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At least 217 records · Page 12Linked to original sources
PubMed2005

Functional brain imaging in hemicrania continua: implications for nosology and pathophysiology.

Hemicrania continua is a strictly unilateral, continuous headache of mild to moderate intensity, with superimposed exacerbations of moderate to severe intensity that are accompanied by trigeminal autonomic features and migrainous symptoms. The syndrome is exquisitely responsive to indomethacin. Its clinical phenotype overlaps with that of the trigeminal autonomic cephalalgias and migraine, in which the hypothalamus and the brain stem, respectively, have been postulated to play central pathophysiologic roles. A recent positron-emission tomography study of a cohort of patients with hemicrania continua demonstrated significant activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons in association with the headache of hemicrania continua. In addition, there was activation of the ipsilateral ventrolateral midbrain, which extended over the red nucleus and the substantia nigra and bilateral pontomedullary junction. No intracranial vessel dilatation was obvious.

Brain↗
PubMed1995

Genetic evidence against a morphologically suggestive conspecificity of Dermacentor reticulatus and D. marginatus (Acari:Ixodidae).

International Journal for Parasitology 25: 1413-1419. Dermacentor reticulatus and D. marginatus exhibit overlapping phenotypes. The possibility of conspecificity was investigated on the nucleotide level by comparing DNA sequences of the second internal transcribed spacer (ITS 2) of the rDNA gene. The inter-specific polymorphism was more than 20-times greater than the intra-specific polymorphism of 3 D. reticulatus strains of different geographic origins. Furthermore, the degree of polymorphisms between D. reticulatus and D. marginatus was found to be of the same order of magnitude as that between D. andersoni and D. variabilis, for which separate species status is accepted. These genomic findings do not support a possible conspecificity of D. reticulatus and D. marginatus.

Animals↗
PubMed1992

Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma.

The immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case.

Adrenal Cortex Neoplasms↗
PubMedDate not supplied

Clinical and EEG findings in eleven patients affected by mitochondrial encephalomyopathy with MERRF-MELAS overlap.

A study of mitochondrial DNA disease was carried out on 12 members belonging to three generations of a family from northern Sardinia. On the basis of the diagnostic criteria currently used in the classification of mitochondrial diseases a typical MERRF-MELAS overlap phenotype was seen in 11 patients with the mtDNA tRNA(lys) mutation at nucleotide position 8356. Clinical and instrumental investigations (EEG in particular) were made. Patients were divided into two groups: severely and mildly affected cases. The follow-up was reported. The aim of this study was to identify, through EEG, the early signs of the disease. The EEG findings recorded during the clinical evolution allowed us to recognize four degrees of cerebral involvement, and could also suggest the prognosis.

Adolescent↗
PubMed2006

Two neurofibromatosis type 1 cases associated with rhabdomyosarcoma of bladder, one with a large deletion in the NF1 gene.

Neurofibromatosis type 1 (NF1) is the most common neurogenetic disorder, affecting approximately 1 in 3,500 individuals worldwide. Mutations of the NF1 tumor suppressor gene predispose individuals to a variety of benign and malignant tumors. Rhabdomyosarcoma (RMS) is an uncommon malignant soft tissue sarcoma and is also a rare tumor type in NF1 patients. We report two cases of NF1 with RMS. The first is that of an infant with overlapping phenotypic features of NF1 and Noonan syndrome (NS) who presented with RMS of the bladder. The second infant likewise exhibited NF1 features and was also associated with bladder RMS. DNA samples were extracted from peripheral blood and tumor tissue samples. We performed loss of heterozygosity (LOH) analysis of the NF1 gene by using seven intragenic markers (IVS27AAAT2.1, IVS27EVI-20, IVS27AC24.8, IVS27AC28.4, M98509, IVS27AC33.1, IVS38TG53.0) and one extragenic polymorphic marker (3'NF1). A large deletion was detected in the NF1 gene in the NF1-Noonan syndrome (NF-NS) case associated with RMS.

Gene Deletion↗
PubMed2025

Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder.

PURPOSE: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date. METHODS: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning. RESULTS: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We found an overlapping phenotype, consistent with a monogenic neurodevelopmental disorder. We demonstrate XPO1 functions in development by ubiquitous and neuron-specific knockdown in Drosophila. GABAergic neuron specific knockdown flies demonstrated impaired habituation. CONCLUSION: Our results establish XPO1 as a novel dominant monogenic neurodevelopmental disorder gene and demonstrate a central role for XPO1 in development.

Exportin 1 Protein↗
PubMed2005

Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma.

Distinguishing renal oncocytoma from chromophobe and other renal carcinomas is essential, considering their differing biological potentials. Although renal oncocytoma is considered a benign tumor, chromophobe renal cell carcinoma has potentially malignant biological behavior. The numerous reported studies on distinguishing these 2 entities have been based on morphological, histochemical, immunohistochemical, ultrastructural, and cytogenetic features. But none of these features has proven to be reliably specific, especially in tumors with overlapping phenotypes. We report a novel immunohistochemical approach based on the expression of a recently described kidney-specific cadherin (Ksp-cadherin) for the differential diagnosis of these 2 tumors. We compared Ksp-cadherin expression in 212 renal tumors, including 102 clear cell renal carcinomas, 46 papillary renal cell carcinomas, 30 chromophobe carcinomas, 3 collecting duct carcinomas, and 31 oncocytomas. In addition, we examined the expression of epithelial membrane antigen, vimentin, CK7, and Hale's colloidal iron staining. We found that chromophobe renal cell carcinomas consistently (96.7% of cases) demonstrated a distinctive membrane pattern of Ksp-cadherin expression, whereas renal oncocytomas (3.2%), clear cell renal cell carcinomas (0%), papillary renal cell carcinomas (2.2%), and collecting duct carcinomas (0%) usually did not express Ksp-cadherin. CK7 expression was found in 90.0%, 6.5%, 7.8%, 76.1%, and 33.3% of these tumor cases, respectively. Whereas CK7 was detected in different types of renal cell carcinomas, Ksp-cadherin was expressed almost exclusively in chromophobe renal cell carcinomas. Immunohistochemical analysis of Ksp-cadherin offers a fast, reliable approach for the distinguishing between renal oncocytoma and chromophobe renal cell carcinoma that is applicable for routine pathology laboratory studies without the need for time-consuming and costly ancillary studies.

Adenocarcinoma↗
PubMed2006

Hereditary woolly hair and keratosis pilaris.

We describe a family with woolly hair and ulerythema ophryogenes spanning four generations. Both woolly hair and ulerythema ophryogenes have been associated with Noonan syndrome and cardiofaciocutaneous syndrome (CFC), two disorders with considerable phenotypic overlap. This family did not exhibit any of the other findings characteristic of either Noonan syndrome or CFC, similar to a previously described pedigree with hereditary woolly hair. Woolly hair elicits a broad differential diagnosis, including woolly hair nevus and several genodermatoses. Our report reviews the evaluation of woolly hair and discusses the conditions associated with this physical finding.

Child, Preschool↗
PubMed2005

Increased T2 signal in the middle cerebellar peduncles on MRI is not specific for fragile X premutation syndrome.

The fragile X premutation tremor/ataxia syndrome (FXTAS) is a recently described adult-onset neurodegenerative disorder, in which ataxia, tremor, cognitive decline, parkinsonism, neuropathy and autonomic dysfunction occur in various combinations. It is reported to display a characteristic MRI appearance, with increased T2 signal in the middle cerebellar peduncles and around the dentate nuclei. Diagnostic criteria have been proposed on the basis of these clinical and radiological features, presupposing that a CGG expansion has been demonstrated. We present three cases in which MRI and clinical findings suggested the possibility of FXTAS, although only one was confirmed on genetic testing. The phenotypic overlap with multiple system atrophy of cerebellar type (MSA-C) and the importance of genetic confirmation are emphasised.

Adult↗
PubMed2004

A-type nuclear lamins, progerias and other degenerative disorders.

Nuclear lamins were identified as core nuclear matrix constituents over 20 years ago. They have been ascribed structural roles such as maintaining nuclear integrity and assisting in nuclear envelope formation after mitosis, and have also been linked to nuclear activities including DNA replication and transcription. Recently, A-type lamin mutations have been linked to a variety of rare human diseases including muscular dystrophy, lipodystrophy, cardiomyopathy, neuropathy and progeroid syndromes (collectively termed laminopathies). Most diseases arise from dominant, missense mutations, leading to speculation as to how different mutations in the same gene can give rise to such a diverse set of diseases, some of which share little phenotypic overlap. Understanding the cellular dysfunctions that lead to laminopathies will almost certainly provide insight into specific roles of A-type lamins in nuclear organization. Here, we compare and contrast the LMNA mutations leading to laminopathies with emphasis on progerias, and discuss possible functional roles for A-type lamins in the maintenance of healthy tissues.

Aging↗
PubMed1976

A "community" of face-limb malformation syndromes.

A boy with faciodigital malformations is reported who bears a striking resemblance to Charlie M, a patient described by Gorlin as representing a new syndrome, and to two other previously reported patients. One may interpret this as supporting the validity of the "Charlie M" syndrome as a nosologic entity. However, these patients share a number of features with several other face-limb malformation syndromes. We suggest that these syndromes form a "community," in which the overlapping phenotypes of the member syndromes reflect underlying developmental relationships.

Abnormalities, Multiple↗
PubMed1982

Apert's syndrome--a report of five cases.

This report presents five cases of Apert's syndrome with features of acrocephaly, characteristic face and complete syndactyly of the hand and foot with bony fusion. Three cases out of five showed preaxial polydactylies of the foot, considered to be one of the characteristic features of Carpenter's syndrome. In the remaining two cases, the first digital ray of the foot was broad and deformed. In addition one case had a postaxial polydactyly of the hand. Three cases showed severe deformity of the shoulder; two had dysplasia and one had synchondrosis of the glenohumeral joint. On the basis of our findings in this, we feel that there is much phenotypic overlap between Apert's and Carpenter's syndrome. A polydactylous presentation of the hand and foot can be found in not a few cases of Apert's syndrome and it is not always an exclusive feature of Carpenter's syndrome.

Acrocephalosyndactylia↗
PubMed2000

Identification of a novel PTEN intronic deletion in Li-Fraumeni syndrome and its effect on RNA processing.

Germline mutations of the TP53 tumor suppressor gene account for the predisposition to cancer observed in many Li-Fraumeni syndrome (LFS) families. A causative genetic factor in the remaining families that harbor no TP53 mutations remains to be elucidated. The PTEN phosphatase tumor suppressor gene is mutated in human cancers observed in LFS. There also exists some phenotypic overlap in the occurrence of cancers in LFS and Cowden's disease (CD), for which germline PTEN mutations are believed to be responsible. We hypothesized that PTEN may be altered in some TP53-wild-type LFS families. We examined LFS primary patient lymphocytes for PTEN alterations using SSCP and sequence analysis. A novel intronic deletion was found in two unrelated individuals, adjacent to the splice acceptor site of PTEN exon 4. Based on an in vitro mRNA processing assay this alteration is predicted to be a polymorphism. The in vivo effects of this proximal splice site deletion are unknown and a genetic cause for the cancers in these families remains to be elucidated. Germline mutations of PTEN were not detected in other families, suggesting that alterations of this tumor suppressor gene do not account for the cancers observed in the subset of LFS individuals with wild-type germline TP53.

Base Sequence↗
PubMed2000

Alkaline phosphatase expression during monocyte differentiation. Overlapping markers as a link between monocytic cells, dendritic cells, osteoclasts and osteoblasts.

Human monocytes (Mo) in culture can be differentiated into macrophages (M phi), dendritic cells (DC) and osteoclasts. In addition, we have established a Mo-derived in vitro granuloma model which here was compared with ex-vivo isolated foreign body granuloma cells. In these models overlapping phenotypes developed between monocyte-derived dendritic cells (MoDC), osteoclasts, M phi, and osteoblasts. In Mo cultures granulomas were induced by immobilized particulate material. AP activity (osteoblast marker) was found to be co-expressed with cytoplasmic tartrate resistant acid phosphatase (TRAP) as a marker of osteoclasts. While proliferating, the number of AP+ cells decreased, being replaced by cells co-expressing the osteoclast markers vitronectin receptor (VNR) and TRAP. Coexpression of the Mo/M phi marker CD68 with AP or VNR confirmed the monocytic origin of the cells. When Mo were treated with interleukin-4 (IL-4), the number of AP+ cells markedly increased and remained stably expressed over 12 days. In explants from ex vivo granulomas obtained from endoprosthetic revisions the major cell type was the AP+ cell co-expressing CD68. The bone-specific alkaline phosphatase (BAP) as a marker of osteoblasts was detected by FACS analysis in the ex vivo granuloma cells. By RT-PCR the mRNA for osteocalcin, which is a highly specific marker for osteoblasts, was detected. From our results we conclude an ontogenetic relationship between macrophages, DC and osteoclasts. Furthermore, the data suggest a transdifferentiation between Mo and osteoblasts.

Alkaline Phosphatase↗
PubMed2004

Secretin for refractory schizophrenia.

In preliminary uncontrolled studies, intravenous injection of the gastrointestinal peptide secretin produced improvements in the symptoms of autism. Because of the phenotypic overlap between autism and some aspects of schizophrenia, we performed a pilot study of secretin for treatment refractory schizophrenia. Twenty-two patients were randomized to a single intravenous dose of porcine secretin or placebo. Patients were evaluated with the Positive and Negative Symptom Scale for Schizophrenia (PANSS) and the Clinical Global Impression Scale (CGI) at baseline, 2 days after secretin infusion and weekly for 4 weeks. There were no statistically significant differences between drug- and placebo-treated patients with repeated measures analysis of variance (ANOVA). However, several patients treated with secretin experienced clinically meaningful, but transient, reductions in symptoms and a greater percentage of patients treated with secretin were rated as improved with the CGI. Further study of brain hypocretins and molecules affecting this system are warranted in schizophrenia.

Adult↗
PubMed2002

Diagnosis of five spinocerebellar ataxia disorders by multiplex amplification and capillary electrophoresis.

The autosomal-dominant spinocerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders with variable expression and phenotypic overlap. An accurate diagnosis relies on detection of a mutation in a specific causative gene, which is typically an abnormal number of CAG trinucleotide repeats. To streamline testing in a clinical setting, we converted our current panel of tests for the spinocerebellar ataxias (SCA) types SCA1, SCA2, SCA3, SCA6, and SCA7 from five independent amplification reactions analyzed by polyacrylamide gel electrophoresis (PAGE) to a single multiplex amplification reaction analyzed by capillary electrophoresis (CE). Multiplex amplification was facilitated by the use of chimeric primers; different lengths and fluorochromes distinguished the amplicons. During CE with commercially available molecular weight standards, the SCA amplicons migrated faster than predicted, thereby underestimating their length compared to that determined previously by PAGE. This was observed to varying degrees for each of the five loci, with the greatest size differential occurring in amplicons with greater (CAG)(n). To determine accurate amplicon length, and therefore an accurate number of CAG repeats, a size correction formula was calculated for each locus. This multiplex semi-automated assay has been reliable during 1 year of use in a clinical setting during which 57 samples were tested and five positive samples were detected.

Ataxin-1↗
PubMed1998

Aberrant phenylalanine metabolism in phenylketonuria heterozygotes.

The wide variation in phenylalanine hydroxylating capacity observed among patients with phenylketonuria (PKU) is primarily due to allelic heterogeneity at the phenylalanine hydroxylase (PAH) locus. In this study, we examined phenylalanine metabolism after an oral phenylalanine load in 148 carriers of known PAH gene mutations. As a group, heterozygotes formed less tyrosine than normozygotes (p < 0.001), and there was a tendency that carriers of a severe PAH mutation formed less tyrosine than carriers of a mild mutation. Nevertheless, the interindividual variation was extensive, and we identified a group of individuals who formed no or very little tyrosine after the phenylalanine load. This tyrosine response was accompanied by a decreased ability to eliminate the phenylalanine test dose but did not correlate with the intrinsic severity of the mutant PAH allele. Examination of the entire coding region of the PAH gene revealed no additional sequence alterations in these subjects. Our data suggest that a subset of PKU heterozygotes have reduced phenylalanine hydroxylating capacity approaching or equalling the levels observed in genetic compounds with non-PKU mild hyperphenylalaninaemia (MHP). Awareness of this phenotypic overlap between PKU carriers and genetic compounds with two mutant alleles may be useful for clinicians and paediatricians involved in diagnosis and genetic counselling.

Adult↗
PubMed2002

Insights from mouse models of absence epilepsy into Ca2+ channel physiology and disease etiology.

1. Changes in intracellular Ca2+ ([Ca2+]i) levels provide signals that allow neurons to respond to a host of external stimuli. A major mechanism for elevating [Ca2+]i is the influx of extracellular Ca2+ through voltage-gated channels (Ca(V)) in the plasma membrane. Malfunction in Ca(V) due to mutations in genes encoding channel proteins are increasingly being implicated in causing disease conditions, termed channelopathies. 2. Seven spontaneous mutations with cerebellar ataxia and generalized absence epilepsy have been identified in mice (tottering, leaner, rolling Nagoya, rocker, lethargic, ducky, and stargazer), and these overlapping phenotypes are directly related to mutations in genes encoding the four separate subunits that together form the multimeric neuronal Ca(V) complex. 3. The discovery and systematic analysis of these animal models is helping to clarify how different mutations affect channel function and how altered channel function produces disease.

Animals↗