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PubMed2004

A case of tuberculous granuloma at the supra-sternal notch that was difficult to differentiate from a thyroid tumor.

BACKGROUND: Despite a decline after World War II, the rate of tuberculosis remains higher in Japan than in other countries. We report a case of tuberculous granuloma at the supra-sternal notch that was difficult to differentiate from a thyroid tumor. CASE REPORT: The patient was a 75-year-old Japanese woman who was referred to our hospital for further investigations and treatment of an anterior neck tumor, that was diagnosed as a suspected of thyroid malignancy by another institute. The thyroid function and biological data were normal except for an elevated erythrocyte sedimentation rate. Imaging studies showed a mass at the supra-sternal notch, and the border between the tumor and the thyroid gland was indistinct. The tuberculosis bacillus group was identified by fine needle aspiration cytology. The patient was treated surgically for tuberculous granuloma, and histopathological findings revealed that the lymph node tuberuculosis had invaded the thyroid gland. We started anti-tuberculous therapy after the operation. The post-operative course was uneventful with good wound healing. CONCLUSIONS: When a markedly elevated erythrocyte sedimentation rate and c-reactive protein value are associated with an anterior neck mass, tuberculosis should be considered in the differential diagnosis of thyroid swelling. Fine needle aspiration cytology is a rapid, simple and effective diagnostic method for extra-pulmonary tuberculous lesions involving the neck. When there is abscess formation or features of compression, or if the mass cannot be differentiated from a thyroid tumor, combined therapy involving anti-tuberculous agents and surgery must be considered.

Aged↗
PubMed2005

[Analysis of spectral properties of novel holographic transmission notch filter].

Optical filter has extremely important applications in spectroscopy, optical measurement and laser physics. Holographic filter, especially the transmission volume holographic notch filters using dichromate gelatin (DCG), is a new kind of filter with the main characteristic of a very narrow bandwidth. In this paper, measurements were carried out on the spectral properties of this transmission volume holographic notch DCG filter using an ultraviolet-visible transmittance spectrometer. The experimental results show that the relative transmittance of main spectrum of this filter is less than 2% in the visible region between 400 and 800 nm, and the relative transmittance of other spectra are more than 85%. Moreover, the filter has a narrow bandwidth with a half-bandwidth less than 12 nm, and a 1/10 width of the bandwidth less than 15 nm. These results indicate that this new kind of filter has an excellent filter characteristic to the main spectrum of Ar+ laser at the wavelength of 514.5 nm.

Holography↗
PubMed1979

Brainstem evoked potentials to tonepips in notched noise.

Notched noise can be used to mask the frequency spread of acoustic energy in the brief tonepips that are used to elicit brainstem evoked potentials. Brainstem responses to tonepips and notched noise can therefore be used to evaluate auditory thresholds at particular frequencies. These thresholds are more frequency-specific than those obtained using tonepips alone, and are accurate to within 20 dB of the conventional audiometric thresholds.

Acoustic Stimulation↗
PubMed1983

[Fractures of the trochlear notch of the ulna in children. Biomechanical and morphological differentiation from the typical injury picture in adults].

Various fractures of the trochlear notch of the ulna seen in children are presented and discussed below. Anatomical differences in bone density and cartilage surfaces as well as a different fracture mechanism make it possible to differentiate these fractures from those in adults. A causal relationship between fracture mechanism, bone density distribution and common fractures of the trochlear notch is discussed.

Adult↗
PubMed1994

[Six cases of petroclival meningiomas with main tumor site of the free tentorial rim--so-called tentorium notch meningiomas].

Petroclival meningiomas especially petroclival meningiomas with prevalent expansion to the tentorial notch are extreme rare. In the present paper we report about six patients with petroclival meningiomas of the tentorial notch who were operated in four years. The particular anatomical relations and the resulting symptoms and the neurosurgical procedures are discussed in detail. The postoperative state of the six patients is without exception satisfactory.

Adult↗
PubMed1996

Effect of FE idealisation, load conditions and interface assumptions on the stress distribution and fatigue notch factor in the human femur with an endoprosthesis.

The load transferred through the hip joint is one of the major forces occurring in the human body. After the replacement of this joint in THR arthroplasty, the load is transferred through the implant to the femoral bone. Loosening of the fixation of the implant and the fatigue failure of prosthetic stems create problems for both patient and surgeon. Both problems can be reduced by the use of Finite Element (FE) analysis to predict stresses and fatigue lifes but the results are sensitive to assumptions regarding the loading conditions and the idealisation of the components. Consequently the stress distributions and resulting fatigue notch factors in the human femur with an endoprosthesis have been determined for different assumptions regarding the form of the idealisation, the load conditions, and the interface conditions. The FE results show that a realistic loading condition without a tension banding force always produces the highest fatigue notch factor and von Mises stresses. An equivalent 2D plane stress model obtained by varying the thickness is likely to give more realistic stresses because it predicts more realistic strains than other 2D approximations. The full bonded interface is a satisfactory approximation for the real interface conditions because it predicts stress distributions of the correct form without excessive stress concentration.

Bone Cements↗
PubMed1977

The jugular "notch".

A characteristic "notch" in the petrous bone is described in relation to the superior outline of the jugular foramen. This notch seems to be a congenital anomaly and has a close relationship with ectasia of the dome of the internal jugular vein, as was demonstrated in two patients.

Female↗
PubMed2025

Genetic insight into lung neuroendocrine tumors: Notch and Wnt signaling pathways as potential targets.

BACKGROUND: The molecular landscape of lung neuroendocrine neoplasms is still poorly characterized, making it difficult to develop a molecular classification and personalized therapeutic approaches. Significant clinical heterogeneity of these malignancies has been highlighted among poorly differentiated histotypes and within the subgroup of well-differentiated neuroendocrine tumors (NET). Currently, the main prognostic factors of lung NET include stage, histotype, grade, peripheral location, and demographic parameters. To gain deeper insights into the genomic underpinnings of lung NETs, we conducted a pilot investigation to uncover potential genetic mutations and copy number variations (CNVs) implicated in their pathogenesis. METHODS: Formalin-fixed, paraffin-embedded intraoperative tumor biopsies and matched peripheral blood mononuclear cell samples were collected from six consecutive patients with lung NETs. The whole exome sequencing (WES) was performed to profile germline and somatic mutations, identify novel genetic alterations, and detect CNVs. Clinical and pathological data were systematically documented at diagnosis and during follow-up. RESULTS: The WES analysis identified a subset of mutations shared between germline and somatic; some were of particular clinical interest as they were associated with tumor proliferation and potential therapeutic targets such as the genes KDM5C, ATR, COL7A1, NOTCH4, PTPRS, SMO, SPEN, SPTA1, TAF1. These mutations were predominantly linked to chromatin remodeling and were involved in critical oncogenic pathways such as Notch and Wnt signaling. CONCLUSIONS: This pilot study highlights the potential role of NGS analysis on solid biopsy in the assessment of the mutational profile of lung NET. A comparison of germline and somatic mutations is critical to identifying putative tumor driver mutations. In perspective, the enrichment of a subpopulation of cancer cells in the blood, with one or more specific mutations, is information of enormous clinical relevance, either for prognosis or therapeutic decisions. Translational studies on large prospective series are required to establish the role of liquid biopsy in lung NET.

Humans↗
PubMed2000

Localisation of members of the notch system and the differentiation of vibrissa hair follicles: receptors, ligands, and fringe modulators.

Hair vibrissa follicle morphogenesis involves several cell segregation phases, in the dermis as well as in the epidermis. The expression of Notch-related genes, which are well established mediators of multiple cell segregation events in Drosophila development, was studied by in situ hybridisation during embryonic mouse vibrissa follicle morphogenesis and the first adult hair cycle. The results show that two receptors, Notch1 and -2, three ligands, Delta1, Serrate1, and -2, and the three Fringe regulators, Lunatic, Manic, and Radical, are expressed in different locations and morphogenetic stages. First, the appearance of hair vibrissa primordia involves the expression of complementary patterns of Notch2, Delta1, and Lunatic Fringe in the dermis and of Notch1, Serrate2, and Lunatic Fringe in the epidermis. Second, this expression pattern is no longer found after stage 3 in the dermis. Meanwhile, in the epidermis, the expression of Notch1, Serrate2, and Lunatic Fringe before the formation of the placode may be involved in determining two populations of epidermal cells in the developing follicle. Third, complementary expression patterns for Notch1, Manic, and Lunatic Fringe, as well as Serrate1 and -2 as previously shown (Powell et al., 1998), are progressively established from stage 4 of embryonic development both in the outer root sheath and in the hair matrix. These patterns are consistent with the one found in the adult anagen phase. During the hair vibrissa cycle, Notch1 and Manic Fringe display temporal and spatial changes of expression, suggesting that they may intervene as modulators of trichocyte activities.

Animals↗
PubMed2004

Association analysis of NOTCH 4 polymorphisms with schizophrenia among two independent family based samples.

The present study investigated polymorphisms of the NOTCH 4 gene in two independent samples from India and USA, consisting of patients with schizophrenia and their parents (n = 182, and n = 148 'trios,' respectively). Five DNA markers, namely (GAAG)(n), (TAA)(n), SNP1, SNP2, and (CTG)(n) were evaluated. Transmission distortion, consistent with a modest association was detected among both samples. Additional association studies at this locus are warranted.

Alleles↗
PubMed2006

Defining the transcriptome of accelerated and replicatively senescent keratinocytes reveals links to differentiation, interferon signaling, and Notch related pathways.

Epidermal keratinocytes (KCs) undergo highly orchestrated morphological and molecular changes during transition from proliferative compartment into growth arrested early and late differentiation layers, prior to dying in outermost cornified layers of normal skin. Creation of stratum corneum is vital to barrier function protecting against infection. Transcriptional events in KCs regulating complex processes of differentiation and host defense required to maintain constant epidermal thickness and resistance to infection in either young or aged skin are largely unknown. Furthermore, as terminal differentiation is characterized by irreversible loss of replicative potential culminating in dead layers at the skin surface, this process may be viewed as a form of senescence. However, a complete transcriptional profile of senescent (SN) human KCs has not been previously defined to permit delineation of molecular boundaries involving differentiation and senescence. To fill this void, we utilized global transcriptional analysis of KCs maintained in vitro as either cultures of proliferating (PR) cells, early and late confluent (LC) (accelerated senescence) cultures, or KCs undergoing replicative senescence. Global gene expression profiling revealed early confluent (EC) KCs were somewhat similar to PR KCs, while prominent differences were evident when compared to LC KCs; which were also distinct from replicatively SN KCs. While confluent KCs have in common several genes regulating differentiation with replicatively SN KCs, the latter cells expressed elevated levels of genes involved in interferon signaling and inflammatory pathways. These results provide new insights into cell autonomous transcriptional-based programs operative within KCs contributing to replicative senescence, with partial sharing of genes involved in differentiation. In addition, regulation of KC senescence may involve participation of interferon signaling pathways derived from the important role of KCs in protecting skin from infection. Integrating all of the transcriptional data revealed a key role for Notch receptor mediated signaling in the confluency induced differentiation phenotype using this model system.

Apoptosis↗
PubMed2004

Cellular and molecular characterization of early and late retinal stem cells/progenitors: differential regulation of proliferation and context dependent role of Notch signaling.

Retinal stem cells/progenitors that define the evolutionarily conserved early and late stages of retinal histogenesis are known to have distinct competence to give rise to stage-specific retinal cell types. However, the information regarding their innate proliferative behavior and phenotypic potential in terms of generating neurons and glia is lacking. Here we demonstrate that, like their counterparts in other central nervous system (CNS) regions during early and late stages of embryonic development, the early and late retinal stem cells/progenitors display different proliferative response to fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) and bias towards generating neurons or glia. Although the former predominantly generate neurons, the latter are partial towards giving rise to glia. Transcription profiling identified classes of genes that are differentially expressed in early and late retinal stem cells/progenitors in proliferating conditions and suggested that the distinct proliferative response to FGF2 and EGF is likely due to differential expression of FGF receptor 1 (FGFR1) and EGF receptor (EGFR). However, the proliferative maintenance of retinal stem cells/progenitors is likely to include other signaling pathways such as those mediated by insulin-like growth factors (IGFs) and stem cell factor (SCF). Transcription profiling of early and late retinal stem cells/progenitors in proliferating and differentiating conditions suggested a context dependent role for Notch signaling, which may constitute one of the mechanisms underlying the stage-dependent phenotypic potential of retinal stem cells/progenitors.

Age Factors↗
PubMed1993

Detection of electrophoretic variants of Notch, PS integrin, and DROP-1 proteins in Drosophila following extraction in guanidine hydrochloride.

A method is presented for the rapid extraction of proteins from Drosophila tissues. This method involves lysis of embryos in high concentrations of guanidine hydrochloride, followed by ultracentrifugation in a guanidine hydrochloride step gradient. Several membrane-associated antigens, including Notch and the beta subunit of PS integrin are enriched in this preparation. The quantity of the proteoglycan, DROP-1, obtained from Drosophila eggs and testes was also greatly improved by the guanidine hydrochloride extraction method. This method should prove useful in the isolation and characterization of many Drosophila antigens, particularly those associated with cell membranes.

Animals↗
PubMed2001

Activin A induces expression of rat Sel-1l mRNA, a negative regulator of notch signaling, in rat salivary gland-derived epithelial cells.

We previously established a rat submandibular gland (SMG)-derived epithelial cell line (RSMG-1) to study the mechanism of morphogenesis in salivary gland development and regeneration. We found that activin A regulated the branching morphogenesis of RSMG-1 cells, suggesting that it is involved in SMG morphogenesis. We used a subtraction cloning procedure with activin-A-treated and untreated RSMG-1 cells to identify activin-A-induced genes. One of the genes detected encoded a rat homologue of Sel-1l (rSel-1l). rSel-1l is a mammalian homologue of C. elegans sel-1, which is a negative regulator of Notch signaling. In this study, we confirmed that activin A induces rSel-1l mRNA expression in RSMG-1 cells, and that rSel-1l is expressed in SMG acinar cells. These results suggest that activin A regulates the differentiation of RSMG-1 cells to acinar cells.

Activins↗
PubMed1999

Dynamic expression of lunatic fringe suggests a link between notch signaling and an autonomous cellular oscillator driving somite segmentation.

The metameric organization of the vertebrate trunk is a characteristic feature of all members of this phylum. The origin of this metamerism can be traced to the division of paraxial mesoderm into individual units, termed somites, during embryonic development. Despite the identification of somites as the first overt sign of segmentation in vertebrates well over 100 years ago, the mechanism(s) underlying somite formation remain poorly understood. Recently, however, several genes have been identified which play prominent roles in orchestrating segmentation, including the novel secreted factor lunatic fringe. To gain further insight into the mechanism by which lunatic fringe controls somite development, we have conducted a thorough analysis of lunatic fringe expression in the unsegmented paraxial mesoderm of chick embryos. Here we report that lunatic fringe is expressed predominantly in somite -II, where somite I corresponds to the most recently formed somite and somite -I corresponds to the group of cells which will form the next somite. In addition, we show that lunatic fringe is expressed in a highly dynamic manner in the chick segmental plate prior to somite formation and that lunatic fringe expression cycles autonomously with a periodicity of somite formation. Moreover, the murine ortholog of lunatic fringe undergoes a similar cycling expression pattern in the presomitic mesoderm of somite stage mouse embryos. The demonstration of a dynamic periodic expression pattern suggests that lunatic fringe may function to integrate notch signaling to a cellular oscillator controlling somite segmentation.

Animals↗
PubMed2002

Notch and Wingless modulate the response of cells to Hedgehog signalling in the Drosophila wing.

During Drosophila wing development, Hedgehog (Hh) signalling is required to pattern the imaginal disc epithelium along the anterior-posterior (AP) axis. The Notch (N) and Wingless (Wg) signalling pathways organise the dorsal-ventral (DV) axis, including patterning along the presumptive wing margin. Here, we describe a functional hierarchy of these signalling pathways that highlights the importance of competing influences of Hh, N, and Wg in establishing gene expression domains. Investigation of the modulation of Hh target gene expression along the DV axis of the wing disc revealed that collier/knot (col/kn), patched (ptc), and decapentaplegic (dpp) are repressed at the DV boundary by N signalling. Attenuation of Hh signalling activity caused by loss of fused function results in a striking down-regulation of col, ptc, and engrailed (en) symmetrically about the DV boundary. We show that this down-regulation depends on activity of the canonical Wg signalling pathway. We propose that modulation of the response of cells to Hh along the future proximodistal (PD) axis is necessary for generation of the correctly patterned three-dimensional adult wing. Our findings suggest a paradigm of repression of the Hh response by N and/or Wnt signalling that may be applicable to signal integration in vertebrate appendages.

Animals↗