Biomedical subjects

N Huang

Publications and source records attributed to N Huang.

At least 91 records · Page 5Linked to original sources

PubMed1996

Centromere mapping and orientation of the molecular linkage map of rice (Oryza sativa L.).

Rice has become a model cereal plant for molecular genetic research. Rice has the most comprehensive molecular linkage maps with more than 2000 DNA markers and shows synteny and colinearity with the maps of other cereal crops. Until now, however, no information was available about the positions of centromeres and arm locations of markers on the molecular linkage map. Secondary and telotrisomics were used to assign restriction fragment length polymorphism markers to specific chromosome arms and thereby to map the positions of centromeres. More than 170 restriction fragment length polymorphism markers were assigned to specific chromosome arms through gene dosage analysis using the secondary and telotrisomics and the centromere positions were mapped on all 12 linkage groups. The orientations of seven linkage groups were reversed to fit the "short arm on top" convention and the corrected map is presented.

Centromere↗

PubMed1996

Altered expression of Pax-5 gene in human myeloma cells.

Recent phenotypic analysis of plasma cells showed that normal plasma cells do express the B-cell lineage-specific molecule CD19, but their malignant counterpart (myeloma cells) are CD19-. To clarify the meaning of loss of CD19 antigen on myeloma cells, we first compared the expression of CD19 and Pax-5 genes among B cells, normal plasma cells, myeloma cell lines, and primary myeloma cells, because the Pax-5 gene was reported to encode the transcriptional factor, B-cell-specific activating protein (BSAP), necessary for CD19 gene expression. Neither CD19 nor Pax-5 mRNA could be detected in those primary myeloma cells and cell lines, whereas normal plasma cells did express both CD19 and Pax-5 mRNA. Furthermore, we could confirm that BSAP-binding activity was not detected in the nuclear extract from CD19- myeloma cell line (KMS-5) but was detected in CD19+ B-cell line (Raji) by gel-shift assay. We further examined the expression of E2A and Id genes, because E2A and Id are considered to be positive and negative regulators in the expression of Pax-5 gene, respectively. However, no significant differences in the expression of these E2A and Id-2 genes could be observed between myeloma cells and normal plasma cells. Therefore, these data suggest that the altered expression of Pax-5, but not E2A or Id, is responsible for the loss of CD19 expression in human myeloma cells, although the underlying mechanism of the altered Pax-5 gene expression remains to be clarified.

Antigens, CD19↗

PubMed1996

Plasma cells induce apoptosis of pre-B cells by interacting with bone marrow stromal cells.

By using two-color phenotypic analysis with fluorescein isothiocyanate-anti-CD38 and phycoerythrin-anti-CD19 antibodies, we found that pre-B cells (CD38+CD19+) signifcantly decreased depending on the number of plasma cells (CD38++CD19+) in the bone marrow (BM) in the cases with BM plasmacytosis, such as myelomas and even polyclonal gammopathy. To clarify how plasma cells suppress survival of pre-B cells, we examined the effect of plasma cells on the survival of pre-B cells with or without BM-derived stromal cells in vitro. Pre-B cells alone rapidly entered apoptosis, but interleukin-7 (IL-7), a BM stromal cell line (KM-102), or culture supernatants of KM-102 cells could support pre-B cell survival. On the other hand, inhibitory factors such as transforming growth factor-beta1 (TGF-beta1) and macrophage inflammatory protein-1beta (MIP-1beta) could suppress survival of pre-B cells even in the presence of IL-7. Plasma cells alone could not suppress survival of pre-B cells in the presence of IL-7, but coculture of plasma cells with KM-102 cells or primary BM stromal cells induced apoptosis of pre-B cells. Supernatants of coculture with KM-102 and myeloma cell lines (KMS-5) also could suppress survival of pre-B cells. Furthermore, we examined the expression of IL-7, TGF-beta1, and MIP-1beta mRNA in KM-102 cells and primary stromal cells cocultured with myeloma cell lines (KMS-5). In these cells, IL-7 mRNA was downregulated, but the expression of TGF-beta1 and MIP-1beta mRNA was augmented. Therefore, these results suggest that BM-derived stromal cells attached to plasma (myeloma) cells were modulated to secrete lesser levels of supporting factor (IL-7) and higher levels of inhibitory factors (TGF-beta1 and MIP-1beta) for pre-B cell survival, which could explain why the increased number of plasma (myeloma) cells induced suppression of pre-B cells in the BM. This phenomenon may represent a feedback loop between pre-B cells and plasma cells via BM stromal cells in the BM.

ADP-ribosyl Cyclase↗

PubMed1996

Identification of early plasma cells in peripheral blood and their clinical significance.

In the peripheral blood (PB) we detected so-called early plasma cells that might already be committed to entering the bone marrow (BM). By two-colour staining with FITC-anti-CD38 antibody, their intensity (CD38++) of expression of CD38 antigen was between that of germinal centre (GC) B cells (low expression (CD38+)) and that of BM plasma cells (high expression (CD38++)), and their phenotype was CD38++ CD19+ CD10- CD20- CD21+ CD24- CD39+ CD5- VLA-4+ VLA-5- MPC-1- without expression of surface membrane IgM (SmIgM). Morphological and immunological examination of the sorted cells confirmed that they were plasmacytoid cells with expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were examined in various diseases. In active systemic lupus erythematosus, bacterial septicaemia and liver cirrhosis, early plasma cell levels were significantly increased in PB, and after subsidence of such inflammation (inactive states) these cells returned to normal levels. In contrast, normal early plasma cells were significantly suppressed in myelomas, whilst normal or slightly increased numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In addition, the number of normal early plasma cells returned to a normal level in myeloma cases with complete responses. Therefore, early plasma cells were identified phenotypically, and an increase and decrease in these cells in PB may reflect mobilization and suppression, respectively, of activated B cells into BM plasma cells.

ADP-ribosyl Cyclase↗

PubMed1995

Expression of CD21 antigen on myeloma cells and its involvement in their adhesion to bone marrow stromal cells.

The mature myeloma cells express very late antigen 5 (VLA-5) and MPC-1 antigens on their surface and adhere to bone marrow (BM) stromal cells more tightly than the VLA-5-MPC-1- immature myeloma cells in vitro. The VLA-5 and MPC-1 antigens possibly function as two of the molecules responsible for interaction of mature myeloma cells with BM stromal cells. However, the immature myeloma cells do interact with BM stromal cells, and it is unclear which adhesion molecules mediate their interaction. In this study, we found that both immature and mature myeloma cells expressed CD21, an adhesion molecule known to bind to CD23. CD21 was also detected on normal plasma cells. To evaluate the role of CD21 expression on myeloma cells, two myeloma cell lines, NOP-2 (VLA-5-MPC-1-) and KMS-5 (VLA-5+MPC-1+), were used as representatives of immature and mature myeloma cell types, respectively, and an adhesion assay was performed between the myeloma cell lines and BM stromal cells. Antibody-blocking results showed that adhesion of the mature type KMS-5 to KM102, a human BM-derived stromal cell line, or to short-term cultured BM primary stromal cells was inhibited by monoclonal antibodies (MoAbs) against CD21, VLA-5, and MPC-1, and inhibition of adhesion of the immature type NOP-2 to KM102 by the anti-CD21 MoAb was observed as well. Furthermore, CD23 was detected on KM102. Treatment of KM102 with an anti-CD23 MoAb also inhibited adhesion of either KMS-5 or NOP-2 to KM102. Therefore, we propose that CD21 expressed on myeloma cells likely functions as a molecule responsible for the interaction of immature myeloma cells as well as mature myeloma cells with BM stromal cells, and CD23 may be the ligand on the stromal cells for the CD21-mediated adhesion.

Base Sequence↗

PubMed1995

Differentiation of early plasma cells on bone marrow stromal cells requires interleukin-6 for escaping from apoptosis.

The bone marrow (BM) is well known to be the major site of Ig production in secondary immune responses; thus, the microenvironment of BM is considered to be essential for final differentiation of plasma cells. We identified in the peripheral blood (PB) early plasma cells (CD38++CD19+VLA-5-) committed to entering the BM. The sorted early plasma cells rapidly entered apoptosis in vitro, but these cells could survive and further differentiate into mature plasma cells (CD38 CD19+) just as BM plasma cells in the presence of a BM-derived stromal cell line (KM-102). Culture supernatants of KM-102 cell lines could also support survival of these cells, and antibody to interleukin-6 (IL-6) completely blocked the effect of these supernatants. Furthermore, recombinant IL-6, but not IL-1 or IL-3, could support their survival and their differentiation into mature plasma cells (CD38 CD19+VLA-5+) with expression of VLA-5 mRNA. Therefore, here is direct evidence that early plasma cells found in the PB differentiated into mature plasma cells with stromal cell-derived IL-6 in vitro; thus, BM stromal cells control the final checkpoint of plasma cell differentiation with secretion of IL-6 in the BM.

ADP-ribosyl Cyclase↗

PubMed1995

PMR study of mortality among Alabama workers and farmers.

Computerized records of all Alabama deaths occurring to persons 16 years of age and over for the 5-year period 1984-1988 were obtained from the Alabama Department of Public Health. Using proportionate mortality ratio (PMR) methodology and death certificate occupation, cause-specific mortality patterns were examined for all Alabama decedents (N = 182,178), for all Alabama workers (N = 125,369), and for the occupational group of "farm operators and managers" (N = 11,691). In comparison with the U.S. general population, little difference was found between cause-specific PMR results for the total Alabama population and those for all workers, suggesting the absence of a generalized "healthy worker effect." In comparison with the U.S. population, PMR results for farmers suggested lowered mortality from all malignant neoplasms and all heart disease, and elevated mortality from all external causes of death. In comparison with the Alabama population, PMR results for farmers continued to suggest lowered mortality from all malignant neoplasms, specifically for cancers of the respiratory, digestive and lymphopoietic systems. However, significantly elevated PMRs for external causes of death appeared only among nonwhite female farmers. Further investigation of these deaths suggested that this finding was more likely attributable to an increased risk of housefire deaths associated with rural lifestyle than with occupational factors.

Accidents, Home↗

PubMed1995

Diffusion-weighted imaging in epilepsy.

Diffusion-weighted imaging (DWI) is a relatively new magnetic resonance imaging (MRI) technique that can be used to probe the microenvironment of water. Contrast in DWI depends on properties different from traditional T1 and T2 contrast, and is derived form the translational motion of water molecules. Since it is reasonable to think that a change in the microenvironment of water might be reflected in a change in water diffusion characteristics, the quantitative assessment of the (apparent) diffusion coefficient ADCw may represent a unique means of assessing tissue status. DWI has already shown great utility in the study of cerebral ischemia in animal models and has proved useful in the early identification of cerebral ischemia in patients. More recent reports have indicated a potential for DWI in studying epilepsy. Here, we briefly review some of what is known about the measurement of ADCw in ischemia and compare these results with what has recently been reported for epilepsy. In this manner we hope to better understand the underlying mechanisms behind changes in water diffusion associated with specific pathologies.

Animals↗

PubMed1995

A new phenotypic classification of bone marrow plasmacytosis.

Here, we propose a new phenotypic classification of bone marrow plasmacytosis. By 2-color phenotypic analysis with FITC anti-CD38 and PE anti-CD19, -CD56, -VLA-5 or MPC-1 antibody, plasma cells are easily identified on the histogram, even though no more than 1% of plasma cells are found in the bone marrow. Hence, plasma cells are phenotypically classified into polyclonal (reactive) (CD19+CD56-) or monoclonal (neoplastic) plasma cells (mostly CD19-CD56+), and furthermore immature (VLA-5-MPC-1-), intermediate (VLA-5-MPC-1+) and mature plasma cells (VLA-5+MPC-1+). According to these findings, plasmacytosis in the bone marrow can be classified into polyclonal marrow plasmacytosis (POMP) and monoclonal marrow plasmacytosis (MOMP) states. The MOMP state is further subclassified into MOMP-1 and MOMP-2, MOMP-3 and MOMP-4; MOMP-1 is defined by co-existence of monoclonal plasma cells and polyclonal plasma cells, and MOMP-2 to MOMP-4 are dependent on increased proportions of VLA-5-MPC-1- immature myeloma (plasma) cells. We found that the cases of benign monoclonal gammopathy (BMG) according to the conventional classification were in the MOMP-1 state, and myelomas could be classified into the MOMP-2 to MOMP-4 state. Subclassification of the MOMP state may be useful in determining the prognosis of myelomas, where an increase in immature myeloma cells is reported to correlate well with their aggravation during the clinical courses. Therefore, this new phenotypic classification of bone marrow plasmacytosis (POMP and MOMP-1 to MOMP-4) will contribute to differential diagnosis and understanding of therapeutic responses and prognosis in myelomas.

Antigens, CD19↗

PubMed1995

High proportions of VLA-5- immature myeloma cells correlated well with poor response to treatment in multiple myeloma.

Using two-colour phenotypic analysis with anti-CD38 antibody, human myeloma cells can be classified into VLA-5- immature and VLA-5+ mature cells. We examined the relationship between variations of these subpopulations and clinical responses during treatment in multiple myeloma (MM). 39 patients with MM were treated with combined chemotherapy. First estimation of clinical responses after induction therapy showed that early clinical responses were correlated with the percentage of immature myeloma cells present after induction therapy (P < 0.01), not at diagnosis. After three courses of cyclic maintenance therapy, immature myeloma cells significantly decreased in proportion along with a decrease in total myeloma cells in maintained or more responsive cases (P < 0.01). On the other hand, immature myeloma cells were still found in high proportions in nonresponsive cases with no change (NC) or minor response (MR) (P < 0.01). Furthermore, in relapsing cases from partial response (PR) or progressive disease (PD) from nonresponsive cases, immature myeloma cells increased markedly. Therefore these results show that high proportions of VLA-5- immature myeloma cells remaining after induction therapy and during maintenance therapy correlate well with a declining clinical course of MM during maintenance therapy.

ADP-ribosyl Cyclase↗

PubMed1995

Characterization of BkdR-DNA binding in the expression of the bkd operon of Pseudomonas putida.

The bkd operon of Pseudomonas putida consists of the structural genes encoding the components of the inducible branched-chain ketoacid dehydrogenase. BkdR, a positive regulator of the bkd operon and a homolog of Lrp of Escherichia coli is encoded by a structural gene adjacent to, and divergently transcribed from, the bkd operon of P. putida. BkdR was purified from E. coli containing bkdR cloned into pCYTEXP1, an expression vector. The molecular weight of BkdR obtained by gel filtration indicates that BkdR is a tetramer, and the abundance of BkdR in P. putida was estimated to be about 25 to 40 copies of the tetramer per cell. BkdR bound specifically to the region between bkdR and bkdA1, the latter being the first gene of the bkd operon. One BkdR-DNA complex was observed in gel mobility shift patterns. Approximately 100 bp was protected from the action of DNase I by BkdR, and the addition of L-branched-chain amino acids enhanced the appearance of hypersensitive sites in the protected region. There are four potential BkdR-DNA binding sequences in this region based on similarity to Lrp-binding consensus sequences. Like many other transcriptional activators, BkdR regulates expression of its structural gene. DNAs from several gram-negative bacteria hybridized to a probe containing bkdR, indicating the presence of bkdR-like genes in these organisms.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed1995

[Single high-dose and fractionated low dose cisplatin in the EP protocol for advanced NSCLC--a prospective randomized trial on 72 patients].

A prospective randomized trial on 72 patients (12 cases in stage III and 60 cases in stage IV) suffering from non-small cell lung cancer (NSCLC) was carried out from January 1993 to March 1994 to assess the immediate results of single high dose DDP and fractionated low doses DDP in the EP (Etoposide and Cisplatin, DDP) protocol. The response rate to the former regimen was 47.1% (16/34) as compared with 39.5% (15/38) of the latter. The difference between these two regimens were not statistically significant (P > 0.10). The former regimen had higher incedence of delayed vomiting (P < 0.01), but the latter had more severe bone marrow suppression (P < 0.05). Without significant difference in renal toxicity (P > 0.10). The authors suggest that, the EP protocol consisting of fractionated doses of DDP, may be more preferrable due to its mild gastro-intestinal toxic reaction and less expensive in the treatment of advanced NSCLC patients. Yet, it is necessary to guard against its renal toxicity and myelosuppression.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

In vitro investigation of blood compatibility of Ti with oxide layers of rutile structure.

Structure characteristics of titanium oxide layer on titanium matrix were investigated by Rutherford Backscattering Spectroscopy (RBS), Auger Electron Spectroscopy (AES) and X-ray diffraction. It has been identified that the titanium oxide layers had rutile structure. The blood compatibility of the titanium oxide layers of different thickness was studied by blood clotting time measurement. It was shown that as the thickness of the titanium oxide layers increased, blood compatibility of these layers was obviously improved.

Animals↗

PubMed1994

[Effect of hemorheological factors on coronary flow during myocardial ischemia].

Intracoronary infusion of some drugs may induce superimposed coronary vasodilation upon endogenous vasodilation during myocardial ischemia, which was suggested as coronary vasodilator reserve. For an investigation of this phenomenon, 8 pigs were anesthetized, chest-opened, LAD (left anterior descending coronary artery)-dissected and instrumented. The LAD pressure was reduced to 4.67 kPa (35mmHg), and then intracoronary infusion of adenosine, saline, or anisodamine (at the same rate of 2ml/min) was started and maintained for 9 minutes. The three solutions all produced a significant increase in the coronary flow, including the saline (compared with the control, P < 0.05). The hemorheological examination of the distal coronary blood revealed a reduced hematocrit, plasma viscosity and whole blood viscosity during the saline and anisodamine infusion periods (P < 0.05), but in the adenosine infusion, the statistical analysis on hemorheological data revealed no significance compared with the control (P > 0.05). The results showed that the coronary vasodilator reserve induced by intracoronary drugs during myocardial ischemia might be partly accounted by regional hemodilution in the LAD bed. The study suggested that a decrease in blood viscosity might play an important role in the improvement of the narrowed coronary circulation, even more important than vasodilator drugs.

Adenosine↗

PubMed1994

[Effect of nifedipine on T wave in ischemic myocardium].

Calcium antagonists are generally considered to have no substantial effect on repolarization of the myocardium, so they have no direct effect on T wave, either. But in a pig model of myocardial ischemia, intracoronary nifedipine was found to reverse the inverted T wave induced by ischemia to upright promptly. Ten pigs were anesthetized with the chest opened, anterior interrentricular branch of left coronary artery (LAD) was narrowed to 4.67 kPa of LAD pressure, and then adenosine or nifedipine was infused into the coronary respectively. During the 9-minute ischemia, intracoronary adenosine or intracoronary nifedipine got the similar HR, LVEDP, LVDP, CAP, CAQ, and the intracoronary adenosine even got higher CAQ than the intracoronary nifedipine did. However, the T wave was retained inverted during the adenosine infused, but during the intracoronary nifedipine, the inverted T wave was promptly turned upright. The relevant factors and mechanisms are discussed.

Adenosine↗

PubMed1994

[Effects of endotoxin on coronary circulation].

To investigate the effects of endotoxin (ETX) on coronary circulation, we infused endotoxin (4ng/ml) intravenously in a small dose (0.3ng/kg.min-1) which did not reduce the blood pressure, nor did it disturb the coronary autoregulation, and the flow kept constant during the ETX infusion. But when the left coronary artery descending branch (LAD) was narrowed and the LAD pressure was reduced to 4.67kPa, the ETX showed a vasodilator effect on the LAD (pre-ETX 65.2 +/- 29.2 ml/min, post-ETX 89.5 +/- 32.7 ml/min, P < 0.05). This effect suggested that the ETX in a small dose had a vasodilator effect on a narrowed coronary artery, even when it did not disturb the hemodynamics. The possible mechanisms were surveyed preliminarily.

Animals↗

PubMed1994

Induction of chromosomal aberrations, cytotoxicity, and morphological transformation in mammalian cells by the antiparasitic drug flubendazole and the antineoplastic drug harringtonine.

The antiparasitic drug flubendazole and the antineoplastic compound harringtonine were studied for ability to induce chromosomal damage in Chinese hamster lung (CHL) cells and cytotoxicity and morphological transformation in C3H/10T1/2 Cl 8 (10T1/2) mouse embryo fibroblasts. Flubendazole caused a dose- and time-dependent induction of polyploidy in CHL cells. In cells treated with 0.78 micrograms/ml flubendazole, the yield of polyploid cells was 95%. Harringtonine caused a dose- and time-dependent induction of chromosome breaks, and 0.195 micrograms/ml harringtonine induced chromosome breaks in 47% of CHL cells. Both flubendazole and harringtonine caused dose-dependent cytotoxicity to 10T1/2 cells at concentration ranges of 0.04-1.60 and 0.05-0.8 micrograms/ml, respectively. Flubendazole and harringtonine at concentrations of 0.08-0.4 and 0.4-0.8 micrograms/ml, respectively, induced morphological transformation (predominantly type II foci) in 10T1/2 cells. Three of four harringtonine-transformed cell lines and two of four flubendazole-transformed cell lines formed foci in reconstruction experiments with non-transformed 10T1/2 cells. All four harringtonine-transformed and all four flubendazole-transformed cell lines formed colonies in soft agar. Similar concentrations of flubendazole and harringtonine induced chromosome damage in CHL cells and cytotoxicity and morphological transformation in 10T1/2 cells. The ability of flubendazole to induce polyploidy may be part of the mechanism by which this compound induces morphological transformation. Similarly, the ability of harringtonine to induce chromosomal aberrations may be part of the mechanism by which this compound induces morphological transformation. Therefore, flubendazole and harringtonine induce cytotoxicity and morphological and anchorage-independent transformation, harringtonine induces chromosome aberrations (breakage, translocation, and rings), and flubendazole induces polyploidy in cultured mammalian cells. The clastogenic and cell transformation-inducing properties of these compounds suggest that these drugs may have carcinogenic potential. This should be investigated rigorously in animal carcinogenesis bioassays. The genotoxicity of these drugs should be considered during their development as antiparasitic and antineoplastic agents.

Animals↗

PubMed1993

Heterogeneous expression of a novel MPC-1 antigen on myeloma cells: possible involvement of MPC-1 antigen in the adhesion of mature myeloma cells to bone marrow stromal cells.

Recent immunophenotypic analysis has shown that the heterogeneous expression of the adhesion molecule VLA-5 classifies myeloma cells into VLA-5+ mature and VLA-5- immature subpopulations. To further clarify the two myeloma subpopulations, we generated a monoclonal antibody, MPC-1, by immunizing mice with an adherent human myeloma cell line, KMS-5. The MPC-1 antibody recognized a 48-Kd surface antigen on KMS-5 but not on U-266, a nonadherent human myeloma cell line. Specificity characterization showed that MPC-1 antigen was expressed on mature myeloma cells, normal plasma cells, and mature B cells, whereas pre-B cells and germinal center B cells lacked its expression. Monocytes and a human bone marrow stromal cell line, KM102, also expressed this antigen. Two subclones of MPC-1+ VLA-5+ (KMS-5Ad) and MPC-1-VLA-5+ (KMS-5NAd) were separated from the KMS-5 cell line. The KMS-5NAd adhered to KM102 more tightly than did the KMS-5NAd, and the U-266 (MPC-1-VLA-5-) displayed almost no adherence to the KM102. The adhesion of the KMS-5Ad was partially inhibited by the MPC-1 antibody. These results, taken together, suggest that the MPC-1 antigen serves as a differentiation marker for B-lineage cells, including plasma cells, and may function as an adhesion molecule involved in the interaction of mature myeloma cells with bone marrow stromal cells.

Animals↗