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PubMed1996

[Nosology of Lennox-Gastaut syndrome].

After a short historical review, the symptomatology of the Lennox-Gastaut syndrome (LGS) as described in the past 30 years is summarized. Next, all papers published in the past 25 years and presenting the author's own patients are critically reviewed. These considerable patient data enabled to some extent supplementary statistical evaluation of the symptoms and signs of LGS. However, only three of the papers reported largely similar symptom complexes whose components were often combined. While not adequate to allow statistical evaluation, these data have been reviewed with descriptive analysis. The resulting diagnostic criteria correspond to those established by Gastaut in 1982 and are convincing because of their frequency of appearance. In addition, they confirm the 1989 description of LGS by the Commission on Classification and Terminology of the International League Against Epilepsy. These criteria and their frequency are: (1) diffuse slow spike waves in the EEG (100%). (2) tonic seizures (94%), (3) atypical absences (80%), (4) runs of rapid spikes in NREM sleep (approx. 70%), (5) status epilepticus (60%), (6) atonic seizures (43%). Resistance to therapy and persistence of epilepsy are amongst the most frequent features. Mental retardation is a leading symptom, occurring on average in 90% of cases. Reliable statistical analysis of the electroclinical data should be performed following the numerical taxonomy and should provide nosological entities and classifications based on objective, reliable and logical fundamentals. This is an indispensable prerequisite for differential diagnosis. Sections follow which discuss recent morphological and neurometabolic findings concerning the etiology as well as the genetics of LGS. The discussion of the differential diagnosis outlines the nosological delineation of LGS from epilepsy with myoclonic-astatic seizures, benign partial epilepsy of childhood with centrotemporal sharp waves, certain focal epilepsies of the frontal and temporal lobe. Lastly, the myoclonic variant of LGS is discussed. This review shows how frequently in the past LGS was investigated using deficient methodology. Additional studies should be undertaken in collaboration with experienced statisticians in order to complement the above analysis of the syndrome.

Adolescent↗
PubMed2025

AncestryGeni: a novel genetic ancestry classification pipeline for small and noisy sequence data.

MOTIVATION: Efforts to address health disparities are often limited by the lack of robust computational tools for inferring genetic ancestry by calculating an individual's genetic similarity to continental groups. We have already shown that a preferred alternative to self-described race is using ancestry-informative markers (AIMs) that can be classified into ancestral components and used to estimate their similarity to those of known populations to identify continental groups. However, real-world genomic data can present challenges, including limited availability of germline DNA, a small number of AIMs for each sample, and the use of different variant calling software, limiting the application of existing solutions. RESULTS: Here, we describe a novel supervised machine-learning tool AncestryGeni, which infers genetic ancestry for samples with even a hundred markers and is applicable to any genomic data, including whole exome sequencing (WES) and RNA sequencing (RNA-Seq) data. Applying AncestryGeni to a real-world genomic dataset obtained from the Multiple Myeloma Research Foundation (MMRF) CoMMpass study, we show that it is more accurate than the commonly used FastNGSadmix when using nonstandard genomic material. We also demonstrate that when using AncestryGeni, the tumor-derived sequence obtained from WES and RNA-Seq can be a robust data source to accurately estimate an individual's genetic similarity to a continental group. AVAILABILITY AND IMPLEMENTATION: AncestryGeni pipeline is available at https://github.com/eelhaik/AncestryGeni/tree/main.

Humans↗
PubMed1992

Germ-cell death during prespermatogenesis in the testis of the golden hamster.

Degenerating prespermatogonial germ cells in the testis of the immature golden hamster [aged 14 days post conceptionem (dpc) to 13 days post partum [dpp)] were studied with regard to their morphology and temporal incidence. Judged by their ultrastructural features, these cells clearly take the form of apoptosis and finally are subjected to phagocytosis by neighboring Sertoli cells; only a few germ cells of a presumably incipient, partly variant degenerative morphology cannot, at present, be assigned to the apoptotic mode of cellular death. Degenerating prespermatogonia occur between the 14th dpc and 3rd dpp and again, after an interval in which no such cells are found, from the 9th dpp onwards. This pattern reveals a striking parallelism to the phases of proliferation of these cells, viz., the appearance of M- and T2-prespermatogonia. Both this obvious temporal association of proliferation and degeneration and the classification of prespermatogonial death as apoptosis suggest some developmental significance of the degenerative phenomena investigated.

Animals↗
PubMed2002

Histologic precursors of gastrointestinal tract malignancy.

Precursor lesions in the GIT include flat dysplasias, adenomas, dysplasia superimposed on nonneoplastic polyps, endocrine cell dysplasia, ACF, and condyloma accuminatum. Interobserver variability can be a problem in reporting dysplasia, and ancillary techniques including flow cytometry, image analysis, proliferation markers, and examination for p53 expression can help in this task. Squamous dysplasia seen in the esophagus and anus is graded on either a two-tiered or three-tiered system largely based on the extent of mucosal involvement. Glandular dysplasia is morphologically similar whether seen as an adenomatous polyp or within the setting of Barrett's esophagus, atrophic gastritis, or idiopathic inflammatory bowel disease. The distinction between LGD and HGD in glandular mucosa is based on the severity of cytologic and architectural distortion. Type I dysplasia is the classic adenomatous pattern seen most commonly and recognized by the presence of elongate hyperchromatic stratified nuclei. Type II, the nonadenomatous variant, contains vesicular nuclei and alteration in nuclear size and shape. Nonantral endocrine dysplasia in the stomach is seen in the setting of corporal predominant atrophic chronic gastritis and Zollinger-Ellison syndrome with Multiple Endocrine Neoplasia syndrome type I. Condyloma accuminatum is a HPV-related lesion most commonly seen in men practicing anal intercourse. Superimposed squamous dysplasia can be seen with HGD most frequently in the HIV-positive population. Recognition of the different classification systems of dysplasia, the most frequent settings in which these lesions are found, and their natural history is important for all practicing gastroenterologists and pathologists.

Carcinoma, Squamous Cell↗
PubMed2007

Mutational analysis of peptidoglycan amidase MepA.

Murein endopeptidase A (MepA) from Escherichia coli is a periplasmic peptidoglycan amidase that cleaves d,d amide bonds between d-alanine and meso-2,6-diaminopimelic acid in E. coli peptidoglycan. MepA and its homologues in other proteobacteria share overall structural similarity with d-Ala-d-Ala metallopeptidases and local similarity around the active site with lysostaphin-type enzymes, which has prompted the classification of these enzymes as LAS enzymes. LAS enzymes contain a single divalent cation in the active site, which is tetracoordinated in the crystal structures. Three of the metal ligands are identical in all structures, but the identity of the fourth ligand varies. Two residues in proximity to the metal might act as a general acid/base, but their role is not clear. Here, we report a new MepA expression system, which allows the separation of MepA variants from the endogenous wild-type enzyme, and an HPLC assay with a defined peptidoglycan fragment, which allows assessment of MepA activity without a refolding step. We find that the conserved metal ligands are required for folding (D120) or catalysis (H113, H211). Separate mutations of the candidate catalytic residues H206 or H209 and of the "fourth" metal ligand H110 are tolerated for folding but drastically reduce activity. Mutation of residue W203 to aspartate impairs substrate binding.

Binding Sites↗
PubMed2005

Identification of human exons overexpressed in tumors through the use of genome and expressed sequence data.

Alternative splicing is one of the major sources of the large transcriptional diversity found in human cells. Splicing variants have been shown to be associated with features like spreading and progression in several human tumors. Therefore, such variants may be of great importance as both diagnostic and therapeutic tools. Here, by using a set of criteria regarding the expression pattern of splicing variants and statistical analyses, we were able to screen the genome for exons overexpressed in tumors of specific tissues. However, as in other analyses attempting to identify tumor-associated variants, our list of candidates was seriously inflated with cases of genes differentially expressed in tumors. To exclude these cases and increase the probability of finding bona fide regulated splicing variants, we performed a serial analysis of gene expression (SAGE), excluding those genes that were shown to be upregulated in tumors. This allowed us to predict the overexpression of single exons in specific tumors. Our final group of candidates includes 1,386 exons belonging to 638 genes. Experimental validation of a few candidates in normal tissue, tumor cell lines, and patient samples suggests that most of these candidates are indeed tumor-associated exons. Further functional classification of our candidate genes shows that our final list is slightly inflated with cancer-related genes.

Alternative Splicing↗
PubMedDate not supplied

[The use of data on the composition and drug resistance of the causative agents of suppuration in a retrospective analysis of the epidemiological situation in a hospital].

The analysis of bacterial 16,530 strains, dynamically isolated from 6,157 patients with purulent septic processes (PSP) in surgical, traumatological, burn, toxicological and resuscitation departments, was made. The computer processing of data on the spread of the causative agents of PSP, depending on their taxonomic classification and drug resistance spectra, was carried out, which made in possible to obtain information on the outbreaks of hospital infections. Correlation of the number of PSP cases and the spread of hospital resistovars was analyzed. The data on the composition and drug resistance of pyogenic microorganisms could be used in the retrospective analysis of the epidemiological situation in a hospital. 3-year observations revealed the tendency to a decrease in the spread of the hospital variants of the causative agents of PSP, multiresistant to antibacterial preparations, which was indicative of the effectiveness of the antiepidemic measures carried out during this period.

Bacteria↗
PubMed2003

[Hereditary neuropathies].

BACKGROUND: Hereditary neuropathies constitute a heterogeneous group of diseases that make up a significant proportion of peripheral nerve disease cases. MATERIAL AND METHODS: The paper is based on a review of recent literature, including searches on Medline, and our own clinical and research experience. RESULTS: Charcot-Marie-Tooth disease, itself a heterogeneous disease, is the most common hereditary neuropathy. Several variants of neuropathy are associated with hereditary metabolic disorders. Diagnostic methods include nerve conduction velocity studies and electromyography, quantitative sensory testing, molecular genetic diagnostic testing, and in selected cases processing of nerve biopsies and skin biopsies for determination of epidermal nerve fibre densities. INTERPRETATION: A thorough family history of neuropathic symptoms and signs, and preferably clinical and electrophysiological examination of relatives is essential for the diagnosis of hereditary neuropathy. Molecular genetic analysis is promising for accurate classification of these diseases. Nerve biopsy is only helpful in selected cases.

Charcot-Marie-Tooth Disease↗
PubMedDate not supplied

[Magnetic resonance in the study of patients of short stature of the hypothalamo-hypophyseal origin. Report on 29 cases].

Although growth hormone (GH) deficiency is a very common cause of short stature, many cases are still diagnosed as idiopathic. Magnetic Resonance Imaging (MRI), more clearly than CT, reveals the anatomy of the hypothalamic-hypophyseal region and of the possible alterations (pituitary hypoplasia, interruption of the stalk) causing hormonal deficit. Twenty-nine patients with short stature underwent MRI examinations of the hypothalamic-pituitary region to assess the significance of the correlation between hormonal test and MR patterns. Five patients had normal variants of short stature (NVSS), 7 had multiple pituitary hormone defects (MPHD) and 17 had isolated growth hormone deficiency (IGHD). In patients with MPHD or with severe isolated growth hormone deficit MRI shows interruption of the pituitary stalk with ectopy of the neurohypophysis or a mass. In patients with less severe IGHD and in NVSS, MRI demonstrates a normal pituitary region or a slightly hypoplastic gland, the neurohypophysis being normally situated. MRI may provide an ethiological classification in short stature patients. Typical MR patterns can be demonstrated in cases of dwarfism secondary to a mass in the hypothalamic-pituitary region or to morphological changes of the pituitary stalk, while in transient GH deficit no anatomical abnormalities are observed.

Adolescent↗
PubMed1997

The primary structure of Trypanosoma (Nannomonas) congolese variant surface glycoproteins.

The complete nucleotide sequences were determined for three transcripts each encoding a different variant surface glycoprotein (VSG) of Trypanosoma (Nannomonas) congolense. The nucleotide sequence was determined also for a transcript encoding a fourth VSG, but this was truncated. The data obtained confirm absence of the canonical polyadenylation signal, lack of conserved sequence elements in the 3' untranslated region, and heterogeneity in the spliced-leader acceptor site in the T. congolense VSG transcripts examined. A comparison of the amino acids deduced from the nucleotide sequences of the four VSGs and those of other VSGs published previously reveals a strong conservation of several structural domains, particularly cysteine residues located throughout most of the molecules. The majority of T. congolense VSGs analyzed in this study resemble most the N-terminal cysteine residue domain type B of T. brucei, characterized by a cysteine residue located toward the N-terminal end, a cluster of cysteine residues in the central region, and at least three cysteine residues between positions 250 and 300 of the molecules. One of the VSGs analyzed, ILNat3.3, did not fit into any of the classification schemes proposed for the VSGs so far studied, and thus may represent a different class of these surface molecules. Unlike VSGs of T. brucei, the T. congolense VSGs have no cysteine residues at the carboxy-terminal end. These data now make it possible to predict general primary structural features of T. congolense VSGs.

Amino Acid Sequence↗
PubMed1992

Cytogenetic studies in subgroups of rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and accounts for 10% of all solid tumors in children. There are three different histologic forms of this tumor: embryonal (RMS-E), alveolar (RMS-A), and primitive (RMS-P). Among these, the embryonal form has responded well to chemotherapy. Identification of the correct subtype is important for both the management and treatment of this malignancy. However, the histopathologic classification of RMS is sometimes difficult and distinguishing between the embryonic and primitive forms can present a diagnostic dilemma. Chromosomal abnormalities have been observed in all subtypes. We present the cytogenetic findings in six cases of RMS or related sarcoma. All four cases with RMS-A had both numerical and structural abnormalities in the tumor and involved bone marrow specimens. Three patients had a common marker, t(2;13)(q37;q14), and one patient had a variant marker involving 13q14, t(1;13) (p36;q14), and double minutes (dmin). The single embryonal RMS patient had modal chromosome numbers in the hypertriploid range and extensive structural abnormalities; the t(2;13) was not present, but translocation of 13q to both 1q and 2p was observed, der(1)t(1;13)(q21;q14) and der(2)t(2;13)(p25;q14). The patient with primitive type RMS had a hypodiploid line with several markers, including a complex translocation involving chromosomes 5 and 13 with a breakpoint at 13q14, and t(11;12)(q24;q12), a chromosome marker heretofore found only in Ewing's sarcoma and related tumors. This patient had atypical RMS with mixed neural and myogenic elements. The significance of these chromosomal markers and their importance in the characterization of childhood tumors are discussed, along with a review of the literature.

Adolescent↗
PubMed1998

Strain differences in cytochrome P4501A1 gene expression caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat liver: role of the aryl hydrocarbon receptor and its nuclear translocator.

Rat strain variation in hepatic cytochrome P4501A1 (CYP1A1) gene expression caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated along with possible underlying mechanism. TCDD at a single oral dose of 13.5 ng/kg body weight significantly increased hepatic CYP1A1 mRNA expression in DRH, Long-Evans Cinamon (LEC), Long-Evans (LE), and Holtzman (HO) rats, but not in Sprague-Dawley (SD), Wistar-Imamichi (WI), Lewis (LEW), and Fisher-344 (F344) strains. All showed significant induction of CYP1A1 mRNA at a dose of 40 ng/kg, the relative levels decreasing in the order DRH, LEC, HO, LE, F344, WI, LEW, and SD. A more than 35-fold difference in the induction of CYP1A1 RNA was evident between the DRH and SD strains. Based on CYP1A1 induction, classification into two distinctly separate groups was possible, high responders (DRH, LEC, HO, and LE) and low responders (SD, LEW, WI, and F344). The expression levels closely correlated with the steady-state aryl hydrocarbon receptor (AhR) mRNA expression, this being approximately four-fold higher in the high than in the low responder group. Analysis of the aryl hydrocarbon receptor nuclear translocator (ARNT) showed the presence of a wild type as well as an alternately spliced variant in all strains, with a 45-bp deletion whose sequence corresponded to part of 5' end of the basic region of the basic helix-loop-helix domain. Expressed levels of both products were almost equal in all the strains except DRH, LEC and HO, where the wild form predominated. The results suggest that differential expression of both AhR and ARNT are responsible for rat strain-specific differences in TCDD induced CYP1A1 expression.

Amino Acid Sequence↗
PubMed1991

Taxonomy of potyviruses: current problems and some solutions.

There are two major requirements for potyvirus taxonomy; group-specific criteria and criteria which discriminate between distinct viruses and strains. This review discusses the relative merits in potyvirus taxonomy of molecular parameters, such as gene sequence data, nucleic acid hybridization, coat protein sequence data, or high-performance liquid chromatography peptide profiles, and phenotypic characteristics, such as particle morphology, host range, symptomatology, cross-protection, cytoplasmic inclusion morphology, and serology. Coat protein and gene sequence data are the most useful criteria, as they can be used to distinguish viruses from strains and to establish evolutionary relationships between groups of distinct potyviruses. This has led to the revised classification of some viruses and strains and to the clarification of previously conflicting and inconsistent biological properties. It has also provided a sound basis for subgrouping potyviruses. An analysis of the data supports the view that the potyvirus group, including the non-aphid-transmitted viruses, should be elevated to family status, that the vector transmission mode, which correlates with major sequence diversity, should define the four genera, and that distinct potyviruses correspond to species and their variants to strains.

Amino Acid Sequence↗
PubMed1991

"Life, Jim, but not as we know it"? Transmissible dementias and the prion protein.

The spongiform encephalopathies are unusual in several respects. Firstly, they are transmissible, and in some cases inheritable. Secondly, variants of these disorders occur in many species and can be transmitted by consumption of infected material; this has led to concern as to the potential risk from eating contaminated animal products. Thirdly, increasing evidence suggests that a 'prion' protein is central to their aetiology and pathogenesis, and that no nucleic acid is involved in the infective process. The role of the prion gene and its protein is outlined and proposed as the basis for an improved classification of the transmissible dementias.

Alzheimer Disease↗
PubMed2004

Nomenclature of the proteins of cows' milk--sixth revision.

This report of the American Dairy Science Association Committee on the Nomenclature, Classification, and Methodology of Milk Proteins reviews changes in the nomenclature of milk proteins necessitated by recent advances of our knowledge of milk proteins. Identification of major caseins and whey proteins continues to be based upon their primary structures. Nomenclature of the immunoglobulins consistent with new international standards has been developed, and all bovine immunoglobulins have been characterized at the molecular level. Other significant findings related to nomenclature and protein methodology are elucidation of several new genetic variants of the major milk proteins, establishment by sequencing techniques and sequence alignment of the bovine caseins and whey proteins as the reference point for the nomenclature of all homologous milk proteins, completion of crystallographic studies for major whey proteins, and advances in the study of lactoferrin, allowing it to be added to the list of fully characterized milk proteins.

Amino Acid Sequence↗
PubMedDate not supplied

[Screening for anti-glycolipid antibody profiles from patients with immune-mediated peripheral neuropathies by Dotzen Ganglio Profile Antibodies].

The presence of anti-glycolipid specific antibodies have been found to be associated with acute and chronic immune-mediated peripheral neuropathies. Recently a number of anti-glycolipid antibody assays have became commercially available. In this study we established specific anti-glycolipid antibody profiles in a series of sera by the Dotzen Ganglio Profile antibodies. This kit screens for the simultaneous detection of ten anti-glycolipid antibodies against GM3, GM2, GM1, GD3, GD1a, GD1b, GT1a, GT1b, GQ1b gangliosides and sulfatides of the IgM and IgG classes. Sera from 89 patients with acute and chronic neuropathies were selected in a well-characterized cohort of banked sera with anti-glycolipid antibody profiles identified by in-house immunodot assay. Serum from 52 clinical variants of Guillain-Barré syndrome with IgG autoantibody profiles and 37 chronic acquired peripheral neuropathy with IgM autoantibody profiles were tested. The assay correctly identified with good agreement 50 of 52 IgG antibody profiles and 32 of 37 IgM antibody profiles. The assay compared well with in-house immunodot assay. It is easy to screen 10 crossreacting glycolipid antibodies to establish specific antibody profiles to define different subgroups of immune-mediated peripheral neuropathies for classification and immune management.

Autoantibodies↗
PubMed1975

[The so-called amaurotic idiocies. Clinical, morphological and biochemical findings as a basis for modern classification].

First of all seven of our own thoroughly investigated cases of so-called amaurotic idiocies are presented, they are two infantile, two juvenile, two late infantile one, as well as one adult case. The two infantile cases represent the typ of a GM2-gangliosidosis: with cerebral symptoms and cherry-red spot in the macula they correspond clinically to the typical picture of Tay-Sachs disease. Lightmicroscopically they show neuronal storage, electronmicroscopically a deposition of "membranous cytoplasmic bodies" and biochemically a strong increase in ganglioside GM2. The two juvenile cases correspond in their symptoms and findings to the so-called ceroid-lipofuscinoses or "Myoclonic variant of amaurotic idiocy", respectively. Clinically most remarkable is the deterioration of vision caused by retinitis-pigmentosa-like changes of the fundus, which sets in at the beginning of the disease and precedes the cerebral symptoms by years. The extinguished electroretinogramm corresponds in the histological retina findings to a severe lesion of the layer of rods and cones in the sense of a tapeto-retinal degeneration. Neuropathologically finegranular, Sudan-Black-B- and PAS-positive material is mainly but not exclusively stored in the neurons. The electronmicroscope shows them to be lipofuscin-like inclusions, as well as "curvilinear" or "fingerprint-bodies". Depositions are also to be found in astrocytes and in the cells of the vascular walls. The ganglioside pattern is normal in the brain tissue of the biochemically investigated case. Of the two late infantile cases the first represents a GM2-gangliosidosis, the second one corresponds to the ceroid-lipofuscinosis. The adult patient, who suffered from an ill-defined psychiatric disease and died at the age of 51 presents a diagnostically problematic case, showing a relatively slight, regionally rather differently accentuated intraneuronal storage of granular material and biochemically a slight increase in ganglioside GM2. On discussing our own findings and commenting on the relevant literature various aspects of amaurotic idiocies are considered, such as genetics, neuropsychiatry, ophthalmology, pathomorphology and biochemistry. In this respect special attention is paid to the pathomorphological substrate documented, as localization, degree and kind of tissue changes determine the clinical picture. This is also the case for the correlation between the findings of the different fields, so e.g. concerning the ophthalmological findings it is shown, that in gangliosidoses with preserved ERG histologically a storage in the nerve cells of the ganglion cell-layer only is to be found, where as the ceroid-lipofuscinoses with early onset of deterioration of vision and extinguished ERG in the histological picture of the retina show an additional severe lesion of the layer of rods and cones...

Adolescent↗
PubMed2003

The prevalence and clinical profile of angiographic coronary ectasia.

Coronary artery ectasia, a variant of coronary atherosclerosis, is a relatively rare entity. Review of literature did not reveal an exclusive study on isolated ectasia. We decided to analyse the clinical presentation and angiographic prevalence of this subset. A retrospective study of patients who underwent coronary angiogram in our institute over the past six years was carried out and the epidemiological, clinical and angiographic characteristics of patients with isolated ectasia were analysed. Distribution of ectasia was with a modification of the Markis classification. Among 6938 angiograms analysed, 134 (2%) had isolated ectasia. Of the 118 symptomatic patients, 34 (25%) had a history of or presented with infarction, with correlation between the territory of infarction and the ectatic vessel in 32 patients. Of 62 patients with lipid abnormality, Hypertriglyceridemia in 42 (65%) was the most common. The left anterior descending artery was the most common vessel involved. Diffuse ectasia most commonly involved the right coronary artery. One patient had spontaneous coronary dissection. There is a relatively high prevalence of isolated coronary ectasia with predominant involvement of the right coronary vessel when diffuse and the left anterior descending artery when discrete. This entity is not innocuous and warrants a detailed study on the available management options.

Adult↗