Biomedical subjects

J A Hedrick

Publications and source records attributed to J A Hedrick.

44 records · Page 3Linked to original sources

PubMed1993

Characterization of the EBV/C3d receptor on the human Jurkat T cell line: evidence for a novel transcript.

EBV is a human herpes virus that causes mononucleosis and is associated with various tumors. EBV infects cells via the CR2 that was previously thought to be expressed only on the surface of B cells and certain epithelial cells. Recent findings in our laboratory and those of others, however, have shown that the EBV receptor is also present on T cells. Our study shows that Jurkat human T cells have a molecule that reacts with both anti-CR2 antibodies and the third component of complement, C3. Furthermore, the data indicate that this molecule binds EBV detected by incubation with biotin-conjugated virus and streptavidin phycoerythrin. Viral binding is specific, as it is inhibited by nonconjugated virus, with anti-CR2 antibodies, and with an antibody reactive with the glycoprotein (gp350) that EBV uses to bind CR2. In addition, EBV variably infects Jurkat cells as demonstrated by the presence of transcripts of Epstein Barr nuclear Ag (EBNA-1) using the polymerase chain reaction. Immunoprecipitation experiments with anti-CR2 antibodies and SDS-PAGE analysis reveal a protein with an apparent molecular mass of 155 kDa which is higher than the one seen in B cells. The size of this molecule is reduced to 119 kDa upon endoglycosidase F treatment. Northern blot analysis of Jurkat poly(A)+ RNA shows a transcript of 4.7 kb upon probing with the B cell CR2 cDNA. This size is consistent with that of B cell CR2 mRNA. Two cDNA clones were identified upon screening of a Jurkat cell cDNA library with the B cell CR2 cDNA. One of the clones possesses an identical nucleotide sequence to the one corresponding to B cell CR2, whereas the other represents a differentially spliced transcript which lacks the exon 8b of B cell CR2. Analysis of Jurkat and Raji mRNA by PCR demonstrated the presence of this novel splice variant in both cell lines.

Amino Acid Sequence↗

PubMed1993

Safety, tolerability and immunogenicity of a formalin-inactivated hepatitis A vaccine (VAQTA) in rural Kentucky children.

This study evaluated the immunogenicity and safety/tolerability profile of an investigational formalin-inactivated hepatitis A virus vaccine (VAQTA; Merck Research Laboratories) in 150 seronegative healthy children, 4 to 12 years old. The vaccine was derived from virus grown in infected MRC-5 cells in either roller bottles or Nunc cell factories (Nunc, Denmark). Subjects were vaccinated intramuscularly in a two dose regimen initially and at 24 weeks: Group A (n = 50) with a 12-unit dose from a roller bottle lot; Group B (n = 50) with a 25-unit dose from another roller bottle lot; and Group C (n = 50) with a 25-unit dose from a Nunc cell lot. Sera for anti-hepatitis A virus antibodies were drawn 3 weeks before vaccination and 4, 24 and 28 weeks after the first dose. Seroconversion from < 10 mIU/ml to > or = 10 mIU/ml by modified HAVAB (Abbott Laboratories) was observed in 99% of subjects at week 4 and persisted in 100% of subjects at week 28 (4 weeks after the second dose). The ranges of geometric mean titers of anti-HAV for all subjects at weeks 4, 24 and 28 were 31 to 49, 51 to 79 and 7059 to 29,609 mIU/ml, respectively. The 12- and 25-unit dose levels of roller bottle yielded similar geometric mean titers. The rise in geometric mean titers after the booster dose was > 120-fold and was highest in the recipients of the 25-unit Nunc cell lot (P < 0.05 for Group C vs. B).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

PubMed1992

Interaction between Epstein-Barr virus and a T cell line (HSB-2) via a receptor phenotypically distinct from complement receptor type 2.

Epstein-Barr virus (EBV), the causative agent of mononucleosis and several human cancers, infects cells via complement receptor type 2 (CR2, CD21) which also serves as the receptor for the third complement component, C3. Expression of this receptor is restricted to B lymphocytes, immature thymocytes, and certain epithelial cells. In the present investigation; we describe the presence of a seemingly novel EBV receptor which is phenotypically distinct from CR2. Among various leukemic T cells studied, one, HSB-2, demonstrates no reactivity to several anti-CR2 antibodies, yet it reacts strongly with EBV as detected by incubation with biotin-conjugated virus and streptavidin-phycoerythrin. The virus binding is specific as demonstrated by blocking with anti-EBV antibodies and with non-conjugated virus. Aggregated C3 also binds HSB-2 and is capable of partially inhibiting EBV binding. The absence of CR2 on HSB-2 is further supported by the lack of expression of specific mRNA, assessed by Northern blotting analysis and polymerase chain reaction. Viral internalization and infection is demonstrated with electron microscopy, with detection of EBV-DNA by Southern blotting, and with detection of EBNA-1 transcripts by the polymerase chain reaction. Even though HSB-2 does not express CR2, it nevertheless displays transcripts which have some homology to a CR2 cDNA probe under low stringency hybridization conditions. This probe encompasses approximately the N-terminal half of CR2 which includes the EBV-binding epitope(s). The HSB-2 message is 5.2 kb, a size distinct from the 4.7-kb message of B cell CR2s. In contrast, the 5.2-kb message in not seen, under similar hybridization conditions, with a probe comprising the C-terminal half of CR2. Collectively, the data indicate that a receptor molecule having distinct phenotypic characteristics from the known CR2 protein on B cells is utilized by EBV to target human T lymphocytes.

Animals↗

PubMed1992

Comparative study of the effectiveness of cefixime and penicillin V for the treatment of streptococcal pharyngitis in children and adolescents.

An open label randomized trial conducted in rural Kentucky compared the efficacy and safety of cefixime (CFX), 8 mg/kg once daily, with those of penicillin V (PEN), 250 mg 3 times daily, in 110 pediatric patients with Group A beta-hemolytic streptococcal pharyngitis. Forty-eight CFX and 47 PEN patients were evaluable for efficacy. At the end of therapy bacteriologic eradication was 45 of 48 (94%) and 36 of 47 (77%) in the CFX and PEN V groups, respectively (P < 0.05). Up to 6 weeks posttherapy 10 (21%) CFX patients and 21 (45%) PEN patients had positive Group A beta-hemolytic Streptococcus cultures (P < 0.05). Concordant serotypes were identified from 4 of 7 CFX and 15 of 17 PEN patients with positive repeat cultures. All discordant serotypes (5 of 31) were identified at greater than 19 days posttherapy. Symptomatic treatment failures (concordant serotypes) occurred in 1 (2%) CFX and 8 (17%) PEN patients (P < 0.05). Drug-related adverse experiences consisted of 2 cases of mild diarrhea and loose stools in the CFX group and none in the PEN group. No clinically significant laboratory test abnormalities occurred in either group. CFX, once daily, was as safe as and significantly more effective than PEN given 3 times daily for the treatment of Group A beta-hemolytic streptococcal pharyngitis.

Adolescent↗

PubMed1991

Infection of human thymocytes by Epstein-Barr virus.

The Epstein-Barr Virus (EBV) causes infectious mononucleosis, and has been strongly associated with certain human cancers. The virus is thought to exclusively bind to B lymphocytes and epithelial cells via receptors (CR2/CD21) that also interact with fragments of the third component of complement (C3). Recent evidence, however, has challenged this belief. We have used two-color immunofluorescence analysis using biotin-conjugated EBV and streptavidin-phycoerythrin along with fluorescein-conjugated anti-T cell antibodies and demonstrated that CD1-positive, CD3-dull (immature) human thymocytes express functional EBV receptors. In four replicate experiments, the binding of EBV to thymocytes ranged between 8 and 18%. This interaction is specific as evidenced by inhibition with nonconjugated virus, anti-CR2 antibodies, aggregated C3, and an antibody to the gp350 viral glycoprotein that the virus uses to bind to CR2. EBV can infect the thymocytes as evaluated by the presence of episomal EBV-DNA in thymocytes that had been incubated with the virus as short as 12 days or as long as 6 weeks. Episomal DNA analysis was performed by Southern blotting with a EBV-DNA probe that hybridizes to the first internal reiteration of the viral DNA. The presence of the EBV genome is also supported by the detection of EBV nuclear antigen 1 in infected thymocytes, assessed by Western blotting with EBV-immune sera. The EBV infection is specific as determined by blocking experiments using anti-CR2 and anti-gp350 antibodies. Finally, virus infection of thymocytes can act synergistically along with interleukin 2 and induce a lymphokine-dependent cellular proliferation. In view of previously reported cases of EBV-positive human T cell lymphomas, the possibility is raised that EBV may be involved in cancers of T lymphocytes that have not been previously appreciated.

Antigens, CD19↗

PubMed1987

Relation of the outcome of conjunctivitis and the conjunctivitis-otitis syndrome to identifiable risk factors and oral antimicrobial therapy.

The epidemiology, microbiology and clinical outcome of the conjunctivitis-otitis syndrome (CJ-AOM) was investigated in a rural private practice concurrent to a double blind placebo-controlled study of orally administered amoxicillin for prevention of acute otitis media (AOM) secondary to conjunctivitis. Bacterial pathogens were isolated when greater than 15 polymorphonuclear leukocytes/high power field were observed on Gram-stained smear of conjunctival secretions. Nontypable Haemophilus influenzae biotype 2 predominated in CJ-AOM; however, Streptococcus pneumoniae was isolated nearly as frequently as H. influenzae in conjunctivitis without AOM. Younger age (P = 0.001) and more episodes of AOM in the previous year (P = 0.006) were risk factors for CJ-AOM. Persistence of AOM was frequently observed in CJ-AOM. The frequency of AOM secondary to conjunctivitis was reduced (P = .01) in amoxicillin recipients (2 of 41) compared with placebo (11 of 42), but amoxicillin failed to eradicate nasopharyngeal carriage of H. influenzae. More episodes of AOM per year (P less than 0.001) and day care (P less than 0.001) were found to be risk factors for AOM secondary to conjunctivitis.

Acute Disease↗

PubMed1981

Septic Arthritis and osteomyelitis caused by an organism of the genus Rhodococcus.

We describe a previously healthy, immunologically normal young girl who presented painless swelling of fingers, a toe, and one knee. Roentgenograms were consistent with osteomyelitis of the phalanges and knee effusion. Rice bodies (corpora oryzoidea) were identified in viscous fluid obtained from the knee during arthroscopy. Culture of this fluid grew an organism initially believed to be a member of the genus Nocardia but which was later presumptively identified as a member of the genus Rhodococcus. The patient was successfully treated with a combination of erythromycin and amoxicillin for a total of 6 months. Previously reported cases of this unusual infection and the microbiological features of the organism are reviewed. The significance of rice bodies found in joint fluid and the therapy of this infection are discussed.

Actinomycetales↗

PubMedDate not supplied

Clarithromycin suspension vs penicillin V suspension in children with streptococcal pharyngitis.

Clarithromycin, an advanced-generation macrolide antibiotic, has demonstrated excellent in vitro activity against group A beta-hemolytic streptococcus (GABHS). Potent activity against Streptococcus pyogenes and a favorable pharmacokinetic profile have made it a reasonable alternative for treatment of patients with streptococcal pharyngitis. The safety and efficacy of clarithromycin and penicillin V were compared in a randomized, investigator-blind study. Children 6 months to 12 years of age received 5 days of clarithromycin suspension 7.5 mg/kg twice daily (n = 268) or 10 days of penicillin V suspension 13.3 mg/kg three times daily (n = 260). Patients were evaluated for signs and symptoms of pharyngitis, and throat swabs for culture were obtained prior to therapy, at the end of therapy, and at follow-up. Clarithromycin and penicillin V produced comparable rates of clinical success (cure + improvement) at the posttreatment (97% and 94%) and follow-up (81% and 82%) evaluations. The GABHS eradication rate, however, was significantly higher with clarithromycin (94% vs 78%, P < .001). Both drugs were well tolerated; gastrointestinal complaints were similar and mild. Resistance did not occur with the short course of clarithromycin or the standard regimen of penicillin V. Five days' treatment with clarithromycin was superior to 10 days of penicillin in eradicating S. pyogenes.

Analysis of Variance↗