid resistance, along with rifampicin resistance, underscoring the need for early detection in vulnerable groups. Whole-genome sequencing showed good accuracy for these drugs, with TB-Profiler performing best. CLINICAL TRIAL NUMBER: Not applicable.

Humans↗

PubMed2025

GWAS of CRP response to statins further supports the role of APOE in statin response: A GIST consortium study.

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response. CRP statin response is the change in log-CRP between off-treatment and on-treatment measurements. Cohort-level Genome-Wide Association Studies (GWAS) of CRP response were performed using 1000 Genomes imputed data, testing ∼10 million common genetic variants. GWAS meta-analysis combined results from seven cohorts and clinical trials totalling 14,070 statin-treated individuals of European ancestry within the GIST consortium. Secondary analyses included statin-by-placebo interaction analyses, and lookups in African ancestry cohorts. Our GWAS identified two genome-wide significant (P < 5e-8) loci: APOE and HNF1A for CRP statin response corrected for baseline CRP. The missense lead variant rs429358 at APOE, contributing to the APOE-E4 haplotype, is a risk locus for dyslipidaemia, Alzheimer's and coronary artery disease (CAD). The HNF1A locus is associated with diabetes, cholesterol levels, and CAD. Both loci are also associated with baseline CRP levels, and neither locus achieved a significant (P < 0.05) result from the statin v. placebo interaction meta-analysis using randomized clinical trial data. However, the interaction result (P-int=0.09) for APOE was suggestive and possibly underpowered. The APOE-E4 signal may therefore be associated with both CRP and LDL-cholesterol statin response. Combined with suggestions in the literature that APOE also leads to differential statin benefit in Alzheimer's, the APOE locus warrants further investigation for potential genetic effects on healthcare with statin treatment.

Humans↗

PubMed1991

The paternal genome in mouse zygotes is less sensitive to ENU mutagenesis than the maternal genome.

The two parental genomes lie separate within the zygote and may be differentially affected by environmental influences. We have shown earlier (Russell et al., 1988) that the maternal genome within the mouse zygote is exquisitely sensitive to the induction of point mutations by N-ethyl-N-nitrosourea (ENU), and that the initial lesion probably occurs in one strand of the DNA. The present experiment measured specific-locus mutation induction in the paternal genome. Zygotes containing a multiple-recessive maternal genome (a; b; p cch; d se; s) and the corresponding wild-type alleles in the paternal one were exposed to 50 mg ENU/kg in vivo at one of two stages: the presumed times of sperm entry and early pronuclear stage. At weaning age, the resulting mice were examined for mutations at the marked loci as well as for other mutations producing externally visible phenotypes. At the marked loci, one possible mosaic (for b) was observed among 2113 classified offspring that had been treated with ENU as zygotes; this animal failed to transmit a mutation. By contrast, in the reciprocal cross (which tests the maternal genome) we had observed 8 specific-locus mutations (6 of them mosaics) among 1555 offspring that had received the same dose of ENU during sperm entry (and completion of oocyte meiosis II). In the present experiment, we also found one mutation at other loci (two at other loci in the reciprocal cross). The frequency of offspring with small white belly spots was significantly greater in the treated groups (3.5 and 1.9% at the earlier and later stage, respectively) than in the control (1.0%), the excess being almost entirely due to daughters. Genetic tests of a large number of such offspring failed to find a genetic cause. Instead, it appears that this phenotype may be influenced by factors in the intrauterine environment. It is concluded that shortly after sperm entry, the paternal genome of the zygote is less sensitive than the maternal one to the induction of mutations by ENU.

Animals↗

PubMed1994

Persistence of respiratory syncytial virus genome and protein after acute bronchiolitis in guinea pigs.

Children with acute respiratory syncytial virus (RSV) bronchiolitis often develop sequelae of recurrent wheezing and asthma. To determine whether RSV persists within the lung after resolution of acute bronchiolitis, we examined the lungs of guinea pigs 60 days after intranasal inoculation with either human RSV (n = 10) or uninfected cell culture supernatant (n = 11). Evidence of viral persistence within the lung was determined by viral culture to test for replicating virus, immunohistochemistry to test for viral protein, and the reverse transcriptase-polymerase chain reaction (RT-PCR) to test for viral genomic RNA. Lungs were also examined histologically for evidence of bronchiolar inflammation or increased numbers of mast cells in the airway walls. All viral cultures were negative; however, there was positive immunohistochemical staining of occasional alveolar macrophages in six of ten RSV-inoculated guinea pigs while RT-PCR was positive in seven of ten RSV-inoculated animals. The six guinea pigs with evidence of RSV by immunohistochemistry and RT-PCR showed excess bronchiolar polymorphonuclear cell infiltrates (p < 0.005) but no increase in the number of airway wall mast cells. These results show that RSV protein and genomic RNA can persist in the lungs of experimentally inoculated guinea pigs for at least 60 days after infection and that persistence of the virus within alveolar macrophages might contribute to the pathogenesis of chronic bronchiolar inflammation.

Animals↗

PubMed2000

Plasmid DNA vaccines: assay for integration into host genomic DNA.

The primary safety concern for DNA vaccines is their potential to integrate into host cellular DNA. We describe a sensitive and quantitative assay for investigating the tissue distribution and integration of plasmid DNA vaccines. By including gonadal tissues in the analysis, the potential for germline transmission is also assessed. At various time points after injection, total DNA is isolated from a variety of tissues and assayed by PCR for the presence of plasmid. To test for integration, genomic DNA is first purified away from free plasmid using a series of different gel electrophoresis procedures. The gel-purified genomic DNA is then assayed for integrated plasmid using PCR. Stringent methods are used to prevent contamination. The assay, validated using a variety of positive and negative controls, is capable of detecting one copy of plasmid per ug DNA (approximately 150,000 diploid cells). Using this assay, we have carried out intramuscular studies in mice or guinea pigs for four different DNA vaccine plasmids. There was no evidence of integration to a sensitivity of about one copy/microg DNA, which is at least three orders of magnitude below the spontaneous mutation frequency.

Animals↗

PubMed1997

DNA diagnosis and identification of carriers of infantile and juvenile neuronal ceroid lipofuscinoses.

The recent identification of the genes and the mutations underlying infantile neuronal ceroid lipofuscinosis and juvenile onset neuronal ceroid lipofuscinosis facilitates specific DNA-based diagnostics for the disorders. We have developed a solid-phase minisequencing test for the identification of the major Finnish INCL mutation, an A to T transversion at nucleotide position 364 of the palmitoyl protein thioesterase gene on chromosome 1. This test has been applied for prenatal diagnosis and for identification of disease carriers in INCL families. For population-based screening for INCL carriers the coverage of the test would be 98%. In addition, by combining the solid-phase minisequencing test with whole genome preamplification, we have developed a procedure that allows reliable identification of the INCLFin-mutation in single blastomeres from in-vitro-fertilized embryos. This method is applicable for preimplantation diagnosis, and thus it offers an alternative to early prenatal diagnosis in the prevention of INCL. A modification of the solid-phase minisequencing test was devised for detection of the major INCL mutation, a 1.02 kb deletion in the CLN3 gene on chromosome 16. The coverage of this test for diagnosis of INCL and identification of carriers is 90% in Finland and > 80% worldwide.

Adolescent↗

PubMed2006

Sequential genome-wide association studies for monitoring adverse events in the clinical evaluation of new drugs.

Pharmacovigilance, the monitoring of adverse events (AEs), is an integral part in the clinical evaluation of a new drug. Until recently, attempts to relate the incidence of AEs to putative causes have been restricted to the evaluation of simple demographic and environmental factors. The advent of large-scale genotyping, however, provides an opportunity to look for associations between AEs and genetic markers, such as single nucleotides polymorphisms (SNPs). It is envisaged that a very large number of SNPs, possibly over 500,000, will be used in pharmacovigilance in an attempt to identify any genetic difference between patients who have experienced an AE and those who have not. We propose a sequential genome-wide association test for analysing AEs as they arise, allowing evidence-based decision-making at the earliest opportunity. This gives us the capability of quickly establishing whether there is a group of patients at high-risk of an AE based upon their DNA. Our method provides a valid test which takes account of linkage disequilibrium and allows for the sequential nature of the procedure. The method is more powerful than using a correction, such as Sidák, that assumes that the tests are independent.

Adverse Drug Reaction Reporting Systems↗

PubMed2005

Genomic DNA macroarrays as a tool for analysis of gene expression in Leishmania.

Gene-array technologies have been applied in a wide number of organisms to study gene expression profiling under several physiological and experimental conditions. Gene-array implementations combined with the information arising from emerging genome sequencing projects are expected to be in the near future a major tool to characterize genes involved in different processes. So far, gene expression profile studies in trypanosomatids have been performed in microarrays that use a glass support to immobilize fragments of genomic DNA followed by fluorescent detection. Here, we wanted to test the potential of genomic DNA macroarrays of Leishmania infantum using nylon membranes and radioactive detection. Nylon macroarrays present a number of advantages since the processing of the membranes is based on standard Southern blotting protocols familiar to molecular biologists, and the data acquisition equipment is available to most research institutions. Nylon macroarrays were employed to search for genes showing increased mRNA abundance during an axenic differentiation of L. infantum promastigotes to amastigotes. Several clones were rescued and, after validation by Northern blot assays, these L. infantum sequences were used to screen the Leishmania major gene database. The L. major contigs with high homology to the L. infantum sequences allowed a consistent identification of the regulated genes.

Animals↗

PubMed2003

Consequences of reductive evolution for gene expression in an obligate endosymbiont.

The smallest cellular genomes are found in obligate symbiotic and pathogenic bacteria living within eukaryotic hosts. In comparison with large genomes of free-living relatives, these reduced genomes are rearranged and have lost most regulatory elements. To test whether reduced bacterial genomes incur reduced regulatory capacities, we used full-genome microarrays to evaluate transcriptional response to environmental stress in Buchnera aphidicola, the obligate endosymbiont of aphids. The 580 genes of the B. aphidicola genome represent a subset of the 4500 genes known from the related organism, Escherichia coli. Although over 20 orthologues of E. coli heat stress (HS) genes are retained by B. aphidicola, only five were differentially expressed after near-lethal heat stress treatments, and only modest shifts were observed. Analyses of upstream regulatory regions revealed loss or degradation of most HS (sigma32) promoters. Genomic rearrangements downstream of an intact HS promoter yielded upregulation of a functionally unrelated and an inactivated gene. Reanalyses of comparable experimental array data for E. coli and Bacillus subtilis revealed that genome-wide differential expression was significantly lower in B. aphidicola. Our demonstration of a diminished stress response validates reports of temperature sensitivity in B. aphidicola and suggests that this reduced bacterial genome exhibits transcriptional inflexibility.

Amino Acid Sequence↗

PubMed2003

Efficient cloning and engineering of entire mitochondrial genomes in Escherichia coli and transfer into transcriptionally active mitochondria.

We have devised an efficient method for replicating and stably maintaining entire mitochondrial genomes in Escherichia coli and have shown that we can engineer these mitochondrial DNA (mtDNA) genome clones using standard molecular biological techniques. In general, we accomplish this by inserting an E.coli replication origin and selectable marker into isolated, circular mtDNA at random locations using an in vitro transposition reaction and then transforming the modified genomes into E.coli. We tested this approach by cloning the 16.3 kb mouse mitochondrial genome and found that the resulting clones could be engineered and faithfully maintained when we used E.coli hosts that replicated them at moderately low copy numbers. When these recombinant mtDNAs were replicated at high copy numbers, however, mtDNA sequences were partially or fully deleted from the original clone. We successfully electroporated recombinant mouse mitochondrial genomes into isolated mouse mitochondria devoid of their own DNA and detected robust in organello RNA synthesis by RT-PCR. This approach for modifying mtDNA and subsequent in organello analysis of the recombinant genomes offers an attractive experimental system for studying many aspects of vertebrate mitochondrial gene expression and is a first step towards true in vivo engineering of mammalian mitochondrial genomes.

Animals↗

PubMed2003

Factor V Leiden mutation in Sneddon syndrome.

Sneddon syndrome (SNS) is characterized by the association of ischaemic cerebrovascular events and widespread livedo racemosa. Its pathophysiology is still controversial. The aim of this study was to evaluate the prevalence of factor V Leiden mutation in consecutive patients referred for SNS according to antiphospholipid antibodies (aPL) status. Fifty-three Caucasian patients were enrolled from 1996 to 2001. Diagnosis of SNS was based on the presence of a widespread livedo racemosa and at least one clinical neurologic ischaemic event. The following investigations were performed: detection of antithrombin III, protein C and protein S deficiency, lupus anticoagulant, anticardiolipin and anti-beta2 glycoprotein I antibodies, biologic false-positive test for syphilis, and factor V Leiden mutation by direct genomic analysis. Fisher's test and t-test were used for statistics. Detection of aPL on multiple determinations was negative in 31 patients (group 1) and positive in 22 patients (group 2). Factor V Leiden mutation was detected in six patients (11.3%), heterozygous in all. The frequency of this mutation was statistically higher in group 1 (6/31, 19.3%) than in group 2 (0/22; P = 0.035). Within aPL-negative SNS, the comparison of patients with versus without factor V Leiden mutation showed no difference for clinical data or familial history of thrombosis. A high prevalence of heterozygous factor V mutation was found in aPL-negative patients with SNS. This finding adds further arguments to consider SNS as a heterogeneous entity.

Adolescent↗

PubMed1978

Observations on cell lines derived from a patient with Hodgkin's disease.

Permanent cell lines have been established from a spleen nodule and lymph node of a male Hodgkin's disease (HD) patient whose father has the same disease. Th in vitro growth pattern morphological and cytogenetic characteristics of these lines maintained continuously for over 2 years are described. The cultures contain a population of mixed cell types that grow in suspension. Between 5 and 10% of the cells have surface immunoglobulins M and D. B-cell alloantigens are also detectable. While the cultures are predominantly lymphoid, some of the large cells, by light and electron microscopy, resemble the Reed-Sternberg and Hodgkin's cells of the original biopsies. Although the cells maintain the human diploid karyotype, they are heterotransplantable in nude mice. After 14 months of culture, chromosome rearrangement and losses, commonly seen in leukemic bone marrow, occurred. Close to 100% of the cells are Epstein-Barr nuclear antigen positive, but they lack Epstein-Barr viral (EBV) capsid antigen and EBV-induced early antigen. Nucleic acid hybridization tests indicated that there were no more than two EBV genome equivalents per cell. Tests with HD sera free of anti-EBV were negative. Electron microscope examination of the cells revealed the presence of intracellular as well as extracellular rare pleomorphic particles ranging from 400 to 1200 A. The nature of these particles, which increased in number after the cultures were treated with halogenated pyrimidines but not with dimethyl sulfoxide, remains questionable. The cultures derived from the mouse-passaged HD cells, however, had reverse transcriptase activity and readily identifiable type C particles which were probably of murine origin. These cultures have some unique features that make them useful in studying the perplexing pathological entity of HD.

Adolescent↗