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PubMed2004

Infantile-onset glycogen storage disease type II (Pompe disease): report of a case with genetic diagnosis and pathological findings.

Glycogen storage disease type II (GSD-II), also known as Pompe disease, is a rare autosomial recessive disease due to deficiency of lysosomal acid alpha-glucosidase (GAA). The infantile-onset form is the most severe, and most patients present with hypotonia and cardiomyopathy in early infancy. We report on a typical case of Pompe disease in a patient who died at 8 months of age due to aspiration pneumonia and hypertrophic cardiomyopathy. Genetic studies showed deficient GAA activity and mutation of the GAA gene with Gly615Arg (exon 13, G1845A). On autopsy, glycogen had markedly accumulated in the liver, myocardium and skeletal muscle. The neurons of the anterior horn of the spinal cord and medulla were also involved, but the cortex was spared. These neurological-histologic findings may explain the clinical features of poor motor function, decreased deep tendon reflexes and lack of mental retardation.

Base Sequence↗

PubMed2001

[Construction of a deep coverage rice BAC library and identification of clones associated with disease-resistant genes].

A BAC library for IRBB56, an accession pyramiding Xa4, xa5 and xa13 three bacterial blight resistance genes, was constructed. The library contains 55,296 clones with an average insert size of 132 kb. Based on a haploid genome size of 450 Mb, the coverage of the library was about 14 genome equivalents that make it one of the most comprehensive BAC libraries available in rice and provide 99.99% possibility to isolate any interested rice genes or sequences in the library. To determine the representation of organelle DNA homologues in the library, the library was screened with three different chloroplast genes and four mitochondrial genes, respectively. Results from this screening showed that less than 1% of clones in the library contain organelle genomic DNA homologues. Then, DNA markers on three different chromosomes linked to Xa4, xa5, and xa13, and a PCR fragment of rice UROD gene, were used to screen the library resulting in a range of 11-106 hits that will promote the isolation of these genes. The deep coverage and the large insert size of the library will facilitate physical mapping, isolation, and cloning of rice genes.

Chromosomes, Artificial, Bacterial↗

PubMed2026

X-linked spondyloepiphyseal dysplasia tarda misdiagnosed as growth hormone deficiency: identification of a novel intronic TRAPPC2 variant by whole-genome sequencing.

BACKGROUND: X-linked spondyloepiphyseal dysplasia tarda (SEDT) is a rare skeletal dysplasia caused by pathogenic variants in TRAPPC2 and typically presents in late childhood or adolescence with short-trunk disproportion and vertebral dysplasia. CASE PRESENTATION: We describe a family series centered on an adolescent male initially diagnosed with GHD due to reduced height velocity and subnormal GH stimulation results, who received recombinant human GH (rhGH) therapy for three years with negligible improvement. During puberty, he developed progressive short-trunk disproportion and characteristic radiographic features, including platyspondyly and posterior hump-shaped vertebral endplates, suggestive of SEDT. Whole-exome sequencing (WES) was nondiagnostic, whereas whole-genome sequencing (WGS) identified a novel intronic TRAPPC2 variant, c.239-20_239-12delinsAATGAA, initially classified as a variant of uncertain significance (VUS). Segregation analysis across the family enabled reclassification of the variant to likely pathogenic, confirming X-linked SEDT. The proband's younger brother exhibited earlier radiologic abnormalities and, notably, a favorable response to rhGH, whereas the younger sister-an asymptomatic heterozygous carrier-showed normal spinal morphology, consistent with expected female carrier phenotypes. CONCLUSIONS: This family-based report underscores the generally limited therapeutic effect of rhGH in SEDT while highlighting potential interindividual variability, as evidenced by the younger male sibling's response. It further emphasizes the diagnostic utility of WGS for detecting deep intronic variants missed by WES and the importance of segregation analysis in resolving VUS in rare skeletal dysplasias.

Humans↗

PubMed1986

Laminar field potentials and unit activity in the cortex during visual evoked potentials in feline generalized penicillin epilepsy.

Modifications of the visual evoked potential during generalized epilepsy were investigated in feline generalized penicillin epilepsy. Visual evoked potentials and their intracortical profiles were averaged during intraburst periods and during the wave of the spike and wave complex to a fixed latency from the preceding spike. During interburst periods, the evoked potentials showed an increase in the amplitude of the early positive peak and the appearance after a variable latency period of a second consistent peak during the late phase of the evoked potential. Laminar profiles of visual evoked potentials and their current source density analysis compared with the activity of single cortical units suggested an early excitation of neuronal populations at layers II, III and IV, as seen before penicillin, followed by a variable inhibitory period and by a subsequent rebounded excitation at those same levels. In evoked potentials recorded during the wave of the spike and wave complex, the early phase was unchanged and the late positive peak and the corresponding deep sink were greatly reduced or nonexistent, although the rebounded activation of cortical units was still evident. These data support the conclusion that during feline generalized penicillin epilepsy a larger number of cortical neurons are activated and a sequence of excitation-inhibition-excitation, probably involving also subcortical structures, is brought about. Moreover, the inhibitory phase of the spike and wave complex is soon disrupted whenever a consistent sensory stimulus arrives at the cortex.

Action Potentials↗

PubMed2006

Analysis of the complete mitochondrial DNA from Anopheles funestus: an improved dipteran mitochondrial genome annotation and a temporal dimension of mosquito evolution.

Virtually no information regarding timing of deep lineage divergences within mosquito family (Culicidae) exists, which poses an important problem in the postgenomic era. To address this issue, the complete 15,354 bp mitochondrial genome of Anopheles funestus was assembled from both mtDNA and cDNA sequences generated from transcripts of the mtDNA-encoded protein and rRNA genes. Analysis of the transcript information allowed an improved genome annotation, revealing that the translation initiation codon for the cox1 gene is TCG, rather than atypical, longer codons proposed in several other insects. The 5'ends of nad1 and nad5 transcripts begin with TTG and GTG triplets, respectively, which apparently serve as the translation initiators for those genes. We used all the A. funestus mtDNA gene sequences and three other publicly available mosquito mtDNA genomes for the estimation of divergence time points within Culicidae. The maximum likelihood date estimates for the splits between Anopheles and Aedes (approximately 145-200 Mya), between Anopheles subgenera Cellia and Anopheles (approximately 90-106 Mya), and between lineages within subgenus Anopheles (approximately 70-85 Mya) inferred from protein-coding genes are roughly twice as high as the dates based on RNA gene sequences. Although existing evidence does not unequivocally favor one of the alternatives, fossil-based predictions of the age of the family Culicidae are in better agreement with dates inferred from protein-coding genes.

Animals↗

PubMed1999

Mitogenomics: digging deeper with complete mitochondrial genomes.

Mitochondrial genomes are being used to study increasingly ancient divergences among animal groups. Recent studies of complete mitochondrial DNA sequences have arrived at somewhat heretical conclusions, raising questions about the use of mitochondrial gene sequences for studying the relationships among highly divergent lineages. Other studies have documented convergent evolution of mitochondrial gene order, casting doubt on the use of these characters for phylogenetic analysis. The use of mitochondrial genomes for studying such deep divergences is coming under increased scrutiny, and these novel results need to be confirmed with data from nuclear genes.

Journal Article↗

PubMed2004

Posterior reversible encephalopathy syndrome: magnetic resonance imaging and diffusion-weighted imaging in 12 cases.

Posterior reversible encephalopathy syndrome (PRES) is a potentially devastating neurologic syndrome, but timely treatment may lead to complete reversal of the disease course. We reviewed 12 cases of PRES and describe the clinical history and imaging findings, including conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and calculated apparent diffusion coefficient (ADC) maps, used to establish the diagnosis of PRES. Three male and nine female patients aged between 11 and 70 years (mean, 37 years) with clinical and imaging findings consistent with PRES were enrolled in the study. All patients had undergone conventional MRI and 10 had undergone additional DWI studies. Ten patients had follow-up MRI studies. DWI was performed using a 1.5T system with a single-shot spin-echo echoplanar pulse sequence. Initial and follow-up neuroimaging and clinical history were reviewed. Lesions were almost always present over the posterior circulation, mainly the parieto-occipital region, affecting primarily the white matter. The anterior circulation region, brainstem, cerebellum, deep cerebral white matter, and thalamus were also involved in five cases. Conventional MRI revealed hyperintensity on T2-weighted and fluid-attenuated inversion recovery images. DWI showed isointensity and increased signal intensity on ADC values in all cases, indicating vasogenic edema. Clinical and MRI follow-up showed that the symptoms and radiologic abnormalities could be reversed after appropriate treatment of the causes of PRES in most patients (9 of 10). In one patient, the ADC value was lower on follow-up images, indicating cytotoxic edema with ischemic infarct. DWI was a useful complement to MRI in the diagnosis of PRES.

Adolescent↗

PubMed2000

The structure of UDP-N-acetylglucosamine 2-epimerase reveals homology to phosphoglycosyl transferases.

Bacterial UDP-N-acetylglucosamine 2-epimerase catalyzes the reversible epimerization at C-2 of UDP-N-acetylglucosamine (UDP-GlcNAc) and thereby provides bacteria with UDP-N-acetylmannosamine (UDP-ManNAc), the activated donor of ManNAc residues. ManNAc is critical for several processes in bacteria, including formation of the antiphagocytic capsular polysaccharide of pathogens such as Streptococcus pneumoniae types 19F and 19A. We have determined the X-ray structure (2.5 A) of UDP-GlcNAc 2-epimerase with bound UDP and identified a previously unsuspected structural homology with the enzymes glycogen phosphorylase and T4 phage beta-glucosyltransferase. The relationship to these phosphoglycosyl transferases is very intriguing in terms of possible similarities in the catalytic mechanisms. Specifically, this observation is consistent with the proposal that the UDP-GlcNAc 2-epimerase-catalyzed elimination and re-addition of UDP to the glycal intermediate may proceed through a transition state with significant oxocarbenium ion-like character. The homodimeric epimerase is composed of two similar alpha/beta/alpha sandwich domains with the active site located in the deep cleft at the domain interface. Comparison of the multiple copies in the asymmetric unit has revealed that the epimerase can undergo a 10 degrees interdomain rotation that is implicated in the regulatory mechanism. A structure-based sequence alignment has identified several basic residues in the active site that may be involved in the proton transfer at C-2 or stabilization of the proposed oxocarbenium ion-like transition state. This insight into the structure of the bacterial epimerase is applicable to the homologous N-terminal domain of the bifunctional mammalian UDP-GlcNAc "hydrolyzing" 2-epimerase/ManNAc kinase that catalyzes the rate-determining step in the sialic acid biosynthetic pathway.

Amino Acid Sequence↗

PubMed2001

Prognostic value of nm23 expression in stage IB1 cervical carcinoma.

BACKGROUND: The purpose of this retrospective study was to evaluate the patterns of nm23 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare nm23 expression with clinicopathological findings and to assess its prognostic value. METHODS: Twenty-seven patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of nm23 was studied immunohistochemically, followed by amplification and direct sequencing of exons 4 and 5 of the nm23 gene. RESULTS: Overexpression of nm23 was detected in 18.5% of the tumors and low expression was seen in 33.3%, while negative expression was found in 48.1% of the tumors. Deep cervical stromal invasion (> or =1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when nm23 overexpression was observed (p = 0.0063). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessel, squamous cell carcinoma (> or =2 ng/ml) and nm23 overexpression had a significantly lower recurrence-free survival rate of the patients. None of the above factors was significant according to multivariate analysis. There were no mutations in exons 4 and 5 of the nm23 gene in stage IB1 squamous cell carcinoma of the uterine cervix. CONCLUSIONS: This study suggests that expression of nm23 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.

Adult↗

PubMed1998

Functional magnetic resonance imaging localization of ictal onset to a dysplastic cleft with simultaneous sensorimotor mapping: intraoperative electrophysiological confirmation and postoperative follow-up: technical note.

INTRODUCTION: Although technically challenging to obtain, ictal functional magnetic resonance imaging has been used to localize ictal onset zones in a small number of patients. We used this technique to demonstrate the inherent epileptogenicity of dysplastic cortex. METHODS: We present a 16-year-old female patient with intractable left-sided sensorimotor seizures and a congenital dysplastic cleft lying along the right rolandic fissure. Preoperative functional magnetic resonance imaging (blood oxygen level-dependent sequence, 1.5 T) localized the motor and sensory cortices to the anterior border of the cleft. During a speech activation run, the patient experienced a 20-second seizure. Initial activation was seen within the dysplastic cortex along the deep posterior margin of the cleft. Intraoperative median nerve stimulation produced a distinct N20/P20 wave inversion over the dysplastic cleft. Stimulation mapping performed with the patient awake confirmed the location of the sensorimotor cortex on the anterior border of the cleft, and preresection electrocorticography identified abundant interictal spikes along the posterior border after opening the cleft. RESULTS: After surgical resection of the dysplastic cortex, the patient exhibited transient minimal weakness and mild neglect, which resolved within 1 week. Two years after surgery, she was neurologically intact and seizure-free. CONCLUSION: This study used functional magnetic resonance imaging to demonstrate the inherent epileptogenicity of dysplastic cortex and to simultaneously map ictal and functional cortex. The N20 wave inversion can be a useful intraoperative tool for identifying the central sulcus (or its equivalent), even in the presence of abnormal cortical architecture.

Adolescent↗

PubMed2006

Structural analysis of Bordetella pertussis BugE solute receptor in a bound conformation.

The Bug proteins form a large family of periplasmic solute-binding receptors present in a number of bacterial species. Here, the crystal structure of Bordetella pertussis BugE, a member of the Bug family coded by the gene BP0250, is reported. It adopts the Venus flytrap architecture of periplasmic binding proteins, with two domains separated by a deep cleft. BugE has a bound ligand, identified as a glutamate. The structure of B. pertussis BugD, which is an aspartic acid transporter, has recently been reported. These structures reveal high conservation of the Bug architecture, despite limited sequence identity. They share a common carboxylate-binding motif defined by two strand-beta-turn-alpha-helix motifs, also involving two water molecules to bridge the carboxylate O atoms to the protein. The two water molecules are hydrogen bonded to a common main-chain carbonyl group. Although the features of the carboxylate-binding motif are totally conserved, the ligand in BugE is bound by its side-chain carboxylate group rather than by its alpha-carboxylate as in BugD. This specific ligand-binding motif is highly conserved in Bug proteins and the BugE structure suggests that the cavity of the Bug proteins might also accommodate carboxylated solutes other than amino acids. The vast expansion of the Bug family in several bacterial genera is likely to be explained by the possible diversity of ligands. No charged residues are involved in glutamate binding by BugE, unlike what has been described for all glutamate receptors reported so far.

Amino Acid Motifs↗

PubMed1968

Ceratoscopelus maderensis: peculiar sound-scattering layer identified with this myctophid fish.

A sound-scattering layer, composed of discrete hyperbolic echosequences and apparently restricted to the Slope Water region of the western North Atlantic, has been identified from the Deep Submergence Research Vehicle Alvin with schools of the meyctophid fish Ceratoscopelus maderensis. By diving into the layer and using Alvin's echo-ranging sonar, we approached and visually identified the sound scatterers. The number of echo sequences observed with the surface echo-soutnder (1/23.76 x 10(5) cubic meters of water) checked roughly with the number of sonar targets observed from the submarine (1/7.45 x 105 cubic meters). The fish schools appeared to be 5 to 10 meters thick, 10 to 100 meters in diameter, and on centers 100 to 200 meters apart. Density within schools was estimated at 10 to 15 fish per cubic meter.

Animals↗

PubMed1997

Spatial variation of T2 in human articular cartilage.

PURPOSE: To determine the spatial variation of in vivo cartilage T2 in young asymptomatic adults. MATERIALS AND METHODS: Quantitative T2 maps of seven asymptomatic young male adults and one male volunteer with a history of previous intraarticular chondroid fragments were calculated by using a multiecho, spin-echo magnetic resonance imaging sequence at 3.0 T. The T2 maps were bilinearly interpolated to generate T2 profiles across the thickness of cartilage. RESULTS: All seven asymptomatic volunteers demonstrated a monotonic increase in T2, which increased from 32 msec +/- 1 in the deep radial zone and 48 msec +/- 1 in the deep transitional zone to 67 msec +/- 2 in the outer transitional superficial zone. The T2 profile of the volunteer with superficial fibrillation observed at arthroscopy demonstrated marked spatial heterogeneity and a statistically significant increase in cartilage T2. CONCLUSION: There is a reproducible pattern of increasing T2 that is proportional to the known spatial variation in cartilage water and is inversely proportional to the distribution of proteoglycans. The authors postulate that these regional T2 differences are secondary to the restricted mobility of cartilage water within an anisotropic solid matrix.

Adult↗

PubMed1992

Stochastic analysis of the duration of the speaker role in the psychotherapy of an AIDS patient.

This paper has presented a quantitative/stochastic research approach to aspects of a psychotherapy with an HIV-positive patient. The Box-Jenkins (ARIMA) method for time-series analysis was applied to the duration of speaker roles for a single male patient in his first three sessions with a male therapist. The results indicate a definitive underlying stochastic structure of order (1, 1, 1). This indicates that the sequence of speaker durations was nonstationary (chaotic), while the rate at which the sequence changed (velocity) showed a clear structure reflecting the influence on the system of the prior state, and of the prior and present shocks. The histograms of the frequency of utterances of varying time lengths revealed a second deep structure through the emergence of an exponential characteristic of a Poisson model. The Poisson rate constants--a measure of interruption and holding tendencies--were stable across interviews. Intervention analysis identified epochs in each interview that significantly altered the progression of the time series. A qualitative investigation of these periods of destabilization suggested that sudden allusions to highly charged topics, including the likelihood of a fatal outcome of the patient's illness, and especially unconscious criticisms of the therapist by the patient, created a large share of these interludes. Finally, there is a discussion of the limitations and implications of these findings, including a comparison with similar analyses for 6 psychotherapy consultation sessions.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Carotenoid and ultrastructure variations in plastids of Arum italicum Miller fruit during maturation and ripening.

The changes in the pigment pattern and composition occurring in the Arum italicum berry during the various steps of maturation (ivory to deep-green stages) and ripening (yellow and red-orange stages) were studied and correlated to the ultrastructural modifications of plastids. Transmission electron microscopy showed that each stage was characterized by a specific plastidial type following the unusual sequence amyloplast-->chloroplast-->chromoplast. Plastidial transitions were accompanied by profound modifications in the pigmental composition, in particular, in the pattern of carotenoids and their precursors. The HPLC analysis of the carotenoids showed that, besides the two usual all-trans metabolic pathways leading to lutein through alpha-carotene and to auroxanthin through beta-carotene, an additional cis-isomeric biosynthetic pathway leading to cis-neoxanthin through cis-beta-carotene exists. During the pre-ripening stages, the three pathways were present even if with qualitative and quantitative variations. When complete ripening was reached, a block occurred at the cyclization level causing the accumulation of both all-trans (i.e. gamma-carotene and neurosporene) and cis-isomer (i.e. lycopene and zeta-carotene) carotene precursors. Because of the occurrence of unusual pigments and the presence of the three main plastidial types, the fruit of A. italicum may constitute a most instructive model for the study of carotenogenesis.

Arum↗

PubMed2001

MR imaging of the human brain at 1.5 T: regional variations in transverse relaxation rates in the cerebral cortex.

BACKGROUND AND PURPOSE: Heterogeneity in cortical signal intensity on T2-weighted MR images has been recently documented. Using a whole-brain, multiecho MR imaging technique, we sought to determine the T2 relaxation times of nine predefined regions in the cerebral cortex and one region in the deep gray matter. METHODS: Ten adult volunteers (nine men and one woman; age range, 18-40 y; average age, 30.8 y) underwent whole-brain imaging with an oblique coronal multiecho 3D Carr-Purcell-Meiboom-Gill MR sequence at 1000/25, 50, 75, 100, 125, and 150 (TR/TE). T2 measurements were obtained, with variably sized regions of interest, from the primary auditory cortex, primary visual cortex, caudate nucleus, superior frontal gyrus, inferior temporal gyrus, middle temporal gyrus, superior temporal gyrus, insula cortex, cingulate gyrus, and hippocampus. Repeated-measures analysis of variance was used to assess the existence of differences in T2 measurements among the anatomic locations. RESULTS: On the basis of T2 measurements, the gray matter structures examined could be divided into four statistically different groups. In ascending order of T2 measurements, the first group consisted of the primary auditory cortex and primary visual cortex; the second group, the caudate nucleus, superior frontal gyrus, inferior temporal gyrus, middle temporal gyrus, and superior temporal gyrus; the third group, the insula cortex; and the fourth group, the cingulate gyrus and hippocampus. CONCLUSION: Significant variation in T2 values among the cortical gray matter of the human brain exists.

Adolescent↗

PubMed2005

Degradation of Populus euphratica community in the lower reaches of the Tarim River, Xinjiang, China.

To investigate the relationships between the degradation of plant community and groundwater level in the lower reaches of the Tarim River, nine monitored sections were set along the main stream, where there had been no runoff for nearly 30 years. The characteristics of plant communities were analyzed. It was found that the coverage of trees gradually decreased along the groundwater depth gradient, while the coverage of shrubs slightly increased rather than decreased at first and then gradually decreased, and the coverage of herbs steadily decreased at the beginning and then quickly decreased. The species diversity and species richness of both herbs and woody plants showed obvious degrading trends, while the variations in species evenness were slight. The degrading sequences of species were related to their physiological and ecological characteristics, especially their sensitivity to changes of groundwater table. The herbs with shallow roots first degenerated or disappeared when the groundwater table fell, and then did the deep-rooted herbs, and finally the trees and shrubs with strong tolerance to drought degenerated. The Populus euphratica communities showed typical degrading characteristics, namely the dominant species Populus euphratica remained its dominant status during the degradation. Overall, the existence of strongly tolerant-drought species was the obvious indication of plant species degradation; while simplification of community structure and the decrease of species richness were the obvious indication of plant community degradation.

China↗

PubMed1985

Cerebral, renal, adrenal, intestinal, and pancreatic circulation in conscious ponies and during 1.0, 1.5, and 2.0 minimal alveolar concentrations of halothane-O2 anesthesia.

Blood flow to the brain, kidneys, adrenal glands, pancreas, and small intestine was studied in 8 healthy ponies while awake (control) and during 1.0, 1.5, and 2.0 minimal alveolar concentrations (MAC) of anesthesia produced, using halothane vaporized in oxygen. During the anesthesia steps, intermittent positive-pressure ventilation was used to ensure isocapnia. Organ blood flow was determined with 15-micron (diameter) radionuclide-labeled microspheres, after allowing 30 minutes of equilibration at each of the 3 preestablished end-tidal halothane concentrations. The sequence of 1.0, 1.5, and 2.0 MAC levels of anesthesia (0.90, 1.35, and 1.80% end-tidal halothane) was randomized for every animal. In the awake ponies, cerebral blood flow in the cortical (106 +/- 15 ml/min/100 g) and deep gray (103 +/- 12 ml/min/100 g) matter was approximately 5-fold of that in the white matter (22 +/- 3 ml/min/100 g). In the brain stem, there was a decreasing gradient of blood flow from the cranial (thalamohypothalamus: 65 +/- 8 ml/min/100 g) to caudal regions (medulla: 34 +/- 5 ml/min/100 g). Vasodilatation occurred in all regions of the brain with halothane-O2 anesthesia; the decrease in vascular resistance reached its nadir at 1.5 MAC. In the medulla and pons, blood flow increased above control values, with each of the 3 concentrations of halothane, but in the midbrain and thalamohypothalamus, it remained similar to the control value. In the cerebral white matter and cerebellum, blood flow increased with 1.0 and 1.5 MAC of halothane anesthesia, whereas mean aortic pressure decreased to 91% and 74% of the control value. Blood flow in the cerebral cortex was not different from the control value, even at 2.0 MAC of halothane, despite a 49% reduction in perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗