Biomedical subjects

K Omori

Publications and source records attributed to K Omori.

At least 91 records · Page 5Linked to original sources

PubMed1999

[Knowledge about AIDS and risk behaviors among hill tribes in northern Thailand].

Two hundred eighty-one Hmong, 240 Mien, and 210 Lahu hill tribe people (ages between 17-39) in northern Thailand were interviewed from March to May 1996 about their knowledge, beliefs, attitudes regarding AIDS, STDs and condoms, and sexual behavior, to guide future tribal AIDS education and care programs. Premarital sex for both men and women and extramarital sex for men seems to be still culturally permissive and wide-spread among the Hmong and Mien people. The Lahu reported lower cultural acceptance, but this group had higher levels of premarital and extramarital sex than the other two groups, excepting extramarital sex for Hmong men. Many men among the three groups knew about condoms, but they do not like to wear condoms because, "it is not natural." Lahu people had the least education, were the least literate, and had the least family income. In addition, Lahu had the lowest level of knowledge of AIDS and STDs and they seem to have the most risky behaviors among the three groups. On the other hand, although Mien people had the highest education, were the most literate, had the most family income, and had the highest level of knowledge of AIDS and STDs, they seem to have high risk sexual behavior, also. There were increasing numbers of hill tribe people migrating to the cities and becoming involved to a greater degree in seasonal or permanent wage labor, including the commercial sex industry among Lahu and Mien groups. Hmong seem to have the lowest number of workers migrating to the cities. The results indicate the need to inform and educate tribal people about AIDS in a socio-cultural specific context.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Morbidity and mortality patterns, health beliefs, and health risk factors of Karen highlanders of northwest Thailand.

Morbidity and mortality patterns, health care practices, and health care beliefs were assessed over three seasons in Pwo and Sgaw Karen preschool children living in the highlands of northwest Thailand. The sample consisted of all preschool children from 77 Pwo and 71 Sgaw households. Although the Pwo and Sgaw Karen residing in the highlands of northwest Thailand live in isolated villages in the same ecozone, utilize similar technologies, have similar access to health facilities, and maintain a certain level of sociocultural homogeneity through their identification as Karen, Pwo preschool children exhibit significantly higher levels of morbidity and mortality than their Sgaw counterparts. It is argued that these differences in morbidity and mortality are primarily the function of historical patterns which resulted in an earlier contact of the Sgaw with modem societies and particularly with an earlier exposure to western health care.

Adult↗

PubMed1998

Antiserum against Cl- pump complex recognizes 51 kDa protein, a possible catalytic unit in the rat brain.

We purified Cl- pump in the rat brain and obtained 520 or 580 kDa protein complexes which consisted of 62, 60, 55 and 51 kDa proteins. An antiserum against 520 kDa protein complex recognized 51 kDa protein in both 520 and 580 kDa complexes, and reduced both Cl(-)-ATPase and Cl(-) pump activities. Such an immunoreactive 51 kDa protein was found in the brain, spinal cord and kidney. When incubated with [gamma-(32)P]ATP, the protein complex yielded phosphorylated 51 kDa protein, the label being hydroxylamine-sensitive and increased in the presence of Cl- and/or an inhibitor of Cl- pump, ethacrynic acid. Thus, the antibody appears to recognize a possible catalytic subunit of Cl- pump, 51 kDa protein, in the rat.

Adenosine Triphosphatases↗

PubMed1998

Novel alternative splice variants of cGMP-binding cGMP-specific phosphodiesterase.

After our recent findings that the amino-terminal portion of rat cGMP-binding, cGMP-specific phosphodiesterase (cGB-PDE) differs from those of bovine and human cGB-PDEs, we found two forms of canine cGB-PDE cDNAs (CFPDE5A1 and CFPDE5A2) in canine lung. Each contained a distinct amino-terminal sequence, CFPDE5A1, possessing an amino-terminal portion with sequence similar to those of bovine and human, and CFPDE5A2, having one similar to that of rat. Other portions coding for the cGMP binding domains and the catalytic domain were conserved. Both CFPDE5A1 and CFPDE5A2 transcripts were detected in the cerebellum, hippocampus, retina, lung, heart, spleen, and thoracic artery. CFPDE5A1 transcripts were particularly abundant in the pylorus, whereas CFPDE5A2 transcripts were quite low in this tissue. CFPDE5A1 and CFPDE5A2 expressed in COS-7 cells had cGMP Km values of 2.68 and 1.97 microM, respectively, and both were inhibited by a low concentration of a cGB-PDE inhibitor, Zaprinast. Both CFPDE5A1 and CFPDE5A2 bound cGMP to their allosteric cGMP binding domains, and this cGMP binding was stimulated by 3-isobutyl-1-methylxanthine. Thus, two types of alternative splice variants of canine cGB-PDE have been identified and shown to have similar biological properties in vitro.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1998

Chloride concentration in cultured hippocampal neurons increases during long-term exposure to ammonia through enhanced expression of an anion exchanger.

The effects of long-term exposure to ammonia on [Cl-]i in cultured hippocampal neurons were examined. Ammonia increased the [Cl-]i time- (>/=24 h) and concentration- (>/=2 mM) dependently, resulting in a depolarizing shift of the equilibrium potential of the GABAA receptor-Cl- channel opening (EGABA). Such an effect of ammonia was diminished by the inhibitors of Cl-/HCO3- exchangers, 0.1 mM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 0.1 mM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), and a carbonic anhydrase inhibitor, 2 mM acetazolamide, but not by a Na+/K+/2Cl-cotransport inhibitor, 50 microM bumetanide, suggesting an enhanced Cl-/HCO3- exchange activity by ammonia. The ammonia-induced increase in [Cl-]i was also abolished by the inhibitors of protein kinase C (PKC), 0.1 microM calphostin C and 10 microM 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine dihydrochloride (H-7), and of transcription and de novo protein synthesis, 1 microM actinomycin D and 0.5 microg/ml cycloheximide, while a PKC activator, 0.1 h microM phorbor 12-myristate 13-acetate (PMA), increased the [Cl-]i. The mRNA level of the AE3 Cl-/HCO3- exchanger was increased by ammonia in a calphostin C- and H-7-sensitive manner. The AE3-like immunoreactivity was also increased by ammonia. These findings suggest that long-term exposure to ammonia increases the expression of AE3 through the activation of PKC, resulting in an increase in [Cl-]i in neurons and a reduction of inhibitory postsynaptic potentials.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1998

Neutralization of aspartate residues in the murine inwardly rectifying K+ channel IRK1 affects the substate behaviour in Mg2+ block.

1. To investigate the molecular basis of the sublevels induced in the outward current during block by intracellular Mg2+, single-channel currents through inwardly rectifying K+ (IRK1) channels were studied. 2. cDNA encoding a functional murine IRK1 channel was transfected into COS-1 cells (a Green Monkey kidney cell line) using the liposome method, and voltage clamp experiments were done after 48-72 h. 3. Intracellular Mg2+ at micromolar concentrations induced sublevels in the outward current at one-third and two-thirds of the unitary amplitude seen in wild-type channels. Replacing Asp 172 with Asn (D172N) and Gln (D172Q) abolished these sublevels, i.e. the channel showed only the fully open and fully blocked states. 4. Both mutations reduced the Mg2+ sensitivity of the channel at 2 microM Mg2+. However, the Mg2+ sensitivity did not differ significantly at higher concentrations (10 microM) and voltages (+70 mV). 5. Channels expressed from D172E showed the sublevels, indicating that a negative charge is indispensable to the substate behaviour. 6. Channels from tandem tetramers of IRK1 with one and two D172N mutant subunits mainly showed sublevels with two-thirds amplitude, while those from tetramers with three D172N mutant subunits showed no sublevels. 7. These findings suggest that differences in Mg2+ binding patterns lead to different conductive states in a single-barrelled channel.

Animals↗

PubMed1998

Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene.

cGMP-binding, cGMP-specific phosphodiesterase which is encoded by the PDE5A gene plays important roles in cardiovascular system, and is a significant target molecule of therapeutic agents. However, little is known about molecular characteristics of the human PDE5A gene. The 4.4-kb cDNA encoding human PDE5A was isolated from lung and placenta cDNA libraries. The deduced amino acid sequence analysis demonstrated that N-terminal amino acid sequence is dissimilar to that of rat PDE5A [Kotera, J., Yanaka, N., Fujishige, K., Imai, Y., Akatsuka, H., Ishizuka, T., Kawashima, K. & Omori, K. (1997) Eur. J. Biochem. 249, 434-442]. Human PDE5A mRNA is produced in high amounts in various tissues such as pancreas, skeletal muscle, placenta, heart, thyroid, adrenal cortex, testis, small intestine and stomach. In addition, the megakaryocyte-like cell line Dami cells and two types of human vascular smooth muscle cells also produce the mRNA. Over 100-kb chromosomal DNA corresponding to the human PDE5A gene was isolated and analyzed. The human PDE5A gene was revealed to contain 21 exons. Comparison of genomic organization with the rod photoreceptor phosphodiesterase beta-subunit gene (PDE6B), which is another kind of cGMP-specific phosphodiesterase, has shown that the PDE5A and PDE6B genes are very similar in their relative exon intron organization. In particular, the evolutionary relatedness of these genes was suggested in the catalytic domain. Furthermore, chromosomal location of the PDE5A gene was defined as being chromosome 4q26 by fluorescent in situ hybridization analysis.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1998

Microvascular permeability of the non-heart-beating rabbit lung after warm ischemia and reperfusion: role of neutrophil elastase.

BACKGROUND: The duration of warm ischemia and reperfusion injury is a major limiting factor in the setting of lung transplantation with non-heart-beating donors (NHBD). We hypothesized that reperfusion with neutrophil elastase inhibitor or leukocyte-depleted blood has an inhibitory effect on the ischemia-reperfusion injury of NHBD rabbit lungs. METHODS: To assess the lung injury, we used a perfused rabbit lung model and measured the hemodynamic parameters and filtration coefficient. The rabbit lungs after hypoxic cardiac arrest for 30, 50, and 60 minutes were harvested at room temperature, and ventilated lungs were reperfused for 1 hour at a constant flow (120 mL/min). The group with 60 minutes of warm ischemia and hypoxia was further divided into three groups to determine the effects of leukocyte-depleted reperfusion or neutrophil elastase inhibitor, (1) no other special treatment, (2) reperfusion with leukocyte-depleted blood, and (3) administration of 10 mg of specific neutrophil elastase inhibitor. The lungs reperfused immediately after harvest from the heart-beating donor were regarded as the control. RESULTS: Sixty minutes of warm ischemia and hypoxia resulted in an increase in filtration coefficient (0.68+/-0.20 g x min(-1) x cm H2O(-1) per 100 g) compared with the control values of 0.13+/-0.03 g x min(-1) x cm H2O(-1) per 100 g. The increase in filtration coefficient after 60 minutes of warm ischemia and hypoxia in NHBD was remarkably suppressed by leukocyte depletion (0.23+/-0.07) and by neutrophil elastase inhibitor (0.21+/-0.08). The shunt fraction and histology results were also near normal. CONCLUSIONS: These results suggested that leukocyte depletion or treatment with neutrophil elastase inhibitor during reperfusion reduces alveolar-capillary damage caused by lung ischemia-reperfusion injury in the NHBD lung transplantation setting. This effect might be mediated by inhibition of neutrophil elastase activity or sequestration, and thus may lead to the increased availability of NHBD lungs.

Animals↗

PubMed1998

Serratia marcescens S-layer protein is secreted extracellularly via an ATP-binding cassette exporter, the Lip system.

The Serratia marcescens Lip exporter belonging to the ATP-binding cassette (ABC) exporter is known to be involved in signal peptide-independent extracellular secretion of a lipase and a metalloprotease. Although the genes of secretory proteins and their ABC exporters are usually all reported to be linked in several gram-negative bacteria, neither the lipase nor the protease gene is located close to the Lip exporter genes, lipBCD. A gene (slaA) located upstream of the lipBCD genes was cloned, revealing that it encodes a polypeptide of 100 kDa and is partially similar to the Caulobacter crescentus paracrystalline cell surface layer (S-layer) protein. The Lip exporter-deficient mutants of S. marcescens failed to secrete the SlaA protein. Electron micrography demonstrated the cell surface layer of S. marcescens. The S-layer protein was secreted to the cultured media in Escherichia coli cells carrying the Lip exporter. Three ABC exporters, Prt, Has and Hly systems, could not allow the S-layer secretion, indicating that the S. marcescens S-layer protein is strictly recognized by the Lip system. This is the first report concerning secretion of an S-layer protein via its own secretion system.

ATP-Binding Cassette Transporters↗

PubMed1998

Pulmonary disease models induced by in vivo hemagglutinating virus of Japan liposome-mediated endothelin-1 gene transfer.

Overproduction and overexpression of endothelin-1 (ET-1) have been reported to contribute to the pathophysiology of pulmonary diseases, including pulmonary fibrosis, obliterative bronchiolitis, and primary pulmonary hypertension. To determine whether ET-1 contributes to the pathogenesis of pulmonary disease, we locally overexpressed ET-1 using an in vivo UV-inactivated hemagglutinating virus of Japan (HVJ) liposome-mediated gene transfer system. Plasmid DNA of ET-1 (pME18fc preproET-1) and high mobility group 1 (HMG1) protein were co-encapsulated in liposomes. Then the plasmid DNA and liposome complexes were introduced into the lung via the trachea in Wistar rats, using HVJ-mediated membrane fusion. Control animals received instillation of HVJ liposome with an empty cassette. Two weeks after in vivo transfection of the preproET-1 gene, hyperplastic connective tissue plaques were seen in the alveolar duct and small conducting airways, indicating histologically distinctive obliterative bronchiolitis. No histopathologic changes were seen in the control animals. These results suggested that local overexpression of ET-1 may play an important role in the pathogenesis of obliterative bronchiolitis.

Animals↗

PubMed1998

Influence of size and etiology of glottal gap in glottic incompetence dysphonia.

This study investigates the relationship between glottal gap and vocal function in patients with glottic incompetence dysphonia. Twenty patients with vocal fold paralysis (VFP), 17 patients with vocal fold atrophy (VFA), and five patients with sulcus vocalis (SV) were examined. Glottal gap area at the most closed point of vibration was measured using digitized videostroboscopic images. Glottal gap area was correlated with acoustic and aerodynamic measures of vocal function. Patients with VFP had the largest glottal gaps and had significantly worse vocal function than did the patients with VFA or SV. Regardless of groups, however, where glottal gap size was similar, there was no difference in vocal function. Therefore vocal function was mainly influenced by glottal gap size, not by whether glottic incompetence was the result of VFP, VFA, or SV.

Acoustics↗

PubMed1998

1,25-Dihydroxyvitamin D3 upregulates natriuretic peptide receptor-C expression in mouse osteoblasts.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], a key regulator of mineral metabolism, regulates expression of several genes related to bone formation. The present study examined the 1,25(OH)2D3-mediated regulation of natriuretic peptide receptor-C (NPR-C) expression in osteoblasts. 1,25(OH)2D3 treatment significantly increased NPR-C-dependent atrial natriuretic peptide-binding activity and synthesis of the NPR-C protein in mouse osteoblastic cells in a cell-specific manner. Western blot analysis also demonstrated that 1, 25(OH)2D3 upregulated expression of NPR-C protein in slow kinetics. Next, Northern blot analysis revealed a significant increase in the steady-state NPR-C mRNA level by 1,25(OH)2D3. Sequence analysis of the 9 kb of the 5'-flanking region of the mouse NPR-C gene revealed an absence of consensus vitamin D-response elements, and promoter analysis using osteoblastic cells stably transfected with mouse NPR-C promoter-reporter constructs showed a slight increase of promoter activity with 1,25(OH)2D3 treatment. In addition, a nuclear run-on assay exhibited that the transcriptional rate of the NPR-C gene was unchanged by 1,25(OH)2D3, whereas that of the osteopontin gene was increased. Evaluation of NPR-C mRNA half-life demonstrated that 1,25(OH)2D3 significantly increased the NPR-C mRNA stability in osteoblastic cells. 1,25(OH)2D3 attenuated intracellular cGMP production in osteoblastic cells stimulated by C-type natriuretic peptide (CNP) without a significant change of the natriuretic peptide receptor-B mRNA level, suggesting enhancement of the clearance of exogenously added CNP via NPR-C. Furthermore, NPR-C and osteopontin mRNAs in mouse calvariae were significantly increased by administration of 1,25(OH)2D3, and immunohistological analysis demonstrated that NPR-C is actually and strongly expressed in mouse periosteal fibroblasts. These findings suggest that 1,25(OH)2D3 can play a critical role for determination of the natriuretic peptide availability in bones by regulation of NPR-C expression through stabilizing its mRNA.

Animals↗

PubMed1998

Localization of clearance receptor in rat lung and trachea: association with chondrogenic differentiation.

The lung is rich in atrial natriuretic peptide binding sites, and the majority of them are considered to be the natriuretic peptide clearance receptor (NPR-C). In this study, localization of NPR-C in the rat lung and trachea was investigated by immunohistochemical analysis with the specific antibody. Positive staining was observed in the epithelial cell layers of the trachea and bronchiole and the myocardium surrounding the pulmonary vein. Moreover, expression of NPR-C was seen in mesenchymal cells; it was especially strong in cells in the perichondrium and decreased in chondrocytes in the cartilage. Because mesenchymal cells in the perichondrium differentiate to chondrocytes, NPR-C expression is suggested to be associated with chondrogenic differentiation. The chondrogenic cell line ATDC5 was used to study NPR-C expression during chondrogenic differentiation in vitro. The undifferentiated ATDC5 cells expressed NPR-C at a much higher level than the differentiated ATDC5 cells, in accordance with the observation of the immunohistochemical analysis in the cartilage. These findings suggest that NPR-C expression is differentially regulated in chondrocytes and that the natriuretic peptides may play a role in regulating chondrocyte development in the lung.

Amino Acid Sequence↗

PubMed1998

Isolation and characterization of the 5'-flanking regulatory region of the human natriuretic peptide receptor C gene.

Phenotypic modulation of vascular smooth muscle cells (SMCs) plays a central role in the pathogenesis of atherosclerosis. Natriuretic peptide receptor-C (NPR-C) is highly expressed in vascular SMCs in the experimental arteriosclerotic neointimal area as well as in cultured SMCs, suggesting that increased expression of the NPR-C gene is related to the phenotypic alteration of vascular SMCs. To elucidate the molecular mechanisms and to identify the essential DNA sequences in NPR-C gene expression, a genomic clone containing over 8 kilobases of the 5'-flanking region of the human NPR-C gene has been isolated. Sequence analysis revealed that a number of putative regulatory elements including unusual tandem repeated AP-2-like sequences were observed in the 5'-flanking region. Primer extension and ribonuclease protection analyses revealed that transcription of the human NPR-C gene starts from two major regions. Promoter analysis using deletion constructs in human cells, highly producing NPR-C transcripts, showing that the region (from - 33 to + 13 relative to the transcription start point) had a potential promoter activity suggested that the region from -33 to + 13, containing a pyrimidine-rich stretch composed of four CTTTTT-repeated sequences, is sufficient for the proximal promoter activity. Moreover, three distinct DNA sequences surrounding the transcription start site (P1, from -60 to -33; P2, from + 14 to +40; P3, from +41 to +66) were revealed to be functional as a cis-acting positive enhancer, and a nuclear protein(s) from the human cells was demonstrated to specifically bind to the sequences, respectively. However, promoter analysis has shown that the P2 and P3 sequences could not activate the human NPR-C promoter in a synergistic manner. On the basis of deoxyribonuclease I footprinting analysis showing that a DNA element from +48 to +60 within the P3 sequence is preferentially protected, the P3 sequence appears to contain a potential regulatory element involved in NPR-C gene expression. The present study demonstrated the structure of the 5'-regulatory region of the human NPR-C gene and multiple cis-acting positive sequences closely located around the transcription start points with an important role in regulation of human NPR-C gene expression.

Amino Acid Sequence↗

PubMed1998

TMC-49A, a novel transcriptional up-regulator of low density lipoprotein receptor, produced by Streptomyces sp. AS1345.

Microbial metabolites were screened for a transcriptional up-regulator of low density lipoprotein (LDL) receptor by a reporter assay. TMC-49A was discovered as an up-regulator obtained from the fermentation broth of Streptomyces sp. AS1345. The structure of TMC-49A was elucidated to be butyl N-phenethylcarbamate by spectroscopic analyses. This compound enhanced the synthesis of LDL receptor in human hepatoma HepG2 cells as assessed by a receptor binding assay. Taxonomy of the producing strain is also described.

Carbamates↗

PubMed1998

[AIDS and STD knowledge and risk behaviors among commercial sex workers in Myitkyina, Myanmar].

This study investigated AIDS and STD (Sexually Transmitted Diseases) knowledge, risk behaviors, and condom use among two different groups of female commercial sex workers (CSWs) in Myitkyina, Myanmar. Individual in-depth interviews were conducted with 65 direct and 65 indirect CSWs. These CSW groups differ in the prices they charge, their places and modes of employment, levels of knowledge concerning HIV and STD transmission and prevention, number of clients served, levels of condom use and STD symptoms. Indirect CSWs have higher levels of knowledge, fewer partners, and more frequent condom use; but still have high levels of STD symptoms and frequently engage in unprotected sex with clients. Many CSWs and their clients were originally from other regions; these people could well be agents in the rapid spread of the HIV virus throughout Myanmar. Interventions targeted to specific groups of CSWs and clients should be undertaken as soon as possible, including educational activities concerning AIDS and STD transmission and prevention, condom promotion and distribution, and activities to improve the health sector's capabilities to help both CSWs and their clients.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Protein kinase C activation down-regulates natriuretic peptide receptor C expression via transcriptional and post-translational pathways.

Natriuretic peptide receptor C (NPR-C) mRNA expression and ANP-binding activity via NPR-C are significantly down-regulated in HeLa cells with phorbol myristate acetate (PMA) treatment. Stabilization of the NPR-C mRNA by PMA indicated that down-regulation of its mRNA was mediated through negative transcriptional regulation. Despite the significant loss of the mRNA, reduction of NPR-C-specific ANP-binding activity after PMA exposure (4 h) was accompanied by a slight decrease in total NPR-C protein (with a 5% loss) and was also produced in the presence of actinomycin D or cycloheximide. The inhibitory effect of a long PMA exposure (18 h) paralleled with a decrease in total NPR-C protein is suggested to be dependent on reduction of de novo NPR-C synthesis. PMA-induced transcriptional and post-translational down-regulation of NPR-C was effectively reversible in the presence of the protein kinase C inhibitor GF109203X. These findings demonstrate that protein kinase C activation down-regulated NPR-C expression through transcriptional and post-translational pathways and that immediate functional receptor loss was mediated via a post-translational mechanism, such as enhanced receptor internalization.

Atrial Natriuretic Factor↗

PubMed1997

The apolipoprotein A-I/C-III/A-IV gene cluster: ApoC-III and ApoA-IV expression is regulated by two common enhancers.

Genetic, epidemiological and clinical evidence have clearly demonstrated the importance of the human apolipoprotein (apo) A-I/C-III/A-IV gene cluster in lipid metabolism and heart attack. The transcriptional regulation of these genes determines the level of the encoded proteins and therefore influences the concentration of triglycerides and cholesterol. Here, we analyze the existence of transcription control elements in the 6.6 kb apoC-III/A-IV intergenic region and their influence on the expression of both genes. Two main positive common control elements were found to modulate apoC-III and apoA-IV expression in HepG2 and in Caco-2 cells: the previously described apoC-III enhancer, located 0.8 kb upstream from the cap site of the gene, and a newly detected activating region located in the center of the intergenic sequence. The activity of both elements is highly increased by the hepatic and intestinal transcription factor HNF-4. Analysis of a 641 bp fragment containing the central element showed that it has the properties of a tissue-specific enhancer. Liver nuclear proteins interact with seven DNA binding sites present in this enhancer and HNF-4 specifically interacts with one of these sites. A third positive element, situated immediately upstream from the apoA-IV minimal promoter, is also activated by HNF-4; however, this element is not involved in apoC-III expression. In addition, two negative regions were identified, one located near the apoA-IV gene and the other one between the apoC-III enhancer and the newly identified central enhancer. In conclusion, negative and positive control elements are located in the apoC-III/A-IV intergenic region, including two enhancers important for the expression of the two genes. These results add new evidence that common regulatory elements for the expression of the apoA-I, apoC-III and apoA-IV genes are interspersed throughout the cluster.

Apolipoprotein A-I↗