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Biomedical subjects

R Yogev

Publications and source records attributed to R Yogev.

At least 91 records · Page 5Linked to original sources
PubMed1991

Serum tumor necrosis factor alpha, interleukin 1-beta, p24 antigen concentrations and CD4+ cells at various stages of human immunodeficiency virus 1 infection in children.

We measured the serum concentrations of tumor necrosis factor (TNF-alpha), interleukin 1-beta (IL-1-beta), p24 antigen, CD4+/CD8+ cells and immunoglobulins in 35 children at various stages of human immunodeficiency virus infection. Serum TNF-alpha concentrations were significantly higher in children with lymphocytic interstitial pneumonitis and in children with mildly symptomatic illness than in asymptomatic children or children with acquired immunodeficiency syndrome. In addition serum IL-1 concentrations were significantly higher in patients with lymphocytic interstitial pneumonitis than in asymptomatic, mildly symptomatic, or acquired immunodeficiency syndrome patients. Children with lymphocytic interstitial pneumonitis had the highest serum TNF-alpha and IL-1 concentrations. Among symptomatic children serum TNF-alpha concentrations correlated positively with those of IL-1, and both were inversely related to the amount of p24 antigen. TNF-alpha values in excess of 50 pg/ml were observed more frequently among patients with CD4+ cell count greater than 400/mm3 than in those with CD4+ cell count less than 400/mm3. We did not find any association between elevated TNF-alpha concentrations and cachexia, opportunistic infections or progressive encephalopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Molecular cloning of a gene involved in lipooligosaccharide biosynthesis and virulence expression by Haemophilus influenzae type B.

A wild-type Haemophilus influenzae type b (Hib) genomic DNA library was constructed in the plasmid shuttle vector pGJB103. A virulence-deficient lipooligosaccharide (LOS) mutant of Hib was used as a recipient for genetic transformation to screen this Hib genomic DNA library for genes involved in LOS expression. A recombinant plasmid containing a 7.8 kb PstI fragment of Hib DNA was shown to transform this LOS mutant to reactivity with a monoclonal antibody (mAb) specific for a wild-type LOS epitope. Transformation of two different virulence-deficient LOS mutants with a 4.4 kb BglII fragment of this recombinant plasmid yielded transformants which expressed LOS that bound the wild-type LOS-specific mAb and yielded profiles in sodium dodecyl sulphate/polyacrylamide gradient gel electrophoresis different from those of the original LOS mutants. These transformants with structurally altered LOS molecules also exhibited increased virulence in an animal model for invasive Hib disease. The virulence-transforming ability was further localized to a 1.8 kb BglII-AlwNI fragment of the Hib DNA insert. Nucleotide sequence analysis indicated the presence of a single large open reading frame within this fragment. This open reading frame contained 19 consecutive repeats of the tetramer CAAT near the 5' end. Linker insertion mutagenesis was used to demonstrate directly the involvement of this open reading frame in both LOS biosynthesis and virulence expression by Hib.

Amino Acid Sequence↗
PubMed1990

Tumors of smooth-muscle origin in HIV-infected children.

We report the occurrence of multiple leiomyomata and leiomyosarcomata in three children with the acquired immunodeficiency syndrome. The children were infected with human immunodeficiency virus as infants (one perinatally and two through transfusions) and each was profoundly immunosuppressed (absolute CD4 cell count, less than 75/mm3). They experienced multiple infections prior to the diagnosis of neoplasms at ages 4, 5, and 8 years, respectively. The tumors in each case were mainly involving the lungs and gastrointestinal tract. The smooth-muscle origin of the tumors was proved by light and electron microscopy and immunohistochemical staining for muscle-specific actin and desmin. Leiomyomata and leiomyosarcomata are rare tumors in childhood, suggesting a nonrandom association of tumors of smooth-muscle origin and the acquired immunodeficiency syndrome. We postulate that human immunodeficiency virus infection may play a direct or indirect role in tumor formation.

Child↗
PubMed1990

Lack of influence of beta-lactamase-producing flora on recovery of group A streptococci after treatment of acute pharyngitis.

Because production of beta-lactamase by normal pharyngeal flora could account for penicillin treatment failure, we studied the effect of anaerobic and aerobic beta-lactamase-producing bacteria on bacteriologic outcome in acute group A beta-hemolytic streptococcal (GABHS) pharyngitis. We compared 10-day courses of orally administered phenoxymethyl penicillin and amoxicillin-clavulanic acid, using a randomized, single-blind treatment protocol. Eligible patients were 2 to 16 years of age and had culture-proven acute GABHS pharyngitis; 89 patients (43 penicillin, 46 amoxicillin-clavulanic acid) were compliant with therapy. beta-Lactamase-producing organisms were isolated before therapy from the throats of 67% of patients treated with penicillin and 63% treated with amoxicillin-clavulanic acid. Throat cultures after completion of therapy were positive for GABHS in 7 (7.9%) of 89 patients. The initial GABHS T type persisted (treatment failure) in only 4 (4.5%) of 89 patients, including 3 (6.5%) of 46 who received amoxicillin-clavulanic acid and in 1 (2.3%) of 43 who received penicillin (not statistically significant). Bacteriologic treatment failure was unrelated to recovery of beta-lactamase-producing bacteria at the time of enrollment or after treatment. We conclude that beta-lactamase production by normal pharyngeal flora does not fully explain the failure of penicillin therapy for acute streptococcal pharyngitis. Using an antibiotic effective against beta-lactamase-producing bacteria will not eliminate the problem of bacteriologic treatment failure.

Adolescent↗
PubMed1990

Cerebrospinal fluid cachectin/tumor necrosis factor-alpha and platelet-activating factor concentrations and severity of bacterial meningitis in children.

In prospective studies, tumor necrosis factor (TNF alpha) was detected in cerebrospinal fluid (CSF) of 33 of 38 children with bacterial meningitis (BM) but in none of 15 with viral meningitis/encephalitis (P less than .001). BM CSF TNF alpha (less than 35 to greater than 25,500 pg/ml) correlated with CSF bacterial density (P less than .01), CSF protein (P less than .001), endotoxin (LPS) in gram-negative disease (P less than .01), and consecutive febrile hospital days (P less than .001); initial CSF TNF alpha greater than 1000 pg/ml was associated with seizures (P less than .05). Only 5 children with BM (13%) had detectable plasma TNF alpha activity on admission. A higher proportion who died had detectable plasma TNF alpha activity compared with survivors (3/4 vs. 2/34, P less than .005). Platelet-activating factor (PAF) in CSF was higher in 19 children with Haemophilus influenzae meningitis than in 17 controls (P less than .01) and correlated with bacterial density (P less than .01), CSF LPS (P less than .01), CSF TNF alpha levels (P less than .01), and the Herson-Todd severity score (P less than .01). Elevated CSF TNF alpha and PAF are often present in children with BM and are associated with seizures and severity of disease. Detectable CSF TNF alpha appears to distinguish BM from viral meningitis.

Adolescent↗
PubMed1990

Effect of mutations in lipooligosaccharide biosynthesis genes on virulence of Haemophilus influenzae type b.

Chemical mutagenesis techniques and genetic transformation methods were used to construct isogenic mutants of Haemophilus influenzae type b (Hib) defective in the ability to synthesize lipooligosaccharide (LOS). A mutant (17B) which expressed a LOS molecule with an altered oligosaccharide was less virulent than the wild-type parent strain, as determined by measurement of the ability of these strains to produce bacteremia in infant rats after intranasal challenge. Further mutagenesis of this mutant strain yielded two new mutants with different LOS phenotypes. Mutant 7A was slightly sensitive to the bactericidal activity present in normal infant rat serum and was even less virulent than its immediate parent strain (17B) in the intranasal challenge model. However, both mutants 17B and 7A could produce bacteremia and meningitis when introduced into infant rats by the intraperitoneal route. The other LOS mutant (14A) derived from mutant 17B exhibited a level of virulence equivalent to that of the original wild-type strain. Genetic transformation of wild-type chromosomal DNA into the essentially avirulent mutant 7A and selection of transformants on the basis of their LOS antigenic characteristics resulted in the sequential restoration of full virulence to this mutant. These findings suggest that LOS is involved on at least two different levels in the ability of Hib to produce invasive disease in the infant rat model. Changes in LOS phenotype can independently affect the ability of Hib to produce bacteremia after intranasal challenge and the sensitivity of Hib to killing by normal infant rat serum. These results reinforce the significance of Hib LOS in the expression of virulence by this pathogen.

Administration, Intranasal↗
PubMed1990

Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate): immunogenicity and safety at various doses.

The Haemophilus influenzae vaccine consisting of purified type b capsular polysaccharide (polyribosylribitol-phosphate [PRP]) was shown in Finland to be protective, with 90% efficacy in children older than 18 to 23 months of age. However, a wide range of estimates of vaccine efficacy has been reported in the United States after its licensure in 1985. These estimates range from -55% to +89%. In addition, the PRP vaccine was not effective in children younger than 18 months of age, in whom 70% to 80% of meningitis cases occur. A further development was the introduction of H influenzae type b polysaccharide-protein conjugate vaccines such as the PRP-D. These conjugate vaccines were found to be more immunogenic than PRP vaccine in children of all ages. Two doses of PRP-D in infants 7 months of age and older induced antibody levels equal to or greater than levels in infants 24 months of age who received the PRP vaccine alone. Recently, Eskola et al reported that repeat vaccinations with PRP-D at 3, 4, 6, and 14 months of age was 83% protective (95% confidence interval, 26% to 96%). Yet PRP-D vaccine elicits only low serum antibody levels in infants younger than 7 months of age. Because of the discrepancy in efficacy results for the PRP vaccine in the United States and Finland and the lack of data about the protective efficacy of PRP-D vaccine in infants in the United States, the PRP-D vaccine is currently recommended only for children 18 months of age or older.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗
PubMed1989

Cerebrospinal fluid endotoxin levels in children with H. influenzae meningitis before and after administration of intravenous ceftriaxone.

Total, cell-free, and cell-bound endotoxin and bacterial density were measured in cerebrospinal fluid (CSF) of 22 children with Hemophilus influenzae meningitis. Also the effect of ceftriaxone on CSF endotoxin levels was investigated in eight patients by reexamining their CSF 2-6 h after the initial dose. Initial CSF bacterial density correlated with initial CSF endotoxin levels (P less than .001). Ceftriaxone induced a marked increase of free endotoxin in CSF, from an initial (mean +/- SE) 0.75 +/- 0.21 to 1.29 +/- 0.23 log10 ng/ml (P less than .01). This increase correlated positively with the number of bacteria killed in the CSF (P less than .01). The increase in free endotoxin was associated with an increase in mean CSF lactate levels from 8.5 to 9.7 units/l (P less than .05) and mean lactate dehydrogenase levels from 102 to 180 mmol/l (P less than .02) and a decrease in mean CSF glucose from 1.17 to 0.46 mmol/l (P less than .05). Initial CSF total endotoxin concentrations correlated both with the Herson-Todd clinical severity score (P less than .001) and with the number of febrile hospital days (P less than .001). These findings suggest that highly bactericidal agents initially lead to release of free endotoxin from gram-negative organisms into CSF, with associated enhanced inflammatory response by the host.

Ceftriaxone↗
PubMed1989

Enzymatic amplification of the human immunodeficiency virus in peripheral blood mononuclear cells from pediatric patients.

The presence of the human immunodeficiency virus type 1 (HIV) provirus was assessed in peripheral blood mononuclear cells (PBMCs) from 27 offspring of HIV-infected mothers, 12 of these mothers, and 4 HIV-uninfected mother-infant control pairs. Enzymatic amplification of specific conserved regions of the gag and env genes was performed directly in PBMC lysates using the polymerase chain reaction (PCR) technique. The enzymatically amplified gene products were evaluated using the oligomer hybridization detection procedure. PBMCs from infected infants (as determined by Centers for Disease Control clinical criteria) and from HIV-infected mothers manifested a characteristic HIV oligomer hybridization product. Clinically uninfected seropositive infants with declining HIV antibody titers and infants who became seronegative lacked an enzymatically amplified HIV gene product. These preliminary data indicate that PCR is a valuable diagnostic technique to detect or exclude HIV infection in young infants and children.

Blotting, Western↗
PubMed1989

Varicella-zoster virus infections in children infected with human immunodeficiency virus.

Primary varicella-zoster (VZ) infection in eight children with perinatally acquired human immunodeficiency virus infection tended to be severe, prolonged, complicated by bacterial infections and in one case fatal. Depletion of CD4-lymphocytes was associated with chronic and recurrent VZ infection. In some patients convalescent VZ antibody titers were low and did not correlate with recurrence of VZ lesions. Administration of acyclovir appeared to be beneficial in suppressing VZ in human immunodeficiency virus-infected children with primary or recurrent VZ infection.

Acyclovir↗