Biomedical subjects

Jianmin Jiang

Publications and source records attributed to Jianmin Jiang.

6 recordsLinked to original sources

PubMed2006

Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7.

TRPM6 and TRPM7 are two known channel kinases that play important roles in various physiological processes, including Mg2+ homeostasis. Mutations in TRPM6 cause hereditary hypomagnesemia and secondary hypocalcemia (HSH). However, whether TRPM6 encodes functional channels is controversial. Here we demonstrate several signature features of TRPM6 that distinguish TRPM6 from TRPM7 and TRPM6/7 channels. We show that heterologous expression of TRPM6 but not the mutant TRPM6(S141L) produces functional channels with divalent cation permeability profile and pH sensitivity distinctive from those of TRPM7 channels and TRPM6/7 complexes. TRPM6 exhibits unique unitary conductance that is 2- and 1.5-fold bigger than that of TRPM7 and TRPM6/7. Moreover, micromolar levels of 2-aminoethoxydiphenyl borate (2-APB) maximally increase TRPM6 but significantly inhibit TRPM7 channel activities; whereas millimolar concentrations of 2-APB potentiate TRPM6/7 and TRPM7 channel activities. Furthermore, Mg2+ and Ca2+ entry through TRPM6 is enhanced three- to fourfold by 2-APB. Collectively, these results indicate that TRPM6 forms functional homomeric channels as well as heteromeric TRPM6/7 complexes. The unique characteristics of these three channel types, TRPM6, TRPM7, and TRPM6/7, suggest that they may play different roles in vivo.

Animals↗

PubMed2005

Knowledge-discovery incorporated evolutionary search for microcalcification detection in breast cancer diagnosis.

OBJECTIVES: The presence of microcalcifications (MCs), clusters of tiny calcium deposits that appear as small bright spots in a mammogram, has been considered as a very important indicator for breast cancer diagnosis. Much research has been performed for developing computer-aided systems for the accurate identification of MCs, however, the computer-based automatic detection of MCs has been shown difficult because of the complicated nature of surrounding of breast tissue, the variation of MCs in shape, orientation, brightness and size. METHODS AND MATERIALS: This paper presents a new approach for the effective detection of MCs by incorporating a knowledge-discovery mechanism in the genetic algorithm (GA). In the proposed approach, called knowledge-discovery incorporated genetic algorithm (KD-GA), the genetic algorithm is used to search for the bright spots in mammogram and a knowledge-discovery mechanism is integrated to improve the performance of the GA. The function of the knowledge-discovery mechanism includes evaluating the possibility of a bright spot being a true MC, and adaptively adjusting the associated fitness values. The adjustment of fitness is to indirectly guide the GA to extract the true MCs and eliminate the false MCs (FMCs) accordingly. RESULTS AND CONCLUSIONS: The experimental results demonstrate that the incorporation of knowledge-discovery mechanism into the genetic algorithm is able to eliminate the FMCs and produce improved performance comparing with the conventional GA methods. Furthermore, the experimental results show that the proposed KD-GA method provides a promising and generic approach for the development of computer-aided diagnosis for breast cancer.

Algorithms↗

PubMed2005

Potentiation of TRPM7 inward currents by protons.

TRPM7 is unique in being both an ion channel and a protein kinase. It conducts a large outward current at +100 mV but a small inward current at voltages ranging from -100 to -40 mV under physiological ionic conditions. Here we show that the small inward current of TRPM7 was dramatically enhanced by a decrease in extracellular pH, with an approximately 10-fold increase at pH 4.0 and 1-2-fold increase at pH 6.0. Several lines of evidence suggest that protons enhance TRPM7 inward currents by competing with Ca(2+) and Mg(2+) for binding sites, thereby releasing blockade of divalent cations on inward monovalent currents. First, extracellular protons significantly increased monovalent cation permeability. Second, higher proton concentrations were required to induce 50% of maximal increase in TRPM7 currents when the external Ca(2+) and Mg(2+) concentrations were increased. Third, the apparent affinity for Ca(2+) and Mg(2+) was significantly diminished at elevated external H(+) concentrations. Fourth, the anomalous-mole fraction behavior of H(+) permeation further suggests that protons compete with divalent cations for binding sites in the TRPM7 pore. Taken together, it appears that at physiological pH (7.4), Ca(2+) and Mg(2+) bind to TRPM7 and inhibit the monovalent cationic currents; whereas at high H(+) concentrations, the affinity of TRPM7 for Ca(2+) and Mg(2+) is decreased, thereby allowing monovalent cations to pass through TRPM7. Furthermore, we showed that the endogenous TRPM7-like current, which is known as Mg(2+)-inhibitable cation current (MIC) or Mg nucleotide-regulated metal ion current (MagNuM) in rat basophilic leukemia (RBL) cells was also significantly potentiated by acidic pH, suggesting that MIC/MagNuM is encoded by TRPM7. The pH sensitivity represents a novel feature of TRPM7 and implies that TRPM7 may play a role under acidic pathological conditions.

Animals↗

PubMed2004

Integration of fuzzy logic and structure tensor towards mammogram contrast enhancement.

In this paper, we describe a combined approach with fuzzy logic and structure tensor towards improved enhancement of possible MCs (microcalcifications) in digital mammograms. The proposed contrast enhancement algorithm has two operational components. One is structure tensor operator and the other is fuzzy enhancement operator, both of which are arranged in parallel to process the input digital mammograms. While the structure tensor operator processes the digital mammograms and produces a corresponding eigen-image to highlight the region-of-interests, the fuzzy enhancement operator fuzzifies the mammogram via the maximum fuzzy entropy principle in fuzzy domain. As a result, the local fuzzy contrast can be extracted and modified adaptively in accordance with the information provided by the eigen-image, and those non-MCs regions are suppressed by being taken as noise. After that, the mammogram is transformed back to the pixel domain and the enhanced mammogram is constructed. Extensive experimental results show that our proposed algorithm outperforms the existing benchmark in terms of cost figures across the whole range of true positive fractions (TPF).

Algorithms↗

PubMed2004

Expression of intracellular domain of epidermal growth factor receptor and generation of its monoclonal antibody.

To prepare monoclonal antibody specific to epidermal growth factor receptor (EGFR) intracellular domain, its gene was amplified from total RNA of A431 cell by RT-PCR. Then the gene was cloned into prokaryotic vector pET30a(+). The recombinant plasmid was transformed into E. coli BL21 (DE3) strain for protein expression. Recombinant protein was induced with IPTG and purified using Ni2+-NTA agarose. Then the anti-EGFR monoclonal antibody (mAb) was prepared with classical hybridoma technique. Positive clones were selected using indirect enzyme-linked immunoabsorbent assay (ELISA). Totally 4 hybridoma clones were obtained and these mAbs were IgG1 (3 clones) and IgG2a (1 clone), respectively. Their light chains were all kappa chains. Western blotting analysis and confocal immunofluorescence assays demonstrated that mAbs could specifically recognize EGFR expressing on A431 carcinoma cell line. The mAbs will be useful in the study of EGFR-mediated signal transduction.

Animals↗

PubMed2002

Identification and characterization of nine novel human small GTPases showing variable expressions in liver cancer tissues.

Digestion and detoxification are the two most important functions of the liver, and liver cells always keep a high metabolism level and active vesicular traffic. The malfunction of the vesicular traffic system might be a cause of the abnormal biological behavior of cancerous liver cells. The Ras superfamily is known to regulate various steps of vesicular traffic in eukaryotic cells. It would be significant to determine the change of vesicular transport molecules such as the members of Ras superfamily in carcinogenesis of liver cells. In the present study, we have cloned nine novel genes encoding human small GTPases: RAB1B, RAB4B, RAB10, RAB22A, RAB24, RAB25 ARL5, SARA1, and SARA2, among which the former six belong to the RAB family and the latter three belong to the ARF/SAR1 family. The identification of these new genes has greatly enlarged the pool of the Ras superfamily. It is interesting to find that they are upregulated in most of the 11 hepatocellular carcinoma and 1 cholangiohepatoma cases. Furthermore, the expression in 16 normal human adult tissues, the chromosome loci, and the gene structures of the nine genes are also described. The above findings could be valuable for understanding the vesicular transport system and elucidating the molecular basis of liver cancer carcinogenesis.

Amino Acid Sequence↗