Biomedical subjects

W Xie

Publications and source records attributed to W Xie.

At least 91 records · Page 5Linked to original sources

PubMed1999

Interaction between the peripheral site residues of human butyrylcholinesterase, D70 and Y332, in binding and hydrolysis of substrates.

Human butyrylcholinesterase displays substrate activation with positively charged butyrylthiocholine (BTC) as the substrate. Peripheral anionic site (PAS) residues D70 and Y332 appear to be involved in the initial binding of charged substrates and in activation control. To determine the contribution of PAS residues to binding and hydrolysis of quaternary substrates and activation control, the single mutants D70G/Y and Y332F/A/D and the double mutants Y332A/D70G and Y332D/D70Y were studied. Steady-state hydrolysis of the charged substrates, BTC and succinyldithiocholine, and the neutral ester o-nitrophenyl butyrate was measured. In addition, inhibition of wild-type and mutant enzymes by tetramethylammonium was investigated, at low concentrations of BTC. Single and double mutants of D70 and Y332 showed little or no substrate activation, suggesting that both residues were important for activation control. The effects of double mutations on D70 and Y332 were complex. Double-mutant cycle analysis provided evidence for interaction between these residues. The category of interaction (either synergistic, additive, partially additive or antagonistic) was found to depend on the nature of the substrate and on measured binding or kinetic parameters. This complexity reflects both the cross-talk between residues involved in the sequential formation of productive Michaelian complexes and the effect of peripheral site residues on catalysis. It is concluded that double mutations on the PAS induce a conformational change in the active site gorge of butyrylcholinesterase that can alter both substrate binding and enzyme acylation.

Binding Sites↗

PubMed1999

Conditional expression of the ErbB2 oncogene elicits reversible hyperplasia in stratified epithelia and up-regulation of TGFalpha expression in transgenic mice.

The ErbB2 receptor tyrosine kinase (RTK) is expressed in basal cells of squamous epithelia and the outer root sheath of hair follicles. We previously showed that constitutive expression of activated ErbB2 directed to these sites in the skin by the keratin 14 (K14) promoter produces prominent hair follicle abnormalities and striking skin hyperplasia in transgenic mice. However, perinatal lethality precluded the establishment of a transgenic line for analysis of ErbB2 function in adult animals. To investigate the significance of ErbB2 signaling in epithelial tissues during and post development, we developed a K14-rtTA/TetRE-ErbB2 'Tet-On' bitransgenic mouse system. These mice were normal until the ErbB2 transgene was induced by exposure to doxycycline (Dox). Prenatal induction resulted in perinatal death. Postnatally, ErbB2 transgene expression was observed at 4 h after the initiation of Dox, and reached a plateau at 24 h. Skin hyperplasia followed after 2 days and these changes reverted to normal upon Dox withdrawal. In adults, as in the neonates, prolonged ErbB2 induction caused prominent skin and hair follicle hyperplasias. Severe hyperplasias in the cornea, eye lids, tongue and esophagus were also observed. ErbB2 transgene induction was accompanied by increased expression of TGFalpha, a ligand of epidermal growth factor receptor (EGFR), and to a lesser extent, EGFR, further enhancing RTK signal transduction. We conclude that ErbB2 plays important roles in both development and maintenance of hair follicles and diverse squamous epithelia and that this ligand-inducible and tissue-specific 'Tet-On' transgenic mouse system provides a means to study transgenes with perinatal toxicity.

Animals↗

PubMed1999

Human serum paraoxonase (PON1): identification of essential amino acid residues by group-selective labelling and site-directed mutagenesis.

Human serum paraoxonase/arylesterase (PON1, EC 3.1.8.1.) is a calcium-dependent enzyme which hydrolyzes a wide variety of organophosphates, including paraoxon, DFP, sarin and soman. Although the 3-D structure of PON has not yet been determined and its sequence shows no similarity with any other crystallized proteins, we undertook to identify some of its essential amino acid residues by two complementary approaches: group-specific labelling and site-directed mutagenesis. Group-specific labelling studies, performed on the purified native enzyme, indicated that one or more Trp, His and Asp/Glu are potentially important residues for PON activity. Based on these results, we identified some of these residues, conserved in the sequenced mammalian PON1, by site-directed mutagenesis. PON1 mutants were transiently expressed in 293T cells. The catalytic constants k(cat) and Km (relative to k(cat) and Km of the wild-type) determined with four different substrates (phenylacetate, paraoxon, diazoxon, chlorpyrifos oxon), were not significantly changed for the following mutants: W193A, W201A, W253A, H160N, H245N, H250N, H347N, E32A, E48A, D88A, D107A, D121A, D273A. By contrast, k(cat) was less than 1% for eight mutants: W280A, H114N, H133N, H154N, H242N, H284N, E52A and D53A. The essential amino acid residues identified in this work could be part of the PON1 active site, acting either as calcium ligands (E52 and D53?) or as substrate binding (W280?) or nucleophilic (His residues?) sites. However, we cannot rule out that the effects of mutations on catalytic properties resulted from a remote conformational change and/or misfolding of mutant proteins.

Amino Acids, Essential↗

PubMed1999

Tryptophan residue(s) as major components of the human serum paraoxonase active site.

Serum paraoxonase (PON1, EC 3.1.8.1.) is a high density lipid- (HDL)-associated, calcium-dependent enzyme whose 3D structure, active site residues and physiological substrates are not known. The kinetic parameters k(cat) and Km (relative to k(cat) and Km of the wild-type), determined with four substrates (phenylacetate, paraoxon, diazoxon and chlorpyrifosoxon) were less than 1, and more than 100% for the W280A and W280F mutant enzymes, respectively. These results indicated that the aromatic/hydrophobic character of the amino acid in position 280 is essential for PON1 activity. In this study, we investigated whether this aromatic residue is in the PON1 active site. Group-specific labelling studies with N-bromosuccinimide, an oxidative agent of tryptophan, strongly suggested that one or several Trp could be in the active site of PON1 but we could not conclude either on the specificity of the labelling reaction or on the number of oxidized Trp. However, although PON activity was not altered by the hydrophilic tryptophan-modifying reagent 2-hydroxy-5-nitrobenzyl chloride (NBC), it was significantly reduced by the p-nitrophenylacetate analog 2-acetoxy-5-nitrobenzyl chloride (ANBC), whose hydrolysis by PON1 generated NBC in the active site. Moreover, since at least one calcium ion is present in the PON catalytic site, we attempted to probe the metal local environment using the calcium analog terbium. The luminescence spectrum of the PON terbium complex exhibited an emission peak at 545 nm characteristic of an aromatic residue (Trp and/or Tyr)-terbium interaction. In conclusion, both the results obtained with the mechanism-based inhibitor of PON1 (ANBC) and the calcium-binding site luminescent probe terbium support the hypothesis of the presence of at least one Trp residue in the PON1 active site. Trp residue(s) may be involved in the binding of aromatic substrates.

Acetates↗

PubMed1999

Knockout of one acetylcholinesterase allele in the mouse.

One allele of the AChE gene (ACHE) was knocked out in embryonic stem (ES) cells by homologous recombination. The targeting vector contained 2 kb of a TK gene cassette for negative selection, 884 bp of ACHE including exon 1, 1.6 kb of a Neo(r) gene cassette for positive selection, 5.2 kb of the ACHE Bam HI fragment including exon 6, and 3 kb of Bluescript. The use of this vector deleted exons 2-5, which removed 93% of the ACHE coding sequence including the signal peptide, the active site serine, and the histidine and glutamic acid of the catalytic triad. The gene targeting vector was transfected into ES cells by electroporation. Colonies resistant to G418 and gancyclovir were screened for homologous recombination by Southern blotting. Out of 200 colonies, four were found to have undergone homologous recombination. These four ACHE (+/-) ES cell lines were expanded to provide cells for microinjection into C57Bl/6 mouse blastocysts. The injected blastocysts were implanted into pseudopregnant CD/l white mice. More than 200 injected blastocysts were transferred into 20 mice. More than 65 mice were born, of which 11 were chimeras. Chimeras were identified by their black and agouti coat color. Littermates were all black. Thus far, seven male chimeras have been bred with more than 130 C57Bl/6 females to generate 26 agouti mice out of 199 living offspring. This demonstrated that the ACHE (+/-) ES cells contributed to the germline. Offspring with agouti coat color have a 50% chance of carrying the knockout allele. The 26 agouti offspring were screened for an ACHE (+/-) genotype by tail biopsy PCR. Ten out of 26 agouti mice are heterozygous ACHE knockout mice, and they are healthy and alive at 29 days of age. We expect a phenotype to appear in nullizygous animals.

Acetylcholinesterase↗

PubMed1999

Unique forms of human and mouse nuclear receptor corepressor SMRT.

Nuclear hormone receptors have been shown to repress transcription in the absence of ligand. This repression is mediated by a corepressor complex that contains the Sin3A protein and histone deacetylases (HDAC1 and 2). Studies by several groups demonstrate that this complex is recruited to nuclear receptors through the highly related corepressors SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor). We describe here the cloning, characterization, and chromosomal mapping of forms of human and mouse SMRT that includes a 1,000-aa extension, which reveals striking homology to the amino terminus of N-CoR. Structure and function studies of wild-type and natural splicing variants suggest the presence of 3-4 amino terminal domains that repress in a cooperative as well as mechanistically distinct fashion.

Amino Acid Sequence↗

PubMed1999

Identification of residues essential for human paraoxonase (PON1) arylesterase/organophosphatase activities.

Human serum paraoxonase (PON1) is a calcium-dependent organophosphatase. To identify residues essential for PON1 activity, we adopted complementary approaches based on chemical modification and site-directed mutagenesis. To detect 45Ca2+ binding to native and chemically modified PON1, we performed nondenaturating gel electrophoresis. The environment of calcium-binding sites was probed using the Ca2+ analogue, terbium. Tb3+ binds to calcium-binding sites as shown by displacement of 45Ca2+ by Tb3+. Binding of Tb3+ is accompanied by a complete loss of enzyme activity. PON1 chemical modification with the Trp-selective reagent, N-bromosuccinimide, and the Asp/Glu-selective, dicyclohexylcarbodiimide, established that Trp and Asp/Glu residues are components of the PON1 active center and calcium-binding sites. Additional evidence for the presence of a Trp residue in the PON1 calcium-binding sites was a characteristic fluorescence emission at 545 nm from the PON1-Tb3+ complex and abolishment of that fluorescence upon modification by N-bromosuccinimide. The importance of aromatic/hydrophobic character of the residue 280 was demonstrated by site-directed mutagenesis: the W280F mutant was fully active while the W280A and W280L mutants had markedly reduced activity. Twelve amino acids among conserved His and Asp/Glu residues were found essential for PON1 arylesterase and organophosphatase activities: H114, H133, H154, H242, H284, D53, D168, D182, D268, D278, E52, and E194. Finally, the cysteines constituting the PON1 disulfide bond (C41 and C352) were essential, but the glycan chains linked to Asn 252 and 323 were not essential for PON1 secretion and activity.

Amino Acids↗

PubMed1999

Polyol-induced activation by excess substrate of the D70G butyrylcholinesterase mutant.

Wild-type human butyrylcholinesterase (BuChE) has a non-Michaelian behaviour showing substrate activation with butyrylthiocholine (BTC) as the substrate. The D70G mutant has a catalytic constant identical to that of the wild-type enzyme, but a 10-fold lower affinity for BTC compared to wild-type enzyme, and it does not exhibit activation by excess BTC under conventional conditions. In the present work it was found that addition of polyols or sugars changed the kinetic behaviour of the D70G mutant with BTC. In the presence of 40% sucrose, the D70G mutant enzyme displayed marked activation by excess substrate. Because D70 is hydrogen bonded to Y332, mutants of Y332 were studied. Mutant Y332F had a behaviour similar to that of wild-type BuChE, whereas mutants Y332A, Y332A/D70G and D70G had negligible substrate activation. The behavior of wild-type, Y332F, Y332A and Y332A/D70G did not change in the presence of high concentrations of sugar. Substrate activation has been explained by binding of a second substrate molecule in the peripheral site at D70. The D70G mutant should be incapable of substrate activation, if D70 were the only residue involved in substrate activation. The ability of the D70G mutant to display substrate activation by medium engineering suggests that other residues are involved in initial substrate binding and activation by excess substrate. Osmolyte-induced change in conformation and/or hydration status of Y332 and other solvent-exposed residues may account for the non-Michaelian behaviour of the D70G mutant.

Binding Sites↗

PubMed1999

Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells.

Dishevelled (Dsh/Dvl) proteins are known to mediate Wnt signaling by up-regulating beta-catenin levels and stimulating T cell factor (TCF)/LEF-1-dependent transcription. We have identified a new Dvl-mediated signaling pathway in that mouse Dvl proteins, when expressed in COS-7 cells, stimulate c-Jun-dependent transcription activity and the kinase activity of the c-Jun N-terminal kinase (JNK). The DEP domain of Dvl1 is essential for JNK activation. By contrast, all three conserved domains of Dvl, including DIX, PDZ, and DEP, are required for up-regulation of beta-catenin and for stimulation of LEF-1-mediated transcription in mammalian cells. Thus, Dvl can lead to two different signaling pathways. Furthermore, the small G proteins of Cdc42 or Rac1, which are involved in JNK activation by many stimuli, do not appear to play a major role in Dvl-mediated JNK activation, because the dominant negative mutants of Cdc42 and Rac1 could not inhibit Dvl-induced JNK activation. This suggests that Dvl may activate JNK via novel pathways.

3T3 Cells↗

PubMed1999

Effects of cerebrospinal fluid from patients with Parkinson disease on dopaminergic cells.

BACKGROUND: The pathogenesis of substantia nigra pars compacta neuronal injury in Parkinson disease (PD) remains unknown. Cerebrospinal fluid (CSF) has been reported to contain factors toxic to dopaminergic neurons. OBJECTIVES: To determine whether the cytotoxic effects of CSF of PD patients are specific for dopaminergic neurons, dependent on prior levodopa therapy, and mediated by the cytokine tumor necrosis factor alpha (TNF-alpha). DESIGN: Specimens of CSF were evaluated in dopaminergic (MES 23.5) and nondopaminergic (N18TG2) cell lines for cytotoxicity by viability assay and by the inhibition of tyrosine hydroxylase. After specificity and time and dose response were established, CSF specimens were assayed in a blinded manner. The TNF-alpha levels in CSF were determined by enzyme-linked immunosorbent assay. The toxicity of TNF-alpha in MES 23.5 cells was determined. SETTING: A university-based research facility. SUBJECTS: There were 4 groups of subjects: normal control subjects (n = 10), control subjects with neurologic disease (n = 8), PD patients treated with levodopa (n = 10), and untreated subjects with PD (n= 20). RESULTS: Specimens of CSF from 15 (50%) of 30 PD patients and 2 (11%) of 18 control subjects were cytotoxic to dopaminergic MES 23.5 cells and were nontoxic to the parental cell line N18TG2. There was no correlation between the degree of PD CSF cytotoxicity, levodopa therapy, or the severity and duration of PD. Terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) for DNA fragmentation suggested the involvement of apoptotic mechanisms. The inhibition of tyrosine hydroxylase was an early effect of cell injury by PD CSF and correlated with the viability assay. The mean TNF-alpha level was 2.6-fold higher in CSF specimens from PD patients than in those of controls. The addition of recombinant human TNF-alpha equivalent to the highest level determined in PD CSF was not cytotoxic to MES 23.5 cultures. CONCLUSIONS: Blinded CSF specimens from PD patients, regardless of therapy, contain factors that cause specific dopaminergic neuronal cell injury. These factors are present in a substantial proportion of CSF specimens from patients with early PD, before the institution of medical therapy. Levels of TNF-alpha are elevated in the CSF of PD patients, but TNF-alpha is not responsible for the cytotoxicity.

Aged↗

PubMed1999

Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity.

Pramipexole, a novel non-ergoline dopamine (DA) agonist, has been applied successfully for treatment of Parkinson's disease (PD). We report here that pramipexole can protect dopaminergic cell line Mes23.5 against dopamine- and levodopa-induced cytotoxicity possibly through a mechanism related to antioxidant activity. In the MES 23.5 cultures, DA and L-DOPA induce a dose- and time-dependent cytotoxicity, as determined by tetrazolium salt and trypan blue assays. Furthermore, an in situ terminal deoxynucleotidyl transferase assay demonstrates that DA-induced cell death is apoptotic. Pretreatment with pramipexole in a concentration range (4-100 microM) significantly attenuates DA- or L-DOPA-induced cytotoxicity and apoptosis, an action which is not blocked by D3 antagonist U-99194 A or D2 antagonist raclopride. Pramipexole also protects MES 23.5 cells from hydrogen peroxide-induced cytotoxicity in a dose-dependent manner. In cell-free system, pramipexole can effectively inhibit the formation of melanin, an end product resulting from DA or L-DOPA oxidation. These results indicate that pramipexole exerts its neuroprotective effect possibly through a mechanism, which is independent of DA receptors but related to antioxidation or scavenging of free radicals (e.g. hydrogen peroxide). As a direct DA agonist and potentially neuroprotective agent, pramipexole remains attractive in the treatment of PD.

Animals↗

PubMed1999

Mycotoxin production by Fusarium proliferatum isolates from rice with Fusarium sheath rot disease.

Twenty samples of unpolished (rough) rice collected in Arkansas and Texas during the 1995 harvesting season from fields exhibiting Fusarium sheath rot disease or panicle blight were previously shown to include 8 samples positive for fumonisin B1 (FB1) in the range 2.2-5.2 ppm, and moniliformin (MON), but no beauvericin (BEA), deoxynivalenol, its derivatives or zearalenone were detected. Fifteen cultures of F. proliferatum were established from the 20 rough rice samples. Single spore isolates of each culture were grown on rice and tested for the production of fumonisins (FB1, FB2, FB3, etc.), MON and BEA. All 15 isolates produced FB1, FB2, MON and BEA in culture on rice. No deoxynivalenol, its derivatives or zearalenone were detected. Seven cultures produced FB1 at > 50 ppm (range 80-230 ppm), with the rest producing FB1 in the range 14-43 ppm. FB2 was produced in the range 5-47 ppm, and those cultures which produced the most FB1 also produced the most FB2. Of the 15 cultures producing MON, 11 produced it at > 100 ppm in the range 188-6018 ppm, with the rest producing in the range 7-64 ppm. BEA was produced in the range 109-1350 ppm. Other derivatives of fumonisins, including FA1, FA2 and partially hydrolyzed FB1, as well as several unknown metabolites including a compound with MW 414, were identified in culture extracts by continuous flow fast atom bombardment with ion spray mass spectrometry (CF/FAB/MS). Further study is needed to identify the factors that control production of FB1, MON and BEA by F. proliferatum in culture and in field samples.

Anti-Bacterial Agents↗

PubMed1999

An agonist anti-human CD40 monoclonal antibody that induces dendritic cell formation and maturation and inhibits proliferation of a myeloma cell line.

CD40, a 48-50 KD cell membrane molecule, member of the nerve growth factor receptor and tumor necrosis factor receptor superfamily, is an important costimulatory molecule during the immune response. Anti-CD40 monoclonal antibody (MAb) has been shown earlier to costimulate with IgM or phorbol esters resting B cells to proliferate, differentiate, secrete immunoglobulins, and switch isotype. Here we report on an agonistic mouse anti-human CD40 MAb 5C11. The specificity of this MAb was verified by flow cytometry, Western blotting, and competition with anti-CD40 MAb 89. We studied the effects of MAb 5C11 on a multimyeloma cell line, XG2, that expresses the CD40 antigen strongly and found that this MAb caused the homotypic aggregation of XG2, strongly suppressed XG2 proliferation, and led to its apoptosis after 24 hr of treatment. Interestingly, MAb 5C11 also triggered the generation, proliferation, and maturation of dendritic cells from peripheral blood monocytes, either by itself or in combination with GM-CSF and IL-4.

Animals↗

PubMed1999

An improved cocaine hydrolase: the A328Y mutant of human butyrylcholinesterase is 4-fold more efficient.

Butyrylcholinesterase (BChE) has a major role in cocaine detoxication. The rate at which human BChE hydrolyzes cocaine is slow, with a kcat of 3.9 min(-1) and Km of 14 microM. Our goal was to improve cocaine hydrolase activity by mutating residues near the active site. The mutant A328Y had a kcat of 10.2 min(-1) and Km of 9 microM for a 4-fold improvement in catalytic efficiency (kcat/Km). Since benzoylcholine (kcat 15,000 min(-1)) and cocaine form the same acyl-enzyme intermediate but are hydrolyzed at 4000-fold different rates, it was concluded that a step leading to formation of the acyl-enzyme intermediate was rate-limiting. BChE purified from plasma of cat, horse, and chicken was tested for cocaine hydrolase activity. Compared with human BChE, horse BChE had a 2-fold higher kcat but a lower binding affinity, cat BChE was similar to human, and chicken BChE had only 10% of the catalytic efficiency. Naturally occurring genetic variants of human BChE were tested for cocaine hydrolase activity. The J and K variants (E497V and A539T) had k(cat) and Km values similar to wild-type, but because these variants are reduced to 66 and 33% of normal levels in human blood, respectively, people with these variants may be at risk for cocaine toxicity. The atypical variant (D70G) had a 10-fold lower binding affinity for cocaine, suggesting that persons with the atypical variant of BChE may experience severe or fatal cocaine intoxication when administered a dose of cocaine that is not harmful to others.

Animals↗

PubMed1999

Estrogen induces adenosine deaminase gene expression in MCF-7 human breast cancer cells: role of estrogen receptor-Sp1 interactions.

Adenosine deaminase (ADA) gene expression is induced by 17beta-estradiol (E2) in MCF-7 human breast cancer cells, whereas the antiestrogens 4'-hydroxytamoxifen and ICI 182,780 exhibit partial estrogen receptor (ER) agonist/antagonist and antagonist activities, respectively. Previous studies have shown that the -211 to +11 region of the ADA gene promoter contains six GC-rich sites (I-VI) that bind Sp1 protein, and these elements are required for high basal expression. In transient transfection studies with pADA211, which contains the -211 to +11 ADA gene promoter linked to a bacterial chloramphenicol acetyl transferase (CAT) reporter gene, E2 and tamoxifen (but not ICI 182,780) induced CAT activity. Ligand-induced transactivation was observed only in cells cotransfected with expression plasmids for wild-type ER or HE11, which does not contain the DNA-binding domain of the ER. Cotransfection with HE15 and HE19, which contain the DNA-binding domain and activation function-1 (AF-1) and AF-2 of the ER, respectively, did not result in E2-induced activity. Subsequent deletion analysis of the ADA gene promoter showed that Sp1 binding site IV (-79 to -73) was primarily responsible for hormone responsiveness. ER activation of ADA gene expression is another example of an E2-induced gene that is dependent on ER/Sp1 interactions with a site-specific GC-rich motif.

Adenosine Deaminase↗

PubMed1999

Constitutive activation of transcription and binding of coactivator by estrogen-related receptors 1 and 2.

In this report, we demonstrate that, in contrast to most previously characterized nuclear receptors, hERR1 and hERR2 (human estrogen receptor-related protein 1 and -2) are constitutive activators of the classic estrogen response element (ERE) as well as the palindromic thyroid hormone response element (TRE(pal)) but not the glucocorticoid response element (GRE). This intrinsically activated state of hERR1 and hERR2 resides in the ligand-binding domains of the two genes and is transferable to a heterologous receptor. In addition, we show that members of the p160 family of nuclear receptor coactivators, ACTR (activator of thyroid and retinoic acid receptors), GRIP1 (glucocorticoid receptor interacting protein 1), and SRC-1 (steroid receptor coactivator 1), potentiate the transcriptional activity by hERR1 and hERR2 in mammalian cells, and that both orphan receptors bind the coactivators in a ligand-independent manner. Together, these results suggest that hERR1 and hERR2 activate gene transcription through a mechanism different from most of the previously characterized steroid hormone receptors.

Acetyltransferases↗

PubMed1999

Isolation and characterization of viridin, a new 65 kDa antifungal protein from the mould Trichoderma viride.

A new extracellular antifungal protein with a yield of 10 mg per liter was isolated from the culture medium of the mould Trichoderma viride. The protein, which we named viridin, was purified by carboxymethyl-cellulose cation-exchange chromatography and Superose 12 HR 10/30 high-performance liquid chromatography. Viridin, a basic protein of approximately 65 kDa as determined by SDS-PAGE, inhibits the growth of the cotton pathogen Verticillum dahliae, the IC50 being 6 microM.

Androstenes↗

PubMed1999

[The treatment of 432 patients with pituitary adenomas via transsphenoidal approach].

OBJECTIVE: To study some clinical features of 432 cases of pituitary adenomas treated by transsphenoidal microsurgery between July 1982 and October 1996. METHODS: Pathological examination, immunohistochemical examination and electronmicroscopic examination were done in 424, 29 and 103 cases respectively. RESULTS: Hyperprolactinemia was found in many so-called non-functioning adenomas besides in prolactinomas. The dura maters were invaded by tumors in 78 cases (the incidence of dural invasion was 65.5%). CONCLUSIONS: Hyperprolactinemia is not peculiar to prolactinomas, and differential diagnosis is necessary when hyperprolactinemia exists. The involvement of the dura mater of sellar floor is an important mark that the adjacent tissues were invaded by pituitary adenomas. The outcome of surgical treatment is significantly different between the patients with dural invasion and without invasion.

Adenoma↗