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PubMed2004

Local field potentials and spiking activity in the primary auditory cortex in response to social calls.

The mustached bat, Pteronotus parnellii, uses complex communication sounds ("calls") for social interactions. We recorded both event-related local field potentials (LFPs) and single/few-unit (SU) spike activity from the same electrode in the posterior region of the primary auditory cortex (AIp) during presentation of simple syllabic calls to awake bats. Temporal properties of the LFPs, which reflect activity within local neuronal clusters, and spike discharges from SUs were studied at 138 recording sites in six bats using seven variants each of 14 simple syllables presented at intensity levels of 40-90 dB SPL. There was no clear spatial selectivity to different call types within the AIp area. Rather, as shown previously, single units responded to multiple call types with similar values of the peak response rate in the peri-stimulus time histogram (PSTH). The LFPs and SUs, however, showed a rich temporal structure that was unique for each call type. Multidimensional scaling (MDS) of the averaged waveforms of call-evoked LFPs and PSTHs revealed that calls were better segregated in the two-dimensional space based on the LFP compared with the PSTH data. A representation within the "LFP-space" revealed that one of the dimensions correlated with the predominant and fundamental frequency of a call. The other dimension showed a high correlation with "harmonic complexity" ("fine" spectral structure of a call). We suggest that the temporal pattern of LFP and spiking activity reflects call-specific dynamics at any locus within the AIp area. This dynamic contributes to a distributed (population-based) representation of calls. Alternatively stated, the fundamental frequency and harmonic structure of calls, and not the recording location within the AIp, determines the temporal structure of the call-evoked LFP.

Acoustic Stimulation↗
PubMed2004

Identification of transthyretin variants by sequential proteomic and genomic analysis.

BACKGROUND: Transthyretin-associated hereditary amyloidosis (ATTR) is an inherited disease in which variants in the primary structure of transthyretin (TTR; prealbumin) lead to the extracellular polymerization of insoluble protein fibrils, causing organ failure and ultimately death when major organs are involved. We have developed an integrated approach to molecular diagnosis with initial analysis of intact plasma TTR by electrospray ionization mass spectrometry (MS) and referral of positive samples for DNA sequence analysis and real-time PCR to confirm the common Gly6Ser polymorphism. METHODS: Samples from 6 patients previously diagnosed with ATTR and from 25 controls with (n = 15) or without (n = 10) polyneuropathy were analyzed in a blinded fashion for the presence of variant TTR. TTR protein was extracted with an immunoaffinity resin from 20 microL of archived plasma samples. The purified TTR was reduced with tris(2-carboxyethyl)phosphine and analyzed by MS. The appearance of two peaks (or a single peak shifted in mass indicative of a homozygous variant), including the wild-type mass of 13,761 Da, was indicative of the presence of a variant, and the individual was referred for DNA sequence analysis. RESULTS: MS analysis of intact reduced TTR correctly identified each of six samples known to contain variant TTR. These results were corroborated by subsequent DNA sequence analysis. Additionally, all Gly6Ser polymorphisms were correctly called based on the +30 mass shift and an equal relative abundance of the +30 polymorphism relative to wild-type TTR. No false-positive results were seen. CONCLUSIONS: This referral method eliminates the necessity of sequencing most samples and allows screening for the familial forms of amyloidosis in a broad patient population in a timely fashion. This method correctly identified all previously known variants and also identified a novel variant, Val94Ala.

Amyloidosis, Familial↗
PubMed1996

Solid variant of an aneurysmal bone cyst (giant cell reparative granuloma) of the 3rd lumbar vertebra.

A 9-year-old girl with a solid variant of an aneurysmal bone cyst in the 3rd lumbar vertebra showed a good response to low-dose radiation as the only treatment. The solid variant of aneurysmal bone cyst is thought to be a reactive response to intraosseous hemorrhage and is also called giant cell reparative granuloma or giant cell reaction. These lesions in the jaw and the short tubular bones of the hands and feet frequently recur after surgery. Aneurysmal bone cysts of the spine also show a fairly high recurrence rate after incomplete resection or radiation therapy. However, 7 previous cases of the solid variant of aneurysmal bone cyst in the spine and this case did not show recurrence after a mean follow-up period of 45 months. This difference in behaviour suggests that the solid variant should be recognized before surgery as being distinct from conventional aneurysmal bone cysts, especially in the spine.

Bone Cysts, Aneurysmal↗
PubMed2002

Differential regulation of a novel variant of the alpha(6) integrin, alpha(6p).

We have reported previously the existence of an M(r) 70,000 form of the alpha(6) integrin called alpha(6p) in a variety of human epithelial cell lines. Four different experimental conditions were used to examine the regulation of alpha(6) and alpha(6p) integrin. The production of the alpha(6) integrin was decreased by 45% using a protein translation inhibitor (2.25 microM puromycin), whereas production of the alpha(6p) variant was unaffected. The alpha(6p) variant was decreased 60% by actin depolymerization (10 microM cytochalasin D) corresponding to a decrease in its surface expression, whereas alpha(6) integrin production was unaffected. The alpha(6p) variant was resistant to endoglycosidase H treatment, whereas the alpha(6) integrin was both sensitive and resistant to endoglycosidase H treatment, indicating retention in the endoplasmic reticulum and processing through the Golgi apparatus. Additionally, digestion by endoglycosidase F demonstrated both alpha(6p) and alpha(6) integrin contained NH(2)-linked glycosylations and both shifted M(r) approximately 10,000 on enzymatic digestion. Finally, inhibition of serine/threonine phosphatases by either calyculin A (15 nM) or okadaic acid (62 microM) did not affect alpha(6p), whereas the production of alpha(6) integrin was decreased by 50%. These data suggest that the production of the alpha(6p) variant is distinct from alpha(6) integrin and may involve a post-translational processing event at the cell surface.

Actins↗
PubMed1994

[Can magnets or additional intermaxillary forces improve the mode of action of jumping-the-bite plates?].

The use of accessory intermaxillary elastic traction or magnets during bite jumping appliance therapy marks a significant improvement in patient treatment. The use of interarch traction results in 100% mouth closure during the night, which is independent of the patient's sleeping position. During the night the guide pegs are subjected to almost no stress, which guarantees a quick adaptation. Additional intermaxillary traction does call for anchoring procedures in the maxillary anterior (torque springs) and mandibular molar region (clasps). According to the dental situation, the application of dynamic force can be withdrawn for a transitory period of time. Use of additional magnets in the anterior, depending on sleeping position, leads to complete mouth closure in up to 70 to 90% of the cases. Extensive measures in the mandibular and maxillary anterior areas must be considered when using this variant. In many cases the application of brackets is an absolute necessity. However, when the dental situation calls for it, magnets cannot be deactivated. All magnets in use today corrode very easily. It is, therefore, recommended that magnets used interorally be especially well shielded. Leaky capsules must considered especially problematic. Correct adjustment in the sagittal plane does not in any case guarantee stabilization. Only when a 3- or 4-stage bite has been reached, can it be said that a good adjustment in the neuromuscular masticatory pattern has been achieved. Depending on patient compliance, this period can be significantly drawn out. A functional analysis is not a suitable method for analyzing an extant stable result. With both of these modifications there is a tendency to greater dentoalveolar effect and diminished influence on the skull. The issue of whether magnets have no place in orthodontics, as Gianelly [3] claims, cannot be definitively answered, however, it can be said that intermaxillary traction, especially when force is applied by using super-elastic springs, is less expensive, demonstrates a better effectiveness, and it is much easier to use.

Activator Appliances↗
PubMed2002

Isolation of a novel mouse variant of the drs tumor suppressor gene.

The drs gene was isolated as a transformation suppressor against the v-src oncogene. Drs protein has a transmembrane domain and three consensus repeats (CRs) called Sushi motifs in the extracellular domain. The drs gene also has the ability to suppress anchorage-independent growth of human cancer cell lines. In this paper, we report the isolation of a novel variant cDNA of mouse drs (mDRS-2) containing two CRs, in addition to a mouse homolog of drs (mDRS-1) containing three CRs. We investigated the suppressor function of these mDRS cDNAs in human cancer cells and found that the lack of one CR is critical for suppression of anchorage-independent growth by drs.

3T3 Cells↗
PubMed1998

[Atraumatic procedures in common abdominal operations].

The surgical tactics and technical improvements are discussed against the background of personal experience with some common abdominal operations, among which the appendectomy variant leaving the cecum intra-abdominally and using chain retrograde ligature in some cases, with choice of access according to the requirements of the individual case. Special attention is called to retrocecal extraperitoneal complications and Meckel's diverticulum--clinical picture and operative tactics. Emphasis is laid on the advantages of intestinal anastomoses--latero-lateral variant, termino-terminal technique in colo-colostomy and possibilities of latero-terminal sigmoidorectoanastomosis.

Abdomen↗
PubMed1997

Secretory meningioma: clinical, histologic, and immunohistochemical findings in 31 cases.

BACKGROUND: Secretory meningioma is a rare histologic variant characterized by a unique epithelial differentiation of meningothelial cells resulting in the production of hyaline inclusions. Most previous reports have presented single case observations. The authors selected 31 cases for a clinicopathologic study to characterize this type of tumor further. METHODS: Clinical data were compiled and the extent of peritumoral edema was assessed from preoperative computed tomography or magnetic resonance imaging scans. Preparations of surgical specimens of all tumors were studied after both conventional histologic and immunohistochemical preparations were made. Immunostaining was performed by either the avidin-biotin complex method or the alkaline phosphatase-antialkaline phosphatase method using 22 primary antibodies. RESULTS: In the tumor collection used in this study, secretory meningiomas represented 3% of meningiomas. The female-to-male ratio was 9:1. Most tumors were located at the sphenoid ridge or at the frontal convexity, and recurrences were not observed. Eighty-four percent of tumors presented with slight to marked peritumoral edema. The MIB-1 staining index showed a mean of 3.8%. Inclusions and surrounding cells consistently expressed epithelial membrane antigen, cytokeratins, carcinoembryonic antigen, and carbohydrate antigen 19-9. In decreasing frequency, they also contained alpha1-antitrypsin, immunoglobulin (Ig)A, alpha1-antichymotrypsin, IgM, and IgG. Cells positive for vimentin and S-100 did not contain inclusions. All tumors were positive for progesterone receptors. Macrophages were stained with antibodies to factor XIIIa, human leukocyte antigen-DR, and alpha1-antitrypsin. In 64% of cases, tumor vessels lacked expression of glucose transporter protein 1. CONCLUSIONS: The classification of secretory meningioma as a distinct variant has been justified on clinical, histologic, and immunohistochemical grounds. The unique epithelial features call attention to the broad spectrum of differentiation properties found in meningiomas.

Adult↗
PubMed1999

Clinical features, evaluation, and treatment of patients with polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS).

A number of common disorders of the peripheral nervous system are closely linked to a monoclonal gammopathy. In a minority of patients, the neuropathy represents the sentinel feature of a malignant plasma cell dyscrasia, such as multiple myeloma or its osteosclerotic variant, Waldenstrom's disease, amyloidosis, cryoglobulinemia or lymphoma; the vast majority have so-called "monoclonal gammopathy of undetermined significance" (MGUS). Sensory symptoms predominate with paresthesias, numbness, imbalance, and gait ataxia. Electrodiagnostic studies show mixed demyelinating and axonal features and often may be indistinguishable from findings in chronic inflammatory demyelinating polyneuropathy. Some have a pure axonal polyneuropathy, and in these patients the relationship to the paraprotein is less certain. With limited success, correlations have been made between the immunoglobulin type (IgM, IgG, or IgA) and the clinical and electromyographic characteristics of the neuropathy. The treatment of MGUS neuropathies poses a considerable challenge. Patients with IgG/IgA-MGUS have improved with corticosteroids or intravenous immune globulin. Only the benefit of plasma exchange has been substantiated in a controlled trial. The IgM neuropathies tend to be more refractory but often improve with similar regimens, particularly if cytotoxic agents are added in doses sufficient to reduce the amount of the M-protein. In addition to plasma exchange, chlorambucil, and cyclophosphamide, interferon-alpha is a novel therapy that holds promise for patients with IgM neuropathies associated with anti-myelin associated antibodies.

Antibody Specificity↗
PubMed2004

First report of a microcystin-containing bloom of the cyanobacteria Microcystis spp. in Lake Oubeira, eastern Algeria.

Lake Oubeira has been used as the main source of drinking water for many communities in the East of Algeria. In this lake, nutrient loading coupled with year-round warm weather favors the growth of cyanobacteria, several of which can produce cyanotoxins, especially the potent liver toxins called microcystins (MCYSTs). The present study evaluated microcystin levels and characterized the different microcystin variants present in the raw water during a 17-month period (April 2000-September 2001), as measured by protein phosphatase inhibition assays and by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, respectively. The results showed that microcystin concentrations in the lake water varied between 3 and 29,163 microg microcystin-LR equivalent per liter. The microscopic examination of the phytoplankton samples showed the dominance of the Microcystis genus in the cyanobacterial bloom. The highest MCYST concentration was observed in August 2001, at 29,163 microg/l. Therefore, the highest total MCYST content per phytoplankton biomass was found in August 2001, with 4,590 microg MCYST-LR equivalents/g dried bloom material. Analysis of the field bloom extract by MALDI-TOF mass spectrometry demonstrated the presence of four variants of microcystins: microcystin-LR (MCYST-LR), microcystin-YR (MCYST-YR), microcystin-RR (MCYST-RR), and a demethylated variant of MCYST-LR (D-MCYST-LR).

Algeria↗
PubMedDate not supplied

Immunochemical analysis of a snake venom phospholipase A2 neurotoxin, crotoxin, with monoclonal antibodies.

Crotoxin is the major neurotoxic component of the venom of the South American rattlesnake, Crotalus durissus terrificus. The crotoxin molecule is composed of two subunits: a basic and weakly toxic phospholipase A2 (PLA2) called component-B (CB), and an acidic, nonenzymatic and nontoxic subunit called component-A (CA). Crotoxin exists as a mixture of several isoforms (or variants) resulting from the association of several subunit isoforms. We prepared monoclonal antibodies (MAbs) against each isolated subunit. Six anti-CA MAbs and eight anti-CB MAbs were tested for their cross-reactivities with each subunit and with other toxic and nontoxic PLA2s. Four of the six anti-CA MAbs cross-reacted with CB, whereas only one of the eight anti-CB MAbs cross-reacted with CA. Two anti-CB MAbs were found to cross-react with agkistrodotoxin, a single chain neurotoxic PLA2 purified from the venom of Agkistrodon blomhoffii brevicaudus. We determined the dissociation constants of each MAb for CA and CB isoforms and their capacities to neutralize the lethality and to inhibit the catalytic activity of crotoxin. We defined three epitopic regions on CA and four on CB, and used a schematic representation of the two subunits to characterize these epitopic regions with respect to: (1) the "toxic" and the "catalytic" sites of CB, and (2) the zone of interaction between the two subunits. We propose three-dimensional structures of the crotoxin subunits in which we localize amino acid residues that might be involved in the epitopic regions described here.

Amino Acid Sequence↗
PubMedDate not supplied

Pulsed cytochrome c oxidase.

The identification of two functionally distinct states, called pulsed and resting, has led to a number of investigations on the conformational variants of the enzyme. However, the catalytic properties of cytochrome oxidase may depend on a number of experimental conditions related to the solvent as well as to the protocol followed to determine the turnover number of the enzyme. This paper reports results which illustrate that the steady-state differences between pulsed and resting oxidase may, or may not, be detected depending on experimental conditions.

Animals↗
PubMed2004

Social behavior: how do fish find their shoal mate?

Fish form social aggregations called shoals which often consist of fish with similar morphologies. Experiments using zebrafish pigment variants demonstrate that fish can select shoal mates solely on the basis of their color patterns, and that early experience plays a key role in determining these shoaling preferences.

Animals↗
PubMed2001

Osteolipoma of the tongue.

Lipomas are common, benign tumours located in any part of the body in which fat is normally present. Some variants of lipoma have been described according to the type of tissue present. A rare variant consists of a lipoma with osseous or cartilaginous metaplasia. These lesions have been called chondrolipoma, osteolipoma, lipoma with chondroid or osseous metaplasia, lipoma with cartilaginous or osseous change, or ossifying lipoma. We present the case of an osteolipoma of the tongue in a 49-year-old female who was referred for a painless mass on the left lateral margin of the tongue, and present for about 8 years. Osteolipomas have been reported in middle-aged or elderly patients with a very long clinical history. These tumours tend to be large and to arise from the deep soft or subcutaneous tissues. The cartilage and bone is probably produced by metaplasia of fibroblasts in chondroblasts or osteoblasts. These lesions are benign and do not recur.

Diagnosis, Differential↗
PubMed1999

Human ubiquitous JCV(CY) T-antigen gene induces brain tumors in experimental animals.

JCV is a papovavirus which is widespread in the human population. The prototype Mad-1 variant of JCV induces a fatal demyelinating disease of the central nervous system (CNS) called Progressive Multifocal Leukoencephalopathy (PML) in immunosuppressed individuals. The unique tropism of JCV (Mad-1) to the CNS is attributed to the tissue-specific regulation of the viral early promoter which is responsible for the production of the viral regulatory protein, T-antigen. The archetype form of this virus, JCV(CY), which has been repeatedly isolated from the urine of PML and non-PML individuals, is distinct from JCV(Mad-1) in the structural organization of the regulatory sequence. To characterize the tissue specific expression of JCV(CY) and to investigate its potential in inducing disease, transgenic mice containing the early region of JCV(CY) were generated. Some of these mice between 9-13 months of age exhibited signs of illness as manifested by paralysis of rear limbs, hunched posture, and poor grooming. Neuropathological examination indicated no sign of hypomyelination of the brain, but surprisingly, revealed the presence of primitive tumors originating from the cerebellum and the surrounding brain stem. The tumor masses also infiltrated the surrounding tissue. Results from RNA and protein studies revealed a high level of T-antigen mRNA expression in hindbrains of clinically normal and affected transgenic mice. However, higher levels of T-antigen RNA and protein were detected in brains of the animals exhibiting severe illness. The close resemblance of JCV(CY) induced tumor in transgenic mice to the human medulloblastoma/primitive neuroectodermal tumor (PNETs) in location, histologic appearance, and expression of marker proteins strongly suggests the utility of this novel animal model for the study of human brain tumors.

Animals↗
PubMed2001

WNK kinases, a novel protein kinase subfamily in multi-cellular organisms.

We have cloned and characterized a novel human serine/threonine protein kinase gene from chromosome 12p13.3 encoding 2382 amino acids. Remarkably, the catalytic domain sequence contains a cysteine in place of a lysine residue conserved in subdomain II of most kinases. The same amino acid alteration was recently described for rat WNK1 (with no K=lysine) in which another nearby lysine residue was shown to confer kinase activity to the protein. Rat WNK1 is 85% identical to a splice variant lacking exons 11 and 12 of the described human kinase which we have called human WNK1. The WNK1 catalytic domain has closest homology with human PAK2, MEKK3, and Raf-1. Three additional, partial human protein kinase sequences, WNK2, WNK3 and WNK4, are also reported here with catalytic domains that are 95% homologous to WNK1. These genes differ both in chromosomal location and tissue-specific expression. Moreover, we have identified in the database a total of 18 WNK-related genes, all exclusively from multi-cellular organisms, which share a WNK kinase sequence signature within subdomains I and II of the catalytic domain. We suggest that they constitute a novel subfamily of protein kinases that evolved together with cell adhesion and tissue-formation.

Amino Acid Motifs↗
PubMed2002

Endocervical adenocarcinoma and its variants: their morphology and differential diagnosis.

Adenocarcinoma of the uterine cervix and its variants account for a much greater number of cases in routine practice of histopathology than they did several decades ago. The varied morphology of these tumours results in diverse problems in differential diagnosis. The overall area of glandular pathology of the cervix, of which invasive adenocarcinoma is only one subset, is further complicated by the fact that there are many benign glandular proliferations of the cervix that can potentially be misinterpreted as adenocarcinoma. In this review the histopathology of endocervical adenocarcinoma and its variants is presented with the emphasis on evaluation of routinely stained sections, still the bedrock of routine practice, relatively little aid being provided by immunohistochemistry or other new techniques, contrary to what is sometimes implied in the literature. Description of the appearance of each subtype of adenocarcinoma or variant thereof is followed by a section on their differential diagnosis. Eighty percent of endocervical carcinomas are of the so-called usual type being characterized by cells with eosinophilic cytoplasm and generally brisk mitotic activity. It is sometimes stated that endocervical adenocarcinomas are mucinous but the usual form just noted often has little or no mucin. Pure or almost pure mucinous adenocarcinoma do occur, however, and have an important subtype, the so-called adenoma malignum (minimal deviation adenocarcinoma). Although treacherous because of its bland cytological features and sometimes deceptive pattern, a cone biopsy or hysterectomy specimen showing this neoplasm typically has easily recognizable features that indicate the presence of an infiltrative adenocarcinoma. An important variant of usual endocervical adenocarcinoma is the well differentiated villoglandular papillary adenocarcinoma, a designation that should be reserved for tumours with grade 1 cytologic features as usual endocervical adenocarcinoma, which is typically grade 2, may have papillae. In our opinion all other variants of pure adenocarcinoma, including endometrioid, are rare and include in addition to the latter clear cell, serous and mesonephric neoplasms. Tumours with a glandular and nonglandular component are also reviewed: adenosquamous carcinoma, glassy cell carcinoma, adenoid basal carcinoma, 'adenoid cystic' carcinoma and adenocarcinoma admixed with a neuroendocrine tumour.

Adenocarcinoma↗
PubMed1998

A novel orphan G protein-coupled receptor primarily expressed in the brain is localized on human chromosomal band 2q21.

A human hippocampus cDNA library was screened with a probe obtained from degenerate RT-PCR aimed at P2Y-homologous sequences. A positive clone, designated hip4, was identified containing an open reading frame of 1,020 bp that had been previously detected in a published genomic clone called R12. Subsequent screening of a human fetal brain cDNA library yielded a splice variant with a 1,104-bp open reading frame, which was named fb1. Both variants display the seven-transmembrane topology that is typical for G protein-coupled receptors. Probing a human multitissue northern blot revealed two brain-specific transcripts of 2.3 and 6.3 kb, respectively. Northern blot analyses with specific fragments confirmed that the two transcripts are generated by alternative polyadenylation yielding two different 3' untranslated regions. A genomic clone from the corresponding gene was isolated and mapped to human chromosomal band 2q21 by fluorescence in situ hybridization.

Amino Acid Sequence↗