Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional effects of APC (adenomatous polyposis coli gene) germ-line mutations on crypt fission and cell proliferation were investigated in the normal intestine of human familial adenomatous polyposis (FAP) and multiple intestinal neoplasia (MIN) mice. Compared with controls, there was a 19-fold increase in the proportion of crypts in fission in FAP colon [95 per cent confidence interval (CI): 11-32, P < 0.0001], and a 75 and 61 per cent increase in MIN colon (95 per cent CI: 1.08-2.82, P < 0.02) and small bowel, respectively (95 per cent CI: 1.31-1.99, P < 0.001). In marked contrast, no significant differences in intra-cryptal epithelial cell proliferation or mitotic distribution were seen. Furthermore, 10.9 per cent of crypts in FAP were in asymmetrical fission as opposed to only 1 per cent in controls (P = 0.001). The largest relative increases in MIN crypt fission were in the colon (proximal and distal colon:190 per cent, P = 0.02 and 83 per cent, P = 0.01), suggesting that Apc mutations exert their maximal influence site-specifically. However, sites with the highest relative increases were also those with the largest eventual tumour sizes, but not the highest polyp counts. Three-dimensional serial section reconstruction analysis corroborated that FAP adenomas enlarge by crypt fission, which was frequently both asymmetrical and atypical. It is proposed that the absence of an increase in intestinal cell division infers that APC regulates intestinal crypt differentiation, specifically through the crypt cycle. This role appears analogous to the control of axis re-duplication in embryonic development, when downstream targets of APC are over-expressed. It is concluded that in vivo, the major defect in pre-neoplastic intestine harbouring APC mutations is elevated rates of crypt fission, and that this is also the mode by which micro-adenomas enlarge.
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PMID:APC in the regulation of intestinal crypt fission. 977 77

Occult aspects of tumor proliferation are likely recorded genetically as their microsatellite (MS) loci become polymorphic. However, MS mutations generated by division may also be eliminated with death as noncoding MS loci lack selective value. Therefore, highly polymorphic MS loci cannot exist unless mutation rates are high, or unless mutation losses are inherently minimized. Mutations accumulate differently when cell fates are determined intrinsically before or extrinsically after division. Stem cell (asymmetrical division as in intestinal crypts) and random (asymmetrical and symmetrical division) proliferation, respectively, represent simulated cell fates determined before or after division. Whereas mutations regardless of selection systematically persist once inherited with stem cell proliferation, mutations are eliminated by the symmetrical losses of both daughter cells with random proliferation. Therefore, greater genetic diversity or MS variance accumulate with stem cell compared with random proliferation. MS loci in normal murine intestinal mucosa and xenografts of cancer cell lines accumulated mutations, respectively, consistent with stem cell and random proliferation. Tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) demonstrated polymorphic MS loci. Overall, three of five adenomas and one of six cancers exhibited high MS variances. Assuming mutation rates are not significantly greater in adenomas than in cancers, these studies suggest the stem cell proliferation and hierarchy of normal intestines persists in many HNPCC adenomas and some cancers. An adenoma stem cell architecture can explain the complex polymorphic MS loci observed in HNPCC adenomas and account for many adenoma features. In contrast, cancers may lose intrinsic control of cell fate. These studies illustrate a feasible phylogenetic approach to unravel and describe occult aspects of human tumor proliferation. The switch from predominantly stem cell to random proliferation may be a critical and defining characteristic of malignancy.
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PMID:Tracing cell fates in human colorectal tumors from somatic microsatellite mutations: evidence of adenomas with stem cell architecture. 977 50

To develop chelating molecules that provide 99mTc-labeled polypeptides of high in vivo stability and high specific activities under mild reaction conditions, an asymmetrical bis(benzohydroxamamide) compound with an amine group, 4'-aminomethyl-N,N'-trimethylenedibenzohydroxamamide [NH2-C3(BHam)2], was designed and synthesized. The amine residue of NH2-C3(BHam)2 was converted to a maleimide group by reaction with N-succinimidyl-6-maleimidohexanoate, and the conjugation product was coupled to thiol groups of a monoclonal antibody against osteogenic sarcoma (OST7, IgG1) pretreated with 2-iminothiolane to prepare C3(BHam)2-OST7. 99mTc radiolabeling of C3(BHam)2-OST7 was performed by the exchange reaction with [99mTc]glucoheptonate. [99mTc]C3(BHam)2-OST7 was further characterized using directly radioiodinated OST7 ([125I]OST7) and [111In]labeled OST7 with 1-[4-[(5-maleimidopentyl)amidobenzyl]ethylenediamine-N,N, N'N'-tetraacetic acid (EMCS-Bz-EDTA) as references. [99mTc]C3(BHam)2-OST7 was obtained with radiochemical yields of over 94% at protein concentrations as low as 0.2 mg/mL at room temperature for 1 h. [99mTc]C3(BHam)2-OST7 remained stable after incubation in freshly prepared murine plasma and in the presence of cysteine. Similar binding affinities to tumor cells were observed between [99mTc]C3(BHam)2-OST7 and [125I]OST7. When injected into normal mice, [99mTc]C3(BHam)2-OST7 exhibited radioactivity levels in the blood similar to [111In]-EMCS-Bz-EDTA-OST7 up to 24 h postinjection with significantly faster elimination rate of the radioactivity from the liver. In nude mice bearing osteogenic sarcoma, no significant differences were observed in the radioactivity levels in the blood and the tumor between [99mTc]C3(BHam)2-OST7 and [125I]OST7 at 24 h postinjection. These findings indicated that C3(BHam)2 provided 99mTc chelate of high stability at low concentrations even when conjugated to an intact antibody. Such characteristics render bis(hydroxamamide) compounds useful as chelating molecules for preparation of 99mTc-labeled polypeptides.
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PMID:Bis(hydroxamamide)-based bifunctional chelating agent for 99mTc labeling of polypeptides. 989 58

Contiguous inflammation of the skin (CIS) is a condition comprising localized inflammatory skin reactions which are secondary to a source of infection originating in deeper anatomical structures (bacterial or sterile abscesses, neoplasm-associated inflammations, foreign bodies, osteomyelitis, sinusitis, etc.). The main clinical symptom of contiguous inflammation of the skin is an asymmetrical, localized and painful erythema in combination with different case-specific symptoms. Four patients are presented below, who developed CIS caused by an ethmoidal carcinoma with superinfection, a postoperative mediastinal abscess, an odontogenic staphylococcal abscess and a purulent sinusitis maxillaris. The purpose of this paper is to bring attention to this condition and to offer guidelines for a rapid diagnosis of its underlying, potentially life-threatening, causal inflammatory focus.
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PMID:Contiguous inflammation of the skin. 992 Sep 89

Computed tomography (CT) based three-dimensional (3-D) lifelike models have proved to be of great value, especially in craniomaxillofacial surgery. They improve and facilitate diagnosis, therapeutic planning, model operations, and definitive treatment in tumor surgery, traumatology, dysgnathia, alveolar atrophy, and congenital and asymmetrical malformations. From 1988 to 1998, 760 stereolithography (STL) and milled 3-D models were employed in our department. These two production methods have become the msot commonly used approaches, and the question as to which is preferable is the subject of controversy in the literature. Using two test models the STL and the milling method were compared with regard to production method and accuracy, and the resulting differences in indications for their use are discussed. The limiting factor for increased accuracy is the distance between each pair of CT scans. Milled models show a higher precision compared to STL models within the CT-scan plane, but the more the measurements deviate from this plane (becoming oblique) the more inaccurate the data becomes. STL exhibits greater deviations, but the inaccuracy is randomly distributed. The mean variation from the original was 0.81 mm for STL and 0.54 mm for milled models. Although 90% of the milled and 80% of the STL values are within a deviation of +/- 1 mm, it should be noted that maximum deviations of 3.15 mm in milled models and 2 mm in STL have been shown. Both methods are sufficiently accurate for clinical use. In standard cases involving the upper and lower jaw, malar bone, orbita, and calvaria the shorter production time and lower costs make milled models preferable. In special cases, in which hollows and fine structures play a major role (e.g., those involving the skull base, paranasal sinuses, inner ear, and mandibular canal), STL is indicated.
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PMID:Stereolithography versus milled three-dimensional models: comparison of production method, indication, and accuracy. 1020 49

Patients with non-Hodgkin's lymphoma occasionally develop widespread invasion of peripheral nerves by tumor cells or neurolymphomatosis (NL). Clinically this usually results in asymmetrical, progressive, and painful polyneuropathy. Diagnosis rests on the identification of tumor cells in peripheral nerves. To avoid false-negative biopsy findings in patients with malignant lymphomatous infiltration of peripheral nerves it has been recommended to biopsy clinically involved nerves. We present two patients with histologically confirmed NL in whom sural the nerve biopsy finding was negative despite clinical and neurophysiological evidence of involvement of the sural nerve a. The clinical features of NL are reviewed. Some patients with neurolyphomatosis have only focal or proximal involvement of nerves, requiring the biopsy of an affected part of these nerves. Magnetic resonance imaging may be useful in identifying affected nerves.
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PMID:Negative sural nerve biopsy in neurolymphomatosis. 1065 8

To determine the role of the FHIT tumor suppressor gene product, a diadenosine 5',5'''-P1,P3-triphosphate (Ap3A) hydrolase, in the regulation of the concentration of Ap3A and diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) in vivo, the levels of the adenosine(5')triphospho(5')nucleoside (Ap3N) and adenosine(5')tetraphospho(5')nucleoside (Ap4N) families were measured by luminometry in a number of human cell lines and correlated with the expression of Fhit determined by immunoblotting. Fhit-positive cells had no Ap3N or a very low level of Ap3N, whereas most Fhit-negative cells had Ap3N in the range 0.2-0.9 pmol/10(6) cells. Ap4N (mean value, 0.17 pmol/10(6) cells) did not correlate with Fhit expression. The results suggest that Fhit efficiently metabolizes Ap3A and Ap3N but not Ap4A or Ap4N in vivo.
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PMID:The Fhit tumor suppressor protein regulates the intracellular concentration of diadenosine triphosphate but not diadenosine tetraphosphate. 1081 Nov 4

The secretion of milk depends on the activity of a large number of membrane transport systems located on the apical and basolateral membranes of mammary secretory cells. It follows that a thorough knowledge of individual mammary tissue membrane transport systems is required if we are to fully understand the process of milk secretion. The distribution of the transporters between the apical and basolateral poles of the mammary epithelium must be asymmetrical given that the mammary gland is capable of vectorial transport. This is particularly evident in the case of glucose and amino acid transport systems: the transport mechanisms for these compounds are predominantly situated in the blood-facing aspect of the secretory cells. In addition. it is apparent that there is a polarized distribution of transport systems (carriers and channels) which accept sodium, potassium, chloride, phosphate, and calcium as substrates.
J Mammary Gland Biol Neoplasia 1998 Jul
PMID:Mammary gland membrane transport systems. 1081 12

Aberrant function of redox-regulated proteins is a possible cause for cellular transformation and loss of cell cycle control. The small protein thioredoxin has oncogenic properties and controls cell cycle movement through G(1), S, and G(2)/M phases. The redox-active, asymmetrical 1-methylpropyl-2-imidazolyl disulfide (IV-2) has previously been shown to react with and inhibit thioredoxin activity in vitro, the proliferation of human tumor cells in culture, and the growth of tumors in mice. We now examined the effects of IV-2 on cell cycle progression. In synchronized tsFT210 mouse mammary carcinoma cells, IV-2 halted cells in mitosis. In asynchronously growing MCF-7 human breast cancer cells, IV-2 exclusively and irreversibly blocked cells in G(2)/M at concentrations that correlated with its growth inhibitory activity. Neither the closely related, less redox active 2-hydroxy-1-methylpropyl-2-imidazolyl disulfide (AIV-2), which differs from IV-2 only by an additional hydroxyl group, nor the symmetrical diallyl disulfide caused a G(2)/M arrest under these conditions. Furthermore, MCF-7 cells treated with IV-2 showed increased Cdk1 kinase activity and a decrease in Cdk1 tyrosine phosphorylation, indicating that IV-2 did not directly inhibit Cdk1 or Cdc25 activities. IV-2 did, however, increase Bcl-2 phosphorylation. These data suggest that the thioredoxin inhibitor IV-2, despite its simple structure, is able to target redox-sensitive processes that are critical for cell cycle progression through mitosis. The results are also consistent with a role of thioredoxin regulating cell cycle progression through G(2)/M.
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PMID:Antitumor imidazolyl disulfide IV-2 causes irreversible G(2)/M cell cycle arrest without hyperphosphorylation of cyclin-dependent kinase Cdk1. 1094 61

With recent technical advances, increasing use of sonography in the initial evaluation of patients with abdominal disease may allow the detection of unexpected tumor within the abdominal cavity. Easiness of sonographic detection of bowel pathology, purposely or unexpectedly, warrants the inclusion of bowel loops during ultrasound examination when a patient complains of symptoms indicating diseases of the bowel. In patients complaining of acute abdominal symptoms or nonspecific gastrointestinal symptoms and showing signs such as abdominal pain, diarrhea, hematochezia, change of bowel habit, or bowel obstruction, sonography may reveal the primary causes and may play a definitive role in making a diagnosis. On ultrasonography, abnormal lesions may appear as fungating mass with eccentrically located bowel lumen (pseudokidney sign) or symmetrical or asymmetrical, encircling thickening of the colonic wall (target sign). In patients with mass or wall thickening detected on ultrasonography, additional work-up such as barium study, CT or endoscopy would be occasionally necessary for making a specific diagnosis.
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PMID:Ultrasound examination of gastrointestinal tract diseases. 1098 83


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