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J Yoo

Publications and source records attributed to J Yoo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.

We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.

Journal Article↗
PubMed2001

The neuron restrictive silencer factor can act as an activator for dynamin I gene promoter activity in neuronal cells.

The neuron restrictive silencer element (NRSE) has been identified in several neuronal genes and confers neuron specificity by silencing transcription in nonneuronal cells. We have previously reported that Sp1 and an NF-kappaB-like element (NE-1) are required for the promoter activity of mouse dynamin I gene. In the present study, we found that the upstream regulatory region of the dynamin I promoter has an NRSE-like sequence and showed that neuron restrictive silencer factor (NRSF) binds to this element in neuronal cells as well as in nonneuronal cells. We also showed that NRSF activates the promoter activity of dynamin I gene in neuronal cells. From the results in this study, we suggest that NRSE might be involved in the neuron restriction of dynamin I expression, and NRSF could act as an activator for promoter activity of dynamin I gene in neuronal cells.

Animals↗
PubMed2001

Negative regulation of YY1 transcription factor on the dynamin I gene promoter.

Dynamin I is highly expressed in brain and plays a critical role in clathrin-mediated endocytosis and synaptic vesicle recycling. To elucidate the molecular mechanism by which expression of dynamin I is tissue-specifically regulated, we previously cloned and characterized the promoter of the mouse dynamin I gene and suggested that there is a negative regulatory element in this promoter region. In the present study, we showed that YY1 binds to this negative regulatory element located at -111 to -107 by using the EMSA and supershift analyses. Cotransfection experiment using an YY1 expression vector revealed that YY1 exerts a repressive role on the dynamin I gene promoter activity. These results demonstrate that transcription factor YY1 negatively regulates dynamin I expression via binding to the negative regulatory element.

Animals↗
PubMed2001

Increased GTP-binding to dynamin II does not stimulate receptor-mediated endocytosis.

Regarding the molecular mechanism of dynamin in receptor-mediated endocytosis, GTPase activity of dynamin has been thought to have a critical role in endocytic vesicle internalization. However, a recent report suggested that GTP-binding to dynamin itself activates the dynamin to recruit molecular machinery necessary for endocytosis. In this study, to investigate the role of GTP binding to dynamin II, we generated two mutant dynamin II constructs: G38V and K44E. G38V, its GTP binding site might be mainly occupied by GTP caused by reduced GTPase activity, and K44E mutant, its GTP binding site might be vacant, caused by its decreased affinity for GTP and GDP. From the analysis of the ratio of GTP vs GDP bound to dynamin, we confirmed these properties. To test the effect of these mutant dynamins on endocytosis, we performed flow cytometry and confocal immunofluorescence analysis and found that these two mutants have inhibitory effect on transferrin-induced endocytosis. Whereas fluorescent transferrin was completely internalized in wild-type (WT) dynamin II expressing cells, no intracellular accumulation of fluorescent transferrin was found in the cells overexpressing K44E and G38V mutant. Interestingly, the amount of GTP bound to K44E was increased when endocytosis was induced than that bound to WT. The present results suggested that the GTPase activity of dynamin II is required for formation of endocytic vesicle and GTP-binding to dynamin II per se is not sufficient for stimulating endocytosis.

3T3 Cells↗
PubMed2001

Differential changes in neuropeptide Y and nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in rat hippocampus after kainic acid-induced seizure.

Changes in neuropeptide Y (NPY) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-positive neurons in the hippocampus were investigated 5, 10 and 20 days after kainic acid (KA) administration using a double labeling method. The numbers of NADPH-d-positive-only and NPY/NADPH-d-positive neurons decreased in the CA1/2-CA3 regions of the hippocampus, 5, 10 and 20 days after KA administration, however, the number of NPY-positive-only neurons increased in the same regions 5 and 10 days after KA administration. In the dentate gyrus (DG) region of the hippocampus, the numbers of NPY-positive-only, NADPH-d-positive-only and NPY/NADPH-d-positive neurons increased 5 days after KA administration, and 20 days after KA administration, the number of NADPH-d-positive-only neurons decreased to levels similar to or lower than the level of the controls. However, the numbers of NPY/NADPH-d-positive and NPY-positive-only neurons in the DG region 20 days after KA administration remained at control levels. These results indicate that, NADPH-d-positive-only neurons are vulnerable to, and NPY-positive-only neurons are resistant to KA-induced seizures in the whole hippocampus, but that NPY/NADPH-d-positive neurons have different sensitivities in subregions of the hippocampus to KA-induced seizures. In addition, the present findings provide the first statistical and morphological evidence, which demonstrates that NPY-positive-only, NADPH-d-positive-only and NPY/NADPH-d-positive neurons in the hippocampus have different sensitivities to KA-induced seizures.

Animals↗
PubMed2001

Prospective evaluation of eyelid function with gold weight implant and lower eyelid shortening for facial paralysis.

OBJECTIVES: To assess which signs and symptoms were relieved by gold weight implantation and which signs and symptoms persisted. DESIGN: Prospective observational cohort. SETTING: Tertiary care neurotology and oncology center. PATIENTS: Sixteen (4 males and 12 females) consecutive patients whose average age was 56 years (age range, 31-76 years). Inclusion criteria were gold weight implant, lagophthalmos of 2 mm or more, and a House-Brackmann score of 3 or less at the completion of follow-up. Mean follow-up was 13 months. INTERVENTIONS: Each patient received a gold weight implant. Six of these patients underwent a lower eyelid procedure. MAIN OUTCOME MEASURES: Surgical complications, static and dynamic lagophthalmos, static and dynamic corneal coverage, visual acuity, keratitis, topical treatment, and patient satisfaction. RESULTS: There were no extrusions. The preoperative mean lagophthalmos was 7.5 mm and the postoperative mean was 0.5 mm, (P<.001). Corneal coverage with eye closure before implantation was 73% and after implantation was 100%, (P<.001). Corneal coverage with normal (reflex) blink was less than 50% in 9 of 14 patients. When wearing correction, no patients had 20/20 visual acuity. The mean patient satisfaction score before the procedure was 3.5 and after was 7.1, (P<.001). Patient satisfaction was most closely related to visual acuity. The relationship was linear and statistically significant (P<.04). CONCLUSIONS: Gold weight implantation provides significant reduction in lagophthalmos and significant improvement in corneal coverage. But owing to delayed closure time and disrupted tear film, irritation may persist. As a result, some patients require ongoing topical treatment of the eye, which can compromise visual acuity.

Adult↗
PubMed2001

Grb2 dominantly associates with dynamin II in human hepatocellular carcinoma HepG2 cells.

The two SH3 domains and one SH2 domain containing adaptor protein Grb2 is an essential element of the Ras signaling pathway in multiple systems. The SH2 domain of Grb2 recognizes and interacts with phosphotyrosine residues on activated tyrosine kinases, whereas the SH3 domains bind to several proline-rich domain-containing proteins such as Sos1. To define the difference in Grb2-associated proteins in hepatocarcinoma cells, we performed coprecipitation analysis using recombinant GST-Grb2 fusion proteins and found that several protein components (p170, p125, p100, and p80) differently associated with GST-Grb2 proteins in human Chang liver and hepatocarcinoma HepG2 cells. Sos1 and p80 proteins dominantly bind to Grb2 fusion proteins in Chang liver, whereas p100 remarkably associate with Grb2 in HepG2 cells. Also GST-Grb2 SH2 proteins exclusively bound to the p46(Shc), p52(Shc), and p66(Shc) are important adaptors of the Ras pathway in HepG2 cells. The p100 protein has been identified as dynamin II. We observed that the N-SH3 and C-SH3 domains of Grb2 fusion proteins coprecipitated with dynamin II besides Sos1. These results suggest that dynamin II may be a functional molecule involved in Grb2-mediated signaling pathway on Ras activation for tumor progression and differentiation of hepatocarcinoma cells.

Adaptor Proteins, Signal Transducing↗
PubMed2001

A comparison of ink-directed and traditional whole-cavity re-excision for breast lumpectomy specimens with positive margins.

BACKGROUND: Excising a breast tumor with negative margins minimizes local recurrence. With a positive margin, the standard re-excision consists of excising the whole cavity and all surrounding breast tissue. By marking the sides of the lumpectomy specimen with six different colored inks, the surgeon can limit the re-excision to the involved margin. We compared the local recurrence rate after these two re-excision methods. METHODS: Records were reviewed of 527 women (546 breasts) treated with lumpectomy at two institutions. The log-rank test was used to compare the local recurrence-free survival. RESULTS: Of 546 tumors, 245 (45%) had negative margins on the initial lumpectomy and were not re-excised. Fifty-five percent had a positive or close margin; 181 underwent whole-cavity re-excision, and 120 had ink-directed re-excision. The mean follow-up time was 3.4 years. There was no significant difference in local recurrence for the patients whose initial margin was negative (3.7%) compared with the 243 patients with initially positive margins who underwent a re-excision (3.3%). Eleven of 181 (6%) patients undergoing a whole-cavity re-excision developed a local recurrence, compared with none of 120 (0%) patients with an ink-directed re-excision (P = not significant). Tissue mass excised was significantly smaller in the ink-directed group (23 vs. 83 g, P < .05). CONCLUSIONS: Ink-directed re-excision of lumpectomy specimens with positive margins minimizes the amount of breast tissue removed without increasing the incidence of local recurrence and is therefore preferable to the standard whole-cavity method.

Breast Neoplasms↗
PubMed2001

Effect of pre-treatment on the surface and electrochemical properties of screen-printed carbon paste electrodes.

The effect of various electrochemical pre-treatment methods on the surface and electrochemical properties of screen-printed carbon paste electrodes (SPCE) prepared with three different commercial products was examined. It was observed that a positively charged redox couple, e.g., hexaammineruthenium(III), exhibited quasi-reversible behavior at the untreated SPCE. However, the cyclic voltammograms (CVs) of the SPCE prepared with general-purpose carbon inks did not exhibit clear redox peaks to other representative redox couples [e.g., hexacyanoferrate(III), hexachloroiridate(IV), dopamine, and hydroquinone] without activation. Electrochemical pre-treatment methods were sought in four different aqueous solutions, i.e., sulfuric acid, potassium chloride, sodium hydrogencarbonate, and sodium carbonate, applying various activation potentials. It was found that the pre-treatment procedure in saturated Na2CO3 solution at 1.2 V provides a mild and effective condition for activating the SPCE. By measuring the water contact angles at the SPCE surfaces and recording their SEM images, it was confirmed that the electrochemical pre-treatment effectively removes the organic binders from the surface carbon particles. A prolonged period of activation (> 5 min) or the use of high potentials (> 1.2 V) increased the capacitance of the electrode over 20 microF cm(-2). The pre-treated SPCE behaved like a random array microelectrode, exhibiting a sigmoidal-shaped CV at a slow scan rate. The short pre-anodization method in Na2CO3 solution was generally applicable to most SPCE prepared with general-purpose carbon inks.

Journal Article↗
PubMed2001

Protein kinase epsilon dampens the secretory response of model intestinal epithelia during ischemia.

BACKGROUND: Luminal fluid sequestration and diarrhea are early manifestations of mesenteric ischemia. This can be modeled in vitro with the use of T84 intestinal epithelia, where ischemia induces Cl(-) secretion with adenosine-mediated autocrine feedback. Protein kinase C (PKC) regulates epithelial transport and, in some organ systems, is involved in the response to ischemic stress. The purpose of this study was to define the role of PKC on epithelial transport during ischemia. METHODS: By voltage-current clamp, short-circuit current (Isc) equals Cl(-) secretion. Ischemic conditions were simulated with the use of a well-established chemical hypoxia protocol. RESULTS: Chemical hypoxia briskly activated Isc. Gö6850, an antagonist of novel and conventional PKC isoforms, markedly enhanced the ischemia-induced Isc response, although Gö6976 (which inhibits only conventional isoforms) had no effect. Rottlerin, a specific inhibitor of PKC delta, did not attenuate ischemic Isc. Both phorbol 12-myristate, 13-acetate and bryostatin-1, which selectively activate PKC epsilon in T84 cells, markedly attenuated the Isc response to ischemia. Both agents also inhibited the Isc response to exogenous adenosine. CONCLUSIONS: PKC (likely the novel epsilon isoform) in intestinal epithelia modulates ischemia-induced alterations in ion transport. Inhibition of PKC epsilon exaggerates the secretory response that is induced by ischemia and by authentic adenosine; conversely, augmented activation of PKC epsilon inhibits secretion. Manipulation of PKC epsilon could limit luminal fluid sequestration during mesenteric ischemia.

Biological Transport↗
PubMed2001

Vocal function following radiation for non-laryngeal versus laryngeal tumors of the head and neck.

OBJECTIVE: The larynx may receive high doses of radiation even in the absence of disease. Preliminary investigation has provided evidence that significant voice alterations exist in patients who received radiotherapy (RT) for non-laryngeal tumors of the head and neck. This study evaluates subjective and objective parameters of vocal function in this patient population compared with a control group of patients irradiated for early glottic tumors. STUDY DESIGN: Retrospective cohort study. METHODS: Vocal function in patients irradiated for non-laryngeal and early glottic tumors was assessed in a comprehensive manner and compared. Microanalytical and macroanalytical acoustic analyses, aerodynamic measurements, and videostroboscopy were performed on vowel production data. The Voice Handicap Index was administered for self-assessment of voice quality. All subjects were male, smokers, and greater than 12 months post-RT. RESULTS: Seventeen patients with non-laryngeal tumors and 13 patients with early glottic tumors were evaluated. Microanalytical acoustic parameters were worse for 75% (6 of 8) of the acoustic measures of vowel production in the non-laryngeal group. These include jitter, relative amplitude perturbation, amplitude perturbation quotient, normalized noise energy, pitch amplitude, and spectral flatness ratio. Macroanalytical acoustic analyses revealed no difference in fundamental frequency but numerically smaller phonational frequency range in the non-laryngeal group. All aerodynamic measures, including mean phonation time, mean airflow, and vocal fold diadochokinetic rate, were decreased in the non-laryngeal group. Videostroboscopy demonstrated increased supraglottic activity in the non-laryngeal group. Voice handicap was significantly greater in the non-laryngeal group. CONCLUSIONS: When compared with patients receiving RT for early glottic tumors, there is objective and subjective evidence of vocal dysfunction in patients treated with wide-field RT for non-laryngeal tumors.

Carcinoma, Squamous Cell↗
PubMed2001

Mesenchymal cell transfer for articular cartilage repair.

Mature articular cartilage has a poor reparative response to injury and its irreparable breakdown is the common feature of degenerative joint diseases. If articular cartilage lesions become symptomatic, the orthopaedic surgeon must decide on a treatment option. The treatment options include conversion of chondral lesions to osteochondral lesions, which facilitates migration of cells from the marrow space to effect repair. In recent years, a greater emphasis has been placed on tissue engineering strategies and thus several new treatment options have been introduced, including the use of cell transplantation. Several tissue sources and cell types can potentially be used for this type of therapy. These include autologous or allograft chondrocytes and mesenchymal progenitor cells from various tissues. These cells may be delivered to articular cartilage lesions by a variety of methods including direct cell injection to the lesion or seeding in a biodegradable scaffold prior to implantation. In this review, the potential of cell transplantation for articular cartilage repair and regeneration will be discussed. The authors will focus on the available technologies and the present limitations of cell-based therapies.

Cartilage, Articular↗
PubMed2001

Effects of head and neck radiation therapy on vocal function.

OBJECTIVE: Radiotherapy (RT) is used to treat a variety of head and neck malignancies. The larynx may receive high radiation doses even in the absence of disease. The effects of RT on the nondiseased larynx are unknown. This study will evaluate subjective and objective parameters of vocal function in patients treated with RT for nonlaryngeal malignancies. DESIGN: Cross-sectional observational study. METHODS: Videostroboscopic, aerodynamic, and acoustic analyses were performed. Results were compared to age- and gender-matched controls. Self-assessment of voice quality was measured using the Voice Handicap Index. RESULTS: A majority of patients demonstrated increased supraglottal activity (i.e., ventricular fold constriction) during stroboscopic evaluation. Significant differences compared to normative data were found in many aerodynamic and acoustic parameters. A substantial proportion (27%) of patients reported significant voice handicap. Younger patients reported greater handicap, and voice quality was worse with time. CONCLUSIONS: Significant objective and subjective changes in vocal function occur in patients radiated for nonlaryngeal head and neck malignancies. Young patients may have the worst impact, and vocal dysfunction may increase with time. A prospective study of this patient population should include a baseline voice quality assessment.

Adult↗
PubMed2000

Characterization of the mouse dynamin I gene promoter and identification of sequences that direct expression in neuronal cells.

Dynamin I is expressed at high levels in brain and its expression is regulated during the developmental stages of brain. To elucidate the molecular mechanism by which the expression is tissue-specifically regulated, we cloned the 5'-flanking region of the mouse dynamin I gene and determined the nucleotide sequence of 1036 bases upstream from the translation start site. Transient transfection studies with a chloramphenicol acetyltransferase reporter gene in neuroblastoma NS20Y and Lewis lung cells demonstrated that the 5'-flanking region has a cell-type-specific promoter activity. Deletion analyses demonstrated that the minimal promoter activity was detected in the proximal region 195 bp upstream of the translation initiation codon (-90 to +105). The minimal promoter was embedded in a GC-rich region (75% GC content), in which an Sp1-binding motif and a nuclear factor (NF)-kappa B-like element (NE-1) were found, but it lacked TATA and CAAT boxes. Mutational analysis and electrophoretic mobility-shift assay analysis revealed that Sp1 binds to the Sp1 site and that this element is critical for the promoter activity of the dynamin I gene. We found that the NE-1 sequence is required for the expression of the dynamin I gene but NEBP (NE-1-binding protein), which binds to the NE-1 sequence, is not NF-kappa B. We also found that one base in the NE-1 sequence (the underlined G residue in GGGATTCGCGGA) is critical for binding specificity to discriminate between NEBP and NF-kappa B. By UV cross-linking analysis, we found that NEBP is an approx. 104 kDa nuclear protein.

Animals↗
PubMed2000

Tetranuclear manganese carboxylate complexes with a trigonal pyramidal metal topology via controlled potential electrolysis.

Controlled potential electrolysis (CPE) procedures are described that provide access to complexes with a [Mn4(mu 3-O)3(mu 3-O2CR)]6+ core (3MnIII,MnIV) and a trigonal pyramidal metal topology, starting from species containing the [Mn4(mu 3-O)2]8+ core (4MnIII). [Mn4O2(O2CMe)6(py)2(dbm)2] (6): triclinic, P1, a = 10.868(3) A, b = 13.864(3) A, c = 10.625(3) A, alpha = 108.62(1) degrees, beta = 118.98(1) degrees, gamma = 89.34(2) degrees, V = 1307 A3, Z = 1, T = -131 degrees C, R (Rw) = 3.24 (3.70)%. [Mn4O2(O2CPh)6(py)(dbm)2] (8): monoclinic, P2(1)/c, a = 14.743(6) A, b = 15.536(8) A, c = 30.006(13) A, beta = 102.79(1) degrees, V = 6702 A3, Z = 4, T = -155 degrees C, R (Rw) = 4.32 (4.44)%. Both 6 and 8 contain a [Mn4O2]8+ core; 8 only has one py group, the fourth MnIII site being five-coordinate. (NBun4)[Mn4O2(O2CPh)7(dbm)2] (10) is available from two related procedures. CPE of 10 at 0.65 V vs ferocene in MeCN leads to precipitation of [Mn4O3(O2CPh)4(dbm)3] (11); similarly, CPE of 6 at 0.84 V in MeCN/CH2Cl2 (3:1 v/v) gives [Mn4O3(O2CMe)4(dbm)3] (12). Complex 11: monoclinic, P2(1)/n, a = 15.161(3) A, b = 21.577(4) A, c = 22.683(5) A, beta = 108.04(3) degrees, V = 7056 A3, Z = 4, T = -100 degrees C, R (wR2) = 8.63 (21.80)%. Complex 12: monoclinic, P2(1)/n, a = 13.549(2) A, b = 22.338(4) A, c = 16.618(2) A, beta = 103.74(1) degrees, V = 4885 A3, Z = 4, T = -171 degrees C, R (Rw) = 4.63 (4.45)%. Both 11 and 12 contain a [Mn4(mu 3-O)3(mu-O2CR)] core with a Mn4 trigonal pyramid (MnIV at the apex) and the RCO2- bridging the MnIII3 base. However, in 11, the carboxylate is eta 2,mu 3 with one O atom terminal to one MnIII and the other O atom bridging the other two MnIII ions, whereas in 12 the carboxylate is eta 1,mu 3, a single O atom bridging three MnIII ions. Variable-temperature, solid-state magnetic susceptibility studies on 11 and 12 show that, for both complexes, there are antiferromagnetic exchange interactions between MnIII/MnIV pairs, and ferromagnetic interactions between MnIII/MnIII pairs. In both cases, the resultant ground states of the complex is S = 9/2, confirmed by magnetization vs field studies in the 2.00-30.0 K and 0.50-50 kG temperature and field ranges, respectively.

Carboxylic Acids↗
PubMed2000

Expression of MAT1/PEA-15 mRNA isoforms during physiological and neoplastic changes in the mouse mammary gland.

MAT1 is a novel transforming gene which was cloned from a mouse mammary tumor induced by N-methyl-N-nitrosourea in vitro in the presence of lithium as a mitogen. Later, it was found to be identical to the 3' untranslated region (UTR) of the 2.5 kb isoform of PEA-15 (phosphoprotein enriched in astrocytes-15 kDa). We re-cloned MAT1/PEA-15 cDNAs and showed 2.5, 2.0 and 1.8 kb isoforms and confirmed MAT1 localization as reported. The 2.0 and 1.8 kb isoforms were produced by alternative splicing and alternative polyadenylation at the 3' UTR, respectively. To analyze the role of MAT1/PEA-15, we examined the expression of MAT1/PEA-15 mRNA in normal mammary tissues and in mammary tumors. The mammary gland during pregnancy, lactation and weaning showed weak but stable expression. Compared with normal mammary gland, mammary tumors showed stronger expression. Aberrant expression of MAT1/PEA-15 isoforms was found in mouse mammary epithelial cell lines, FSK7 and TM6, which lost the 2.5/2.0 and 2.5 kb isoforms, respectively. In contrast to other oncogenes like c-myc, MAT1/PEA-15 mRNA was extremely stable after actinomycin D and cycloheximide treatments suggesting that other protein expression is prerequisite for degradation of MAT1/PEA-15 mRNA. It evoked the possibility of the 3' UTR of MAT1/PEA-15 (designated as MAT1-T) as a riboregulator in mammary tumorigenesis and necessity for further analysis of human breast cancers as well as mouse mammary tumors.

Animals↗
PubMed2000

H-ras gene mutations in salivary gland mucoepidermoid carcinomas.

BACKGROUND: The authors' recent investigation of salivary gland tumors in ras gene alteration has suggested that K-ras activation may not play a role in their oncogenesis but H-ras may, especially in mucoepidermoid carcinomas. A study was undertaken to assess the overall incidence of mutated H-ras genes in mucoepidermoid carcinomas and to discover its potential correlation with clinicopathologic parameters. METHODS: Fifty samples from patients with salivary gland mucoepidermoid carcinoma were analyzed for point mutations at codons 12, 13, and 61 of the H-ras gene using the polymerase chain reaction followed by automated direct sequencing methodology. RESULTS: Mutated H-ras genes were detected in 9 patients, for an overall incidence of 18% (9 of 50 patients). All but 1 of the mutations occurred at codon 12: a GGC-to-GTC transversion in 8 patients and a GGC-to-GAC transition in 1 patient, resulting in the amino acid substitution of valine and aspartic acid, respectively, for glycine. One of the samples showed concurrent mutations at codons 12 (GGC-to-GTC) and 13 (GGT-to-GGA). None of the samples demonstrated mutations involving codon 61. The H-ras mutations were observed in 5% (1of 21), 17% (2 of 12), and 35% (6 of 17) of low, intermediate, and high grade lesions, respectively. CONCLUSIONS: These data suggest involvement of H-ras activation in conjunction with other yet-unknown events in the development and/or progression of mucoepidermoid carcinomas. It is noteworthy that a stepwise increase in the frequency of H-ras mutations strongly correlates with tumor grade (P = 0.017). Molecular analysis of this gene alteration may provide assistance in the determination of tumor grade and differentiation.

Adenine↗