Immunoglobulin isotypes of anti-HBc and anti-HBe and hepatitis B virus (HBV) DNA elimination in acute hepatitis B

Antibodies to hepatitis B core antigen (anti-HBc) and e antigen (anti-HBe) were assayed in 46 sera from ten patients with acute hepatitis B utilizing immunoglobulin class- and subclass-specific enzyme immunoassays (EIAs). The sera were sampled 1 to 512 days after onset of hepatic symptoms. Four patients cleared HBsAg rapidly, within 24 days, and six patients cleared HBsAg slowly, within 27-74 days after the onset of symptoms. In three of the patients with rapid clearance of HBsAg, hepatitis B virus (HBV) DNA was not detected in sera tested during the first week after onset. The fourth patient was not tested until 12 days after onset and was then found to be negative for HBV DNA. In four of the patients with slow clearance of HBsAg, HBV DNA was present during the first week of illness. In the other two patients, HBV DNA was not detected in the first serum, 11 and 17 days after the onset of illness. Anti-HBc IgM and IgA1 were detected in all patients, with maximum titers shortly after onset. Anti-HBc IgG1 was present in all sera tested. Anti-HBc IgG2 was not detected in any of the sera. Anti-HBc IgG3 and IgG4 were detected in all patient sera, with IgG3 paralleling IgG1, and IgG4 mainly in sera long after onset. Anti-HBe IgG1, IgG3, and IgG4 were detected in three, two, and two patients, respectively. Anti-HBe IgG2, IgM, IgA1, or IgA2 was not found in any patient. The time required for maximum titer of anti-HBc IgG1 was shorter in the patients with rapid clearance of HBsAg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis of Mycoplasma pneumoniae Pneumonia in Children

We evaluated a commercial immunoglobulin M (IgM)-capture immunoassay for the detection of Mycoplasma pneumoniae infections in 278 pediatric patients with community-acquired, radiographically defined pneumonia. Acute- and convalescent-phase serum samples were collected from all patients and were tested for M. pneumoniae-specific IgM and IgG antibodies by Platelia enzyme immunoassays (Sanofi Diagnostica Pasteur, Marnes la Coquette, France). Nasopharyngeal aspirates (NPAs) were collected at the time of admission to the hospital. A total of 227 NPAs were subjected to the detection of M. pneumoniae DNA by PCR, and 191 NPAs were cultured by using the Pneumofast kit (International Mycoplasma, Signeswere, France). Southern hybridization of PCR products and the IgM test with solid-phase antigen (Serion Immunodiagnostica, Würzburg, Germany) were used for additional confirmation of a positive result, which required agreement of at least two different methods. A total of 24 (9%) confirmed diagnoses of mycoplasma infection were made, 5 (21%) of which were in children <5 years of age. Of the positive children, 24 of 24 (sensitivity, 100%) were positive by the IgM-capture test with convalescent-phase serum, 19 of 24 (79%) were positive by the IgM-capture test with acute-phase serum, 19 of 24 (79%) were positive by IgG serology, 10 of 20 (50%) were positive by PCR, and 8 of 17 (47%) were positive by culture. An additional 5 (of 254) children were positive by the Platelia IgM test alone (specificity, 98%). When the PCR with Southern hybridization result was combined with the IgM-capture test result with the acute-phase sera, the sensitivity of rapid laboratory diagnosis increased to 95%. In conclusion, the IgM serology test was the single most valuable tool for the diagnosis of M. pneumoniae pneumonia in children of any age.     

A 90-year-old monozygotic female twin pair discordant for Alzheimer's disease

The present study describes PET, MRI, and neuropsychological findings in 90-year-old monozygotic female twins, who have remained discordant for probable Alzheimer's disease (AD) for at least 7 years. These findings were compared with those of healthy persons composing the reference group (seven women, three men; the mean+/-S.D. age: 73.3+/-3.3 years). Twins' life histories were remarkably similar, except for continuous NSAID use of the unaffected twin for decades. The regional cerebral glucose metabolic rates (rCMRgluc) and all but two CERAD test scores of the affected twin were more than 2 S.D. below the mean values of the reference group. These values were normal in the unaffected twin. The affected twin had moderate hippocampal and temporoparietal atrophy, whereas the hippocampi were intact, and cortical atrophy was mild in the unaffected twin. These findings indicate that the twins were discordant for AD, even though they had reached the age in which the prevalence of AD is high among women. Our results further address the influence of environmental factors on the onset of AD, especially the possible protective effect of anti-inflammatory medication.     

Effect of immunoglobulins on mineral dust-induced production of reactive oxygen metabolites by human macrophages

Mineral dust-induced production of reactive oxygen metabolites (ROMs) by human monocyte-derived macrophages was investigated using lucigenin-dependent chemiluminescence. Chrysotile asbestos alone caused only weak ROM production by macrophages, but the addition of polyclonal immunoglobulin enhanced the reaction strongly. The phenomenon was seen with 1-, 4-, and 7-day-old cell cultures. Polyclonal immunoglobulin also slightly enhanced the ROM responses induced by amosite, crocidolite, and quartz dust. The enhancing effect could be achieved with several monoclonal immunoglobulins (isolated from the sera of myeloma patients), but IgA and IgG had the strongest effects. We suggest that immunoglobulins may interact with mineral dusts in a nonimmunological, antigen-independent way and that the so-formed dust-immunoglobulin complexes may amplify the production of ROMs by inflammatory cells. This may explain a number of in vivo phenomena in which immune responses (for instance hypergammaglobulinemia and the presence of autoantibodies) have been shown to relate to the progression of mineral dust-induced pulmonary disease.     

Prediction of density and mechanical properties of human trabecular bone in vitro by using ultrasound transmission and backscattering measurements at 0.2-6.7 MHz frequency range

The ultrasound (US) backscattering method has been introduced as an alternative for the through-transmission measurement of sound attenuation and speed in diagnosis of osteoporosis. Both attenuation and backscattering depend strongly on the US frequency. In this study, 20 human trabecular bone samples were measured in transmission and pulse-echo geometry in vitro. The aim of the study was to find the most sensitive frequency range for the quantitative ultrasound (QUS) analyses. Normalized broadband US attenuation (nBUA), speed of sound (SOS), broadband US backscatter (BUB) and integrated reflection coefficient (IRC) were determined for each sample. The samples were spatially scanned with five pairs of US transducers covering a frequency range of 0.2-6.7 MHz. Furthermore, mechanical properties and density of the same samples were determined. At all frequencies, SOS, BUB and IRC showed statistically significant linear correlations with the mechanical properties or density of human trabecular bone (0.51 < r < 0.82, 0.54 < r < 0.81 and 0.70 < r < 0.85, respectively). In contrast to SOS, IRC and BUB, nBUA showed statistically significant correlations with mechanical parameters or density at the centre frequency of 1 MHz only. Our results suggest that frequencies up to 5 MHz can be useful in QUS analyses for the prediction of bone mechanical properties and density. Since the use of higher frequencies provides better axial and spatial resolution, improved structural analyses may be possible. While extensive attenuation of high frequencies in trabecular bone limits the clinically feasible frequency range, selection of optimal frequency range for in vivo QUS application should be carefully considered.     

Pseudosubstrate regulation of the SCF(beta-TrCP) ubiquitin ligase by hnRNP-U

beta-TrCP/E3RS (E3RS) is the F-box protein that functions as the receptor subunit of the SCF(beta-TrCP) ubiquitin ligase (E3). Surprisingly, although its two recognized substrates, IkappaB(alpha) and beta-catenin, are present in the cytoplasm, we have found that E3RS is located predominantly in the nucleus. Here we report the isolation of the major E3RS-associated protein, hnRNP-U, an abundant nuclear phosphoprotein. This protein occupies E3RS in a specific and stoichiometric manner, stabilizes the E3 component, and is likely responsible for its nuclear localization. hnRNP-U binding was abolished by competition with a pIkappaB(alpha) peptide, or by a specific point mutation in the E3RS WD region, indicating an E3-substrate-type interaction. However, unlike pI(kappa)Balpha, which is targeted by SCF(beta-TrCP) for degradation, the E3-bound hnRNP-U is stable and is, therefore, a pseudosubstrate. Consequently, hnRNP-U engages a highly neddylated active SCF(beta-TrCP), which dissociates in the presence of a high-affinity substrate, resulting in ubiquitination of the latter. Our study points to a novel regulatory mechanism, which secures the localization, stability, substrate binding threshold, and efficacy of a specific protein-ubiquitin ligase.     

Cortical processing of vowels and tones as measured by event-related desynchronization

Summary Event-Related Desynchronization (ERD) and Synchronization (ERS) were studied in 20 normal subjects during a Sternberg-type auditory memory-scanning paradigm. Half of the subjects performed the experiment with vowels and the other half with tones as stimuli. The stimuli consisted of 100 msec long synthesized vowels and 100 msec long tones produced by eight different synthesized instruments. In this paradigm each trial started with the presentation of a visual warning signal, after which a four-stimulus set was presented for memorization whereafter a probe stimulus was presented and identified by the subject as belonging or not belonging to the memorized set. The ERD/ERS of the lower (8–10 Hz) and upper (10–12 Hz) alpha frequency bands differed in their reactivity to stimulus type; the differences between the two frequency bands reached statistical significance only in the case of vowels. The presentation of the memory set elicited ERS which was more pronounced in the 10–12 Hz frequency band and greater for vowels than for tones. On the other hand, the presentation of the probe elicited ERD which was greater for vowels than for tones, especially in the upper alpha frequency band. The results of this exploratory study suggest that ERD is closely related to memory processes and that the ERD/ERS-technique might provide a valuable tool for future reseach encompassing more complex auditory stimulation like speech and music.This study was financially supported by the Council for Social Sciences, Academy of Finland (project 7338).     

Transdermal estrogen for female stress urinary incontinence in postmenopause

Objective: To evaluate the effect of transdermal estrogen for stress urinary incontinence in postmenopause. Study design: An open within patient, dose-finding study with transdermal 17-β-estradiol combined with cyclic medroxyprogesterone acetate was conducted over 9 months in 21 patients (mean age 57.3 years) suffering from urodynamically verified mild to moderate stress incontinence without detrusor instability. Results: Subjective improvement was noted in 16 out of 21 patients (76%). The dose level of 50 μg was better tolerated than 100 μg and sufficient enough to achieve continence. Conclusion: Transdermal estrogen therapy plays an adjuvant role in conservative therapy for mild to moderate stress urinary incontinence in postmenopausal women.     

A survey of the use of electronic scientific information resources among medical and dental students

Background  

To evaluate medical and dental students' utilization of electronic information resources.