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Identification of secondary structure in the 5'-untranslated region of the human adrenomedullin mRNA with implications for the regulation of mRNA translation.

Adrenomedullin (AM) is a multifunctional regulatory peptide with important angiogenic and mitogenic properties. Here we identify a region of stable secondary structure in the 5'-untranslated region (5' UTR) of human AM mRNA. Reverse transcriptase-polymerase chain reaction of the 5' UTR consistently resulted, in addition to the product with the expected size of 155 base pair (bp), in a second product with an approximately 65-bp deletion from the central region of the 5' UTR, suggesting the presence of a secondary structure. The presence of a stem-loop structure was confirmed by probing the 5' UTR with RNases with selectivity for single- or double-stranded RNA. We investigated the role of this stem-loop structure in expression of luciferase reporter gene in cultured cell lines. Reporter assays using a chimeric mRNA that combined luciferase and the 5' UTR of AM mRNA demonstrated a dramatic decrease of the reporter activity owing to a decreased translation, whereas the deletion of the stem-loop structure localized between nt +31 and +95 from the cap site led to the recovery of activity. Gel migration shift assays using cytosolic extracts from mammalian cell lines demonstrate a specific binding of a cytosolic protein to riboprobes containing the 5' UTR of AM but not to riboprobes either corresponding to other areas of the message or containing the 5' UTR but lacking the region of secondary structure. Although we conclude that the 5' UTR of the human AM mRNA can modulate the translation of AM mRNA in vivo, and that the predicted stem-loop structure is necessary for this inhibition, the functional consequences of the cis element-binding activity remain to be determined.

5' Untranslated Regions↗

DARPP-32 genomic fragments drive Cre expression in postnatal striatum.

To direct Cre-mediated recombination to differentiated medium-size spiny neurons (MSNs) of the striatum, we generated transgenic mice that express Cre recombinase under the regulation of DARPP-32 genomic fragments. In this reported line, recombination of an R26R reporter allele occurred postnatally in the majority of medium-size spiny neurons of the dorsal and ventral striatum (caudate nucleus and nucleus accumbens/olfactory tubercle), as well as in the piriform cortex and choroid plexus. Although regulatory fragments were selected to target MSNs, low levels of Cre-recombinase expression, as detected by beta-galactosidase activity from the R26R reporter gene, were also apparent in widely dispersed areas or cells of the forebrain and hindbrain. These included the primary and secondary motor cortex, and association cortex, as well as in the olfactory bulb and cerebellar Purkinje cells. Notably, expression in these regions was well below that of endogenous DARPP-32. Analysis of colocalization of beta-galactosidase, as detected either by histochemistry or immunocytochemistry, and DARPP-32 revealed double-labeling in almost all DARPP-32-expressing MSNs in the postnatal striatum, but not in extrastriatal regions. The DARPP-32Cre transgenic mouse line thus provides a useful tool to specifically express and/or inactivate genes in mature MSNs of the striatum.

Animals↗

Tumor promoter phorbol myristic acetate stimulates immunoglobulin secretion correlated with growth cessation in human B lymphocyte cell lines.

Immunoglobulin production by lymphoblast cell lines was studies using protein A-red blood cell plaque formation to detect individual secreting cells. Immunoglobulin (Ig) secretion by 6 of 12 human B-cell lines tested could be stimulated up to twentyfold by phorbol myristic acetate (PMA) at subtoxic concentrations of 10-1000 ng/ml depending on the line. Stimulation was found with both IgM and IgG cell lines. No switch of Ig class synthesis was found in the cell lines as a result of PMA incubation. Increase in Ig secretion was closely associated with cessation of growth resembling induction of terminal differentiation in the cells. PMA induction of Ig secretion in B lymphocytes from normal peripheral blood requires the cooperation of T cells. PMA stimulation of certain cell lines reported here suggests that the lines are late in the differentiation pathway to plasmacyte and can be easily triggered to secrete Ig by membrane-altering agents.

Antibody Formation↗

Product line management requires change in financial reports.

Product line management places new financial reporting demands on healthcare organizations. The new reports should provide profitability information that helps management make decisions and fairly evaluate the roles that operating managers and product managers have in their organizations.

Accounting↗

Left mediastinal central line malposition--a case report.

Central venous line malpositioning in the left mediastinum is a rare event. A case of left superior intercostal vein central venous line placement is reported. Chest radiographs, especially lateral views and contrast studies, are useful for position evaluation. Catheter removal is prudent although the purpose of the catheter and the symptomatology can dictate further management of the malpositioned catheter.

Aged↗

Use of new T-cell-based cell lines expressing two luciferase reporters for accurately evaluating susceptibility to anti-human immunodeficiency virus type 1 drugs.

Two new T-cell-based reporter cell lines were established to measure human immunodeficiency virus type 1 (HIV-1) infectivity. One cell line naturally expresses CD4 and CXCR4, making it susceptible to X4-tropic viruses, and the other cell line, in which a CCR5 expression vector was introduced, is susceptible to both X4- and R5-tropic viruses. Reporter cells were constructed by transfecting the human T-cell line HPB-Ma, which demonstrates high susceptibility to HIV-1, with genomes expressing two different luciferase reporters, HIV-1 long terminal repeat-driven firefly luciferase and cytomegalovirus promoter-driven renilla luciferase. Upon HIV infection, the cells expressed firefly luciferase at levels that were highly correlated (r2=0.91 to 0.98) with the production of the capsid antigen p24. The cells also constitutively expressed renilla luciferase, which was used to monitor cell numbers and viability. The reliability of the cell lines for two in vitro applications, drug resistance phenotyping and drug screening, was confirmed. As HIV-1 efficiently replicated in these cells, they could be used for multiple-round replication assays as an alternative method to a single-cycle replication protocol. Coefficients of variation for drug susceptibility evaluated with the cell lines ranged from 17 to 41%. The new cell lines were beneficial for evaluating antiretroviral drug resistance. Firefly luciferase gave a wider dynamic range for evaluating virus infectivity, and the introduction of renilla luciferase improved assay reproducibility. The cell lines were also beneficial for screening new antiretroviral agents, as false inhibition caused by the cytotoxicity of test compounds was easily detected by monitoring renilla luciferase activity.

Anti-HIV Agents↗

Somitic origin of limb muscle satellite and side population cells.

Repair of mature skeletal muscle is mediated by adult muscle progenitors. Satellite cells have long been recognized as playing a major role in muscle repair, whereas side population (SP) cells have more recently been identified as contributing to this process. The developmental source of these two progenitor populations has been considerably debated. We explicitly tested and quantified the contribution of embryonic somitic cells to these progenitor populations. Chick somitic cells were labeled by using replication-defective retroviruses or quail/chick chimeras, and mouse cells were labeled by crossing somite-specific, Pax3-derived Cre driver lines with a Cre-dependent reporter line. We show that the majority of, if not all, limb muscle satellite cells arise from cells expressing Pax3 specifically in the hypaxial somite and their migratory derivatives. We also find that a significant number of, but not all, limb muscle SP cells are derived from the hypaxial somite. Notably, the heterogeneity in the developmental origin of SP cells is reflected in their functional heterogeneity; somitically derived SP cells are intrinsically more myogenic than nonsomitically derived ones. Thus, we show that the somites, which supply embryonic and fetal myoblasts, are also an important source of highly myogenic adult muscle progenitors.

Animals↗

Specific chromosomal abnormalities characterize four established cell lines derived from malignant human gliomas.

The four permanent human glioma-derived cell lines reported here are the first such lines for which the karyotypes have been followed from the original biopsies through the establishment of the lines in culture. Although ploidy changes were seen, each line retained either distinctive marker chromosomes or the overall original chromosomal distribution allowing the origin of each line to be established with certainty. D-263 MG expresses glial fibrillary acidic protein, all lines except D-245 MG are tumorigenic in athymic mice, and each line displays a unique pattern with respect to in vitro growth parameters and expression of biochemically defined markers, oncofetal antigens and lymphoid-associated markers. D-245 MG and D-259 MG are able to grow in the absence of supplemental glutamine; glutamine synthetase was detected in these cell lines both by immunocytochemistry and by direct assay. Thus, the four permanent human glioma-derived cell lines described here are representative of glioma lines in their general characteristics. D-259 MG retains numerous double minute chromosomes (DMs), D-263 MG contains two marker chromosomes with breaks in 9p, and D-247 MG and D-245 MG with stemlines containing 96 and 89 chromosomes contain eight and six normal copies (respectively) of chromosome No. 7. The retention in these four cell lines of the most common chromosomal abnormalities seen in biopsies of malignant human gliomas provides the opportunity to investigate the meaning of these specific chromosomal changes.

Animals↗

Graded expression of ceh-14 reporters in the hypodermis is induced by a gonadal signal.

ceh-14, a LIM class homeobox gene from Caenorhabditis elegans, is the orthologue of the vertebrate Lhx3/Lhx4 genes. ceh-14 reporter constructs are expressed in several different cell types: head and tail neurons, spermatheca and hypodermis. An intriguing aspect of the hypodermal expression pattern is that it takes the form of a gradient which is strongest in the central body region in L4 to young adult hermaphrodites. Promoter deletion analyses revealed that important regulatory elements for hypodermal expression are located within the transcribed region of ceh-14. Since a large part of the hypodermis is a syncytium, we hypothesized that this expression is triggered in a non-cell-autonomous fashion, a possible source being the underlying gonad. In males, which have a different gonadal organisation, the ceh-14 reporter constructs are expressed in a gradient that is strongest in the tail. By laser ablation of the gonadal precursor cells we found that ceh-14 reporter construct expression is eliminated in the hermaphrodite hypodermis, suggesting that the gonad plays a role in the generation of the gradient. Several signaling pathways are known in the gonad and the vulva, thus we crossed the mutations lin-3, egl-17 and lin-12 with the ceh-14 reporter lines. However, the expression of the reporter constructs is not affected in these mutant backgrounds. This suggests that another, presently unknown, signal triggers the graded hypodermal expression.

Animals↗

Podocytes populate cellular crescents in a murine model of inflammatory glomerulonephritis.

Cellular crescents are a defining histologic finding in many forms of inflammatory glomerulonephritis. Despite numerous studies, the origin of glomerular crescents remains unresolved. A genetic cell lineage-mapping study with a novel transgenic mouse model was performed to investigate whether visceral glomerular epithelial cells, termed podocytes, are precursors of cells that populate cellular crescents. The podocyte-specific 2.5P-Cre mouse line was crossed with the ROSA26 reporter line, resulting in irreversible constitutive expression of beta-galactosidase in doubly transgenic 2.5P-Cre/ROSA26 mice. In these mice, crescentic glomerulonephritis was induced with a previously described rabbit anti-glomerular basement membrane antiserum nephritis approach. Interestingly, beta-galactosidase-positive cells derived from podocytes adhered to the parietal basement membrane and populated glomerular crescents during the early phases of cellular crescent formation, accounting for at least one-fourth of the total cell mass. In cellular crescents, the proliferation marker Ki-67 was expressed in beta-galactosidase-positive and beta-galactosidase-negative cells, indicating that both cell types contributed to the formation of cellular crescents through proliferation in situ. Podocyte-specific antigens, including WT-1, synaptopodin, nephrin, and podocin, were not expressed by any cells in glomerular crescents, suggesting that podocytes underwent profound phenotypic changes in this nephritis model.

Animals↗

Gene deletion in urothelium by specific expression of Cre recombinase.

Urothelium that lines almost the entire urinary tract acts as a permeability barrier and is involved in the pathogenesis of major urinary diseases, including urothelial carcinoma, urinary tract infection, and interstitial cystitis. However, investigation of urothelial biology and diseases has been hampered by the lack of tissue-specific approaches. To address this deficiency, we sought to develop a urothelium-specific knockout system using the Cre/loxP strategy. Transgenic mouse lines were generated in which a 3.6-kb mouse uroplakin II (UPII) promoter was used to drive the expression of Cre recombinase (Cre). Among the multiple tissues analyzed, Cre was found to be expressed exclusively in the urothelia of the transgenic mice. Crossing a UPII-Cre transgenic line with a ROSA26-LacZ reporter line, in which LacZ expression depends on Cre-mediated deletion of a floxed "stop" sequence, led to LacZ expression only in the urothelium. Gene recombination was also observed when the UPII-Cre line was crossed to an independent line in which a part of the p53 gene was flanked by the loxP sequences (floxed p53). Truncation of the p53 gene and mRNA was observed exclusively in the urothelia of double transgenic mice harboring both the UPII-Cre transgene and the floxed p53 allele. These results demonstrate for the first time the feasibility and potentially wide applicability of the UPII-Cre transgenic mice to inactivate any genes of interest in the urothelium.

Animals↗

Establishment and characterization of three immortal bovine muscular epithelial cell lines.

We have established three immortal bovine muscular epithelial (BME) cell lines, one spontaneously immortalized (BMES), the second SV40LT-mediated (BMEV) and the third hTERT-mediated (BMET). The morphology of the three immortal cell lines was similar to that of early passage primary BME cells. Each of the immortal cell lines made cytokeratin, a typical epithelial marker. BMET grew faster than the other immortal lines and the BME cells, in 10% FBS-DMEM medium, whereas neither the primary cells nor the three immortal cell lines grew in 0.5% FBS-DMEM. The primary BME cells and the immortal cell lines, with the exception of BMES, made increasing amounts of p53 protein when treated with doxorubicin, a DNA damaging agent. On the other hand, almost half of the cells in populations of the three immortal cell lines may lack p16(INK4a) regulatory function, compared to primary BME cells that were growth arrested by enforced expression of p16(INK4a). In soft-agar assays, the primary cells and immortal cell lines proved to be less transformed in phenotype than HeLa cells. The three immortal epithelial-type cell lines reported here are the first cell lines established from muscle tissue of bovine or other species.

Animals↗

Status of the three-phase line tension: a review.

From a thermodynamic point of view, the concept of line tension is on solid ground; it is well recognized and defined. There is a notion in the literature that there is little consensus with regards to magnitude or sign of line tension. Partly, inappropriate comparisons of line tension values may have contributed to the current uncertainty, especially some between theoretical and experimental values. A wide range of reported line tension values may not necessarily be a result of conflicting findings, but it may reflect the diversity of systems studied. However, differences among similar approaches and systems observed are sometimes caused by one or several of the following factors: difficulties in sample preparation, poor experimental techniques, non-equilibrium, or conceptual and theoretical difficulties and over simplifications. It is important to clearly establish the magnitude and sign of line tension as it may determine its relevance to technological applications such as microfluidic systems. This review has examined a wide range of recent and past studies on the subject of line tension. The review classifies line tension studies into theoretical and experimental; it further groups the studies into liquid-liquid-vapor and solid-liquid-vapor systems for each category. The review provides a comparison between similar studies in an attempt to clarify the current status of line tension research. The majority of theoretical line tension studies (excluding the near wetting studies) have estimates for line tension of about 10(-10) N; however, for special cases, values as high as 10(-6) N are also reported. There is less consensus regarding the sign for the line tension as theoreticians often assert that line tension can have either a positive or a negative sign. In experimental studies of liquid-liquid-vapor systems the majority of studies reported positive values for line tension; for film studies, the magnitude of line tension reported was between 10(-9) and 10(-7) N, whereas for studies of liquid lens values as high as 10(-6) N were also reported. The clear majority of studies for solid-liquid-vapor systems reported a positive sign for line tension. In studies involving particles, line tension values ranged from 10(-9) to 10(-6) N. Studies using drop size dependence of contact angles reported values mostly in the span of 10(-9)-10(-6) N; however, a clear majority of the reported values fell in the higher end of the above range. The special topic of line tension near wetting was also studied. While the interface displacement model appears to have brought about consensus with respect to certain aspects of line tension behavior near wetting, this model maybe still too phenomenological to be satisfactory from a more fundamental standing. Experimentalists have just begun studying line tension for systems near wetting, this is encouraging, but more comprehensive studies are needed.

Chemistry, Physical↗

The impact of sequence divergence and DNA mismatch repair on homeologous recombination in Arabidopsis.

We examined the effects of substrate divergence and DNA mismatch repair (MMR) on recombination in Arabidopsis thaliana. Relative to the frequency observed in plants with a homologous construct (0% divergence), recombination was decreased 4.1-, 9.6-, 11.7- or 20.3-fold, respectively, in lines with constructs containing 0.5%, 2%, 4% or 9% divergence between the recombination substrates. To evaluate the contribution of the MMR system in this decrease, 12 independent reporter lines (two or three lines per reporter construct) were crossed to an AtMSH2 T-DNA insertional mutant. We examined the recombination frequency in progeny homozygous for a reporter T-DNA and homozygous either for the wild type or the mutant allele of AtMSH2. The loss of MMR activity led to a two- to ninefold increase in homeologous recombination and the size of the increase did not seem to correlate with the amount of divergence. Inversely, complementation of the insertional mutant with a wild-type cDNA of AtMSH2 reduced recombination. Our results demonstrate clearly that sequence divergence can dramatically reduce the recombination frequency in plants and that the MMR system plays a part in this decrease.

Alleles↗

Radiology casebook. Unusual misplacement sites for central venous catheters: three case reports.

Umbilical venous catheters and percutaneously placed central venous lines play an integral role in the management of critically ill newborn infants. Health care providers involved with the placement of these catheters must be familiar with, and able to diagnose, subtle sites for catheter misplacements. Three cases are presented illustrating potential sites of misplacement. The indications, placement, and associated complications of central venous lines reported in the literature are briefly reviewed.

Catheterization, Central Venous↗

The MHC of a broiler chicken line: serology, B-G genotypes, and B-F/B-LB sequences.

Although the major histocompatibility complex of chickens (encoded in the B complex) has been studied for a number of years, almost all work has focused on the White Leghorn breed. Broiler (meat-type) chickens were derived from other breeds, including Cornish and Plymouth Rock. It was our hypothesis that new B haplotypes, not previously identified in White Leghorns, might be present in lines of broiler chickens. Furthermore, alloantisera used to identify B serotypes in Leghorn lines reportedly do not work well outside the line in which they were raised, with the result that broiler B haplotypes have not been incorporated into the universal nomenclature system. Our approach was to use a panel of B alloantisera produced to identify B serotypes within a commercial broiler breeder line (designated line A). B homozygotes identified serologically were compared by B-G genotyping using restriction fragment length polymorphism analysis. Furthermore, reverse transcription-polymerase chain reaction was used to amplify variable domains of expressed B-LB and B-F genes of homozygotes of most of the B serotypes in Line A, followed by cloning and nucleotide sequence determination. Comparison of B-LB and B-F sequences with standard Leghorn haplotypes demonstrated the existence of new alleles of B-L and B-F in a broiler breeder line, as well as the presence of alleles previously identified in Leghorns. In some cases, Leghorn-type alleles were in linkage with different B-G alleles in the broiler line than the common haplotypic associations found in Leghorn lines.

Alleles↗

Experimental and theoretical Stark broadening studies of the hydrogen Paschen beta line.

Experimental and theoretical Stark broadening studies of the Paschen beta line of hydrogen (lambda=1.28 microm) are reported. Line shape measurements were performed at electron densities of the plasma between 3.5 x 10(15) cm(-3) and 7.5 x 10(15) cm(-3), applying as the light source a wall-stabilized arc operated at atmospheric pressure in a helium-hydrogen gas mixture. The radiation of the plasma, emitted from nearly homogeneous plasma layers in the end-on direction, was registered with the use of a grating spectrometer equipped with a charge coupled device detector. The measured light outputs were calibrated against signals obtained from a tungsten strip radiation standard. The experimentally determined line profiles are compared with results of new Stark broadening calculations based on simulation techniques. The measured broadening, shift, and asymmetry parameters are also compared with results of previous Stark broadening calculations and other experimental data obtained at electron densities higher as well as lower than ours.

Journal Article↗

Leptin and the pituitary.

In 1994, Zhang et al. of Rockefeller University in New York reported the first successful complementary DNA (cDNA) cloning of leptin by the positional cloning method. Leptin was identified as the gene of ob/ob mouse in genetic obesity syndromes. It has very strong food intake control, and body weight and energy expenditure. The name "leptin" derived from the Greek word leptos, meaning "thin." We hereby review major advances leading to our current finding of leptin, leptin receptor and its structure, the outline of homozygote, and also influence of leptin in the pituitary. (The structure of leptin) The mouse obese gene has been localized to chromosome 6. With human leptin gene on chromosome 7q31.3, its DNA has more than 15000 base pairs and consists of three exons and two introns. For bioactivation of leptin the importance of disulfide-binding site is suggested. Human leptin which replaced the 128-th arginine with glutamine has the function of an aldosteron antagonist, which is reported to have the function of athrocytosis inhibition. The resemblance of leptin precursor of human, mouse and rat is very high, i.e., mouse and rat homology is 96% and mouse and human homology is 83%. (The structure of leptin receptor) The mutant gene, which is the cause of obesity, was shown on map on diabetic mouse (db/db) chromosome 4, and it was proven to be the same as the leptin receptor gene cloned by Tartaglia et all. Further studies have found the Zucker fatty rat (fa/fa) to be incorporated into a linkage map of rat chromosome 5, whose region of rat is the equivalent to the region of conserved synteny of the db/db mouse gene. The leptin receptor is glycoprotein consisting of a single transmembrane-spanning component. The primary structure of leptin receptor belongs to the cytokine-class1 family, the single membrane-spanning receptor, and is highly related to the gp130 signal-transducing component of the interleukin-6 (IL-6) receptor, the granulocyte colony-stimulating factor (G-CSF) receptor, and the leukemia inhibitory factor (LIF) receptor. The leptin receptor is known to have at least six existing isoforms (Ob-Ra, b, c, d, e, f) from the difference in splicing. (Homozygote Mutation of Leptin and Leptin Receptor :Hormone Secretion Disorders) The point mutation of ob/ob mouse and the splicing mutation of db/db mouse show remarkable obesity and hyperphagia. These obesity models show a reproduction disorder with both the male and the female, and they develop with homozygote. The cause is thought to be the gonadotropin secretory abnormality in pituitary. Three family lines report the cases of this deficiency, and it is considered that the secretory abnormality in pituitary develops into hypogonadotropic. These patients show low value in plasma FSHbeta (follicle stimulating hormone-beta and LHbeta (luteinizing hormone-beta which are produced from pituitary, and the plasma GnRH (gonadotropin releasing hormone) level is also low. Furthermore, the leptin receptor deficient family line was reported in 1998, in which case only the homozygote developed. The plasma leptin concentration of normal human is about 8.0 ng/ml, and this case with leptin receptor deficiency has high value of 500-700 ng/ml, which is the equivalent to the db/db mouse. (Role of Leptin in Hypothalamus-Pituitary-Periphery Function) The role of leptin which regulates pituitary hormones suggests the promotion the GHRH (growth hormone releasing hormone) secretion in hypothalamus-pituitary axis, with the possibility of the rise in secretion of GH (growth hormone) in pituitary, i.e. effects of icv (intracerebroventricular) infusion of leptin has spontaneously stimulated GHRH, which promotes GH secretion in the normal rats. On the other hand, topical treatment of GH3 (derived from a rat pituitary GH-secreting cell line) with leptin directly inhibits cell proliferation. The obesity model animals (ob/ob, db/db, fa/fa) have equally plump body compared to the normal models, which shows signs of sufficient growth. (Localization and Functional Relevance of Leptin and Leptin Receptor in Rodents Pituitary) Aside from being the food intake inhibitor and the energy control factor, leptin takes part in controlling the pituitary hormones. Promoting the secretion of GH, PRL (prolactin), TSHbeta (thyroid stimulating hormone-beta, FSHbeta/LHbeta, and inhibiting the secretion of ACTH (adrenocorticotropic hormone) are the major changes of pituitary hormones which are brought on by leptin. The expressive localization is specific, and immunohistochemistry (IHC) method recognized leptin in granular state in FSHbeta, LHbeta and TSHbeta positive cells. In our biochemical examination, the bulk of the expression of leptin is recognized in fraction of the secretory granule. In particular, FSHbeta cells had the highest percentage rate of colocalized leptin in rat pituitary. On the other hand, leptin receptor has been reported to be found only in normal rat pituitary, human pituitary adenoma, and respective cell lines in pituitaries by the RT-PCR method until now, but we disclosed for the first time the localization of leptin receptor on the plasma membrane of GH-secreting cells with the IHC method that has not been cleared so far. These findings show that leptin and leptin receptor have been expressed in different cells, and that the rat pituitary glands entertain paracrine mechanism between leptin (FSHbeta/LHbeta cells) and leptin receptor (GH cells). The function of paracrine in this pituitary suggests a new point of view in hypothalamus-pituitary axis, and it shall be concerned with many aspects such as hormone secretions and proliferation/inhibition. (Human Pituitary Adenoma) Preliminary report of leptin and leptin-receptor relationship with pituitary adenoma that has secretion abnormality has been filed, and its manifestation is being observed by the RT-PCR. Leptin and leptin receptor are expressed in most adenoma, and it is thought to function by autocrine and paracrine pathway in the adenomas. Leptin has been located in ACTH-secreting adenoma most frequently, especially in ACTH carcinoma. The leptin receptor is detected in all adenomas with high percentage rate, with both long and short forms, and then many cases of nonfunctioning pituitary adenomas, compared with other adenomas, have been reported to be positive with both long and short forms of leptin receptor as detected by RT-PCR. The HP75 cell line is derived from the nonfunctioning pituitary adenoma, which produces FSHbeta and LHbeta. The expression of leptin receptor in nonfunctioning pituitary adenoma, and the suppression of HP75 multiplication may lead to the possible hypothesis of leptin becoming one factor for the treatment of pituitary adenoma, especially in gonadotropin adenomas.

Animals↗