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Biomedical subjects

L Shen

Publications and source records attributed to L Shen.

At least 109 records · Page 6Linked to original sources
PubMed1999

Human immunoglobulin A receptor (FcalphaRI, CD89) function in transgenic mice requires both FcR gamma chain and CR3 (CD11b/CD18).

Even though more immunoglobulin A (IgA) is produced in humans than all other isotypes combined, relatively little is known about receptors that bind the Fc part of IgA. The myeloid IgA receptor, FcalphaRI (CD89), triggers various effector functions in vitro, but its in vivo role remains unclear. Here, a transgenic mouse model is described in which FcalphaRI is expressed under its own regulatory sequences. Receptor expression and regulation by cytokines was comparable to the human situation and hFcalphaRI can trigger phagocytosis and lysis of tumor cells. To analyze the contribution of the FcR gamma chain or the beta2 integrin CR3 (CD11b/CD18) in FcalphaRI biological function, FcalphaRI transgenic mice were crossed with either FcR gamma chain -/- or CR3 -/- mice. In contrast to in vitro data, FcR gamma chain was essential for surface expression of hFcalphaRI in vivo. Functional studies in hFcalphaRI/ gamma-/-mice were, therefore, limited. In vitro studies showed FcR gamma chain to be necessary for phagocytosis. Neither hFcalphaRI expression nor phagocytosis, triggered via hFcalphaRI, were influenced by CR3. Remarkably, the capacity to lyse tumor targets was ablated in hFcalphaRI transgenic/ CR3-/- mice, although binding of neutrophils to tumor cells was intact. This shows a previously unrecognized importance of CR3 for hFcalphaRI-mediated antibody-dependent cellular cytotoxicity (ADCC).

Animals↗
PubMed1999

Probing the activation of protein C by the thrombin-thrombomodulin complex using structural analysis, site-directed mutagenesis, and computer modeling.

Protein C (PC) is activated to an essential anticoagulant enzyme (activated PC or APC) by thrombin (T) bound to thrombomodulin (TM), a membrane receptor present on the surface of endothelial cells. The understanding of this complex biological system is in part limited due to the lack of integration of experimental and structural data. In the work presented here, we analyze the PC-T-TM pathway in the context of both types of information. First, structural analysis of the serine protease domain of PC suggests that a positively charged cluster of amino acids could be involved in the activation process. To investigate the importance of these basic amino acids, two recombinant PC mutants were constructed using computer-guided site-directed mutagenesis. The double mutant had the K62[217]N/K63[218]D substitution and in the single mutant, K86[241] was changed to S. Both mutants were activated by free thrombin at rates equivalent to that of wild-type PC (wt-PC) and they demonstrated similar calcium-dependent inhibition of their activation. The K86[241]S mutant and wt-PC were activated by thrombin bound to soluble TM at a similar rate. In contrast, the K62[217]N/ K63[218]D mutant was activated by the T-TM complex at a 10-fold lower catalytic efficiency due to a lowering in k(cat) and increase in Km. Molecular models for PC and thrombin bound to a segment of TM were developed. The experimental results and the modeling data both indicate that electrostatic interactions are of crucial importance to orient PC onto the T-TM complex. A key electropositive region centered around loops 37[191] and 60[214] of PC is defined. PC loop 37[191] is located 7-8 A from the TM epidermal growth factor (EGF) 4 while the loop 60[214] is about 10 A away from TM EGF4. Both loops are far from thrombin. A key function of TM could be to create an additional binding site for PC. The Gla domain of PC points toward the membrane and away from thrombin or the EGF modules of TM during the activation process.

Cell Line↗
PubMed1999

Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain complex.

During the development of multicellular organisms, gene expression must be tightly regulated, both spatially and temporally. One set of transcription factors that are important in animal development is encoded by the homeotic (Hox) genes, which govern the choice between alternative developmental pathways along the anterior-posterior axis. Hox proteins, such as Drosophila Ultrabithorax, have low DNA-binding specificity by themselves but gain affinity and specificity when they bind together with the homeoprotein Extradenticle (or Pbxl in mammals). To understand the structural basis of Hox-Extradenticle pairing, we determine here the crystal structure of an Ultrabithorax-Extradenticle-DNA complex at 2.4 A resolution, using the minimal polypeptides that form a cooperative heterodimer. The Ultrabithorax and Extradenticle homeodomains bind opposite faces of the DNA, with their DNA-recognition helices almost touching each other. However, most of the cooperative interactions arise from the YPWM amino-acid motif of Ultrabithorax-located amino-terminally to its homeodomain-which forms a reverse turn and inserts into a hydrophobic pocket on the Extradenticle homeodomain surface. Together, these protein-DNA and protein-protein interactions define the general principles by which homeotic proteins interact with Extradenticle (or Pbx1) to affect development along the anterior-posterior axis of animals.

Amino Acid Sequence↗
PubMed1999

Effect of complement consumption by cobra venom factor on the course of primary infection with simian immunodeficiency virus in rhesus monkeys.

Cobra venom factor (CVF)-induced consumption of complement proteins was used to investigate the role of complement in vivo in the immunopathogenesis of simian immunodeficiency virus of macaques (SIVmac) infection in rhesus monkeys. Repeated administration of CVF was shown to deplete complement to <5% of baseline hemolytic activity of serum complement for 10 days in a normal monkey. Three groups of SIVmac-infected animals were then evaluated: monkeys treated with CVF resulting in complement depletion from days -1 to 10 postinfection, monkeys treated with CVF resulting in complement depletion from days 10 to 21 postinfection, and control monkeys that received no CVF. CD8+ SIVmac-specific cytotoxic T lymphocyte (CTL) generation and CD4+ T lymphocyte depletion during primary infection were not affected by CVF treatment. Viral load, assessed by measurements of plasma p27gag antigen and viral RNA, was transiently higher during the first 4 weeks following infection in the CVF-treated monkeys and the subsequent clinical course in these treated animals was accelerated. These results suggest that complement proteins may participate in immune defense mechanisms that decrease virus replication following the initial burst of intense viremia during primary SIVmac infection. However, we cannot rule out that the observed increased virus replication was induced by immune activation resulting from the administration of a foreign antigen to these monkeys.

Animals↗
PubMed1999

Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves.

BACKGROUND & AIMS: Development of interstitial cells of Cajal (ICC) requires signaling via Kit receptors. Kit is activated by stem cell factor (SCF), but the source of SCF in the bowel wall is unclear and controversy exists about whether enteric neurons express the SCF required for ICC development. METHODS: Glial cell line-derived neurotrophic factor (GDNF) knockout mice, which lack enteric neurons throughout most of the gut, were used to determine whether neurons are necessary for ICC development. ICC distributions were determined with Kit immunofluorescence, and function of ICC was determined by intracellular electrical recording. RESULTS: ICC were normally distributed throughout the gastrointestinal tracts of GDNF-/- mice. Intracellular recordings from aganglionic gastrointestinal muscles showed normal slow wave activity at birth in the stomach and small intestine. Slow waves developed normally in aganglionic segments of small bowel placed into organ culture at birth. Quantitative polymerase chain reaction showed similar expression of SCF in the muscles of animals with and without enteric neurons. Expression of SCF was demonstrated in isolated intestinal smooth muscle cells. CONCLUSIONS: These data suggest that enteric neurons are not required for the development of functional ICC. The circular smooth muscle layer, which develops before ICC, may be the source of SCF required for ICC development.

Animals↗
PubMed1999

The major metabolite of equilin, 4-hydroxyequilin, autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone.

The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with a slight increased cancer risk. Previously, we showed that equilenin, a minor component of Premarin (Wyeth-Ayerst), was metabolized to highly cytotoxic quinoids which caused oxidative stress and alkylation of DNA in vitro [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. (1998) Chem. Res. Toxicol. 11, 1113-1127]. In this study, we have compared the chemistry of the major catechol metabolite of equilin (4-hydroxyequilin), which is found in several estrogen replacement formulations, to the equilenin catechol (4-hydroxyequilenin). Unlike endogenous catechol estrogens, both equilin and equilenin were primarily converted by rat liver microsomes to 4-hydroxylated rather than 2-hydroxylated o-quinone GSH conjugates. With equilin, a small amount of 2-hydroxyequilin GSH quinoids were detected (4-hydroxyequilin:2-hydroxyequilin ratio of 6:1); however, no peaks corresponding to 2-hydroxyequilenin were observed in incubations with equilenin. These data suggest that unsaturation in the B ring alters the regiochemistry of P450-catalyzed hydroxylation from primarily 2-hydroxylation for endogenous estrogens to 4-hydroxylation for equine estrogens. 4-Hydroxyequilenin-o-quinone reacts with GSH to give two mono-GSH conjugates and one di-adduct. The behavior of 4-hydroxyequilin was found to be more complex than 4-hydroxyequilenin as conjugates resulting from 4-hydroxyequilenin were detected in addition to the 4-hydroxyequilin-GSH adducts. The mechanism of decomposition of 4-hydroxyequilin likely involves isomerization to a quinone methide which readily aromatizes to 4-hydroxyequilenin followed by autoxidation to 4-hydroxyequilenin-o-quinone. Similar results were obtained with 2-hydroxyequilin, although, in contrast to 4-hydroxyequilenin, 2-hydroxyequilenin does not autoxidize and the reaction stops at the catechol. Since 4-hydroxyequilin is converted to 4-hydroxyequilenin and 4-hydroxyequilenin-o-quinone, similar effects were observed for this equine catechol, including consumption of NAD(P)H likely by the 4-hydroxyequilenin-o-quinone, depletion of molecular oxygen by 4-hydroxyequilenin or its semiquinone radical, and alkylation of deoxynucleosides and DNA by 4-hydroxyequilenin quinoids. Finally, preliminary studies conducted with the human breast tumor cell line MCF-7 demonstrated that the cytotoxic effects of the catechol estrogens from estrone, equilin, and 2-hydroxyequilenin were similar, whereas 4-hydroxyequilenin was a much more potent cytotoxin ( approximately 30-fold). These results suggest that the catechol metabolites of equine estrogens have the ability to cause alkylation/redox damage in vivo primarily through formation of 4-hydroxyequilenin quinoids.

Animals↗
PubMed1999

Biosynthesis and characterization of 4-fluorotryptophan-labeled Escherichia coli arginyl-tRNA synthetase.

Escherichia coli 4-fluorotryptophan-substituted arginyl-tRNA synthetase was biosynthetically prepared and purified from a tryptophan auxotroph which could overproduce this enzyme. A method was developed to separate 4-fluorotryptophan from tryptophan and to determine accurately their contents in the 4-fluorotryptophan-containing proteins. It was confirmed that more than 95% of the tryptophan residues in the purified 4-fluorotryptophan-substituted arginyl-tRNA synthetase were replaced by 4-fluorotryptophan. Studies on the effect of the 4-fluorotryptophan replacement on properties of the enzyme showed that, when compared with the native enzyme, both the specific activity and the first-order rate constant of the fluorinated enzyme decreased by approximately 20% with just slightly higher Km values. CD studies, however, did not reveal any difference between the secondary structure of the native and fluorinated enzymes. In addition, thermal unfolding studies showed that the 4-fluorotryptophan replacement did not significantly affect the thermal stability of the enzyme. We may conclude that the substitution of 4-fluorotryptophan in arginyl-tRNA synthetase had no substantial effect on the structure and function of the enzyme. Finally, a preliminary study of 19F nuclear magnetic resonance spectroscopy of the fluorinated enzyme has shown promising prospect for further investigation of its structure and function with NMR.

Arginine-tRNA Ligase↗
PubMed1999

The role of enterostatin and apolipoprotein AIV on the control of food intake.

Procolipase is secreted as a protein consisting of 101 amino acids. In the intestinal lumen, procolipase is activated by trypsin and cleaves to form the active colipase and the pentapeptide from the amino terminus. This pentapeptide is called enterostatin. Pancreatic procolipase synthesis is stimulated by a high-fat diet. A large body of evidence has been gathered in the past decade demonstrating the role of enterostatin in the inhibition of food intake; in particular, fat intake. This aspect of enterostatin will be discussed in this review. Other functions of enterostatin such as the inhibition of insulin secretion, will not. Apolipoprotein AIV is a protein synthesized by the human intestine. Similar to procolipase, the synthesis and secretion of apo AIV are also stimulated by fat absorption. In 1992, Fujimoto et al. first demonstrated that apo AIV is a satiety signal secreted by the small intestine following the ingestion of a lipid meal. Subsequently, this initial observation was followed by a number of studies supporting apo AIV's role in the inhibition of food intake. This review will discuss the role of apo AIV in inhibiting food intake.

Animals↗
PubMed1999

Induction of p53-dependent, insulin-like growth factor-binding protein-3-mediated apoptosis in glioblastoma multiforme cells by a protein kinase Calpha antisense oligonucleotide.

Protein kinase Calpha (PKCalpha) expression is related to tumor progression in glioblastoma multiforme (GBM), the most common malignant brain tumor in adults. To determine whether PKCalpha regulates an anti-apoptotic survival pathway in GBM, A172 GBM cells were treated with a PKCalpha-selective antisense oligonucleotide. PKCalpha antisense oligonucleotide treatment was accompanied by reduction in PKCalpha levels and the induction of wild-type p53 and insulin-like growth factor-binding protein-3 (IGFBP3) 24-72 h after treatment, a period that coincided with the appearance of apoptotic cell death as detected by DNA fragmentation. There were no significant changes in the levels of Bcl-XL, Bax, and p21(WAF1). Induction of p53 after PKCalpha down-regulation was not associated with increased mRNA expression, but increased IGFBP3 levels were accompanied by increased mRNA levels. Recombinant human IGFBP3 induced an apoptotic effect that was similar to the PKCalpha antisense oligonucleotide, and its effect was blocked by IGF-I. These results suggest that one mechanism by which PKCalpha produces its antiapoptotic activity in GBM cells is by suppressing the p53-mediated activation of IGFBP3.

Apoptosis↗
PubMed1999

Cholesterol oxidation products induce vascular foam cell lesion formation in hypercholesterolemic New Zealand white rabbits.

Circulating cholesterol oxidation products (ChOx) have long been implicated in the etiology of early atherosclerosis; however, direct in vivo evidence elucidating their role in atherogenesis is only recently becoming available. This study investigated ChOx effects on vascular lesion formation in New Zealand White rabbits under controlled hypercholesterolemic conditions. By closely monitoring plasma cholesterol levels and adjusting dietary cholesterol intake during a 78-day period, total plasma cholesterol exposures (cumulative plasma cholesterol levels over time) were controlled between 27 000 and 34 000 mg/dLxday (final plasma cholesterol concentration, 467+/-77 mg/mL), representing a threshold range for sudanophilic lesion formation in the aorta. Twenty injections of a ChOx mixture (70 mg per injection) were made bearing an oxysterol composition similar to that found in circulating oxidatively modified low density lipoprotein. At sacrifice, the ChOx-injected rabbits (n=5) had (1) significantly higher plasma ChOx levels, (2) significantly increased cholesterol content in the aortas, mainly as esterified cholesterol, and (3) significantly greater sudanophilic lesion size and frequency in the aortas compared with vehicle-injected control rabbits (n=5). The aortic cholesterol content and extent of sudanophilic lesion area were correlated significantly with total plasma ChOx exposure (P<0.003 and P<0.0001, respectively) but not with total cholesterol exposure. The results indicate that for moderate experimental hypercholesterolemia, a situation more relevant to physiological hypercholesterolemia in humans, circulating ChOx may play an important role in inducing formation of early atherosclerotic lesions. Because ChOx are often present in cholesterol-containing diets, foam cell lesion formation induced by ChOx rather than cholesterol cannot be overlooked.

Animals↗
PubMed1999

Neural correlates of visual form and visual spatial processing.

Cortico-cortical projections for visual processing that originate from the striate cortex are organized into two streams. The dorsal stream projects to the parietal region and the ventral stream to the inferior temporal region. One hypothesis is that the dorsal stream processes visual spatial information, and the ventral stream processes visual object information. Although recognition of human faces or common objects has been shown preferentially to activate the ventral stream, the issue of when such processing starts to engage the ventral or the dorsal stream is not clear. The question explored in this study is whether processing of visual form per se without evoking the brain mechanisms that are associated with recognition of human faces or common objects is sufficient to activate the ventral stream more significantly relative to the condition when only visual spatial processing is involved. Functional magnetic resonance images were acquired while subjects performed a delayed comparison task in which either visual spatial or visual form information was processed. Cortical areas that were preferentially activated in visual spatial or visual form processing showed not only ventral-dorsal segregation, but also hemispheric laterality. The results extended previous findings by showing that preferential activation in the ventral pathway is not contingent upon such powerful stimuli as faces and common objects. Processing of simple visual form information is cause enough for such activation to be observed. A strong left hemisphere dominance in visual form recognition was also revealed. The observed laterality may be a reflection that the left hemisphere is more important in symbolic and/or semantic coding of visual form information.

Adult↗
PubMed1999

Involvement of Lys 62(217) and Lys 63(218) of human anticoagulant protein C in heparin stimulation of inhibition by the protein C inhibitor.

Inhibition of activated protein C (APC) by protein C inhibitor (PCI) is stimulated by heparin, whereas inhibition by alpha1-antitrypsin (AAT) is heparin-independent. Three lysine residues located in a positively charged cluster in the serine protease domain of protein C (PC) were mutated to probe their involvement in the heparin stimulation of inhibition by PCI. These mutations were selected after analysis of the three-dimensional structure of APC and of molecular models for PCI and the APC-PCI complex. A double mutant, K62[217]N/K63[218]D, a single mutant, K86[241]S, and wild-type PC were expressed in embryonic human kidney 293 cells. Heparin stimulated the rate of inhibition of wt-APC by PCI approximately 400-fold, with second order rate constants (k2) in the absence and presence of heparin of 0.72 x 10(3) M(-1)s(-1) and 2.87 x 10(5) M(-1)s(-1), respectively. In contrast, heparin only yielded a 52-fold stimulation of the rate of inhibition of the double mutant APC by PCI as the rate constants in the absence and presence of heparin were k2 = 2.44 x 10(3) M(-1)s(-1) and k2 = 1.26 x 10(5)M(-1)s(-1), respectively. The double mutant K62N/K63D eluted at approximately 10% lower NaCl concentration from a heparin Sepharose column than the K86S mutant or wt-APC. These data suggest K62 and K63 in APC to be part of a heparin binding site which is important for heparin-mediated stimulation of inhibition of APC by PCI.

Anticoagulants↗
PubMed1999

Interspecies loop grafting in the protease domain of human protein C yielding enhanced catalytic and anticoagulant activity.

Human anticoagulant activated protein C (hAPC) is less potent than the bovine APC (bAPC) molecule and our aims were to elucidate the molecular background for this difference and to create an APC with enhanced anticoagulant activity. In the protease domain of human protein C (hPC), the loop 148 (GWGYHSSREKEAKRN) is four residues longer than the corresponding loop in bovine APC (GWGY RDETKRN). To investigate whether this caused the species difference, the loop in hPC was replaced by the shorter bovine loop, whereas the longer human loop was introduced in bovine protein C. The mutation in hAPC yielded enhanced catalytic activity against chromogenic (4-fold) as well as natural (factors Va and VIIIa) substrates and 2-3-fold increased anticoagulant activity. The opposite effects were obtained with the bovine mutant. As compared to wild-type hAPC, the mutant hAPC was inhibited slightly faster by the protein C inhibitor, whereas the inhibition by alpha1-antitrypsin was unaffected by the mutation. A computer model of bAPC was developed in order to analyse further our data. Collectively, our results demonstrate enhanced catalytic efficiency to result from mutagenesis in the loop 148 and show that APC mutant with increased anticoagulant activity can be created.

Amino Acid Sequence↗
PubMed1999

[CAG trinucleotide mutation detection in patients with hereditary spinocerebellar ataxia].

OBJECTIVE: To assess the frequency of the SCA1, SCA2,SCA3/MJD, SCA6, SCA7 and DRPLA CAG trinucleotide repeat expansions(CAG)n among individuals diagnosed with hereditary spinocerebellar ataxia(SCA) from Chinese families. METHODS: The SCA1, SCA2, SCA3/MJD, SCA6, SCA7 and DRPLA(CAG)n mutations were detected by polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis and silver staining technique in 167 patients with autosomal dominant SCA from 85 Chinese families and 37 sporadic SCA patients. RESULTS: Among 85 families, four families(4.70%) had seven SCA1 patients with the CAG repeat expanded to 53 to 62 repeats, five (5.88%) had twelve SCA2 patients with the CAG repeat expanded to 43 to 47 repeats, and 41 (48.23%) had 83 SCA3/MJD patients with the CAG repeat expanded to 68 to 83 repeats. Analysis of the mutation in these families showed a strong negative correlation between the size of the expanded CAG repeat and the age of disease onset. None of the SCA patients were positive for SCA6, SCA7, or DRPLA. Nor was any of the sporadic SCA patients positive for the CAG repeat expansion in the SCA1, SCA2, SCA3/MJD, SCA6, SCA7, or DRPLA gene. CONCLUSION: The frequency of SCA3/MJD is substantially higher than that of SCA1 and SCA2 in the autosomal dominant SCA from Chinese families. Chinese SCA3/MJD patients are non-Portuguese. Clinical expressions of the various SCAs overlap one another and hence can make the phenotype-based diagnostic classification inaccurate in many instances. It is important for SCA clinical studies to make an SCA gene diagnosis and genotype analysis.

Adult↗
PubMed1999

Study on vertical transmission of Chlamydia trachomatis using PCR and DNA sequencing.

OBJECTIVE: To investigate the vertical transmission rate of Chlamydia trachomatis (CT) in Chongqing, China. METHODS: Specimens taken from 278 women and from their 79 infants were examined by cell culture, polymerase chain reaction (PCR) and DNA sequence analysis. Chlamydia trachomatis was isolated in McCoy cell culture. CT DNA was extracted with a modified Nal method. After cloning, recombinant plasmids were used for sequence analysis with the dideoxy chain termination method. RESULTS: 10.8% (30/278) of the cervical cultures of pregnant women were positive for Chlamydia trachomatis, while the positive rate tested by PCR was 14.0% (39/278). The vertical transmission rate of Chlamydia trachomatis was 55.0% (11/20). The incidences of conjunctivitis and pneumonia in infants with Chlamydia trachomatis positive mothers were 27.3% and 18.2%, respectively. DNA sequences of Chlamydia trachomatis isolated from the cervix of a mother and the nasopharynx of her baby were identical. CONCLUSION: Chlamydia trachomatis infection is quite common in Chongqing, China. Our report is the first report of CT vertical transmission proved by DNA sequence analysis.

Adult↗
PubMed1999

Subclasses of warm autoantibody IgG in patients with autoimmune hemolytic anemia and their clinical implications.

OBJECTIVE: To explore the mechanism of autoimmune hemolysis and establish a more sensitive test for autoimmune hemolytic anemia (AIHA). METHODS: IgG subclasses were tested in 40 patients with idiopathic or secondary AIHA by Coombs test with monoclonal antibodies. Hb, TBil, RC and FHb, as hemolytic parameters, were used to analyze the clinical implications of subclasses of AIHA warm autoantibody IgG. RESULTS: In most patients IgG incomplete warm autoantibody was IgG1 (27 patients), but IgG3 (20 patients), rarely IgG2 (14 patients) and IgG4 (9 patients) also occurred. Three groups were analyzed: Group A included 20 patients with IgG3; Group B included 14 patients with IgG1 bit without IgG3; Group C included 6 patients without IgG1 and IgG3. There were significant differences (P < 0.01) between groups in Hb, TBil, RC and FHb. Moreover, we also found that the sensitivity of Coombs test with polyclonal antiserums was 90.0%, while that of Coombs test with monoclonal antibodies was 97.5%. The effect of treatment was worst in patients with positive IgG3 autoantibody, whose hemolysis recurred frequently. CONCLUSION: IgG3 autoantibody was the most effective in bringing about red cell destruction, IgG1 autoantibody was less effective, IgG2 even less, whereas IgG4 autoantibody was shown to hardly affect red cell survival. Coombs test with monoclonal antibodies was more sensitive than that with polyclonal antiserums. Patients' respondence to treatment correlated with the type of IgG subclasses.

Adult↗
PubMed1999

[Clinicopathologic study of 11 patients with Paget's disease of scrotum].

OBJECTIVE: To probe the relationship of clinicopathologic presentations and prognosis of Paget's disease primarily involving the scrotum. METHODS: 11 cases of scrotal Paget's disease were studied retrospectively from 1984 to 1997. PAS was stained and EMA, S-100, HMB45, CEA and CA15-3 were immunostained in all cases for the differential diagnosis from Bowen's disease and malignant melanoma. RESULTS: Six of 11 cases involved hair follicle and/or sweat glands, and 3 cases involved dermis (one had metastasis of left superficial and deep inguinal lymph nodes, and left internal iliac lymph nodes). Paget's cells were positive for PAS (11/11), EMA (11/11), CEA (6/11), CA15-3 (11/11), and negative for S-100, HMB45. Wide local excision of the lesions was performed in 10 of 11 patients both for primary disease and recurrent disease. 3 of the 10 patients underwent lymph nodes resection and metastasis was found in 1 case pathologically. One patient accepted chemotherapy and died, from respiratory insufficiency after one month. The other 10 patients were followed up for 6 to 127 months and no patient died of Paget's disease. CONCLUSIONS: Involvement of hair follicles and sweat glands by Paget's cell does not influence the prognosis.However, invasion of dermis by Paget's cells may suggest possible metastasis.

Aged↗