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PubMed2002

Analysis of the genetic variability of genes encoding the RNA III-activating components Agr and TRAP in a population of Staphylococcus aureus strains isolated from cows with mastitis.

The expression of Staphylococcus aureus virulence proteins is under the control of RNA III, a central pleiotropic regulator transcribed from the agr locus. RNA III is activated by at least two two-component systems, one encoded by the agr locus (AgrC-AgrA) and another encoded outside of this locus (TRAP-RAP). In this work, we developed new typing methods based on genes encoding these two systems, which we used to characterize a nonclonal population of S. aureus bovine mastitis isolates. Twelve agr restriction types were identified in this population, but the majority of strains (56.3%) were grouped in the R III-A1 type. No strain isolated from humans, whose agr sequence is available from GenBank, was found to belong to this major type. Restriction maps constructed for all of those agr variants allowed the linking of all types in an evolution scheme and their grouping in one of the four agr interference groups. This analysis indicates that groups 2, 3, and 4 probably evolved from the more frequently encountered type, which belongs to group 1. agr group 1 was also found to be the most prevalent (69.0% of the strains) and the most polymorphic interference group. By developing an agr group-specific multiplex PCR, we confirmed the above classification of strains in the agr interference groups. Four allelic variants of trap were also identified, indicating that this two-component system is also polymorphic. The majority of strains was grouped in the trap 1 type (71.8%). Whereas no relationships between agr group and trap types were found, strains of similar agr restriction type were also of similar trap type (with the exception of strains belonging to the agr R IV-A5 and R VI-A8 types). Our analysis indicates that S. aureus isolated from cows has predominantly a clonal structure and that the highly prevalent agr R III-A1, trap 1 type (56.3% of the strains) probably possesses a genetic background which endows it with superior ability to infect the bovine mammary gland.

Animals↗

PubMed2006

Differentiation of sCJD and vCJD forms by automated analysis of basal ganglia intensity distribution in multisequence MRI of the brain--definition and evaluation of new MRI-based ratios.

We present a method for the analysis of basal ganglia (including the thalamus) for accurate detection of human spongiform encephalopathy in multisequence magnetic resonance imaging (MRI) of the brain. One common feature of most forms of prion protein diseases is the appearance of hyperintensities in the deep grey matter area of the brain in T2-weighted magnetic resonance (MR) images. We employ T1, T2, and Flair-T2 MR sequences for the detection of intensity deviations in the internal nuclei. First, the MR data are registered to a probabilistic atlas and normalized in intensity. Then smoothing is applied with edge enhancement. The segmentation of hyperintensities is performed using a model of the human visual system. For more accurate results, a priori anatomical data from a segmented atlas are employed to refine the registration and remove false positives. The results are robust over the patient data and in accordance with the clinical ground truth. Our method further allows the quantification of intensity distributions in basal ganglia. The caudate nuclei are highlighted as main areas of diagnosis of sporadic Creutzfeldt-Jakob Disease (sCJD), in agreement with the histological data. The algorithm permitted the classification of the intensities of abnormal signals in sCJD patient FLAIR images with a higher hypersignal in caudate nuclei (10/10) and putamen (6/10) than in thalami. Defining normalized MRI measures of the intensity relations between the internal grey nuclei of patients, we robustly differentiate sCJD and variant CJD (vCJD) patients, in an attempt to create an automatic classification tool of human spongiform encephalopathies.

Algorithms↗

PubMed2000

Haemolysin-deficient variants of Streptococcus pyogenes and S. dysgalactiae subsp. equisimilis may be overlooked as aetiological agents of pharyngitis.

Variants of large colony beta-haemolytic Lancefield group A, C and G streptococci that are non-haemolytic or alpha-haemolytic on sheep blood agar have been detected in clinical specimens due to their enhanced haemolytic activity when grown on a new selective and differential blood agar medium containing colistin, nalidixic acid and pH 7.5-adjusted PIPES buffer (CNA-P). The large colony Lancefield group C and G isolates were identified as Streptococcus dysgalactiae subsp. equisimilis by API 20 Strep classification and 16S rDNA profiling. The haemolytic activity of these variants on various blood agar media, including CNA-P, was closely similar to that of known streptolysin S-defective mutants of S. pyogenes and was blocked by addition of cholesterol, a specific inhibitor of the streptolysin O family of haemolysins. As haemolysin variants could be detected in large numbers in cultures from patients with clinical symptoms of pharyngitis it is suggested that they may function as primary pathogens in such infections. The high frequency with which haemolysin variants were isolated from clinical specimens during a 3-month trial (3%, 13% and 10%, respectively, of group A, C and G streptococcal isolates) indicated that a substantial proportion of streptococcal infections may go undetected if only conventional sheep blood agar media are used in clinical laboratories for the detection of beta-haemolytic streptococci. As haemolysin variants have been implicated in the development of serious streptococcal sequelae, further investigation of the full extent of their contribution to streptococcal disease is indicated.

Antigens, Bacterial↗

PubMed2004

Psychosis in body dysmorphic disorder.

Body dysmorphic disorder (BDD) has both psychotic and nonpsychotic variants, which are classified as separate disorders in DSM-IV (delusional disorder and a somatoform disorder). Despite their separate classification, available evidence indicates that BDD's delusional and nondelusional forms have many similarities (although the delusional variant appears more severe), suggesting that they may actually be the same disorder, characterized by a spectrum of insight. And contrary to what might be expected, BDD's delusional form, although classified as a psychotic disorder, appears to respond to serotonin-reuptake inhibitors alone. These and other data suggest that a dimensional view of psychosis (in particular, delusions) in these disorders may be more accurate than DSM's current categorical view. A dimensional model might also facilitate more consistent and accurate classification of other disorders that are likely characterized by a spectrum of insight, such as obsessive compulsive disorder, hypochondriasis, and anorexia nervosa. Further research is needed to better understand these classification issues, which likely have treatment implications.

Adult↗

PubMed1980

Ovarian neoplasms resembling sex cord tumors with annular tubules.

A clinicopathologic analysis of 6 patients with ovarian neoplasms resembling sex cord tumors with annular tubules (SCTAT) was performed. The patients' ages ranged from 20 to 43 years. Most had signs and symptoms of estrogenic hormonal imbalance; none had evidence of the Peutz-Jeghers syndrome. The tumors were unilateral in all cases and, except for one lesion of microscopic size, were from 3 to 18 cm in greatest dimension. One tumor was combined with a germinoma. Surgery alone was the primary mode of therapy in all cases. Lymph nodal metastases developed in 2 patients 7.5 and 10.5 years postoperatively. They are the first documented examples of malignant behavior recorded. At the time of last known contact, all patients were alive without demonstrable tumor for intervals from 1.5 to 16.3 years (mean, 7.8 years) after initial treatment. While the annular patterns of growth have often been attributed to Sertoli cell differentiation, histologic and cytologic features of granulosa cell tumor were observed in areas of the primary tumors and in metastatic lesions. True lumen formation was never observed in the so-called tubules. We propose classification of SCTAT as a distinctive annular and membranous variant of granulosa cell tumor in view of the morphologic similarities and comparable clinical behavior of these two neoplasms.

Adult↗

PubMed1999

Selected cutaneous vascular neoplasms. A review.

This article reviews the pathology of benign, borderline, and malignant vascular neoplasms of the skin. The classification of vascular lesions of childhood is presented. Defined variants of hemangioma (including sinusoidal, microvenular, glomeruloid, epithelioid, and targetoid hemosideric hemangioma, as well as acquired tufted hemangioma and angiofibroma) are discussed. Borderline hemangioendotheliomas are classified. Kaposi sarcoma is reviewed with an update on the role of human herpesvirus type 8 in its pathogenesis. Angiosarcoma and acquired progressive lymph-angioma are also discussed.

Biopsy, Needle↗

PubMed2003

Ameloblastic carcinoma of the maxilla.

The maxilla is an unusual site for an ameloblastoma, and certainly for an ameloblastic carcinoma. Ameloblastomas are considered as benign, yet locally aggressive neoplasms in the vast majority of cases. However, very rarely, these tumors demonstrate a clinical course of malignancy. Recently, a classification system was published differentiating between malignant odontogenic carcinoma variants. The two such forms include malignant ameloblastoma, and ameloblastic carcinoma. In the differential diagnosis, the designation of malignant ameloblastoma is reserved for lesions that, despite their benign histology, metastasize as well-differentiated cells. The diagnosis of ameloblastic carcinoma is reserved for tumors that demonstrate a malignant morphologic appearance, regardless of whether metastasis is a proven fact at the time of discovery and treatment. We discuss the presentation, pathology, and treatment of the 18th case of a maxillary ameloblastic carcinoma in the literature.

Aged↗

PubMed2003

Neurological aspects of osteopetrosis.

The osteopetroses are caused by reduced activity of osteoclasts which results in defective remodelling of bone and increased bone density. They range from a devastating neurometabolic disease, through severe malignant infantile osteopetrosis (OP) to two more benign conditions principally affecting adults [autosomal dominant OP (ADO I and II)]. In many patients the disease is caused by defects in either the proton pump [the a3 subunit of vacuolar-type H(+)-ATPase, encoded by the gene variously termed ATP6i or TCIRG1] or the ClC-7 chloride channel (ClCN7 gene). These pumps are responsible for acidifying the bone surface beneath the osteoclast. Although generally thought of as bone diseases, the most serious consequences of the osteopetroses are seen in the nervous system. Cranial nerves, blood vessels and the spinal cord are compressed by either gradual occlusion or lack of growth of skull foramina. Most patients with OP have some degree of optic atrophy and many children with severe forms of autosomal recessive OP are rendered blind; optic decompression is frequently attempted to prevent the latter. Auditory, facial and trigeminal nerves may also be affected, and hydrocephalus can develop. Stenosis of both arterial supply (internal carotid and vertebral arteries) and venous drainage may occur. The least understood form of the disease is neuronopathic OP [OP and infantile neuroaxonal dystrophy, MIM (Mendelian inheritance in man) 600329] which causes rapid neurodegeneration and death within the first year. Although characterized by the finding of widespread axonal spheroids and accumulation of ceroid lipofuscin, the biochemical basis of this disease remains unknown. The neurological complications of this disease and other variants are presented in the context of the latest classification of the disease.

Animals↗

PubMed2001

Variations of the arterial pattern in the upper limb revisited: a morphological and statistical study, with a review of the literature.

A total of 192 embalmed cadavers were examined in order to present a detailed study of arterial variations in the upper limb and a meta-analysis of them. The variable terminology previously used was unified into a homogenous and complete classification, with 12 categories covering all the previously reported variant patterns of the arm and forearm.

Aged↗

PubMed2000

Histologic subtyping and malignancy assessment of cutaneous squamous cell carcinoma.

BACKGROUND: Squamous cell carcinomas (SCCs) of the skin have a wide range of histologic subtypes and there are indications of differences in prognosis. OBJECTIVE: The morphologic variety of SCCs with respect to its biological behavior and the further course of disease is analyzed, with emphasis on histopathologic criteria, briefly quoting the main clinical and pathogenetic aspects. METHODS: Referring to the international tumor classification of the World Health Organization, histologically different carcinoma variants are presented and discussed, based on a review of the literature regarding each subtype, and also including the desmoplastic SCC type. RESULTS: Histologically, common invasive SCCs are most frequently found, while metastases mainly occur in tumors of high thickness and poor differentiation. The immature spindle cell carcinoma type resembles sarcoma and may grow rapidly with an aggressive clinical course. Lymphoepithelioma-like carcinoma of the skin is extremely rare and its histogenesis remains to be elucidated. Thus far, one case with metastasis and lethal outcome has been reported. As details determining the progression ability have so far only been scanty and partially contradictory, more investigations are necessary, especially for acantholytic SCCs and invasive SCCs developing from Bowen's disease, whereas verrucous carcinomas can be categorized as low malignancy neoplasms. Desmoplastic SCCs, especially with large tumor thickness, should be separated from other SCC subtypes due to their high risk of local recurrence and metastatic spread. CONCLUSION: The future outcome of SCCs of the skin is significantly influenced by their histologic grade and tumor thickness. In addition, subtyping represents another valuable histopathologic tool for improving the assessment of malignancy.

Bowen's Disease↗

PubMed1953

Multiplication and survival of tubercle bacilli in the organs of mice.

Cultures of tubercle bacilli (typical bovine and human strains) known to differ in the severity of the lesions they induce in experimental animals, were injected in various doses into the cerebrum, peritoneal cavity, or blood stream of mice. Quantitative determinations of the numbers of living bacilli present in the tissues at different intervals of time after infection led to the following classification of the cultures tested:- (a) Certain well known variant forms of tubercle bacilli were found to be unable to multiply in vivo, although they could survive for many weeks in the tissues of mice. These organisms proved to be truly avirulent. (b) Other variant forms underwent multiplication in vivo, even when extremely small infective doses were used, but could not give rise to progressive disease. It is proposed to designate these strains, which produce only abortive infections, as "attenuated." Different levels of attenuation could be detected. The maximum numbers of living bacilli that were recovered from the tissues corresponded directly to the severity and duration of the abortive lesions that could be produced by the strain in guinea pigs or in mice and were characteristic for each strain tested. The two BCG substrains tested were found to differ markedly in their level of attenuation. (c) The cultures virulent for guinea pigs were also capable of establishing a progressive infection in mice even when small infective doses were used. In the case of the attenuated and virulent strains, the population of living bacilli present in the lungs was at first much lower than that in the spleen, but it continued to increase in the former organs throughout the period of observation. This was notably true in the case of the virulent cultures. In contrast, the numbers of living bacilli in the spleen rapidly reached a maximum in the case of all cultures and then decreased progressively. For a given infective dose, and a given interval of time after inoculation, the maximum levels of living bacterial population attained in the spleen and in the lungs proved to be a direct expression of the virulence of the strain.

Animals↗

PubMed1998

The role of alternative splicing of the adhesion molecule, CD44, in lymphoid malignancy.

AIM: To investigate the expression of CD44 isoforms containing variant exon 6 (v6) in a well characterised cohort of patients with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), and to correlate this with phenotype and disease course. METHODS: Cryostat sections of OCT embedded diagnostic nodal material from NHL patients and cryopreserved mononuclear preparations from CLL patients were used as sources of RNA. After reverse transcription, PCR was carried out with amplimers positioned at either side of the variant exon insertion site to amplify all possible CD44 isoforms. Those isoforms containing v6 were identified after Southern blotting and hybridisation with a radiolabelled oligonucleotide. RESULTS: Of 32 NHL samples analysed, 16 did not express CD44 isoforms containing v6, six expressed an isoform containing exon v6 alone, and 10 expressed v6 long isoforms which contained exon v6 in addition to other variant exons. These data did not correlate with lymphoma classification, disease staging, or the presence or absence of extranodal disease. However, those patients expressing v6 long CD44 isoforms had a worse overall survival than those that did not. The plateau of the survival curves was 50% compared with 82%. No v6 long isoforms were detected in the 21 CLL samples investigated. CONCLUSIONS: The expression of v6 long CD44 isoforms is associated with aggressive disease in NHL, independent of grade, stage, or presence of extranodal disease.

Alternative Splicing↗

PubMed2005

Neural models for predicting viral vaccine targets.

We applied artificial neural networks (ANN) for the prediction of targets of immune responses that are useful for study of vaccine formulations against viral infections. Using a novel data representation, we developed a system termed MULTIPRED that can predict peptide binding to multiple related human leukocyte antigens (HLA). This implementation showed high accuracy in the prediction of the promiscuous peptides that bind to five HLA-A2 allelic variants. MULTIPRED is useful for the identification of peptides that bind multiple HLA-A2 variants as a group. By implementing ANN as a classification engine, we enabled both the prediction of peptides binding to multiple individual HLA-A2 molecules and the prediction of promiscuous binders using a single model. The ANN MULTIPRED predicts peptide binding to HLA-A*0205 with excellent accuracy (area under the receiver operating characteristic curve--AROC>0.90), and to HLA-A*0201, HLA-A*0204 and HLA-A*0206 with high accuracy (AROC>0.85). Antigenic regions with high density of binders ("antigenic hot-spots") represent best targets for vaccine design. MULTIPRED not only predicts individual 9-mer binders but also predicts antigenic hot spots. Two HLA-A2 hot-spots in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) membrane protein were predicted by using MULTIPRED.

Algorithms↗

PubMed2003

Antithrombin Phe229Leu: a new homozygous variant leading to spontaneous antithrombin polymerization in vivo associated with severe childhood thrombosis.

There is increasing evidence that serpin conformational alteration caused by single point mutations can be responsible for protein deficiency associated with human diseases. A typical example is the alpha1-antitrypsin deficiency caused by the Z variant carrying a Glu342Lys substitution. Only a few cases of "conformational disease" involving other serpins have been described so far. We investigated a severe antithrombin deficiency in a 13-month-old child with fever and cerebral venous thrombosis. The infant was found to be homozygous for a new antithrombin gene mutation (7396T>C, predicting a Phe229Leu antithrombin variant), and heterozygous for the factor V Leiden mutation. Mild atypical antithrombin deficiency was found in both parents, who were first cousins, asymptomatic, and heterozygous for the same antithrombin gene mutation. The Phe229Leu variant, which does not readily fit into the current classification of antithrombin deficiency, was shown to be a thermolabile antithrombin that spontaneously polymerized in the proband's circulation. This points to a key role for the conserved Phe at position 229, which is near the reactive site loop in a region critical for serpin function and stability. Molecular modeling suggested how the mutation might destabilize this region of the protein and thereby favor reactive site loop insertion and polymerization. This study provides the first direct evidence of antithrombin polymerization in vivo causing antithrombin deficiency and severe thrombotic disease.

Antithrombin III↗

PubMed2006

[Analysis of the relationship between pathology and recurrence of primary lacrimal epithelial tumors].

OBJECTIVE: To analyze the relationship between pathology and recurrence of primary lacrimal epithelial tumors. METHODS: 128 cases of primary lacrimal epithelial tumors including benign mixed tumor (74 cases, 57.8%), adenoid cystic carcinoma (22 cases, 17.2%) and malignant mixed tumor (18 cases, 14.1%) were subjected in the study. Pathological features were analyzed and compared with their recurrence. RESULTS: The recurrent rate of benign mixed tumor, adenoid cystic carcinoma and malignant mixed tumor was 23.0%, 18.2% and 27.8%, respectively. The recurrence of benign mixed tumor was statistically related to pathological classification and encapsulates. CONCLUSIONS: Primary lacrimal epithelial tumors show variant types and high recurrent rate. The pathological features were decisive in diagnosis, selection of treatment and the time of follow-up.

Adult↗

PubMed1990

A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction.

The patients with inherited bleeding diathesis related to quantitative, structural, and/or functional abnormalities of von Willebrand factor (vWF) are said to have von Willebrand's disease (vWD). We report here the clinical and laboratory features of a 50-year-old woman with a life-long history of excessive bleeding. Her particular laboratory data are factor VIII (FVIII) deficiency, subnormal bleeding time, and the presence of all plasma and platelet vWF multimers in normal amounts. Infused with FVIII/vWF concentrate, she showed a persistent increase in FVIII that led us to discard hemophilia A carrier or "acquired hemophilia" diagnoses. vWF devoid of FVIII purified from normal and patient's plasma by immunoaffinity on anti-vWF monoclonal antibody (MoAb) was immobilized onto polystyrene tubes that were further incubated with purified normal FVIII. The bound FVIII was evidenced using radiolabeled anti-FVIII MoAb. The data showed that the patient's vWF, in contrast to vWF purified from normal plasma, was unable to bind FVIII. Furthermore, no inhibitor of FVIII/vWF interaction was evidenced in incubating purified normal vWF with the patient's plasma before the addition of FVIII and anti-FVIII MoAb. These results support the concept that the bleeding diathesis of this patient appears to be due mainly to her abnormal vWF preventing FVIII/vWF interaction. This abnormality, which is not yet described in present classification of vWD, could be considered as a new variant of vWD.

Factor VIII↗

PubMedDate not supplied

Von Willebrand factor and von Willebrand's disease: a complex protein and a complex disease.

Von Willebrand factor is a complex protein which is important in several ways for normal hemostasis. Von Willebrand's disease results when there is either a quantitative or qualitative disorder of von Willebrand factor. In this review, the structure and function of von Willebrand factor are discussed. Additionally, the current laboratory and clinical classification of von Willebrand's disease and closely related variants are outlined.

Factor VIII↗

PubMed2025

CAKL: Commutative algebra k-mer learning of genomics.

Despite the availability of various sequence analysis models, comparative genomic analysis remains a challenge in genomics, genetics, and phylogenetics. Commutative algebra, a fundamental tool in algebraic geometry and number theory, has rarely been used in data and biological sciences. In this study, we introduce commutative algebra k-mer learning (CAKL) as the first-ever nonlinear algebraic framework for analyzing genomic sequences. CAKL bridges between commutative algebra, algebraic topology, combinatorics, and machine learning to establish a new mathematical paradigm for comparative genomic analysis. We evaluate its effectiveness on three tasks-genetic variant identification, phylogenetic tree analysis, and viral genome classification-typically requiring alignment-based, alignment-free, and machine-learning approaches, respectively. Across eleven datasets, CAKL outperforms five state-of-the-art sequence analysis methods, particularly in viral classification, and maintains stable predictive accuracy as dataset size increases, underscoring its scalability and robustness. This work ushers in a new era in commutative algebraic data analysis and learning.

Journal Article↗