Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 15-year-old black male presented with shortness of breath, leg weakness, and pain in his back and rib cage. Four years previously he had noticed a lump in his upper back and complained of pain when playing basketball, especially on contact to that area. Recently, the pain had become more constant and increased in intensity. This was associated with loss of control in his legs, weakness, and paraesthesia. General physical examination revealed a palpable mass in the right midline upper back. Laboratory results were within normal limits. Radiographic scans demonstrated a destructive soft tissue mass at T6 vertebral body with scattered stippled calcification (Figure 1). The patient underwent a biopsy followed by excision of the mass (Figure 2) and decompressive laminectomy with reconstruction.
Pediatr Pathol Mol Med
PMID:Pathology quiz: small cell osteosarcoma. 1148 38

The Thomsen-Friedenreich (T) antigen is a cryptic glycoprotein, referred to as tumor antigen or cancer-associated antigen because it is absent or masked by some carbohydrates in normal tissues, but present in many human cancers. The latter include gastrointestinal, lung, pancreatic, mammary, and some ovarian carcinomas. Cancer cells frequently undergo incomplete glycosylation resulting in the appearance of precursor structures that normally would be absent like the case with the T antigen. T antigen can be detected by several different reagents including monoclonal antibodies and several plant lectins-e.g., Arachis hypogea (peanut agglutinin). The aim of the current study was to evaluate the expression of T antigen in sebaceous carcinoma and to compare it with its simulators. The authors studied the immunohistochemical expression of T antigen in 45 skin biopsy and excisional specimens obtained from the archives of their dermatopathology laboratories, including 8 cases of sebaceous carcinoma, 15 cases of sebaceous adenoma, 9 cases of sebaceoma, 1 case of basal cell carcinoma with sebaceous differentiation, and 12 cases of basal cell carcinoma with cytologic atypia. Sebaceous carcinoma was unique in expressing a strong, diffuse cytoplasmic T antigen reactivity (7 of 8 cases) along the immature basaloid cells and the intermediate cells. However, sebaceous adenoma, sebaceoma, and basal cell carcinomas expressed negative reaction in the basaloid cells and mild reactivity in the intermediate cells. Mature sebocytes showed a strong reaction in all cases. The authors concluded that T antigen expression may be a helpful tool in differentiating sebaceous carcinoma from other sebaceous lesions that may simulate it histologically.
Appl Immunohistochem Mol Morphol 2001 Sep
PMID:Thomsen-Friedenreich (T) antigen: a possible tool for differentiating sebaceous carcinoma from its simulators. 1155 53

The nucleolus is a ubiquitous, mostly spheroidal nuclear structure of all protein-synthesizing cells, with a well-defined functional compartmentalization. Although a number of nonribosomal proteins involved in ribosome formation have been identified, the elements responsible for the shape and internal architecture of nucleoli are still largely unknown. Here, we report the molecular characterization of a novel protein, NO145, which is a major and specific component of a nucleolar cortical skeleton resistant to high salt buffers. The amino acid sequence of this polypeptide with a SDS-PAGE mobility corresponding to M(r) 145,000 has been deduced from a cDNA clone isolated from a Xenopus laevis ovary expression library and defines a polypeptide of 977 amino acids with a calculated mass of 111 kDa, with partial sequence homology to a synaptonemal complex protein, SCP2. Antibodies specific for this protein have allowed its recognition in immunoblots of karyoskeleton-containing fractions of oocytes from different Xenopus species and have revealed its presence in all stages of oogenesis, followed by a specific and rapid degradation during egg formation. Immunolocalization studies at the light and electron microscopic level have shown that protein NO145 is exclusively located in a cage-like cortical structure around the entire nucleolus, consisting of a meshwork of patches and filaments that dissociates upon reduction of divalent cations. We propose that protein NO145 contributes to the assembly of a karyoskeletal structure specific for the nucleolar cortex of the extrachromosomal nucleoli of Xenopus oocytes, and we discuss the possibility that a similar structure is present in other cells and species.
Mol Biol Cell 2001 Dec
PMID:A novel karyoskeletal protein: characterization of protein NO145, the major component of nucleolar cortical skeleton in Xenopus oocytes. 1173 89

The most efficient means of protein internalization from the membrane are through clathrin-coated pits, which concentrate protein interactions with the clathrin-associated assembly protein complex AP-2 and internalization signals in the cytoplasmic domain of transmembrane proteins. Binding of clathrin assembly protein to clathrin triskelia induces their assembly into clathrin-coated vesicles (CCVs). Due to a difficulty of isolating clathrin molecules from their complex or assembly state in the cells, most of the studies were carried out with recombinant clathrin proteins, which may present different conformation and structural variation. In this study, we have developed an efficient method of isolating the native clathrin assembly protein lymphoid myeloid (CALM) from the bovine brain that is enriched with clathrin and clathrin associated proteins and characterized by their sensitivity to proteases and it's ability to form CCV. The purified CALM has molecular weight of approximately 100,000 dalton on SDS-PAGE, which is consistent with the result of in vitro translation. The purified CALM protein could promote the assembly of clathrin triskelia into clathrin cage, and cleaved CALM proteolysed by caspase 3 and calpain could not promote them. In this respect, our data support a model in which CALM functions like AP180 as a monomeric clathrin assembly protein and might take part in apoptotic process in neuronal cells.
Exp Mol Med 2001 Dec 31
PMID:Cleavage of purified neuronal clathrin assembly protein (CALM) by caspase 3 and calpain. 1179 87

SOX transcription factors with high-mobility-group DNA-binding domain (HMG box) play key roles in embryogenesis. Some members of the SOX family are negative regulators of the WNT-beta-catenin-TCF signaling pathway. We have previously cloned and characterized human SOX17, constituting a subfamily with SOX7 and SOX18. Another group mapped SOX7 gene to human chromosome 8p22, and reported almost ubiquitous expression of 5.0-kb SOX7 mRNA in human normal tissues. Here, expression of SOX7 mRNA was investigated by using SOX7 specific probe, which hybridized to 3.8-kb human SOX7 mRNA, but not to 5.0-kb mRNA. SOX7 mRNA was relatively highly expressed in adult lung, trachea, lymph node, placenta, fetal lung, and heart. In adult heart, SOX7 mRNA was more highly expressed in ventricules, inter-ventricular septum and apex than in atriums. SOX7 mRNA was significantly up-regulated in pancreatic cancer cell lines BxPC-3, PSN-1, Hs766T, and in 4 cases out of 8 cases of primary gastric cancer. SOX7 mRNA was relatively highly expressed in a gastric cancer cell line MKN45, esophageal cancer cell lines TE2, TE3, TE4, TE5, TE7, TE8, TE11, TE12, and TE13. On the other hand, SOX7 mRNA was significantly down-regulated in 7 out of 18 cases of primary colorectal tumors, in 4 out of 9 cases of primary breast cancer, in 4 out of 14 cases of primary kidney tumors, and also in some cases of primary lung and prostate cancer. SOX7 gene might be one of cancer-associated genes on human chromosome 8p22.
Int J Mol Med 2002 Apr
PMID:Expression of human SOX7 in normal tissues and tumors. 1189 28

The subpellicular microtubules of the trypanosome cytoskeleton are cross-linked to each other and the plasma membrane, creating a cage-like structure. We have isolated, from Trypanosoma brucei, two related low-molecular-weight cytoskeleton-associated proteins (15- and 17-kDa), called CAP15 and CAP17, which are differentially expressed during the life cycle. Immunolabeling shows a corset-like colocalization of both CAPs and tubulin. Western blot and electron microscope analyses show CAP15 and CAP17 labeling on detergent-extracted cytoskeletons. However, the localization of both proteins is restricted to the anterior, microtubule minus, and less dynamic half of the corset. CAP15 and CAP17 share properties of microtubule-associated proteins when expressed in heterologous cells (Chinese hamster ovary and HeLa), colocalization with their microtubules, induction of microtubule bundle formation, cold resistance, and insensitivity to nocodazole. When overexpressed in T. brucei, both CAP15 and CAP17 cover the whole subpellicular corset and induce morphological disorders, cell cycle-based abnormalities, and subsequent asymmetric cytokinesis.
Mol Biol Cell 2002 Mar
PMID:Two related subpellicular cytoskeleton-associated proteins in Trypanosoma brucei stabilize microtubules. 1190 82

Alley running has been successfully used as an operant to demonstrate both the positive and negative reinforcing effect of intravenously administered drugs of abuse in a bona fide operant conditioning paradigm, the Ettenberg runway, in which confounding drug effects on motor performance and drug accumulation are avoided. While Ettenberg and colleagues focus on the intravenous route of drug administration, we tested the practicability of the subcutaneous route of administration in this runway paradigm in Sprague Dawley rats, using morphine as the investigated drug of abuse. We also modified the Ettenberg runway, most notably in that either food (sweetened condensed milk), no food, morphine, or saline was presented outside the runway in a separate cage. This made shaping, i.e., the initial presentation of a food reinforcer within the runway, necessary to establish responding. The manipulations necessary to administer subcutaneous (sc) injections were well tolerated by over 90% of the tested rats (n = 93). However, sc injections increased runtimes to the experimenter cutoff of 60 s within 20 once-daily sessions. Because of strong experimenter effects, all morphine doses or saline had to be adminstered blind. Under these experimenter-blind conditions, 0.1 and 1 mg/kg subcutaneous morphine proved to be reinforcing in that these doses significantly slowed down the gradual increase in runtimes imposed upon by the sc injection procedure. Thus, morphine can be demonstrated to be a positive reinforcer in a modified Ettenberg runway even when given subcutaneously. This effect, however, is eventually overcome by the negative reinforcing effect of subjecting the animals to sc injection procedure.
J Mol Neurosci
PMID:Reinforcing effect of subcutaneous morphine in a modified Ettenberg runway. 1193 43

Understanding the role of neuropeptides in mediating emotional behaviors is an important avenue for discovering novel drug targets for anxiety disorders. A role for galanin in mediating anxiety-related behavior is suggested by the pattern of distribution in the CNS and the coexistence of galanin with norepinephrine in the locus coeruleus. Studies in rats have shown that central administration of galanin modulates anxiety-related behaviors, and galanin release blocks the proanxiety effects of noradrenergic activation in prestressed rats. To further investigate the role of galanin in anxiety behaviors, we conducted a comprehensive behavioral phenotyping of galanin overexpressing transgenic mice (GAL-tg). GAL-tg mice were normal on measures of general health, neurological reflexes, home cage social behaviors, sensory functions, motor coordination, and exploratory locomotor activity. In three separate tests for anxiety-related behaviors, the elevated plus-maze, light <--> dark exploration, and open field center time, GAL-tg mice showed no anxiety-like phenotype. GAL-tg mice and wild-type littermate controls were equally responsive to the anxiolytic effects of chlordiazepoxide (10 mg/kg) in the light <--> dark exploration test, indicating normal benzodiazepine receptor function in GAL-tg mice. Stimulation of noradrenergic cells via administration with an alpha2 adrenoreceptor antagonist, yohimbine (2.5 mg/kg), produced proanxiety effects in wild type mice in the light <--> dark exploration test, but not in the GAL-tg mice. These data suggest that galanin contributes to the modulation of anxiety states induced by high levels of noradrenergic activation, but is silent under less challenging situations. A specific role for galanin in extreme anxiety states represents an attractive target for the development of novel anxiolytic treatments.
J Mol Neurosci
PMID:Evaluation of an anxiety-related phenotype in galanin overexpressing transgenic mice. 1193 46

Blockade of cholecystokinin (CCK) receptors potentiates the morphine-induced disruption of maternal behavior. The present study was undertaken to determine whether treatment with lorglumide, a CCK1 antagonist during late pregnancy and early lactation can influence the maternal behavior during lactation. A possible influence of this treatment on general activity was also assessed. Twenty-seven female Wistar rats were pretreated with lorglumide (1.0mg/kg/day; sc) or saline for seven days, starting on the 17th d of pregnancy. After the withdrawal of this treatment, animals were acutely challenged with saline on day 5 and with morphine sulfate (3.0mg/kg; sc) on days 6,10, and 17 of lactation. Groups were pretreated with saline and challenged with saline (group SS) and morphine (group SM), pretreated with lorglumide and challenged with saline (group LS) and morphine (group LM). Animals were also tested for general activity on days 25 and 33 postpartum after an acute challenge with saline and morphine, respectively. Maternal behavior testing began 30 min after the acute injections at which time pups were placed throughout each mother's cage. Latencies for pup retrieval, grouping, crouching and for full maternal behavior responses were scored. Lorglumide pretreatment inhibited maternal behavior of LS vs SS group and potentiated the morphine-induced disruption of this behavior in all days of test (LM vs SM group). No significant differences were found in general activity on days 25 and 33 postpartum. These data suggest that blockade of CCK1 receptors during puerperal period has long-term implications for maternal behavior.
J Mol Neurosci
PMID:Puerperal blockade of cholecystokinin (CCK1) receptors disrupts maternal behavior in lactating rats. 1193 55

The breast cancer susceptibility gene product BRCA1 is a tumour suppressor but the biochemical and biological functions that underlie its role in carcinogenesis remain to be determined. Here, we characterise the solution properties of the highly conserved C terminus of BRCA1, consisting of a tandem repeat of the BRCT domain (BRCT-tan), that plays a critical role in BRCA1-mediated tumour suppression. The overall free energy of unfolding of BRCT-tan is high (14.2 kcal mol(-1) at 20 degrees C in water) but unfolding occurs via an aggregation-prone, partly folded intermediate. A representative set of cancer-associated sequence variants was constructed and the effects on protein stability were measured. All of the mutations were highly destabilising and they would be expected to cause loss of function for this reason. Over half could not be purified in a soluble form, indicating that these residues are critical for maintaining structural integrity. The remaining mutants exhibited much greater aggregation propensities than the wild-type, which is most likely a consequence of their reduced thermodynamic stability relative to the partly folded intermediate. The mutations characterised here are located at different sites in the BRCT-tan structure that do not explain fully their effects on the protein's stability. Thus, the results indicate an important role for biophysical studies in assessing the significance of sequence variants and in determining how they cause disease.
J Mol Biol 2002 Jul 12
PMID:Characterisation of the BRCT domains of the breast cancer susceptibility gene product BRCA1. 1209 1


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