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Biomedical subjects

M Peeters

Publications and source records attributed to M Peeters.

At least 145 records · Page 8Linked to original sources

Biological phenotypes of HIV-1 subtypes A and B strains of diverse origins.

The identification of specific biologic phenotypic traits that can be correlated with different HIV-1 genetic subtypes was sought. The genetic subtypes were determined by either sequencing (Cameroonian strains, n = 18) or by the heteroduplex mobility assay (HMA) (Belgian strains, n = 21 and Ivorian strains, n = 25). Seventeen (81%) of the 21 Belgian isolates belonged to subtype B and 4 (17%) were subtype A strains. Subtype A variants were predominant in the two African countries studied; 11 (61%) of 18 strains from Cameroon and 23 (92%) of 25 strains from the Ivory Coast. Of the 64 isolates, 38 (58%) and 19 (29%) belonged to subtypes A and B, respectively. No significant difference was observed for biological phenotypes (slow/low and rapid/high) of both genetic subtypes. In symptomatic individuals, however, a significantly higher number of subtype B isolates were of rapid/high phenotype, compared with subtype A (5 of 10; 50%) vs. 2 of 22; 9%), respectively; X2 = 6.7, P = 0.02). The findings suggest that overall HIV-1 isolates belonging to genetic subtype B are not distinguishable from subtype A variants on the basis of their biological phenotypes. Syncytium-inducing variants were less prevalent regardless of the geographic origin of the isolates.

Base Sequence↗

Effect of prior isometric muscle action on concentric torque output during plantar flexion.

The influence of different levels of prior isometric muscle action on the concentric torque output during plantar flexion was examined at two angular velocities (60 degrees.s-1 and 120 degrees.s-1) in ten healthy female subjects. The levels of the prior muscle actions were 25%, 50%, 75% and 100% of the maximal voluntary isometric contraction (MVIC). A KINetic-COMmunicator II dynamometer was used to measure torque output during plantar flexion within a range of motion of 78 degrees-120 degrees of the ankle joint. Simultaneous recordings of electromyograms (low-pass filtered and rectified) were obtained from the gastrocnemius medialis muscle and the soleus muscle. Torque-angle curves were made for the plantar flexions using different prior muscle actions. Up to 75% of MVIC, the torque output in the first part of the range of motion increased with the level of the prior isometric muscle action; at higher levels of MVIC the torque did not appear to increase any further. Later in the range of motion, after 24 degrees in the plantar flexion at a velocity of 60 degrees.s-1 and 31 degrees at 120 degrees.s-1, the prior muscle actions had no further influence. No increase was found in the electromyograms, with one exception, during the concentric movements when preceded by higher levels of MVIC. It would seem therefore that the increase in torque output early in the range of motion cannot be explained on the basis of differences in electrical muscle activation in this study.

Adult↗

Controlled trial of metronidazole treatment for prevention of Crohn's recurrence after ileal resection.

BACKGROUND/AIMS: New lesions recur within weeks to months after ileal resection and ileocolonic anastomosis for Crohn's ileitis. A double-blind controlled trial was performed using metronidazole to prevent recurrence after ileal resection. METHODS: Sixty patients who underwent curative ileal resection and primary anastomosis were included within 1 week after surgery. Thirty patients received metronidazole (20 mg/kg body wt) daily for 3 months, and 30 patients received placebo. Treatment was then discontinued. Nine patients dropped out during treatment, 7 in the metronidazole group and 2 in the placebo arm. RESULTS: At 12 weeks, 21 of 28 patients (75%) in the placebo group had recurrent lesions in the neoterminal ileum as compared with 12 of 23 patients (52%) in the metronidazole group (P = 0.09). The incidence of severe endoscopic recurrence was significantly reduced by metronidazole (3 of 23; 13%) as compared with placebo (12 of 28; 43%; P = 0.02). Patients in the metronidazole arm had more frequent side effects. Metronidazole therapy statistically reduced the clinical recurrence rates at 1 year (4% vs. 25%). Reductions at 2 years (26% vs. 43%) and 3 years (30% vs. 50%) were not significant. CONCLUSIONS: Metronidazole therapy for 3 months decreases the severity of early recurrence of Crohn's disease in the neoterminal ileum after resection and seems to delay symptomatic recurrence.

Adult↗

Correlation between genetic and biological properties of biologically cloned HIV type 1 viruses representing subtypes A, B, and D.

The relationship between the genetic variability in the V3 loop and the biological characteristics of 38 biological clones from 5 European and 7 African HIV-1 isolates belonging to 3 different subtypes (subtype A, B, and D) was investigated. Seventeen of 19 clones displaying a syncytium-inducing (SI) capacity had a positively charged amino acid located at position 11 and/or 25 in the V3 loop sequence. All 19 non-syncytium-inducing (NSI) virus clones lacked such a positive charge at the same positions (p < 0.001). The mean of net charge in the overall V3 loop sequences of the SI clones was higher than that of the NSI clones (p < 0.001). Within the same strains, the SI clones replicated faster/higher than the NSI clones in peripheral blood mononuclear cells (p < 0.01), but not in CD4+ T cell cultures (p > 0.1). All SI clones but only 5 of 19 NSI clones could replicate in human continuous T cell and monocytic cell lines (p < 0.001). A higher number of positively charged amino acid substitutions was found among the subtype D SI clones. Only one of eight autologous sera tested had the ability to neutralize the contemporaneously isolated NSI clones, but not the SI clones. This study indicates that the V3 loop amino acid sequences of HIV-1 biological clones from different origins belonging to different genetic subtypes are clearly correlated with viral syncytium-inducing capacity, cell tropism, and replication rate.

Amino Acid Sequence↗

Equal IgG antibody response to pneumococcal vaccination in all stages of human immunodeficiency virus disease.

To evaluate the immunogenicity and safety of a 23-valent pneumococcal vaccine in human immunodeficiency virus (HIV)-seropositive patients, 80 men and 18 women received 1 dose of the vaccine (Pneumo 23; Pasteur Mérieux MSD, Brussels). The total IgG antibody response against all 23 Streptococcus pneumoniae capsular antigens was measured. Antibody levels were expressed in arbitrary units per microliter, referring to a standard curve. Geometric mean titers of the total IgG capsular antibodies on the day of vaccination and 30-45 days later were compared. The ratios of titers after and before vaccination in patients with > 500, 200-500, and < 200 CD4 lymphocytes/microL were 10, 10, and 12.6, respectively. Nonresponse (ratio < 4) occurred in 17% of patients and was unrelated to CD4 cell count. The vaccine was well tolerated; no serious side effects occurred. In 83% of the patients with HIV infection, the total antipneumococcal IgG level was higher after vaccination.

Adult↗

Phenotypic and functional parameters of cellular immunity in a chimpanzee with a naturally acquired simian immunodeficiency virus infection.

The cellular immunologic and virologic status of a chimpanzee, naturally infected with a human immunodeficiency virus type 1 (HIV-1)-like lentivirus (SIVcpz-ant), was compared longitudinally with those of 3 HIV-1-infected and 5 uninfected chimpanzees for a period of 49 months. Evidence of immune deficiency was not observed in the HIV-1-infected chimpanzees, nor could virus be isolated from plasma. Virus could be isolated from plasma of the SIVcpz-ant-infected chimpanzee, but clinical signs of immune deficiency were never observed. Absolute CD4+ cell counts remained relatively stable, but NK cells fluctuated significantly over time and tended to correlate inversely with the virus titer in peripheral blood. Although only CD8+ T cells were directly demonstrated to exert a suppressive effect on viral replication in vitro, the observed fluctuation of NK cells suggests that these cells may also be involved in the interaction with lentivirus infection in this species.

Animals↗

Reduced capacity of antibodies from patients infected with human immunodeficiency virus type 1 (HIV-1) group O to neutralize primary isolates of HIV-1 group M viruses.

Neutralizing antibody patterns in sera of persons infected with human immunodeficiency virus type 1 (HIV-1) groups M and O to their homologous and heterologous primary isolates were determined in a peripheral blood mononuclear cell-based neutralization assay and correlated with their ability to bind to V3 loop synthetic peptides. Most HIV-1 group M sera (9/16) neutralized HIV-1 group O viruses, whereas fewer group O sera (3/13) only weakly neutralized HIV-1 group M viruses. Group M sera neutralizing HIV-1 group O viruses neutralized other HIV-1 group M viruses with titers of 1:10-1:1280. V3 loop binding capacity of sera did not reflect their neutralizing capacity of the homologous isolate. Despite the reduced neutralizing capacity of group O-infected patients' sera to group M viruses, some group M-infected patients' sera neutralized both HIV-1 group M and O isolates, suggesting that they share some conserved neutralizing epitopes.

Acquired Immunodeficiency Syndrome↗

Virus load in chimpanzees infected with human immunodeficiency virus type 1: effect of pre-exposure vaccination.

Many reports indicate that a long-term asymptomatic state following human immunodeficiency virus type 1 (HIV-1) infection is associated with a low amount of circulating virus. To evaluate the possible effect of stabilizing a low virus load by non-sterilizing pre-exposure vaccination, a quantitative virus isolation method was developed and evaluated in four chronically infected chimpanzees infected with a variety of HIV-1 related isolates. This assay was then used to monitor a group of chimpanzees (n = 6) challenged with HIV-1 following vaccination with gp120 or gp160. Data indicated that of the three vaccinated animals which became infected after challenge, the animal with the lowest neutralizing titre at the time of challenge acquired a virus load similar to the control animals, whereas the two other chimpanzees had reduced numbers of virus producing cells in their peripheral circulation. One animal became virus isolation negative, developed an indeterminant PCR signal on lymph node DNA and subsequently became negative for HIV-1 DNA as determined by PCR on PBMC (peripheral blood mononuclear cells) and bone marrow DNA. Recently, the second animal has also become PCR negative. To confirm observations from quantitative virus isolations, quantification of HIV-1 DNA in PBMC and virus RNA in serum was performed by PCR on serially diluted samples at two different time points. Comparison of virus load as determined by these three methods confirmed that there was an effect of vaccination in reducing virus load and demonstrated a correlation between decreased numbers of virus producing cells, HIV-1 DNA containing cells and virus RNA molecules in serum.

Animals↗

The Coffin-Siris syndrome: data on mental development, language, behavior and social skills in 12 children.

In this report we present data on cognitive development, language, behavior and social skills in 12 children and adolescents, nine girls and three boys, aged between 2.5 and 19 years, with Coffin-Siris syndrome (CS). 1. Mental retardation was mild in three patients and moderate in the nine others. 2. Speech onset was severely retarded with little interest in language. In the older group (seven patients aged 7 to 19 years), language comprehension was appropriate to the mental level. 3. Gross-motor functioning and autonomy, with the lowest score on "Task-orientation", were equal to the mental development. 4. Most frequently, aggressive disturbed behavior was observed, especially in the youngest children, while mixed disturbed behavior was observed in the oldest patients. Almost half of the CS patients (5/11) presented symptoms of pervasive developmental disorder, with 2/11 scoring in the pathological range. Obsessive interests, strong dependence on patterns and rituals and unusual fears were characteristic behavioral problems also when they got older.

Adolescent↗

Design and evaluation of new, highly sensitive and specific primers for polymerase chain reaction detection of HIV-1 infected primary lymphocytes.

Primer pairs in the HIV-1 POL and ENV genes were evaluated by performing a PCR on lysed peripheral blood mononuclear cells (PBMCs) from 96 HIV-1 seropositive and 40 seronegative individuals originating from 16 different geographical localities in Africa, Europe and Haiti. A single PCR using primer pairs to the LTR, GAG and ENV regions and detection by radioactively labelled oligonucleotide probes was compared to a nested PCR scheme using newly designed POL and ENV primers which used ethidium-bromide staining of the amplified product on agarose gel. The newly designed POL nested primer pair was shown to be highly sensitive (93%) and specific (100%) for the detection of HIV-1 proviral DNA of very diverse geographical and genetic origin, including highly aberrant HIV-1 isolates. The sensitivity of the newly designed ENV primers was 68.7%, which does not differ significantly from the sensitivity of the classical primers, SK 68/69. Both ENV primers were unable to amplify two SIVcpz isolates from naturally infected chimpanzees.

Africa↗

Increased permeability of macroscopically normal small bowel in Crohn's disease.

To investigate permeability alterations of the macroscopically normal jejunum in Crohn's disease, the permeation of two probes was measured during perfusion of an isolated jejunal segment. The data were compared with the results obtained by the standard per oral test in the same patients. Test probes were PEG-400 and [51Cr]EDTA. Ten normal individuals, 12 patients with Crohn's ileitis or ileocolitis, and seven patients with isolated Crohn's colitis all with normal jejunum on x-ray series were studied. Upon perfusion of the proximal small bowel, the 3-hr [51Cr]EDTA excretion was significantly increased in ileitis patients (P = 0.023) as compared to normals. The excretion exceeded the highest value of normals in eight of 12 ileitis patients. The excretion in Crohn's colitis patients was not significantly increased (P = 0.24) and abnormal excretion was found only in one of the Crohn's colitis patients. PEG-400 permeation during perfusion did not differentiate between the groups, but five of the seven patients with isolated Crohn's colitis had PEG-400 excretion exceeding the highest value in normals. Overall, 13 of the 19 patients had increased permeation of one of the two probes through jejunal mucosa during perfusion. These data suggest that the permeability is increased in the majority of patients even in segments that seem normal on x-ray.

Adult↗

Effect of methodology on detection of HIV-1/HIV-2 dual infections in Côte d'Ivoire.

Dual seroreactivity to the human immunodeficiency virus (HIV) types 1 and 2 is common in Côte d'Ivoire. To assess whether dual infection is the reason for dual seroreactivity, different methods for detection of HIV-1 and HIV-2 viruses were compared. PCR on primary uncultured lymphocytes of 56 dually seropositive samples revealed the presence of both HIV-1 and HIV-2 proviral DNA in 23 (41%) cases. In 7 other dual seropositive persons, PCR was carried out on the primary lymphocytes as well as on lymphocytes after 3 and 6 weeks of cocultivation. More cultures, 5/7 (71%), were positive for both viruses at 3 weeks compared to 0/7 at 6 weeks post cultivation. Moreover, 2 out of 3 samples, where only HIV-1 was detected in uncultured cells, were positive for both viruses after 3 weeks of cultivation. These data indicate that the sensitivity of HIV-2 detection can be increased by stimulation of patients' lymphocytes. A higher number of dual seropositive individuals (10/23 (48%)) had antibodies able to neutralize simultaneously both HIV-1 and HIV-2 prototype viruses than did HIV-1 antibody-positive sera (5/21 (24%)) or HIV-2 antibody positive sera (3/18 (17%)). The prevalence of dual seropositives being infected with both viruses is highly dependent on the method used to detect infection. There is a need to standardize virological markers in order to gain a better insight into the relative proportions of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected persons.

Antibody Specificity↗

Genetic and antigenic variability of HIV type 1 in Brazil.

Six Brazilian strains of human immunodeficiency virus type 1 (HIV-1) were isolated from infected individuals residing in different regions of Brazil between 1987 and 1989. Phylogenetic analysis based on an 860-base pair env fragment, including V3, V4, V5, and the beginning of gp41, classified the Brazilian strains significantly in genotype B, with interhost distances between 5.9 and 13.1% (mean value, 10%). Amino acid sequence analysis of the V3 loop revealed that three strains contained the North American/European GPGR motif as the tip of the loop whereas in the other three strains proline (P) was substituted by tryptophan (W), methionine (M), or phenylalanine (F). A consensus peptide, Bra-cons, was designed containing GWGR as the tip of the loop. Serological reactivity to the Bra-cons peptide and other V3 peptides (MN, SF2, HBX2, RF, MAL, ELI, Z6, and a Côte d'Ivoire peptide, CI-cons) was compared for 114 HIV-1-positive sera from Rio de Janeiro. Sixty-nine sera (60.5%) reacted with peptides belonging to genotype B, of which 10 sera also reacted with peptides belonging to genotype A (n = 7) and D (n = 3). Eighteen sera (15.8%) had binding antibodies to the Bra-cons peptide. A high number of sera (n = 43; 37.7%) had no antibodies to any of the V3 peptides tested. This result suggests that HIV-1 variants with aberrant V3 loops may circulate in Rio de Janeiro.

Acquired Immunodeficiency Syndrome↗

Isolation of simian immunodeficiency viruses from two sooty mangabeys in Côte d'Ivoire: virological and genetic characterization and relationship to other HIV type 2 and SIVsm/mac strains.

OBJECTIVE: To search for the presence of SIV in sooty mangabeys and other monkey species in Côte d'Ivoire, West Africa, and to compare viral isolates with HIV-2 strains from the same region. METHODS: Forty-three captive housed monkeys (28 African green monkeys, 6 sooty mangabeys, 6 baboons, and 6 patas monkeys) were tested for the presence of HIV and SIV antibodies. Virus was isolated from the peripheral blood lymphocytes of seropositive animals and from HIV-2 antibody-positive patients originating from Côte d'Ivoire, Ghana, Senegal, and Belgium. Viruses were characterized by Western blot and radioimmunoprecipitation assay. Proviral DNA was amplified by PCR, cloned, and sequenced to construct a phylogenetic tree. RESULTS: One African green monkey and three sooty mangabeys had antibodies that cross-reacted with HIV-2. From two mangabeys lentiviruses were isolated and designated as SIVsmCI2 and SIVsmCI8. Serological, virological, and sequence data showed that these isolates are members of the HIV-2/SIVsm/SIVmac group of primate lentiviruses. Furthermore, in the phylogenetic tree, these two new viruses form a distinct subgroup that is equidistant to the HIV-2 strains and the previously described SIVsm/SIVmac viruses. CONCLUSION: This study provides additional evidence that sooty mangabey monkeys can be infected with a lentivirus in their natural habitat. Within the SIVsm and SIVmac viruses extensive genetic variation is observed.

Acquired Immunodeficiency Syndrome↗