Acute myocarditis. Serologic diagnosis, clinical findings and follow-up

In a prospective study, 57 patients with a preliminary diagnosis of myocarditis were investigated. Twenty-four patients were considered to have an acute myocarditis, 14 had a suspected myocarditis, while in 19 patients myocarditis was excluded. Episodes of frequent supraventricular and/or ventricular extrasystoles during hospital stay were seen in 8/24 cases (33%) with myocarditis and in 1/19 cases (5%) without myocarditis. On follow-up 1 month later, no supraventricular extrasystoles were observed in either group. Echocardiographic signs consistent with left ventricular insufficiency were noted in 7/24 cases (29%) with myocarditis, in 1/14 cases (7%) with suspected myocarditis and in no case without myocarditis. With a "routine" serologic test battery covering influenza viruses A and B, adenovirus, Coxsackie virus group B, ECHO viruses, Chlamydia psittaci, Mycoplasma pneumoniae and hemolytic streptococci group A, a possible etiology could be documented in 9/24 cases (38%) with myocarditis and in 4/19 cases (21%) without myocarditis. Enterovirus-specific IgM was detected with solid-phase reverse immunosorbent test (SPRIST) in 12/23 (48%) cases with myocarditis and in 3/16 cases (19%) without myocarditis. In SPRIST-IgM-positive cases, IgM antibodies were detected in 15/20 (75%) of the sera taken on admission. The overall serological results indicated a recent infection in 16/24 cases (67%) with myocarditis and in 5/19 cases (26%) without myocarditis (p less than 0.05).     

The ionic mechanisms underlying N-methyl-D-aspartate receptor-induced, tetrodotoxin-resistant membrane potential oscillations in lamprey neurons active during locomotion

Activation of N-methyl-D-aspartate (NMDA) receptors can induce tetrodotoxin (TTX)-resistant membrane potential oscillations as well as fictive locomotion in the in vitro preparation of the lamprey spinal cord. The ionic basis of these oscillations were investigated in the presence of N-methyl-D,L-aspartate and TTX. Addition of blocking agents (2-amino-5-phosphonovalerate and tetraethylammonium (TEA)) and selective removal or substitution of certain ions (Mg2+, Ca2+, Na+, Ba2+) were used in the analysis of the oscillations. The depolarizing phase of the oscillation requires Na+ ions but not Ca2+ ions. The depolarization becomes larger if TEA is administered in the bath, which presumably is due to a blockade of potassium (K+) channels activated during the depolarizing phase. The repolarization appears to depend on a Ca2+ entry, which presumably acts indirectly by an activation of Ca2+-dependent K+ channels. Together with the NMDA-induced voltage dependence, this will bring the membrane potential back down to a hyperpolarized level.     

A quantitative study of the brainstem cholinergic projections to the ventral part of the oral pontine reticular nucleus (REM sleep induction site) in the cat

The ventral part of the cat oral pontine reticular nucleus (vRPO) is the site in which microinjections of small dose and volume of cholinergic agonists produce long-lasting rapid eye movement sleep with short latency. The present study determined the precise location and proportions of the cholinergic brainstem neuronal population that projects to the vRPO using a double-labeling method that combines the neuronal tracer horseradish peroxidase–wheat germ agglutinin with choline acetyltransferase immunocytochemistry in cats. Our results show that 88.9% of the double-labeled neurons in the brainstem were located, noticeably bilaterally, in the cholinergic structures of the pontine tegmentum. These neurons occupied not only the pedunculopontine and laterodorsal tegmental nuclei, which have been described to project to other pontine tegmentum structures, but also the locus ceruleus complex principally the locus ceruleus and peri-, and the parabrachial nuclei. Most double-labeled neurons were found in the pedunculopontine tegmental nucleus and locus ceruleus complex and, much less abundantly, in the laterodorsal tegmental nucleus and the parabrachial nuclei. The proportions of these neurons among all choline acetyltransferase positive neurons within each structure were highest in the locus ceruleus complex, followed in descending order by the pedunculopontine and laterodorsal tegmental nuclei and then, the parabrachial nuclei. The remaining 11.1% of double-labeled neurons were found bilaterally in other cholinergic brainstem structures: around the oculomotor, facial and masticatory nuclei, the caudal pontine tegmentum and the praepositus hypoglossi nucleus. The disperse origins of the cholinergic neurons projecting to the vRPO, in addition to the abundant noncholinergic afferents to this nucleus may indicate that cholinergic stimulation is not the only or even the most decisive event in the generation of REM sleep.     

Induction of tyrosine kinase receptor b by retinoic acid allows brain-derived neurotrophic factor-induced amyloid precursor protein gene expression in human SH-SY5Y neuroblastoma cells

Retinoic acid (RA) is a potent regulator of morphogenesis, growth and cell differentiation. Incubation with RA causes arrest of proliferation and neurite extension in SH-SY5Y cells, a neuroblastoma cell line of human origin. In these cells, RA regulates the expression of the β-amyloid precursor protein. The retinoid increases the levels of intracellular and secreted forms of APP (amyloid precursor protein), APP–mRNA levels and the activity of the APP promoter in transient transfection studies. These responses require long periods of exposition to the ligand, thus suggesting a nondirect effect of the RA receptors on the APP gene. Also in these cells, RA induces the expression of TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF), and 4 days of pretreatment with retinoic acid confers BDNF responsiveness to the APP promoter.     

Dose-dependent circulating immunoglobulin A antibody-secreting cell and serum antibody responses in Swedish volunteers to an oral inactivated enterotoxigenic Escherichia coli vaccine

The immunogenicity of different preparations of an oral inactivated enterotoxigenic Escherichia coli (ETEC) vaccine was evaluated in Swedish volunteers previously unexposed to ETEC infection. The vaccine preparations consisted of recombinant cholera toxin B subunit (CTB) and various amounts of formalin-killed whole bacteria expressing the most prevalent colonization factor antigens (CFAs). Significant immunoglobulin A (IgA) antibody-secreting cell (ASC) responses against CTB and the various CFA components were seen in a majority of volunteers after two doses of ETEC vaccine independent of the vaccine lot given. The IgA ASC responses against CTB were significantly higher after the second than after the first immunization, whereas the CFA-specific IgA ASC responses were almost comparable after the first and second doses of ETEC vaccine. Two immunizations with one-third of a full dose of CFA-ETEC bacteria induced lower frequencies of IgA ASC responses against all the different CFAs than two full vaccine doses, i.e., 63 versus 80% for CFA/I, 56 versus 70% for CS1, 31 versus 65% for CS2, and 56 versus 75% for CS4. The proportion of vaccinees responding with rises in the titer of serum IgA antibody against the various CFA antigens was also lower after immunization with the reduced dose of CFA-ETEC bacteria. These findings suggest that measurements of circulating IgA ASCs can be used not only for qualitative but also for quantitative assessments of the immunogenicity of individual fimbrial antigens in various preparations of ETEC vaccine.     

Assessment of pathogenicity criteria for constitutional missense mutations of the hereditary nonpolyposis colorectal cancer genes MLH1 and MSH2

To determine the role played by MLH1 and MSH2 missense variants in cancer susceptibility, we have investigated the following genetic and biological characteristics associated with six MLH1 and four MSH2 missense changes identified in Italian hereditary nonpolyposis colorectal cancer (HNPCC) families: co-segregation with disease phenotype and/or bonafide pathogenetic mutations; presence of the variant in healthy control subjects; evolutionary conservation of the involved aminoacid and type of aminoacid change; and presence/absence of microsatellite instability (MSI) in tumour DNA. Overall, nine variants did not fulfil > or = 2 pathogenicity criteria. MSI was investigated in tumour samples from carriers of nine different missense mutations. Only 3/9 variants were associated with MSI in tumour DNA. In addition, four variants were not present in affected pedigree members, and five variants were observed in the control population. Based upon these results, we conclude that most MLH1 and MSH2 missense changes are unlikely to act as major causative factors in colorectal cancer susceptibility and development.     

Comparative evaluation of two commercial assays for direct detection ofMycobacterium tuberculosis in respiratory specimens

Two commercial systems for the amplification and detection ofMycobacterium tuberculosis directly from respiratory samples were compared. The Roche Cobas Amplicor MTB Test and the Roche manual Amplicor MTB Test (Roche Diagnostic Systems, USA) were applied to 755 decontaminated respiratory specimens collected from 470 patients. Results were compared with those of acid-fast staining and culture. A total of 251 specimens were collected from 156 patients diagnosed with pulmonary tuberculosis, including 28 specimens corresponding to 13 patients that were receiving antituberculous treatment. Given the overall positivity rate of 33.2% (251/755), the sensitivity, specificity, and positive and negative predictive values were 92.4, 100, 100, and 96.5%, respectively, for the Cobas Amplicor MTB Test and 90.8, 100, 100, and 95.8%, respectively, for the Amplicor MTB Test. For 204 (81.3%) smear positive specimens and 47 (19.7%) smear negative specimens, the sensitivity values were 100 and 59.6%, respectively, for the Cobas Amplicor MTB Test and 100 and 51%, respectively, for the Amplicor MTB Test. There were no statistically significant differences in sensitivity or specificity between the two assays and culture (p>0.05). The overall results of both assays were concordant for 99.5% of the samples. It is concluded that although both nucleic acid amplification methods are rapid and specific for the detection ofMycobacterium tuberculosis complex in respiratory specimens, the Cobas Amplicor MTB Test appears to be slightly more sensitive than the Amplicor MTB Test when smear negative specimens are investigated.     

Primary manifestation of Hodgkin’s disease in the central nervous system

 A 62-year-old woman presented with loss of memory and a mild hemiparesis. Neuroradiology demonstrated a left frontoparietal tumour. Biopsy specimens of this lesion revealed intracerebral Hodgkin’s lymphoma, a diagnosis supported by immunohistochemical reactions of the tumour cells for the CD30 antigen. Additional cell cycle studies revealed a high proliferative activity of the tumour cells in association with absence of apoptosis. There was no evidence that overexpression of bcl-2 or Epstein-Barr virus infection was involved in the pathogenesis of this neoplasm. Lymphomas in the lung were detected 3 months later. Following neurosurgical excision, radiotherapy, and chemotherapy, the patient had no evidence of Hodgkin’s disease after 13 months of follow-up. Received: 8 October 1997 / Accepted: 8 December 1997     

High prevalence of tuberculosis in AIDS patients in Spain

A total of 67 cases of tuberculosis was diagnosed in the first 100 cases of AIDS, diagnosed according to the former CDC criteria, at a hospital in Madrid, Spain. This is the highest known prevalence of tuberculosis in AIDS patients both within and outside Spain. The clinical manifestations of tuberculosis were very variable and atypical. The rate of isolation ofMycobacterium tuberculosis from blood was particularly high: of 25 patients in whom blood cultures were performed, 16 were positive. In a third of the patients with proven mycobacteremia, blood was the first or the only positive specimen. In general, therapy resulted in rapid clinical improvement, but in some cases mycobacteria were isolated from clinical or necroscopy specimens months after what was considered adequate therapy.     

CD23 and CD21 function as adhesion molecules in homotypic aggregation of human B lymphocytes

We have previously found that interleukin-4 and CD40 monoclonal antibodies (mAb) are strong potentiatiors of homotypic B cell aggregation which is dependent on LFA-1. We show here that CD23 mAb were also able to inhibit aggregation to a similar extent as LFA-1 antibodies. This inhibition was restricted to the MHM6 epitope of CD23 and antibodies to other epitopes [Epstein-Barr virus (EBV) CS-1, EBV CS-2, EBV CS-5 and mAb 25] or occupation of the Fc-binding site by IgE had no or a slightly enhancing effect on aggregation. When testing two antibodies to CD21, the recently defined ligand for CD23, one of these (BU32) was found to be inhibitory whereas the other (THB5) had no effect. By combining antibodies to LFA-1 and CD23, aggregation was often completely inhibited. These data suggest that LFA-1/ICAM-1 and CD23/CD21 are the major molecules involved in homotypic aggregation of human B cells.