Properties of Dye-Sensitized Solar Cells Using Carbon Nanowall Counter Electrodes.

This research investigates plasma-treated and metal-coated carbon nanowalls (CNWs) for use as counter electrodes of dye-sensitized solar cells (DSSCs). The CNWs were synthesized on a fluorine-tin-oxide (FTO) glass substrate using the microwave plasma-enhanced chemical vapor deposition (PECVD) system with methane (CH4) gas. The post-plasma treatment was performed on the CNWs with hydrogen (H2) plasma using PECVD, and the CNWs were sputter-coated with metal films using the RF magnetron sputtering system with a four-inch tungsten (W) target. Then the post-plasma-treated and metal-coated CNWs were used as counter electrodes for the fabrication of the DSSCs. Field-emission scanning electron microscopy (FE-SEM) was performed to obtain cross-sectional and planar images of the grown CNWs. The energy conversion efficiencies of the DSSCs manufactured using the post-plasma-treated and metal-layer-coated CNWs as the counter electrodes were measured.

Anatomy of the deep branch of the ulnar nerve.

UNLABELLED: The aim of this study was to provide a clear description of the course, precise branching pattern and distribution of the deep branch of the ulnar nerve. A total of 36 hands from 18 preserved cadavers were dissected. The vertical distance from the pisoscaphoid line to the crossing points between the deep branch of the ulnar nerve and each metacarpal was about 4 cm. The deep branch of the ulnar nerve gave off two types of muscular branches: (1) trunks that innervate more than two intrinsic hand muscles; and (2) multiple separate branches innervating only a single muscle. The median numbers of trunks and separate branches were 5 and 6, respectively. LEVELS OF EVIDENCE: N/A.

Morphological and morphometric study of the androgenetic alopecic scalp using two- and three-dimensional analysis comparing regional differences.

BACKGROUND: Androgenetic (male-type) alopecia (AGA) is caused by genetic and androgenetic effects. The progression of baldness results in smaller hair papillae, thinner hair and a shortened hair cycle. Alopecia occurs mainly in the frontal region and, to a lesser extent, in the occipital region. OBJECTIVES: The morphological differences in the hair follicular units between the alopecic frontal scalp and the vertex and occipital regions were compared using cross-sectional histology and three-dimensional reconstruction. METHODS: Skin specimens were obtained from the frontal, vertex and occipital regions of 24 male human cadavers with fully progressed AGA, and from the frontal region of 32 normal cadaveric scalps. These specimens were fixed, processed using routine histological methods, serially sectioned at a thickness of 10 µm and then stained with Masson's trichrome. The serial sections were reconstructed three-dimensionally using 'Reconstruct' software. RESULTS: The ratios between the numbers of terminal and vellus hairs in the frontal and occipital regions in the AGA scalps were 0·2 : 1 and 3·5 : 1, respectively. Almost all of the hair follicles in the frontal region were vellus hair follicles. The sebaceous gland and arrector pili muscle were larger in the frontal region than in the occipital region. CONCLUSIONS: The morphology of the AGA scalp has been characterized. The terminal-to-vellus hair ratio in the occipital (normal) region was different from that in the frontal (alopecic) region. Moreover, sebaceous glands were larger in the frontal alopecic region than in the occipital region. These larger glands may be associated with other dermatological pathologies, such as seborrhoeic dermatitis.

Extra- and intramuscular nerves distributions of the triceps surae muscle as a basis for muscle resection and botulinum toxin injections.

PURPOSE: To compare the distribution of extramuscular nerve branches with their intramuscular ramifications in the triceps surae muscle, thus providing anatomical substantiation for the topography of muscle resection and botulinum toxin injections. METHODS: Dissection and modified Sihler's staining of 18 whole-mount human cadaveric specimens. RESULTS: The distance between the areas with the highest extramuscular branch density and the area of densest intramuscular arborization in gastrocnemius and soleus muscles is approximately 10% of the calf length. This finding should be taken into consideration during nerve blocking and botulinum toxin injections for the treatment of spasticity. Intramuscular nerve arborization patterns make it possible to outline neuromuscular segments in the gastrocnemius and soleus muscles. CONCLUSIONS: Surgical or therapeutic interventions in areas of high extramuscular and intramuscular nerve density can increase the efficacy and safety of botulinum toxin injections and neurotomy. Intramuscular nerve branching patterns should be taken into consideration during triceps surae resection.

Topographic anatomy of the zygomatic arch and temporal fossa: a cadaveric study.

The zygomatic arch (ZA) is a long, slender and laterally protruding structure of the face that is vulnerable to fracture by various types of trauma. Knowledge of the topographic anatomy of the ZA and temporal fossa is important for appropriate management of ZA problems. Thirty-seven male and 33 female cadavers were investigated in this study. Skin, subcutaneous tissue, fascia and periosteum were completely removed from around the ZA. Several depths and distances were measured based on three landmarks on the ZA: the anterior, middle and posterior portions of its superior margin. The thickness of the ZA was relatively constant in the three portions. The distance from the internal surface of the ZA to the surface of the temporalis muscle was similar in the anterior and middle portions, at about 8mm, and slightly lesser in the posterior portion. The distance from the external surface of the ZA to the temporal bone was the greatest at the anterior portion, and there was a large difference between the anterior and middle portions. The temporalis muscle was the thickest in the anterior portion and the thinnest in the posterior portion. This study suggests that the maximum distance from the internal surface of the ZA to the surface of the temporalis muscle is 8mm, and this should be considered when performing reduction malarplasty on the ZA.

Topography and location of the depressor anguli oris muscle with a reference to the mental foramen.

The labiomandibular fold (LMF) is the area of the face that extends from the mouth corner to the mandibular border, and its prominence tends to increase with age. The LMF can be formed by the medial or lateral border of the depressor anguli oris (DAO). The aim of this study was to demonstrate the topographical anatomy between the DAO and mental foramen, thereby providing critical information for the safest and most effective site at which to inject botulinum toxin type A (BTX-A). Thirty-four hemifaces from Korean adult cadavers were dissected. The maximum width between the medial borders of the bilateral DAO, parallel to the intercheilion horizontal line, was 59.9 +/- 4.6 (mean +/- SD) mm below the lower lip. The minimum width between the medial borders of the attachment of bilateral DAO was 29.7 +/- 4.8 mm at the mandibular border. The mental foramen was located in the middle third from the cheilion to the mandibular border in 28 cases (90.3%), and it was mostly confined within the DAO muscle coverage in 21 cases (67.7%). The buccal branch of the facial nerve entered through the middle third of the lateral border of DAO and then distributed. Concomitantly, the marginal mandibular branch of the facial nerve entered through the lower third of the lateral border of DAO in 17 cases (60.7%). These results represent additional reference data for identifying the position of the mental foramen on the facial skin, and will be useful for providing criteria for the most effective site for injecting BTX-A when treating the LMF.

A study of the secretion mechanism of the sebaceous gland using three-dimensional reconstruction to examine the morphological relationship between the sebaceous gland and the arrector pili muscle in the follicular unit.

BACKGROUND: New models of the structural relationship between the arrector pili (AP) muscle and the sebaceous gland (SG) have been proposed recently. OBJECTIVES: The purpose of the present study was to establish the actual morphological relationship between components of the follicular unit (FU) including the hair follicles, AP muscle and SG using 3D reconstruction of serially sectioned specimens so as to expand previous explanations of the secretory mechanism of the SG and to suggest other possible mechanisms based on newly proposed model. METHODS: Scalp skin specimens were processed using routine histological procedures, with serially sectioned tissue slides being stained with Masson's trichrome. 'Reconstruct' software was used to align, assemble and reconstruct the sections, with observations of the 3D-reconstructed FU [including hair follicles (HFs), AP muscle and SG]. RESULTS: Fifty FUs were reconstructed. The AP muscle was curved and concave as it supported the basal portion of the sebaceous lobules in the perifolliculum. Sebaceous lobules were located between the AP muscle and HFs (angular area) and some sebaceous lobules located in the opposite (counter-angular) area. CONCLUSIONS: We propose that the concave part of the AP muscle pushes up the basal portion of the sebaceous lobule between the HFs and AP muscle during AP muscle contraction and hair erection. In addition, the sebaceous lobule located at the counter-angular position is squeezed by the HF during AP muscle relaxation and hair repositioning. Combined with the previous mechanism of SG secretion, this newly established mechanism based on the 3D structure of the FU will improve our understanding of AP muscle function and SG secretion.

Asymmetry of the palpebral fissure and upper eyelid crease in Koreans.

The purpose of the present study was to quantify the asymmetry of the palpebral fissure (PF) and upper eyelid crease in normal Koreans. Photographs were taken of 273 males and 321 females aged from 20 to 49 years with a standard head position and eyes open. We investigated the presence of asymmetries of the PF inclination (PFI), PF height (PFH), PF width (PFW) and the upper eyelid crease. The criteria for asymmetry were 2 degrees for PFI, 1mm for PFH and 3mm for PFW. The PFH was larger on the right side than on the left side, whereas the PFW was larger on the left than on the right. The prevalence of asymmetry of the PFI, PFH and PFW was 22.3%, 24.2% and 18.3% in males, and 35.8%, 26.5% and 18.7% in females, respectively. In most cases of PF asymmetry, the PFH was larger on the right and the PFW was larger on the left. A left-only upper eyelid crease was more common than a right-only upper eyelid crease in both sexes. The asymmetry of the PF was generally more common in females.

Anatomical and radiological study of the superior and inferior gluteal arteries in the gluteus maximus muscle for musculocutaneous flap in Koreans.

The position, distribution pattern, and perforating branch of the superior gluteal artery (SGA) and the inferior gluteal artery (IGA) in the gluteus maximus muscle (GMM) were investigated through fine dissection and the radiological method. The SGA was located at about the upper one-third of the posterior superior iliac spine (PSIS)-greater trochanter of the femur (GT) line and medially at about 1cm from the line. The IGA was located at around the middle point of the PSIS-ischial tuberosity (IT) line. The perforating branches passed through the muscle to the subcutaneous tissue and were distributed to the GMM that divided the upper and lower parts; the SGA supplied to the upper two-fifths of the GMM; and the IGA supplied to the rest of the muscle. The course of the SGA and the IGA in the GMM were classified into four types according to their distribution patterns, and the most common type was the typical type whereby the IGA supplied an area larger than the SGA. These results were somewhat different from previous studies, but these differences must be considered for a safe and effective flap procedure.

Branching patterns of the arterial branches supplying the middle vascular pedicle of the sternocleidomastoid muscle: a topographic anatomical study with surgical applications for the use of pedicles osteomuscular flaps.

When making a sternocleidomastoid (SCM) osteomuscular flap to include the clavicle and determining the rotation arc of the osteomuscular flap, it is very important to know the location and the origin of the superior thyroid artery and the distribution pattern of the SCM branch. Accordingly, in this study, the 50 SCM muscles and their arteries were dissected in 26 Korean cadavers, and the results were analyzed. The average distances from the origin of the superior thyroid artery to the clavicular and sternal heads of the SCM muscle were 87.6 mm (57.7-123.8 mm) and 131.2 mm (99.7-166.8 mm), respectively. The average distance from the origin of the superior thyroid artery to the SCM branch entering the SCM muscle was 30.1 mm (16.0-37.7 mm). After entering the SCM muscle, the SCM branches of the superior thyroid artery bifurcated into the clavicular and sternal branches at a point located an average of 58.8 mm (28.4-130.4 mm) above the clavicle. The distribution patterns of the superior thyroid artery were classified into six types based on the branching order and the dual supplies to the SCM muscle. Among them, type I in which the laryngeal branch first divided from the superior thyroid artery was the most common case (36%).

Aberrant cholesterol transport and impaired steroidogenesis in Leydig cells lacking estrogen sulfotransferase.

Estrogen sulfotransferase (EST) is a cytosolic enzyme that catalyzes the sulfoconjugation and inactivation of estrogens. It is expressed abundantly in the mammalian testes in which it may modulate the activity of locally produced estrogen. We demonstrate here that testicular Leydig cells from mice rendered deficient in EST expression by targeted gene deletion acquire a phenotype of increased cholesterol ester accumulation and impaired steroidogenesis with natural aging or in response to estrogen challenge. Abnormal accumulation of cholesterol ester in the mutant Leydig cells correlated with induced expression of the scavenger receptor type B class I, and cultured EST-deficient but not wild-type Leydig cells avidly uptook high-density lipoprotein cholesterol ester ex vivo. EST-deficient Leydig cells in culture produced 50-70% less testosterone than wild-type cells. This deficiency was reversed by androstenedione but not progesterone supplementation, indicating that reduced activities of 17-alpha-hydroxylase-17, 20-lyase were responsible. This conclusion was corroborated by decreased expression levels of 17-alpha-hydroxylase-17, 20-lyase but not of other key steroidogenic enzymes in the mutant cells. These results suggest that EST plays a physiologic role in protecting Leydig cells from estrogen-induced biochemical lesions and provide an example of critical regulation of tissue estrogen sensitivity by a ligand-transformation enzyme rather than through estrogen receptors.

Estrogen sulfotransferase: discrete and androgen-dependent expression in the male reproductive tract and demonstration of an in vivo function in the mouse epididymis.

Estrogen sulfotransferase (EST) catalyzes the sulfoconjugation and inactivation of the steroid hormone estrogen. It is known previously that EST is expressed abundantly in Leydig cells of the testis. We recently have shown that male mice with targeted EST gene disruption developed age related Leydig cell and seminiferous tubule abnormalities as a consequence of increased local estrogen stimulation. In the same study, we also found that epididymal sperm isolated from the mutant mice had significantly reduced motility, but whether this reflected impaired epididymal function or was secondary to the testicular lesions was not known. The purpose of the current study was to investigate if EST is normally present in the mouse epididymis and/or other parts of the male reproductive tract where, as in testis, it may play a role in regulating local estrogen homeostasis. We describe here that EST is expressed in the epithelium of corpus and cauda but not caput regions of the mouse epididymis. It is also expressed in the luminal epithelium and smooth muscle cells of the vas deferens but was present at very low levels, if at all, in the prostate or seminal vesicle/ coagulating gland. Hypophysectomy, castration, and epididymal ligation experiments, together with the use of an androgen receptor antagonist, established that EST expression in the epididymis and vas deferens is critically dependent on pituitary hormone(s) and androgen but not on other factors in the testicular fluid. Administration of exogenous estradiol to mice with surgically ligated epididymis resulted in a more pronounced reduction in sperm motility in EST mutant mice than in wild-type mice. We conclude that EST is discretely expressed and regulated in the male reproductive tract and plays a physiological role in maintaining the functional integrity of the epididymis by regulating luminal estrogen homeostasis.

Targeted disruption of the mouse estrogen sulfotransferase gene reveals a role of estrogen metabolism in intracrine and paracrine estrogen regulation.

Elicitation of biological responses by estrogen in target tissues requires the presence of ER as well as receptor-active ligand in the local microenvironment. Though much attention has been devoted to the study of the receptor in estrogen target tissues, the concept is emerging that tissue estrogen sensitivity may also be regulated by ligand availability through metabolic transformation in situ. Here, we show that targeted disruption, in the mouse, of an estrogen metabolic enzyme, estrogen sulfotransferase (EST), causes structural and functional lesions in the male reproductive system. EST catalyzes the sulfoconjugation and inactivation of estrogen and is expressed abundantly in testicular Leydig cells. Although knockout males were fertile and phenotypically normal initially, they developed age-dependent Leydig cell hypertrophy/hyperplasia and seminiferous tubule damage. Development of these lesions in the testis could be recapitulated by exogenous E2 administration in younger knockout mice, suggesting that they arose in older knockout mice from chronic estrogen stimulation. Older knockout mice were also found to have reduced testis and epididymis weights but increased seminal vesicle/coagulating gland weight because of tissue swelling. Furthermore, total and forward sperm motility of older knockout mice was reduced by 60% and 80%, respectively, and these mice produced smaller litters compared with age-matched wild-type males. These findings establish a role for EST in the male reproductive system and indicate that intracrine and paracrine estrogen activity can be modulated by a ligand transformation enzyme under a physiological setting. Thus, inhibition of estrogen metabolic enzymes by environmental chemicals, as has been demonstrated recently for the human EST, may constitute a novel mechanism of endocrine disruption in vivo.

Characterization of glycosylphosphatidylinositol-anchored decay accelerating factor (GPI-DAF) and transmembrane DAF gene expression in wild-type and GPI-DAF gene knockout mice using polyclonal and monoclonal antibodies with dual or single specificity.

Decay-accelerating factor (DAF, CD55) is a glycosylphosphatidylinositol (GPI)-linked membrane inhibitor of complement activation. While human and other mammalian species contain only one DAF gene, two distinct DAF genes, referred to as GPI-DAF and transmembrane (TM)-DAF, respectively, have been identified in the mouse. Using several independently generated monoclonal and polyclonal antibodies, either with dual or single specificity for GPI-DAF and TM-DAF gene products, we have examined the expression of the two DAF genes in tissues of the wild-type and a strain of knockout mouse whose GPI-DAF gene has been inactivated. By fluorescence-activated cell sorting (FACS) analysis, we found that DAF protein is present on the wild-type mouse erythrocytes and lymphocytes but no signal was detectable on the same cells of GPI-DAF gene knockout mice. Both T and B lymphocytes and splenic macrophages express the GPI-DAF gene but the expression level is higher on B lymphocytes than on T lymphocytes. Within the T cell population, both CD4+ and CD8+ T cells are positive. DAF protein was detected by immunohistochemistry at high levels on wild-type mouse spermatids and mature sperm. In contrast, only mature sperm stained positive in the GPI-DAF gene knockout mouse testis, suggesting that GPI-DAF but not the TM-DAF gene is expressed on spermatids. Examination of the fetoplacental unit at the day 7.5 stage revealed that GPI-DAF but not the TM-DAF gene is expressed in the maternal decidua cells surrounding the trophoectoderm of the embryo. No DAF expression was detected on trophoblast or the embryo proper. These findings suggest that although the TM-DAF gene is irrelevant on mouse blood cells, the two DAF genes may have different roles in germ cell development and/or mature sperm function. Because complement receptor 1-related gene/protein y (Crry) has been shown to be expressed on early mouse embryos, the complete lack of GPI-DAF and TM-DAF gene expression in early mouse development may explain the observed sensitivity of Crry-deficient embryos to maternal complement attack.

Increased susceptibility of decay-accelerating factor deficient mice to anti-glomerular basement membrane glomerulonephritis.

To prevent complement-mediated autologous tissue damage, host cells express a number of membrane-bound complement inhibitors. Decay-accelerating factor (DAF, CD55) is a GPI-linked membrane complement regulator that is widely expressed in mammalian tissues including the kidney. DAF inhibits the C3 convertase of both the classical and alternative pathways. Although DAF deficiency contributes to the human hematological syndrome paroxysmal nocturnal hemoglobinuria, the relevance of DAF in autoimmune tissue damage such as immune glomerulonephritis remains to be determined. In this study, we have investigated the susceptibility of knockout mice that are deficient in GPI-anchored DAF to nephrotoxic serum nephritis. Injection of a subnephritogenic dose of rabbit anti-mouse glomerular basement membrane serum induced glomerular disease in DAF knockout mice but not in wild-type controls. When examined at 8 days after anti-glomerular basement membrane treatment, DAF knockout mice had a much higher percentage of diseased glomeruli than wild-type mice (68.8 +/- 25.0 vs 10.0 +/- 3.5%; p < 0.01). Morphologically, DAF knockout mice displayed increased glomerular volume (516 +/- 68 vs 325 +/- 18 x 10(3) microm(3) per glomerulus; p < 0.0001) and cellularity (47.1 +/- 8.9 vs 32.0 +/- 3.1 cells per glomerulus; p < 0.01). Although the blood urea nitrogen level showed no difference between the two groups, proteinuria was observed in the knockout mice but not in the wild-type mice (1.4 +/- 0.7 vs 0.02 +/- 0.01 mg/24 h albumin excretion). The morphological and functional abnormalities in the knockout mouse kidney were associated with evidence of increased complement activation in the glomeruli. These results support the conclusion that membrane C3 convertase inhibitors like DAF play a protective role in complement-mediated immune glomerular damage in vivo.

Genomic structure, functional comparison, and tissue distribution of mouse Cd59a and Cd59b.

CD59 is a crucial complement regulatory protein that inhibits the terminal step of the complement activation cascade by interfering with the binding of C9 to C5b-8, thus preventing the formation of the membrane attack complex (MAC). We recently reported that the mouse genome contains two Cd59 genes, while the human and rat genomes each contain only one Cd59 gene (Qian et al. 2000). Here, we describe the genomic structure, comparative activity, and tissue distribution of these two mouse genes, designated Cd59a and Cd59b. The mouse Cd59 genes encompass a total of 45.6 kb with each gene having four exons. Cd59a spans 19 kb, and Cd59b spans 15 kb, with approximately 11.6 kb of genomic DNA separating the two genes. The overall sequence similarity between Cd59a and Cd59b is approximately 60%. The sequence similarity between exon 2, exon 3, and exon 4 and the respective flanking regions between the two genes is over 85%, but exon 1 and its flanking regions are totally different. Comparative studies of the activity of both genes as inhibitors of MAC formation revealed that Cd59b has a specific activity that is six times higher than that of Cd59a. Using polyclonal antibodies specific to either Cd59a or Cd59b, we showed that Cd59a and Cd59b are both widely expressed in the kidneys, brain, lungs, spleen, and testis, as well as in the blood vessels of most mouse tissues. Interestingly, testicular Cd59a appeared to be expressed exclusively in spermatids, whereas Cd59b was expressed in more mature sperm cells. These results suggest that even though Cd59a and Cd59b are expressed in multiple tissues, they may play some different roles, particularly in reproduction.

Membrane complement regulatory proteins: insight from animal studies and relevance to human diseases.

The complement system plays an important role in host defense. However, if not properly regulated, activated complement can also cause significant damage to host tissues. To prevent complement-mediated autologous tissue damage, host cells express a number of membrane-bound complement regulatory proteins. These include decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and CD59. Recent studies of membrane complement regulatory proteins from various animal species have revealed similarities as well as significant differences from the corresponding human proteins. In this review, we summarize recent advances in this area and contrast the structure, function and tissue distribution of membrane complement regulatory proteins in human and nonprimate mammalian species. We also discuss how the characterization of the animal proteins has provided important clues and might continue to show relevance to the pathogenesis and therapeutics of a number of human diseases.

Glutathione stimulates sulfated estrogen transport by multidrug resistance protein 1.

Multidrug resistance protein 1 (MRP1) is an ATP-binding cassette (ABC) transporter that transports a range of hydrophobic xenobiotics, as well as relatively hydrophilic organic anion conjugates. The protein is present at high levels in testicular Leydig and Sertoli cells. Studies with knockout mice suggest that MRP1 may protect germ cells from exposure to some cytotoxic xenobiotics, but potential endobiotic substrates in this organ have not been identified. Previously, we have shown certain D-ring, but not A-ring, estrogen glucuronides can act as competitive inhibitors of MRP1 mediated transport, suggesting that they are potential substrates for the protein. In the case of 17 beta-estradiol-17 beta-d-glucuronide, this has been confirmed by direct transport studies. The Leydig cell is the major site of estrogen conjugation in the testis. However, the principal products of conjugation are A-ring estrogen sulfates, which are then effluxed from the cell by an unknown transporter. To determine whether MRP1/mrp1 could fulfill this function, we used membrane vesicles from MRP1-transfected HeLa cells to assess this possibility. We found that estradiol and estrone 3-sulfate alone were poor competitors of MRP1-mediated transport of the cysteinyl leukotriene, leukotriene C(4). However, in the presence of reduced glutathione (GSH), their inhibitory potency was markedly increased. Direct transport studies using [(3)H]estrone 3-sulfate confirmed that the conjugated estrogen could be efficiently transported (K(m) = 0.73 microm, V(max) = 440 pmol mg(-)1 protein min(-)1), but only in the presence of either GSH or the nonreducing alkyl derivative, S-methyl GSH. In contrast to previous studies using vincristine as a substrate, we detected no reciprocal increase in MRP1-mediated GSH transport. These results provide the first example of GSH-stimulated, MRP1-mediated transport of a potential endogenous substrate and expand the range of MRP1 substrates whose transport is stimulated by GSH to include certain hydrophilic conjugated endobiotics, in addition to previously identified hydrophobic xenobiotics.

Biochemistry and reproductive endocrinology of estrogen sulfotransferase.

Estrogen sulfotransferase is a cytosolic enzyme that catalyzes the sulfoconjugation and inactivation of estrogens. Significant progress has been made in the last few years regarding the structure, substrate specificity, tissue expression, and regulation of mammalian estrogen sulfotransferases. The enzyme has high affinity for estrogens and is expressed in a number of estrogen target tissues, including the male and female reproductive systems. Expression of the enzyme in the testis has been particularly well characterized. In the testis, estrogen sulfotransferase is localized selectively to Leydig cells and its expression in these cells is dependent on LH and androgen. It was concluded, from both in vitro and in vivo studies, that estrogen sulfotransferase can function as an effective modulator of local estrogen activity in target tissues. The finding that certain hydroxylated polychlorinated biphenyls are potent inhibitors of the human estrogen sulfotransferase enzyme raises the possibility that environmental chemicals can cause endocrine disruption by enhancing endogenous estrogen activity through inhibition of steroid transformation enzymes such as estrogen sulfotransferase. This provides a new paradigm in explaining the endocrine disrupting potential of environmental chemicals that have low or no binding affinities for steroid hormone receptors.

Identification and functional characterization of a new gene encoding the mouse terminal complement inhibitor CD59.

CD59 is a 18- to 20-kDa, GPI-anchored membrane protein that functions as a key regulator of the terminal step of the complement activation cascade. It restricts binding of C9 to the C5b-8 complex, thereby preventing the formation of the membrane attack complex (C5b-9 of complement). A single human CD59 gene has been identified, and corresponding genetic homologues from rat, mouse, and pig have been characterized in previous studies. In this study, we report the discovery and functional characterization of a separate cd59 gene in the mouse (referred to as cd59b, the previously characterized mouse cd59 gene as cd59a). Mouse cd59b is 85% and 63% identical to cd59a at the nucleotide and amino acid level, respectively. In cDNA transfection experiments with Chinese hamster ovary cells, peptide-tagged cd59b was detected on the cell surface by flow cytometry and was shown to be susceptible to phosphatidylinositol-specific phospholipase C cleavage. Chinese hamster ovary cells expressing cd59b were significantly more resistant than control cells to human and mouse complement-mediated lysis. These results suggest that cd59b encodes a GPI-anchored protein that is functionally active as a membrane attack complex inhibitor. Northern blot analysis revealed that cd59b is expressed selectively in the mouse testis. In contrast, the major transcript of cd59a was shown to be expressed at high levels in the heart, kidney, liver, and lung, but only minimally in the testis. These results revealed the existence of two distinct cd59 genes in the mouse that are differentially regulated and that may have nonoverlapping physiological functions in vivo.