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PubMed2004

Diet and the development of atopic disease.

PURPOSE OF REVIEW: The present review addresses the current literature regarding the impact of diet and the development of atopic disease. A search of the literature was carried out covering the following topics: diet and nutrition combined with immediate hypersensitivity, atopy, atopic disease, atopic dermatitis, and food allergy. RECENT FINDINGS: The search results identified a significant contribution in the form of reviews considering this important topic, which ultimately led to the author's recommendation of these reviews to impress upon readers the impact of the atopy triad: atopic dermatitis to allergic rhinitis and asthma. SUMMARY: A great deal of information exists in the pathomechanisms of atopic disease that will affect the classification of allergic and non-allergic atopic diseases. Increasing data on the genetic, humoral and cellular forms associated with these diseases will provide more clear-cut diagnostic criteria, treatment regimens and a more strict definition of the disease variants.

Animals↗
PubMed2026

BCL11B enhancer hijacking by t(14;16)(q32;q24) translocation defines a novel high-risk subtype of T-ALL.

The molecular classification of T-cell acute lymphoblastic leukemia (T-ALL) remains incomplete, limiting risk stratification and the development of targeted therapies. Enhancer hijacking is a critical oncogenic mechanism that deregulates proto-oncogenes by repositioning cisregulatory regions via structural variants. Here, we performed an integrated analysis of pediatric and adult T-ALL and mixed-phenotype acute leukemias (MPALs), using whole-genome and whole-transcriptome sequencing. This analysis identified a group of 14 patients with predominantly T-lineage neoplasms driven by a t(14;16)(q32;q24) translocation, harboring universal GATA3 mutations and CDKN2A/B deletions. Mechanistically, this translocation repositions the ThymoD locus downstream of BCL11B, causing monoallelic, ectopic overexpression of FENDRR and mesenchymal transcription factor genes FOXF1 and FOXC2 and activating epithelial-mesenchymal transition transcription signatures. Immunophenotypic and single-cell RNA sequencing analyses revealed marked lineage ambiguity with myeloid and B-cell differentiation potentials specific to this subtype. Furthermore, functional analyses in CD34+ cord blood cells demonstrated that FOXF1 overexpression promotes myeloid differentiation while suppressing T-cell differentiation, serving as a key factor for lineage specification. Clinically, this subtype was detected in 0.15% to 4.0% of T-ALL/MPAL cases depending on the cohort, showing a median age of 15 years and enrichment in adolescents and young adults. Importantly, patients with t(14;16)(q32;q24) have an extremely poor prognosis, showing a trend toward worse outcomes than high-risk groups such as KMT2A-rearranged early T-cell progenitor-like, SPI1-rearranged, and LMO2 γδ-like T-ALLs. The unique molecular landscape and poor prognosis of patients with the t(14;16)(q32;q24) translocation underscore the need for the development of novel subtype-specific therapeutic approaches.

Humans↗
PubMed1997

[Chronic airway inflammation and atopic features in cough variant asthma].

OBJECTIVE: To elucidate the chronic airway inflammation and atopic features in 17 patients with cough variant asthma (CVA). METHODS: (1) Allergen skin prick test, and the atopy index (AI) calculation. (2) Fiberoptic bronchoscopy, inflammatory score of airway membrane under bronchoscopy. (3) Biopsy of the airway membrane and calculation of the eosinophil infiltration. (4) Bronchoalveolar lavage, classification of various cells in the BALF. (5) House dust mite and rabbit antihuman IgE induced histamine release from mast cell. The results were compared with those in 9 patients with typical asthma (Group 8) and 7 normal subjects (Group C). RESULTS: The number of EOS and mast cells in BALF and the AI of CVA group were found higher than in control group. CONCLUSION: (1) Similar to typical asthma, IgE dependent type I allergic reaction plays an important role in the pathogenesis of CVA. (2) Chronic inflammation including eosinophil infiltration was shown in airway membrane in CVA. (3) Bronchial hyperresponsiveness and chronic inflammation of the airway membrane in CVA are less severe than those in typical asthma. (4) In patients who are in difficulty of making a diagnose of CVA clinically. BAL and biopsy of the bronchial membrane will help to make a definite diagnosis.

Adult↗
PubMed1991

Clinical symptoms and DNA repair characteristics of xeroderma pigmentosum patients from Germany.

Sixty-one xeroderma pigmentosum (XP) patients living in the Federal Republic of Germany were investigated. Clinical symptoms were correlated with DNA repair parameters measured in fibroblasts grown from skin biopsies. Classification according to the international complementation groups revealed that of the 61 patients 3 belonged to group A, 26 to group C, 16 to group D, 3 to group E, and 2 to group F; 11 were of the XP variant type. A striking clinical aspect was the frequency of histogenetically different skin tumors varying from one XP complementation group to the other: squamous and basal cell carcinomas predominated in XP group C; lentigo maligna melanomas were most frequent in group D; basal cell carcinomas occurred preferentially in group E and XP variants. Three DNA repair parameters were determined for 46 fibroblast strains: colony-forming ability (D0); DNA repair synthesis (G0); and DNA-incising capacity (E0). Dose-response experiments with up to 13 dose levels were performed throughout to achieve sufficient experimental accuracy. DNA-damaging treatments included UV light, the "UV-like" carcinogen N-acetoxy-2-acetylaminofluorene, and the alkylating carcinogens methyl methanesulfonate and N-methyl-N-nitrosourea. Comparison of clinical signs and repair data was made on the basis of D0, G0, and E0 values of both individual cell strains and weighted means of XP complementation groups. Despite considerable clinical and biochemical heterogeneity within complementation groups distinctive features emerged. In general, D0, G0, and E0 values of all XP strains investigated, including XP variants, were found to be reduced upon treatment with UV light or N-acetoxy-2-acetylaminofluorene. After treatment with UV light or N-acetoxy-2-acetylaminofluorene, cell strains in which DNA-incising capacity was reduced also showed a similar reduction in both colony-forming ability and DNA repair synthesis. Consequently, the weighted mean D0, G0, and E0 values of XP complementation groups and XP variants correlated with each other. Furthermore, the onset of both early dermatological symptoms of XP and tumor growth correlated with the extent of DNA repair defects. Of 45 XP fibroblast strains checked for colony-forming ability after treatment with methyl methanesulfonate only 3 cell strains from group D were found to be more sensitive than normal controls, suggesting that overall repair in XP strains was equal to that in controls. Weighted means of DNA repair synthesis of XP complementation groups, however, showed reductions hinting at impaired excision of distinct alkylated bases.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetoxyacetylaminofluorene↗
PubMed1990

[Vector cardiography features of right ventricular activation delays: nosologic classification and clinical correlation].

Electrovectorcardiographic features of 150 patients showing right ventricular activation delays (RVAD) has been analyzed. This analysis of RAVD, especially for type I, which is the group with the widest morphologic variability, has permitted a more detailed classification: a type I with 5 subtypes, a type II with 1 subtype, a type III and an intermediate type between type II and III. Fifty-five per cent of the patients were included in type I and its variant and most were classified, often without cardiac disease, as belonging to the classic type I. Thirty per cent of RVAD were of type II; 12% of type III and the remaining were in the intermediate group between type II and III. The various morphologies, moreover, were correlated with the clinical picture: the classic type I was never seen in subjects with cardiac disease, while the others types and subtypes were present either in subjects with cardiac disease or in elderly subjects, also without relevant pathologies (senile heart, especially, the type IA") or in otherwise healthy subjects. In a medical-social context, checking for RVAD, in the absence of cardiac disease, might usefully avoid further investigation. It is underlined the usefulness of this correlation for clinical prognostic judgement.

Adolescent↗
PubMed2003

Paraclinoid Carotid Aneurysms: Surgical Management, Complications, and Outcome Based on a New Classification Scheme.

The site of origin, projection, and relationship of aneurysms arising from the ophthalmic segment of the internal carotid artery (ICA) to adjacent structures are heterogeneous. Based on a retrospective analysis of 61 patients with aneurysms in this location, we developed a simple numerical classification system to guide surgical planning. We used angiographic findings to categorize the aneurysms. We followed the nomenclature of the carotid segments by Bouthillier et al (Neurosurgery 1996;38:425-432), C4 being the intracavernous ICA, C5 the clinoidal segment, and C6 the ophthalmic segment of the ICA. The aneurysms were divided into four major types: Types Ia and Ib projected superiorly and arose from the dorsal surface of C6. Type Ia was related to the ophthalmic artery. Type Ib aneurysms were sessile and had no branch relations. Type II aneurysms were related to the ventral wall of the C6 segment without any branch relation. Type IIIa variant arose from medial wall of the C6 segment and was related to the superior hypophyseal artery. Type IIIb arose from the medial wall of the C5 segment below the dural reflection without any branch relation. Large type IV aneurysms arose from the C5 and C6 segments, widening the distal dural ring. Patients' postoperative status and visual and overall outcomes were analyzed. Ultimately, this classification helped us to plan operative approaches and clip selection.

Journal Article↗
PubMed2006

D324N single-nucleotide polymorphism in the FLT3 gene is associated with higher risk of myeloid leukemias.

Mutations within the FLT3 gene are of growing importance for classification, risk assessment, and therapeutic targeting of acute myeloid leukemia (AML). We analyzed 656 AML patients for a recently described single-nucleotide polymorphism (SNP) in the third immunoglobulin-like domain of the extracellular region of FLT3. The FLT3 D324N variant was present in 42 cases (6.4%), but it was not associated with a specific AML subtype and did not show an elevated leukocyte count, as do other FLT3 mutations. In remission samples, a 50% ratio of the normal to the D324N variant was detectable. Stably expressed in IL-3 dependent Ba/F3 cells, the D324N variant did not confer receptor autophosphorylation, factor independent growth, or increased resistance to apoptotic cell death in response to varying doses of FLT3 ligand. In 400 healthy donors, the FLT3 D324N variant was detected in 6 cases (1.5%) and segregated in a family. Thus, it was shown to be a polymorphism with a lower frequency in healthy controls than in patients with AML (P < 0.001). In addition, 21 of 234 CML (9.0%) and 7 of 155 ALL (4.5%) cases carried the FLT3 D324N. Our data suggest that the FLT3 D324N variant might be associated with a predisposition to different subtypes of leukemia.

Acute Disease↗
PubMed1999

[Hereditary motor-sensory neuropathies (Charcot-Marie-Tooth syndrome) and related neuropathies. Current classification and genotype-phenotype correlation].

Charcot-Marie-Tooth (CMT) disease is the most common inherited disorder of the peripheral nervous system with an incidence of 40:100,000. Clinically, it is characterized by distal muscle weakness and wasting, primarily of the legs and later of the arms, foot deformity, diminished or absent tendon reflexes, and mild-to-moderate sensory loss. Molecular genetic studies over the past 2 decades have revealed the genetic heterogeneity of this disorder and the identification of different genes or gene loci, respectively. Therefore, a current CMT classification though constantly changing due to ongoing detection of further genetic defects must take into consideration both phenotypic and genotypic criteria. Since certain clinical features appear to be associated with specific genetic subtypes, we provide a detailed description of characteristic phenotypic variants to facilitate differential diagnosis and allow more precise referral to subsequent genetic investigations.

Charcot-Marie-Tooth Disease↗
PubMed2006

Octaplex PCR and fluorescence-based capillary electrophoresis for identification of human diarrheagenic Escherichia coli and Shigella spp.

A multiplex PCR assay, amplifying seven specific virulence genes and one internal control gene in a single reaction, was developed to identify the five main pathotypes of diarrheagenic Escherichia coli and Shigella spp. The virulence genes selected for each category were Stx1, Stx2, and eaeA for enterohemorrhagic E. coli (EHEC), eaeA for enteropathogenic E. coli (EPEC), STIb and LTI for enterotoxigenic E. coli (ETEC), ipaH for enteroinvasive E. coli (EIEC) and Shigella spp., and aggR for enteroaggregative E. coli (EAEC). Each forward primer was labelled with a fluorochrome and the PCR products were separated by multicolour capillary electrophoresis on an ABI PRISM310 Genetic Analyzer (Applied Biosystems). If present, several gene variants of each virulence gene were identified. The internal control gene rrs, encoding 16S rRNA, was amplified in all 110 clinical strains analyzed. Virulence genes were demonstrated in 103 (94%) of these strains. In the majority of the cases (98/103, 95%), classification obtained by the novel multiplex PCR assay was in agreement with that previously determined by phenotypic assays combined with other molecular genetic approaches. Numerous multiplex PCR assays have been published, but only a few of them detect all five E. coli pathotypes within a single reaction, and none of them has used multicolour capillary electrophoresis to separate the PCR products. The octaplex PCR assay followed by capillary electrophoresis presented in the present paper provides a simple, reliable, and rapid procedure that in a single reaction identifies the five main pathotypes of E. coli, and Shigella spp. This assay will replace the previous molecular genetic methods used in our laboratory and work as an important supplement to the more time-consuming phenotypic assays.

Adhesins, Bacterial↗
PubMed1996

Reproducibility of videokeratographic digital subtraction maps after excimer laser photorefractive keratectomy.

BACKGROUND: Digital subtraction photokeratography can best identify topographic changes after excimer laser photorefractive keratectomy (PRK). To evaluate the reproducibility of these topographic maps, the authors used a topographic modeling system to generate multiple subtraction maps from different combinations of technically acceptable preoperative and postoperative maps for eyes that underwent PRK. The assigned patterns for each patient then were evaluated for consistency. METHODS: Seven hundred twenty-two individual subtraction maps were generated for 64 eyes that underwent PRK. A mean of 11.3 maps were generated for each eye. The topography of each map was individually classified as normal, central island, peninsula, or asymmetric. All maps within a set (consisting of examinations for 1 patient at a single postoperative interval) then were examined as a unit to determine the overall topographic classification for that set of maps. Each set in which each constituent map had the same topographic assignment as the set was considered "nonvariant," whereas those sets in which one or more individual subtraction maps had different topographic assignments were considered "variant." RESULTS: Of the 64 sets, 33 (52%) were variant and 31 (48%) were nonvariant. CONCLUSIONS: Any one subtraction map produced by the topographic modeling system may not be a reliable indicator of the excimer effect.

Cornea↗
PubMed2004

A new type of minocycline-induced cutaneous hyperpigmentation.

Pigmentary disorders are recognized adverse effects of the semi-synthetic tetracycline derivative antibiotic, minocycline. Three distinct types of minocycline-induced cutaneous pigmentation have been described. Type I, blue-black pigmentation confined to sites of scarring or inflammation on the face; Type II, blue-grey circumscribed pigmentation of normal skin of the lower legs and forearms; and Type III, diffuse muddy brown pigmentation of normal skin accentuated in sun-exposed areas. We report two patients with acne vulgaris with a fourth type of minocycline-induced cutaneous pigmentation. They presented with circumscribed blue-grey pigmentation within acne scars confined to the back. Histology showed pigment within dendritic cells, and extracellularly throughout the dermis. Histochemistry identified a calcium containing melanin-like substance. Iron was absent. Immunohistochemistry confirmed some pigment-containing cells to be macrophages. Electron microscopy demonstrated electron-dense granules, free and membrane-bound, within macrophages and fibroblast-like cells. Energy-dispersive X-ray analysis confirmed the presence of calcium. Iron was absent. This fourth type of cutaneous minocycline hyperpigmentation may be a variant of Type I, but based on clinical, pathological and microanalytical differences, appears to be a new entity. The pigment may be a drug metabolite-protein complex chelated with calcium, or an insoluble minocycline-melanin complex. We propose a classification of cutaneous minocycline pigmentation based on clinico-pathological criteria.

Acne Vulgaris↗
PubMed1996

The offensive subtype of Taijin-kyofu-sho in New York City: the phenomenology and treatment of a social anxiety disorder.

BACKGROUND: Taijin-kyofu-sho (TKS) is thought to be a common, culture-bound disorder of social anxiety in Japan and Korea. Its phenomenology has been noted to overlap with that of social phobia. The "offensive type" of TKS, which has no direct parallel in Western classification, is characterized by a fear of offending others in social situations, which leads to social avoidance. There has been only one case of offensive-type TKS reported in the United States, and this case was not regarded as a variant of social phobia. METHOD: The phenomenology and treatment of six patients who presented to New York City anxiety disorders research clinic psychiatrists with the offensive type of TKS are described. Features of TKS are compared with those of social phobia, as described in Western countries. Treatment outcomes for four patients are discussed and compared with TKS treatment experience in Japan and Korea and with treatment outcome in social phobia. RESULTS: In this anxiety clinic sample, features of the offensive type of TKS showed much overlap with symptoms of social phobia. Only two of four treated patients in this TKS sample received adequate trials of medication known to be effective for social phobia, and one of the two improved significantly. CONCLUSION: The offensive type of TKS may not be as culture-bound as previously thought. Further study is needed to determine whether such cases respond to medications and to cognitive-behavioral approaches that are effective for social phobia. How to classify the offensive type of TKS is uncertain, but social phobia should be considered in the differential diagnosis.

Adolescent↗
PubMed1990

[The classification of chronic pancreatitis].

To make the II Marseilles Classification of Pancreatitis more applicable to everyday clinical practice, a new systemic approach is suggested basing on clinical, laboratory, CT and ultrasound evidence. Upon examination of 182 chronic sufferers with pancreatitis, interstitial--edematous, parenchymatous, fibrous--sclerotic (indurative), hyperplastic (pseudotumorous) and cystic variants of the disease were established in 34.6%, 30%, 21.1%, 4.4% and 9.9%, respectively. Clinical features typical for each variant of the disease and most common complications are reviewed.

Chronic Disease↗
PubMed1989

[Proximal selective vagotomy in the treatment of uncomplicated forms of duodenal ulcer].

Experience is recorded with 893 operations of duodenal ulcer for a period of 15 years. Of these, 872 patients (97.6 per cent) were operated as nonemergency planned cases, 48 of them subjected during a period of 7 years to proximal selective vagotomy in 3 variants. During the postoperative period one patient died of fatty pulmonary embolism. During the early postoperative period in 4 patients developed bronchopneumonia (8.3 per cent), in 3 transient cardiospasm (6.2 per cent) successfully controlled without surgical intervention. According to Visick's classification, excellent and very good postoperative results were recorded in 41 patients (87.2 per cent). Recurrent ulcer was demonstrated in 3 patients (6.4 per cent); only one of them required operative treatment--antrumectomy with revagotomy. It is pointed out that postoperative pH-metry of the stomach is not a pathognomonic sign, but may be criterion for a potentially possible recurrence. Continuous control is needed, since the majority of recurrent ulcers are not manifested by characteristic clinical symptoms.

Adult↗
PubMed1981

Characteristics of listeria strains, isolated from micromammalia in Bulgaria.

56 Listeria strains isolated from the intestine contents of 13 species of micromammalia in Bulgaria were studied. 10 of the strains belong to the serovars 1/2a, 4A, 4b and 5 of Listeria monocytogenes and 44 of the strains belong to 10 antigenic variants of Listeria innocua. According to their characteristics these strains could hardly cause diseases in humans or domestic animals. Two strains have antigenic formulae O-V, VII, XIV and O-V, XIV and cannot be included in the existing classification. Prevalent are the strains antigen O-XV. They are more often isolated from synanthropic rodents. The hemolytic properties of the studied strains have the best correlation with the pathogenicity. The decomposition of rhamnose and xylose and the production of lysozyme could be a suitable basis for their classification in biotypes.

Animals↗
PubMed2004

Single nucleotide polymorphism-based validation of exonic splicing enhancers.

Because deleterious alleles arising from mutation are filtered by natural selection, mutations that create such alleles will be underrepresented in the set of common genetic variation existing in a population at any given time. Here, we describe an approach based on this idea called VERIFY (variant elimination reinforces functionality), which can be used to assess the extent of natural selection acting on an oligonucleotide motif or set of motifs predicted to have biological activity. As an application of this approach, we analyzed a set of 238 hexanucleotides previously predicted to have exonic splicing enhancer (ESE) activity in human exons using the relative enhancer and silencer classification by unanimous enrichment (RESCUE)-ESE method. Aligning the single nucleotide polymorphisms (SNPs) from the public human SNP database to the chimpanzee genome allowed inference of the direction of the mutations that created present-day SNPs. Analyzing the set of SNPs that overlap RESCUE-ESE hexamers, we conclude that nearly one-fifth of the mutations that disrupt predicted ESEs have been eliminated by natural selection (odds ratio = 0.82 +/- 0.05). This selection is strongest for the predicted ESEs that are located near splice sites. Our results demonstrate a novel approach for quantifying the extent of natural selection acting on candidate functional motifs and also suggest certain features of mutations/SNPs, such as proximity to the splice site and disruption or alteration of predicted ESEs, that should be useful in identifying variants that might cause a biological phenotype.

Alleles↗
PubMed1979

Rhabdomyosarcoma of infancy and childhood. Problems of morphologic classification.

The classification of the histologic types of rhabdomyosarcoma is based on poorly defined criteria. This has resulted in marked disparities in studies reported from different institutions, as well as difficulties in assessment of the clinical behavior of the different histologic types. A retrospective morphologic analysis of 36 consecutive cases of rhabdomyosarcoma of childhood was undertaken according to predefined and strict guidelines for diagnosis. Undeflecting adherence to such criteria identified the embryonal type as the most common form, and the alveolar variant as a distinct clinicopathologic entity with a much more aggressive course; it also resulted in a large proportion (approximately one-fourth) of sarcomas of undertermined histogenesis. In spite of either prolonged follow-up observation with repeated biopsies, autopsy study, or electron-microscopic study of tumor tissue, no evidence could be obtained to substantiate the rhabdomyogenic derivation of the latter group of neoplasms. Precise systematization of the morphology of these cases may be contingent upon careful inventory of their fine structural features; current classifications appear to have disregarded the morphologic heterogeneity of this group of tumors.

Adolescent↗
PubMed2001

ABCA6, a novel a subclass ABC transporter.

Here we report the cDNA cloning of a novel member of the ABC A transporter subfamily from human macrophages. The identified coding sequence is of 5.0 kb size and contains an open reading frame which encodes a 1617 amino acid polypeptide. Structurally, the putative ABC transporter protein product consists of two tandemly oriented subunits, each composed of a transmembrane domain followed by a nucleotide binding fold, and thus conforms to the group of full-size ABC transporters. We also demonstrate the existence of an alternative transcript that codes for a 637 amino acid protein variant bearing the features of a truncated half-size transporter. Among the human ABC transporter subfamily A the novel transporter shows highest protein sequence homology with ABCA8 (60%), followed by ABCA2 (32%) and ABCA1 (32%), respectively. In agreement with the proposed classification, the novel transporter was designated ABCA6. The ABCA6 gene is ubiquitously expressed with highest mRNA levels in liver, lung, heart and brain. Analysis of the genomic organization demonstrated that the ABCA6 gene is composed of 38 exons which extend across a region of 62 kb size on chromosome 17q24.2. Based on its structural features and its cholesterol-responsive regulation ABCA6 is potentially involved in macrophage lipid homeostasis.

ATP Binding Cassette Transporter 1↗