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M Bakker

Publications and source records attributed to M Bakker.

At least 19 recordsLinked to original sources

Motor imagery of gait: a quantitative approach.

Motor imagery (MI) is widely used to study cognitive aspects of the neural control of action. Prior studies were mostly centred on hand and arm movements. Recently a few studies have used imagery tasks to explore the neurophysiology of human gait, but it remains unclear how to ascertain whether subjects actually perform imagery of gait as requested. Here we describe a new experimental protocol to quantify imagery of gait, by behaviourally distinguishing it from visual imagery (VI) processes and by showing its temporal correspondence with actual gait. Fourteen young healthy subjects performed two imagery tasks and an actual walking (AW) task. During both imagery tasks subjects were sitting on a chair and faced a computer screen that presented photographs of walking trajectories. During one task (MI), subjects had to imagine walking along the walking trajectory. During the other task (VI), subjects had to imagine seeing a disc moving along the walking trajectory. During the AW task, subjects had to physically walk along the same walking trajectory as presented on the photographs during the imagery tasks. We manipulated movement distance by changing the length of the walking trajectory, and movement difficulty by changing the width of the walking trajectory. Subjects reported onset and offset of both actual and imagined movements with a button press. The time between the two button presses was taken as the imagined or actual movement time (MT). MT increased with increasing path length and decreasing path width in all three tasks. Crucially, the effect of path width on MT was significantly stronger during MI and AW than during VI. The results demonstrate a high temporal correspondence between imagined and AW, suggesting that MI taps into similar cerebral resources as those used during actual gait. These results open the possibility of using this protocol for exploring neurophysiological correlates of gait control in humans.

Adult↗

Nasal nitric oxide in cystic fibrosis with and without humming.

BACKGROUND: Nasal nitric oxide (nNO) values are reduced in patients with cystic fibrosis (CF). Humming during nNO measurement increases nNO values in healthy subjects. Nasal NO is reduced in patients with CF, sinus disease or nasal polyps. Humming nNO values have not been reported in CF patients yet. Our aim was to explore humming nNO values in CF patients and assess whether nNO during humming is a better discriminator than silent nNO measurements in this patient group. MATERIALS AND METHODS: In a cross sectional study we measured nNO concentrations in healthy controls (HC) and in CF patients (n = 23 and 31, respectively). The participants held their breath for 10 s while air was passively extracted from one nostril with 700 mL min(-1) for direct NO measurements (NIOX chemiluminescence analyser). Subsequently nNO was measured during humming with the mouth closed for 10 s. RESULTS: Mean nNO in parts per billion (p.p.b.) (SD) during breath hold was 499 (164) and 240 (139), respectively. The median nNO peak (p.p.b., minimum-maximum) during humming was 1500 (425-4100) for HC and 120 (23-500) for CF. There was a highly significant difference between nNO both with and without humming between CF and HC (P < 0.01). The sensitivity and specificity of nNO for detecting CF were better with humming. CONCLUSION: Nasal NO concentrations with and without humming are significantly decreased in CF. Humming nNO is an excellent discriminator between HC and CF and performs better than silent nNO.

Adult↗

Synthesis and biodistribution of [11C]R107474, a new radiolabeled alpha2-adrenoceptor antagonist.

R107474, 2-methyl-3-[2-(1,2,3,4-tetrahydrobenzo[4,5]furo[3,2-c]pyridin-2-yl)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one, was investigated using in vitro and in vivo receptor assays and proved to be a potent and relatively selective alpha(2)-adrenoceptor antagonist. Performed assays in vitro were inhibition of binding to a large number of neurotransmitter receptor sites, drug receptor binding sites, ion channel binding sites, peptide receptor binding sites, and the monoamine transporters in membrane preparations of brain tissue or of cells expressing the cloned human receptors. The compound has subnanomolar affinity for halpha(2A)- and halpha(2C)-adrenoceptors (K(i) = 0.13 and 0.15 nM, respectively) and showed nanomolar affinity for the halpha(2B)-adrenoceptors and 5-hydroxytryptamine(7) (h5-HT(7)) receptors (K(i) = 1 and 5 nM, respectively). R107474 interacted weakly (K(i) values ranging between 81 and 920 nM) with dopamine-hD(2L), -hD(3) and -hD(4), h5-HT(1D)-, h5-HT(1F)-, h5-HT(2A)-, h5-HT(2C)-, and h5-HT(5A) receptors. The compound, tested up to 10 microM, interacted only at micromolar concentrations or not at all with any of the other receptor or transporter binding sites tested in this study. In vivo alpha(2A)- and alpha(2C)-adrenoceptor occupancy was measured by ex vivo autoradiography 1h after subcutaneous (sc) administration of R107474. It was found that R107474 occupies the alpha(2A)- and alpha(2C)-adrenoceptors with an ED(50) (95% confidence limits) of 0.014 mg/kg sc (0.009-0.019) and 0.026 mg/kg sc (0.022-0.030), respectively. Radiolabeled 2-methyl-3-[2-([1-(11)C]-1,2,3,4-tetrahydrobenzo[4,5]furo[3,2-c]pyridin-2-yl)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one ([(11)C]R107474) was prepared and evaluated as a potential positron emission tomography (PET) ligand for studying central alpha(2)-adrenoceptors. [(11)C]R107474 was obtained via a Pictet-Spengler reaction with [(11)C]formaldehyde in 33 +/- 4% overall decay-corrected radiochemical yield. The total synthesis time was 55 min and the specific activity was 24-28 GBq/micromol. The biodistribution of [(11)C]R107474 in rats revealed that the uptake of [(11)C]R107474 after in vivo intravenous administration is very rapid; in most tissues (including the brain) it reaches maximum concentration at 5 min after tracer injection. In agreement with the known distribution of alpha(2)-adrenoceptors in the brain, highest uptake of radioactivity was observed in septum (3.54 +/- 0.52 ID/g, 5 min pi) and entorhinal cortex (1.57 +/- 0.10 ID/g, 5 min pi). Tissue/cerebellum concentration ratios for septum (5.38 +/- 0.45, 30 min pi) and entorhinal cortex (3.43+/-0.24, 30 min pi) increased with time due to rapid uptake followed by a slow washout. In vivo blocking experiments using the non-selective alpha(2)-adrenoceptor antagonist mirtazapine demonstrated specific inhibition of [(11)C]R107474 binding in selective brain areas. The receptor binding profile of mirtazapine is reported and the selectivity of inhibition of binding is discussed. These results suggest that [(11)C]R107474 deserves further investigation as a potential radioligand for studying alpha(2)-adrenoceptors using PET.

Adrenergic alpha-2 Receptor Antagonists↗

A system of networks and continuing education for physical therapists in rheumatology: a feasibility study.

PURPOSE: To evaluate the feasibility of regional physical therapy networks including continuing education in rheumatology. The aim of these networks was to improve care provided by primary care physical therapists by improving specific knowledge, technical and communicative skills and the collaboration with rheumatologists. METHODS: In two regions in The Netherlands continuing education (CE) programmes, consisting of a 5-day postgraduate training course followed by bimonthly workshops and teaching practices, were organised simultaneously. Network activities included consultations, newsletters and the development of a communication guideline. Endpoint measures included the participation rate, compliance, quality of the CE programme, teaching practices, knowledge, network activities, communication, number of patients treated and patient satisfaction. RESULTS: Sixty-three physical therapists out of 193 practices (33%) participated in the project. They all completed the education programmes and were formally registered. All evaluations of the education programmes showed positive scores. Knowledge scores increased significantly directly after the training course and at 18 months. A draft guideline on communication between physical therapists and rheumatologists was developed, and 4 newsletters were distributed. A substantial proportion of physical therapists and rheumatologists reported improved communication at 18 months. The mean number of patients treated by physical therapists participating in the networks increased significantly. Patients' satisfaction scores within the networks were significantly higher than those from outside the networks at 18 months. CONCLUSIONS: Setting up a system of networks for continuing education for physical therapists regarding the treatment of patients with rheumatic diseases is feasible. Further research will focus on the effectiveness of the system and its implementation on a larger scale.

Journal Article↗

Short-term digestive tolerance of different doses of NUTRIOSE FB, a food dextrin, in adult men.

OBJECTIVE: To determine the tolerance of increasing dosages of an incompletely hydrolysed and/or incompletely absorbed food dextrin coming from wheat starch, NUTRIOSE FB, at daily levels of 10 and 15 g up to 60 and 80 g, respectively. DESIGN: A randomized, double-blind, multiple dose, placebo-controlled, combined crossover and parallel trial. SETTING: The metabolic ward of TNO Nutrition and Food Research. SUBJECTS: A total of 20 healthy men (age 31.7 +/- 9.1 y; BMI 24.5 +/- 2.9 kg/m2). INTERVENTION: One group of 10 subjects consumed on top of their diet 10, 30 and 60 g of NUTRIOSE FB or maltodextrin (placebo) daily. The other group of 10 subjects consumed 15, 45 and 80 g daily. Each dose was consumed for 7 days. RESULTS: Compared with placebo, flatulence occurred more frequently over the last 6 days on 30, 60 or 80 g/day of NUTRIOSE FB (P < 0.05). During the last 24 h, that is, days 6-7, of 60 and 80 g/day of NUTRIOSE FB, the frequency of flatulence was even higher (P < 0.05). During the last 24 h on a daily dose of 60 g NUTRIOSE FB, the frequency of defecation decreased (P < 0.05). Bloating occurred more often during the last 24 h on 80 g/day of NUTRIOSE FB (P < 0.05). None of the doses of NUTRIOSE FB resulted in diarrhoea. Compared to baseline levels, breath H2 excretion, which was only measured after a week with 10 and 15 g of NUTRIOSE FB daily, increased (P < 0.05). However, no difference in area under the curve was found. CONCLUSIONS: NUTRIOSE FB is a fermentable carbohydrate and is well tolerated up to a dose of 45 g daily. Higher daily dosages (60 and 80 g) may result in flatulence, but does not result in diarrhoea. SPONSORSHIP: TNO Nutrition and Food Research was assigned by Roquette Frères to perform the study.

Adult↗

Prognostic modelling of therapeutic interventions in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a disease with a widely varying prognosis. The majority of patients survive about 3 years, but a significant number survive for 10 years or more, leading to problems in clinical trial design. OBJECTIVE: To demonstrate that simple clinical variables can be used to construct a robust predictive model for survival, and to assess the effect of a known treatment within this model. METHODS: We carried out a retrospective multivariate modelling of a database of 841 patients with ALS seen over a 10-year period in a specialist motor neuron disorders clinic. The use of riluzole was tested as a prognostic factor within the model. RESULTS: A prognostic score generated from one cohort of patients predicted survival for a second cohort of patients (r(2) = 0.78). Prognostic variables included site of onset, age of onset, time from symptom onset to diagnosis, and El Escorial category at presentation. Riluzole therapy was an independently significant prognostic factor (relative risk of death 0.48, P < 0.0001, model chi(2) 297, P < 0.0001). CONCLUSIONS: Clinical databases can be used to generate multivariate prognostic models in ALS. Such models could be used to predict survival, to improve criteria for matching of patients in future clinical trials, and to test the impact of interventions.

Age of Onset↗

Kaposi's sarcoma and human herpesvirus 8 infection do not protect HIV-1 infected homosexual men from AIDS dementia complex.

OBJECTIVE: To examine the association between Kaposi's sarcoma (KS), human herpes virus 8 (HHV8) and AIDS dementia complex (ADC). DESIGN: A total of 599 HIV-1 infected homosexual men participated in a prospective cohort study (Amsterdam, 1984-1996). METHODS: The risk for ADC in patients with prior KS or HHV8 infection was estimated using the Cox proportional hazards method with adjustments for antiretroviral medication and low CD4 cell counts. RESULTS: Of the 599 participants, 290 (48.4%) had HHV8 antibodies, 99 (16.5%) had KS and 30 (5.0%) had ADC. ADC was diagnosed in 5.2% of participants with KS and 5.0% of those without KS, and in 4.8% of HHV8 seropositive compared to 5.2% seronegative individuals and thus was not associated with KS or HHV8 infection. Using a time-dependent Cox proportional hazards analysis with the date of KS as risk factor, the risk for ADC was 2.7 [95% confidence interval (CI), 0.92-7.96; P = 0.07) and when only definite ADC was considered it was 3.5 (95% CI, 1.00-12.26;P = 0.05). After adjusting for decreases in CD4 cell count and use of medication, the hazards ratio for participants with KS to develop ADC was 2.0 (95% CI, 0.66-5.77; P = 0.23) and 2.6 (95% CI, 0.73-9.12; P = 0.14), respectively. HHV8 seropositivity, adjusted for the same variables, showed a risk for ADC of 0.85 (95% CI, 0.41-1.77;P = 0.66) and for definite ADC 0.69 (95% CI, 0.27-1.73; P = 0.42). The expected neuroprotective effects of antiretroviral medication were observed. CONCLUSIONS: KS or HHV8 does not significantly influence the risk for developing ADC in a group with a uniform risk for developing KS therefore we recommend caution in searching for a KS-associated or HHV8-derived therapy for ADC.

AIDS Dementia Complex↗

Potent antiretroviral therapy initiates normalization of hypergammaglobulinemia and a decline in HIV type 1-specific antibody responses.

Next to a profound T cell immunodeficiency, HIV-1 infection induces activation and dysfunction of B cells, resulting in hypergammaglobulinemia. Whereas T cell immune reconstitution with potent antiretroviral therapy has been extensively documented, limited data are available on B cell immune reconstitution. We studied the effect of potent antiretroviral therapy on antibody titers to the viral proteins gp120 and p24 and on total IgG concentrations. Three retrospectively chosen groups were studied: a successfully treated group, untreated controls, and subjects with virological failure after several months of successful therapy. In the successfully treated group, the median total IgG concentrations normalized, whereas they remained elevated in the untreated group and rebounded after an initial decline in the therapy failure group. The HIV-1-specific antibody titers declined in the successfully treated group and followed the rebound of the HIV RNA levels in the therapy failure group. With potent antiretroviral therapy the hypergammaglobulinemia normalized whereas HIV-1-specific immune responses were weakened. The weakening of antiviral immunity with therapy may be relevant for current attempts to gain immunological control over the virus through structured treatment interruptions or therapeutic vaccinations.

Adult↗

Chloroperoxidase-catalyzed enantioselective oxidations in hydrophobic organic media.

Chloroperoxidase from Caldariomyces fumago, a peroxidase that performs P450-like chemistry, was immobilized via covalent attachment into polyurethane foam as well as conjugated with a surfactant or polymer via colyophilization. The resulting preparations catalyzed enantio- and regioselective oxidations in hydrophobic organic media with tert-butyl hydroperoxide as the oxidant. Dried PUR-foam immobilized CPO mediated the selective oxidation of indole to 2-oxindole (regioselectivity: 99%) in water-saturated isooctane or 1-octanol. Thioanisole was converted into the corresponding (R)-sulfoxide (ee > 99%) in isooctane medium. The complexes of CPO with sodium octadecylsulphate or ethyl cellulose mediated the oxidation of thioanisole in water-immiscible organic media with variable enantioselectivity due to radical side-reactions. In the presence of alpha-tocopherol, acting as radical scavenger, the (R)-sulfoxide was formed with ee > 90%. The effect of the water activity on the catalytic activity of the complexes was investigated. The CPO complexes likewise mediated the regioselective oxidation of indole into 2-oxindole in water-saturated isooctane or 1-octanol and its kinetics were investigated. The reaction suffered from substrate inhibition when carried out in isooctane.

Catalysis↗

Single rapid real-time monitored isothermal RNA amplification assay for quantification of human immunodeficiency virus type 1 isolates from groups M, N, and O.

Because human immunodeficiency virus type 1 (HIV-1) subtypes and circulating recombinant forms (CRFs) are spreading rapidly worldwide and are becoming less confined to a geographical area, RNA assays that can detect and quantify all HIV-1 isolates reliably are in demand. We have developed a fast, real-time monitored RNA assay based on an isothermal nucleic acid sequence-based amplification technology that amplifies a part of the long terminal repeat region of the HIV-1 genome. Real-time detection was possible due to the addition of molecular beacons to the amplification reaction that was monitored in a fluorimeter with a thermostat. The lower level of detection of the assay was 10 HIV-1 RNA molecules per reaction, and the lower level of quantification was 100 copies of HIV-1 RNA with a dynamic range of linear quantification between 10(2) and 10(7) RNA molecules. All HIV-1 groups, subtypes, and CRFs could be detected and quantified with equal efficiency, including the group N isolate YBF30 and the group O isolate ANT70. To test the clinical utility of the assay, a series of 62 serum samples containing viruses that encompassed subtypes A through G and CRFs AE and AG of HIV-1 group M were analyzed, and these results were compared to the results of a commercially available assay. This comparison showed that the quantification results correlated highly (R(2) = 0.735) for those subtypes that could be well quantified by both assays (subtypes B, C, D, and F), whereas improved quantification was obtained for subtypes A and G and CRFs AE and AG. A retrospective study with six individuals infected with either a subtype A, B, C, or D or an AG isolate of HIV-1 group M, who were treated with highly active antiretroviral therapy, revealed that the assay was well suited to the monitoring of therapy effects. In conclusion, the newly developed real-time monitored HIV-1 assay is a fast and sensitive assay with a large dynamic range of quantification and is suitable for quantification of most if not all subtypes and groups of HIV-1.

Anti-HIV Agents↗

One-tube real-time isothermal amplification assay to identify and distinguish human immunodeficiency virus type 1 subtypes A, B, and C and circulating recombinant forms AE and AG.

To halt the human immunodeficiency virus type 1 (HIV-1) epidemic requires interventions that can prevent transmission of numerous HIV-1 subtypes. The most frequently transmitted viruses belong to the subtypes A, B, and C and the circulating recombinant forms (CRFs) AE and AG. A fast one-tube assay that identifies and distinguishes among subtypes A, B, and C and CRFs AE and AG of HIV-1 was developed. The assay amplifies a part of the gag gene sequence of the genome of all currently known HIV-1 subtypes and can identify and distinguish among the targeted subtypes as the reaction proceeds, because of the addition of subtype-specific molecular beacons with multiple fluorophores. The combination of isothermal nucleic acid sequence-based amplification and molecular beacons is a new approach in the design of real-time assays. To obtain a sufficiently specific assay, we developed a new strategy in the design of molecular beacons, purposely introducing mismatches in the molecular beacons. The subtype A and CRF AG isolates reacted with the same molecular beacon. We tested the specificity and sensitivity of the assay on a panel of the culture supernatant of 34 viruses encompassing all HIV-1 subtypes: subtypes A through G, CRF AE and AG, a group O isolate, and a group N isolate. Assay sensitivity on this panel was 92%, with 89% correct subtype identification relative to sequence analysis. A linear relationship was found between the amount of input RNA in the reaction mixture and the time that the reaction became positive. The lower detection level of the assay was approximately 10(3) copies of HIV-1 RNA per reaction. In 38% of 50 serum samples from HIV-1-infected individuals with a detectable amount of virus, we could identify subtype sequences with a specificity of 94% by using sequencing and phylogenetic analysis as the "gold standard." In conclusion, we showed the feasibility of the approach of using multiple molecular beacons labeled with different fluorophores in combination with isothermal amplification to identify and distinguish subtypes A, B, and C and CRFs AE and AG of HIV-1. Because of the low sensitivity, the assay in this format would not be suited for clinical use but can possibly be used for epidemiological monitoring as well as vaccine research studies.

Base Sequence↗

Highly efficient immobilization of glycosylated enzymes into polyurethane foams.

Glycosylated enzymes, including aminoacylase from Aspergillus melleus, chloroperoxidase from Caldariomyces fumago, and phytase from Aspergillus ficuum, were covalently immobilized into polyurethane foams with very high enzyme loadings of up to 0.2 g protein per gram dry foam. The immobilization efficiency (retained activity) ranged from 100% at a low loading to 60% at high loadings. In contrast to many other immobilization methods no leaching of the enzyme from the support took place under the reaction conditions. In short, a universal method for the immobilization of enzymes from fungal sources was developed, affording a highly active, stable, and reusable biocatalyst.

6-Phytase↗

Improved operational stability of peroxidases by coimmobilization with glucose oxidase.

The operational stability of peroxidases was considerably enhanced by generating hydrogen peroxide in situ from glucose and oxygen. For example, the total turnover number of microperoxidase-11 in the oxidation of thioanisole was increased sevenfold compared with that obtained with continuous addition of H(2)O(2). Coimmobilization of peroxidases with glucose oxidase into polyurethane foams afforded heterogeneous biocatalysts in which the hydrogen peroxide is formed inside the polymeric matrix from glucose and oxygen. The total turnover number of chloroperoxidase in the oxidation of thioanisole and cis-2-heptene was increased to new maxima of 250. 10(3) and 10. 10(3), respectively, upon coimmobilization with glucose oxidase. Soybean peroxidase, which normally shows only classical peroxidase activity, was transformed into an oxygen-transfer catalyst when coimmobilized with glucose oxidase. The combination catalyst mediated the enantioselective oxidation of thioanisole [50% ee (S)] with 210 catalyst turnovers.

Chloride Peroxidase↗

Human herpesvirus 8 infections in the Amsterdam Cohort Studies (1984-1997): analysis of seroconversions to ORF65 and ORF73.

We have shown previously that human herpesvirus 8 (HHV8) seroconversion for antibodies to the latency-associated nuclear antigen encoded by ORF73 and/or the lytic capsid antigen (vp19) encoded by ORF65 is associated with orogenital contact and is strongly linked to the development of Kaposi's sarcoma among HIV-infected individuals in the Amsterdam Cohort Studies. Here, we investigate the relationship between seroconversion to these antigens and primary HHV8 infection. Between 1984 and 1997, 215 HHV8 seroconversions to ORF73 (106 cases or 49%) and/or to ORF65 (159 cases or 74%) were recorded in the cohort of homosexual men. The HHV8 seroconversion rate among HIV-infected homosexual men (6.2 per 100 person years) was consistently higher than among HIV-uninfected men (2.6 per 100 person years). In HIV-infected but not in uninfected individuals, seroconversion to ORF73/latency-associated nuclear antigen precedes that to ORF65/vp19. Antibody levels to both ORF65- and ORF73-encoded antigens were higher in HIV-infected than in HIV-uninfected men, and among HIV-seropositives, antibody levels to ORF65/vp19 rise even higher with declining CD4 cell counts and peak with Kaposi's sarcoma development, suggesting continuing and increasing viral replication. In 10.3% of HHV8 seroconversions, transient serum viremia could be demonstrated before or at seroconversion. Together with the previously reported link between unprotected orogenital sex and HHV8 seroconversion, our observations suggest that HHV8 seroconversions result from primary infections.

Antibodies, Viral↗

A 4-base pair deletion in the mitochondrial cytochrome b gene associated with parkinsonism/MELAS overlap syndrome.

Five patients with diminished activity of complex III of the mitochondrial respiratory chain have been screened for mutations in the mitochondrial cytochrome b (cyt b) gene. In 1 patient, a young boy with an akinetic rigid syndrome and a mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), a novel 4-base pair deletion was identified. This mutation in this highly conserved gene is considered to be pathogenic since it is a heteroplasmic frame shift mutation predicted to lead to a truncated protein.

Adult↗

Low T-cell responses to CD3 plus CD28 monoclonal antibodies are predictive of development of AIDS.

OBJECTIVE: Decreased T-cell reactivity in vitro is strongly associated with progression to AIDS and low CD4+ T-cell numbers. Low T-cell responses in vitro induced by CD3 monoclonal antibody (mAb) are predictive for progression to AIDS independent of low CD4+ T-cell counts and high HIV-1 RNA levels. We developed a whole-blood lymphocyte culture system in which T cells were stimulated by a combination of CD3 and CD28 mAb. Combined stimulation of CD28, a costimulatory molecule, and CD3 considerably enhances T-cell responses in vitro and reduces variation coefficients, which may increase the prognostic power of T-cell responses. DESIGN: A prospective study of HIV-1-infected homosexual men followed for 35 months. METHODS: The predictive value of low T-cell responses to CD3 plus CD28 mAb relative to low CD4+ T-cell counts, high HIV-1 RNA levels and the presence of syncytium-inducing (SI) HIV-1 variants was evaluated longitudinally in 202 HIV-1-infected homosexual men followed for 35 months. RESULTS: In multivariate analysis, decreased T-cell responses at baseline were predictive of development of AIDS, independent of low CD4+ T-cell numbers and high HIV-1 RNA levels. In a time-dependent model, HIV-1 RNA levels lost their predictive value, whereas low T-cell responses, low CD4+ T-cell numbers and the presence of SI HIV-1 variants independently predicted AIDS. CONCLUSIONS: These data demonstrate that combined use of virological and immunological markers may be useful in monitoring disease progression and response to antiretroviral therapy.

Antibodies, Monoclonal↗

Epilepsia partialis continua associated with a homoplasmic mitochondrial tRNA(Ser(UCN)) mutation.

Epilepsia partialis continua (EPC) is a rare epileptic syndrome characterized by continuous focal seizures. We report on a 16-year-old girl who died of prolonged pharmacoresistant EPC in whom we identified a 7472insC mutation within the mitochondrial transfer ribonucleic acid (tRNA)(ser(UCN)). Additional symptoms included ataxia, lactic acidosis, myopathy, sensorineural hearing loss, severe headaches, and mental retardation. Quantification revealed 100% mutant mitochondrial DNA (mtDNA) in the patient, 4% in her mother, and none in her half-sister. This highly skewed mtDNA distribution is most improbable (approximately 3 x 10(-30)) if only explained by random genetic drift. Clustering of dysfunctional mitochondria and replicatory advantage of mutant mtDNA may play a role in the rapid segregation towards homoplasmy within one generation.

Base Sequence↗