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PubMed1992

Drug-associated "bite cell" hemolytic anemia.

PURPOSE: "Bite cell" hemolytic anemia is a variant of drug-related hemolysis usually associated with methemoglobinemia and Heinz body inclusions in red blood cells secondary to oxidant drug injury. Bite cells are morphologically characterized as poikilocytes with one or more semicircular portions removed from the cell margin. The purpose of this report is to emphasize the importance of peripheral smear examination in patients with possible drug-associated hemolytic anemia. The morphologic characteristics of bite cells by light microscopy and scanning electron microscopy are detailed in this study, and the pathophysiologic mechanism is discussed. PATIENTS AND METHODS: Clinical and laboratory data were retrospectively studied on eight patients (two men and six women, aged 29 to 85 years) who showed evidence of bite cell hemolytic anemia associated with drug exposure. Multiple standard hematologic laboratory evaluations for hemolytic anemia were performed. Five hundred red blood cells were counted from randomly selected peripheral smear fields for the calculation of bite cell percentage. RESULTS: Peripheral smears showed predominantly normochromic normocytic red cells with prominent bite cells and occasional blister cells. Bite cell counts ranged from 5.5% to 13.6% (mean, 8.7 +/- 3.0% SD) associated with a hematocrit reduction of 3.0% to 13.2% (mean, 8.5 +/- 3.8% SD) and concomitant reticulocytosis of varying degree from 2.3% to 15.4% (mean, 7.3 +/- 4.9% SD). Withdrawal of the offending drug(s) and treatment of underlying diseases resulted in improvement of hemolytic anemia and eventual disappearance of bite cells. A close correlation between hematocrit reduction, reticulocyte response, and bite cell percentage increase was seen. The usual biochemical markers of hemolysis were not consistently observed. Scanning electron microscopy confirmed the light microscopic evidence of bite cell morphology and revealed a keratocytic variant. CONCLUSION: This study emphasizes the importance of peripheral smear examination for early diagnosis and management of bite cell hemolytic anemia. Withdrawal of the putative offending drug(s) and treatment of underlying disorders should result in improvement of this form of drug-associated hemolysis.

Adult↗

PubMed2006

Hybrid superaggregate morphology as a result of aggregation in a cluster-dense aerosol.

From the digitized pictures of soot clusters formed after the explosion of a hydrocarbon gas mixed with oxygen, the cluster morphology was determined by two different methods: structure factor and perimeter analysis. We find a hybrid, superaggregate morphology characterized by a fractal dimension of D approximately equal to 1.8 between the monomer size, ca. 50 nm, and 1 microm and D approximately equal to 2.6 at larger length scales up to approximately 10 microm. The superaggregate morphology is a consequence of late-stage aggregation in a cluster-dense regime near a gel point.

Journal Article↗

PubMed1997

Characterization of infectious salmon anemia virus, an orthomyxo-like virus isolated from Atlantic salmon (Salmo salar L.).

Infectious salmon anemia (ISA) virus is the cause of infectious salmon anemia in farmed Atlantic salmon. The virus has been shown to contain RNA with structural characteristics similar to those of accepted members of the Orthomyxoviridae. Further biochemical, physiochemical, and morphological characterization of ISA virus was undertaken to clarify its taxonomic position. The virus was found to be sensitive to chloroform, heat, and low pH and agglutinated erythrocytes from fish. Erythrocytes from mammals or birds were not agglutinated. Receptor-destroying enzyme activity was detected, and the nature of this enzyme was suggested to be an acetylesterase. The buoyant density of the virus was 1.18 g/ml in sucrose and CsCl gradients. The maximum rate of virus replication was observed at 15 degrees C, while no virus was produced at 25 degrees C. Actinomycin D inhibited viral replication, and viral antigen was detected in nuclei by immunofluorescence. The addition of trypsin to the culture medium during virus replication had a beneficial effect on virus replication. ISA virus contains four major polypeptides with estimated molecular sizes of 71, 53, 43, and 24 kDa. Electron microscopy revealed structures closely resembling the nucleocapsids of influenza virus. Mushroom-shaped surface projections were a distinctive morphological feature, which differed from the rod-shaped hemagglutinin projections of the influenza viruses. The data reported here support the relationship of ISA virus to the Orthomyxoviridae, although ISA virus differs from influenza viruses in some morphological characteristics and in showing restricted hemagglutination, in different specificity of the receptor-destroying enzyme, in different polypeptide profile, in being unable to replicate at temperatures above 25 degrees C, and in host range.

Acetylesterase↗

PubMed2006

First isolation of Dysgonomonas mossii from intestinal juice of a patient with pancreatic cancer.

BACKGROUND: Dysgonomonas species were first designated in 2000. However, clinical infections due to this microorganism have rarely been described. Our aim was to present the first isolation of Dysgonomonas mossii from intestinal juice of a patient with pancreatic cancer. METHODS: Predominantly appearing grayish-white colonies grown on chocolate and sheep blood agar plates were characterized morphologically by Gram stain, biochemically by automated instrument using Vitek II ID-GNB card together with commercially available kit systems, ID-Test HN-20 and API rapid ID 32A32A, and genetically by sequencing the 16S rRNA gene of the organism using a Taq DyeDeoxy Terminator Cycle Sequencing and a model 3100 DNA sequencer instrument. The isolate was further characterized by antimicrobial susceptibility using MicroFast 4J Panels and additional biochemical and physiological properties. RESULTS: The isolate was finally identified as D. mossii from the findings of the morphological, cultural, and biochemical properties together with the comparative sequence of the 16S rRNA genes. The isolate was highly susceptible to many antibiotics but resistant to penicillins and cephems. CONCLUSIONS: As D. mossii was rarely encountered in the clinical microbiology laboratory, it may be misidentified as an X-factor-dependent Haemophilus species due to its negative result for the porphyrin test. Accumulation of the case reports with the isolation of this species is expected to elucidate the infections due to D. mossii. The presence of D. mossii caused no significant clinical infection despite repeated isolations, as the patient had no conspicuous abdominal complaints. However, our report is a noteworthy and useful piece of information.

Bacterial Infections↗

PubMed1995

Substrate modulation of morphology, growth, and tear protein production by cultured human lacrimal gland epithelial cells.

Human lacrimal gland biopsies were serially incubated in chelating and enzymatic solutions. Viable single cells were evaluated for outgrowth in growth factor enriched medium using the following culture substrates: Matrigel, Type I collagen gel with or without fibroblasts, and plastic. Each epithelial outgrowth was characterized morphologically and immunohistochemically, and their growth and viability were examined by BrdU labeling and a quantitative cell viability assay. Synthesized proteins were evaluated by ELISA, SDS-PAGE, and 14C-labeled amino acid incorporation. Lacrimal gland epithelial cells plated on Matrigel formed clusters with central cavities that contained lactoferrin, mimicking acinar complexes in vivo. Cells plated on collagen gel or collagen gel containing fibroblasts formed islands or a monolayer, and lactoferrin was detected in incomplete cavities of epithelia on the latter substrate. Epithelial cells plated on plastic formed a monolayer and cellular expression of lactoferrin was weak and sporadic. Cellular release of the lactoferrin measured by ELISA supported the results of immunohistochemistry. Cells grown on plastic had the highest proliferative rate, whereas those grown on Matrigel showed the lowest proliferative rate. These results indicate that different substrates modulate lacrimal gland epithelial cell morphology, proliferative rate, and production of the tear protein lactoferrin. Matrigel promotes acinar differentiation to a greater extent than collagen gel and plastic. Incorporation of fibroblasts in collagen gel substrate promotes significant effects on growth and differentiation.

Adult↗

PubMed1999

Centriolar satellites: molecular characterization, ATP-dependent movement toward centrioles and possible involvement in ciliogenesis.

We identified Xenopus pericentriolar material-1 (PCM-1), which had been reported to constitute pericentriolar material, cloned its cDNA, and generated a specific pAb against this molecule. Immunolabeling revealed that PCM-1 was not a pericentriolar material protein, but a specific component of centriolar satellites, morphologically characterized as electron-dense granules, approximately 70-100 nm in diameter, scattered around centrosomes. Using a GFP fusion protein with PCM-1, we found that PCM-1-containing centriolar satellites moved along microtubules toward their minus ends, i.e., toward centrosomes, in live cells, as well as in vitro reconstituted asters. These findings defined centriolar satellites at the molecular level, and explained their pericentriolar localization. Next, to understand the relationship between centriolar satellites and centriolar replication, we examined the expression and subcellular localization of PCM-1 in ciliated epithelial cells during ciliogenesis. When ciliogenesis was induced in mouse nasal respiratory epithelial cells, PCM-1 immunofluorescence was markedly elevated at the apical cytoplasm. At the electron microscopic level, anti-PCM-1 pAb exclusively labeled fibrous granules, but not deuterosomes, both of which have been suggested to play central roles in centriolar replication in ciliogenesis. These findings suggested that centriolar satellites and fibrous granules are identical novel nonmembranous organelles containing PCM-1, which may play some important role(s) in centriolar replication.

Adenosine Triphosphate↗

PubMed1988

Intestinal anaphylaxis: rapid changes in mucosal ion transport and morphology.

Anaphylactic reactions can be elicited by beta-lactoglobulin (beta LG) in the isolated colonic and ileal mucosae of guinea pigs fed cow milk. We have shown that these tissues respond to antigen challenge with a rapid rise in short-circuit current (SCC) due to net chloride secretion in the colon and less well-characterized ion movements in the ileum. Here, tissues were characterized morphologically at or near the peak of the SCC response 2 min after antigen addition. These sensitized preparations, or naive tissues passively sensitized with immune sera and challenged with beta LG, showed numerous structural alterations that correlated significantly with the change in SCC. In the ileum, these changes included compound exocytosis of mucous granules from goblet cells of crypts but not of villi and a decrease in the intercellular space of the crypts. In contrast, colonic goblet cells of both crypts and luminal surface showed no evidence of secretion, but crypt architecture was reproducibly and characteristically altered. Thus antigen challenge of intestinal mucosa results in temporally related but diverse changes in morphology and ion transport.

Anaphylaxis↗

PubMed1996

In-vitro cell culture models of the nasal epithelium: a comparative histochemical investigation of their suitability for drug transport studies.

PURPOSE: To evaluate different in-vitro cell culture models for their suitability to study drug transport through cell monolayers. METHODS: Bovine turbinate cells (BT; ATCC CRL 1390), human nasal septum tumor cells (RPMI, 2650; ATCC CCL 30), and primary cell cultures of human nasal epithelium were characterized morphologically and histochemically by their lectin binding properties. The development of tight junctions in culture was monitored by actin staining and transepithelial electrical resistance measurements. RESULTS: The binding pattern of thin-sections of excised human nasal respiratory epithelium was characterized using a pannel of fluorescently-labelled lectins. Mucus in goblet cells was stained by PNA, WGA and SBA, demonstrating the presence of terminal N-acetylglucosamine, N-acetylgalactosamine and galactose residues respectively in the mucus of human nasal cells. Ciliated cells revealed binding sites for N-acetylglucosamine, stained by WGA, whereas Con A, characteristic for mannose moieties, labelled the apical cytoplasm of epithelial cells. Binding sites for DBA were not present in this tissue. Comparing three different cell culture models: BT, RPMI 2650, and human nasal cells in primary culture using three lectins (PNA, WGA, Con A) as well as intracellular actin staining and transepithelial electrical resistance measurements we found, that only human nasal epithelial cells in primary culture showed differentiated epithelial cells, ciliated nasal cells and mucus producing goblet cells, which developed confluent cell monolayers with tight junctions. CONCLUSIONS: Of the in-vitro cell culture models studied, only human nasal cells in primary culture appears to be suitable for drug transport studies.

Actins↗

PubMed1994

Amplification and linearization of distal synaptic input to cortical pyramidal cells.

1. Computer simulations were used to study the effect of voltage-dependent calcium and potassium conductances in the apical dendritic tree of a pyramidal cell on the synaptic efficacy of apical synaptic input. The apical tuft in layers 1 and 2 is the target of feedback projections from other cortical areas. 2. The current, Isoma, flowing into the soma in response to synaptic input was used to assess synaptic efficacy. This measure takes full account of all the relevant nonlinearities in the dendrities and can be used during spiking activity. Isoma emphasizes current flowing in response to synaptic input rather than synaptically induced voltage change. This measure also permits explicit characterization of the input-output relationship of the entire neuron by computing the relationship between presynaptic input and postsynaptic output frequency. 3. Simulations were based on two models. The first was a biophysically detailed 400-compartment model of a morphologically characterized layer 5 pyramidal cell from striate cortex of an adult cat. In this model eight voltage-dependent conductances were incorporated into the somatic membrane to provide the observed firing behavior of a regular spiking cell. The second model was a highly simplified three-compartment equivalent electrical circuit. 4. If the dendritic tree is entirely passive, excitatory synaptic input of the non-N-methyl-D-aspartate (non-NMDA) type to layers 1, 2, and 3 saturate at very moderate input rates, because of the high input impedance of the apical tuft. Layers 1 and 2 together can deliver only 0.25 nA current to the soma. This modest effect is surprising in view of the important afferents that synapse on the apical tuft and is inconsistent with experimental data indicating a more powerful effect. 5. We introduced in a controlled manner a voltage-dependent potassium conductance in the apical tuft, gK, to prevent saturation of the synaptic response. This conductance was designed to linearize the relationship between presynaptic input frequency and the somatic current. We also introduced a voltage-dependent calcium conductance along the apical trunk, gCa, to amplify the apical signal, i.e., the synaptic current reaching the soma. 6. To arrive at a specific relationship between the presynaptic input rate and the somatic current delivered by the synaptic input, we derived the activation curves of gK and gCa either analytically or numerically. The resultant voltage-dependent behavior of both conductances was similar to experimentally measured activation curves.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2001

Histochemical characterization of primary capillary endothelial cells from porcine brains using monoclonal antibodies and fluorescein isothiocyanate-labelled lectins: implications for drug delivery.

Primary endothelial cells isolated from cerebral microvessels by combined mechanical and enzymatic treatment from porcine brains were characterized with regard to identity, purity and membrane surface characteristics. Cells were grown in culture to adherent monolayers and characterized morphologically and histochemically by their binding for fluorescently-labelled lectins and monoclonal antibodies detected by indirect immunofluorescence. The binding patterns of the cells were compared with the affinity of frozen tissue sections of porcine brain cortex for the markers. Endothelial cells in culture were characterized by the binding of von Willebrand factor, vimentin and fibronectin antibodies. They failed to react with anti-glial fibrillary acid protein, anti-galactocerebroside C and anti-neurofilament 160 antibodies characteristic for astrocytes, oligodendrocytes and neurons, respectively. Cell cultures were stained by the lectins, wheat germ agglutinin, horse gram agglutinin and soybean agglutinin, demonstrating the presence of N-acetylglucosamine and N-acetylgalactosamine residues on membrane surface. Binding sites for concanavalin A and peanut agglutinin characteristic for mannose and galactose could not be detected. Cell age and differentiation had no effect on lectin and antibody staining. Cell cultures gave staining results similar to those of microvessels in frozen tissue sections. The results of morphology, antibody and lectin staining pattern indicate that our in vitro endothelial cell culture model retained many histological characteristics observed for capillary microvessels in vivo and appears to be suitable for studying uptake and targeting properties of drug carrier systems with regard to the blood-brain barrier.

Animals↗

PubMed2004

Expression and characterization of human tumor necrosis factor-related apoptosis inducing ligand in methylotrophic yeast Pichia pastoris.

Recombinant human TRAIL was successfully expressed in a secreted form in methyltrophic yeast Pichia pastoris induced by methanol. The expressive product was immunoreactive to TRAIL antibody. The addition of the expressive product into cultured human lung cancer cell A549 showed moderate cell death, typical morphological characterization of apoptotic bodies, and DNA fragmentation. This result provided a new method to produce recombinant human TRAIL as a cancer therapeutic drug.

Apoptosis↗

PubMed1984

Characterization of two patients with lymphomas of large granular lymphocytes.

Two patients with non cutaneous well-differentiated lymphocytic lymphoma with leukemic spread are reported. The large majority of their peripheral blood mononuclear cells (PBMC) formed rosettes with sheep erythrocytes, had receptors for the Fc portion of IgG, and an enzymatic profile of relatively mature T-cells. These cells were morphologically characterized as large granular lymphocytes. Studies with monoclonal antibodies in one of the cases showed an OKT3+, OKT10-, OKT4-, OKT8-, HNK-1-, OKM1+ phenotype, whereas PBMC from the other case were OKT3+, OKT10-, OKT4-, OKT8+, HNK-1+, OKM1-. PBMC from the first patient were able to suppress in vitro B-cell differentiation and were capable of a strong antibody dependent cellular cytotoxicity (ADCC) activity. Natural killer (NK) activity was reduced. Cells from the other patient who was hypogammaglobulinemic, exerted suppressor activity in immunoregulatory assays, and showed ADCC and NK activity. These data support the existence of LGL lymphomas consisting of the proliferation of mature appearing cells capable of functional activity.

Antibodies, Monoclonal↗

PubMed2003

A characterization of the egg capsules of Anacroneuria starki and A. talamanca (Plecoptera: Perlidae), with a suggestion about the distribution of stoneflies in the Tropics.

In this study, the structure of egg capsules of two species of Neotropical Perlidae: Anacroneuria starki Fenoglio and Morisi (2001 a) and A. talamanca Stark (1998), were examined. Eggs were studied using a scanning electron microscope. A morphological characterization of these eggshells is presented: layers, attachment structures and other anatomical features are described. The egg capsules of the two species differ in some aspects, but both are characterized by thin-layered egg coverings (vitelline envelope, chorion and extrachorion). On the basis of these observations, the importance of eggshell structure for the biogeographical distribution of Plecoptera in the tropics is discussed. A key role for egg capsules in the adaptation process of Plecoptera to aquatic environments of the Neotropics is hypothesized.

Adaptation, Physiological↗

PubMed2001

Differential regulation of growth and checkpoint control mediated by a Cdc25 mitotic phosphatase from Pneumocystis carinii.

Pneumocystis carinii is an opportunistic fungal pathogen phylogenetically related to the fission yeast Schizosaccharomyces pombe. P. carinii causes severe pneumonia in immunocompromised patients with AIDS and malignancies. Although the life cycle of P. carinii remains poorly characterized, morphologic studies of infected lung tissue indicate that P. carinii alternates between numerous small trophic forms and fewer large cystic forms. To understand further the molecular mechanisms that regulate progression of the cell cycle of P. carinii, we have sought to identify and characterize genes in P. carinii that are important regulators of eukaryotic cell cycle progression. In this study, we have isolated a cDNA from P. carinii that exhibits significant homology, but unique functional characteristics, to the mitotic phosphatase Cdc25 found in S. pombe. P. carinii Cdc25 was shown to rescue growth of the temperature-sensitive S. pombe cdc25-22 strain and thus provides an additional tool to investigate the unique P. carinii life cycle. Although P. carinii Cdc25 could also restore the DNA damage checkpoint in cdc25-22 cells, it was unable to restore fully the DNA replication checkpoint. The dissociation of checkpoint control at the level of Cdc25 indicates that Cdc25 may be under distinct regulatory control in mediating checkpoint signaling.

Amino Acid Sequence↗

PubMed2005

A bacterium belonging to the Rickettsiaceae family inhabits the cytoplasm of the marine ciliate Diophrys appendiculata (Ciliophora, Hypotrichia).

Bacteria of the family Rickettsiaceae (order Rickettsiales, alpha-Proteobacteria) are mainly known to be endosymbionts of arthropods with the capability to infect also vertebrate cells. Recently, they have also been found as leech endocytobionts. In the present paper, we report the first finding of a bacterium belonging to the family Rickettsiaceae in a natural population of a marine ciliate protozoan, namely Diophrys appendiculata, collected in the Baltic Sea. Bacteria were unambiguously identified through morphological characterization and the "full-cycle rRNA approach" (i.e., 16S rRNA gene characterization and use of specifically designed oligonucleotide probes for in situ detection). Symbionts are rod-shaped bacteria that grow freely in the cytoplasm of the host cell. They present two different morphotypes, similar in size, but different in cytoplasmic density. These are typical morphological features of members of the family Rickettsiaceae. 16S rRNA gene sequence showed that Diophrys symbionts share a high similarity value (>92%) with bacteria belonging to the genus Rickettsia. Phylogenetic analysis revealed that these new endosymbionts are clearly included in the clade of the family Rickettsiaceae, but they occupy an independent phylogenetic position with respect to members of the genus Rickettsia. This is the first report of a member of this family from a host protozoan and from a marine habitat. This result shows that this bacterial group is more diversified and widespread than supposed so far, and that its ecological relevance could until now have been underestimated. In light of these considerations, the two 16S rRNA oligonucleotide probes here presented, specific for members of the Rickettsiaceae, can represent useful tools for further researches on the presence and the spread of these microorganisms in the natural environment.

Animals↗

PubMed1996

[Involvement of the large intestine in neurofibromatosis type 1].

This report presents the cases of two female patients aged 54 and 57 years, both with colon involvement of type 1 neurofibromatosis. The first woman had a polypoid neuronal hyperplasia containing small Wagner-Meissner corpuscles, which had allowed identification of the neuronal nature of the lesion in a small mucosal biopsy specimen taken previously. The second patient had an idiopathic megacolon of the sigmoid, which had to be extirpated because of acute obstruction and ileus. Morphological examination revealed a typical plexiform neurofibroma of the bowel wall and neuronal hyperplasia of the colonic mucosa and submucosa, which had obviously caused disordered gut mobility leading to functional stenosis and extreme dilatation of prestenotic bowel parts. Gastrointestinal neurofibromatosis is rare and is characterized morphologically by neuronal hyperplasia of the mucosa and submucosa, sometimes containing small aggregates of ganglion cells by which it can easily be identified. However, in the majority of cases the increase of proliferating mucosal nerve fibres can only be confirmed by S-100 protein immunostaining. Furthermore, solitary, multiple and plexiform neurofibromas are found, but only the last, which arises from mesenteric or subserosal nerves, is virtually pathognomonic for neurofibromatosis. Gastrointestinal neurofibromas are usually late manifestations of the disease, but in exceptional cases they can be the initial sign of neurofibromatosis in patients who have no external stigmata that arouse suspicion. The occurrence of gastrointestinal neurofibromas should therefore lead to a careful search for other features of NF-1 in the affected patients and in their families.

Adenomatous Polyposis Coli↗

PubMed1997

Chronic lymphatic leukemias of T and NK cell type.

T cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) and large granular lymphocyte leukemia of T or NK cell type (T-LGL or NK-LGL leukemia) are chronic lymphoproliferative diseases derived from post-thymic immunocompetent lymphoid cells. T-PLL is morphologically characterized by a prominent central nucleolus in a medium-sized cell expressing a mature T cell immunophenotype. Clonal genetic changes involving chromosome 14 and T cell receptor gene rearrangements are characteristics of these diseases. They are usually progressive and there is no efficient treatment available. The classification of some cases presenting with a morphological picture similar to B-CLL, but with immunophenotypic and clinical features resembling T-PLL, as T-CLL is still controversial. The phenotypic profiles and the establishment of clonality are the hallmarks of defining T-LGL leukemia and NK-LGL leukemia. The CD3+/CD57+/CD56- immunophenotype and the clonal rearrangement of the T cell receptor genes characterize T-LGL leukemia, which presents clinically with a rather indolent course of disease, complicated by frequent infections secondary to neutropenia. NK-LGL leukemia cells express CD3-/CD56+/CD57-, but in most cases clonality cannot easily be established. Clinically the patient may either present with constitutional symptoms and suffer a short and aggressive course of disease or may have a more chronic disease similar to T-LGL leukemia. Therefore, it may be reasonable to subdivide NK-LGL proliferation into the more aggressive 'NK-LGL leukemia/lymphoma' and 'chronic NK cell lymphocytosis'.

Antigens, CD↗

PubMed2006

Development of MEG sleep patterns and magnetic auditory evoked responses during early infancy.

OBJECTIVE: To follow the development of MEG sleep patterns and auditory evoked responses (AERs) during the first six months of life. METHODS: The subjects were 18 neonates, born at conceptional age (CA) 36-42 weeks, following uncomplicated pregnancies. During each session, several 10-min MEG recordings were acquired in the presence of auditory stimulation. The recordings were classified into three distinct MEG patterns-low amplitude irregular; high-amplitude slow; and mixed-based largely on MEG amplitude and frequency. Averaged AERs were computed for the entire recording and for each MEG pattern within the recording. The results were based on analysis of 61 recording sessions of the 10 subjects who yielded three or more sessions of usable data. RESULTS: Developmental changes in the MEG sleep patterns were most pronounced at the earliest ages. By CA 48 weeks the patterns had progressed to a more mature form, characterized by the prevalence of delta wave sleep, absence of discontinuity, and development of spindling and higher amplitude delta rhythms. In contrast to the MEG patterns, the AERs did not change markedly during the first 8 weeks (CA 40-48 weeks) and showed a simple morphology, consisting of a prominent deflection at 250 ms (P250m) and a more diffuse one at around 750 ms (N750m). During the period CA 48-54 weeks, however, a relatively abrupt transition occurred to a more complex morphology, characterized by a double peak with peak latencies 150ms (P150m) and 350 ms (P350m). Beyond this period the AERs continued to evolve, showing biphasic complexes and the emergence of late components arising from outside the auditory cortex. CONCLUSIONS: Over the age range of this study the MEG sleep patterns and AER developed in succession, rather than concurrently; i.e. development of the sleep patterns was most rapid during the first 8 weeks (CA 40-48 weeks) while major development of the AERs commenced after this time. SIGNIFICANCE: This finding suggests that the brain must achieve a certain level of overall maturity, reflected in the character of the MEG sleep patterns at CA 48 weeks, before the cortex enters a phase of significant functional development, reflected in the more rapid evolution of the AER after CA 48 weeks. The results of this study affirm the efficacy of MEG for spatiotemporal characterization of neonatal brain activity.

Acoustic Stimulation↗