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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 631 records · Page 35Linked to original sources
PubMed1998

An infectious viral disease of penaeid shrimp newly found in Korea.

Since 1993, massive mortalities have occurred among the penaeid shrimp Penaeus orientalis cultured in Korea. The major gross findings of the naturally occurring cases were 2 to 6 mm sized white spots on the inside of the carapace and reddish discolorization. Amphophilic to basophilic intranuclear inclusion bodies were readily observed in the epithelia of epidermis, foregut, gills, and lymphoid organs. Electron microscopy revealed enveloped and non-occluded ellipsoid to rod-shaped virus particles within the nucleus of lymphoid organ cells and the interstitial cells of the hepatopancreas of both naturally and experimentally infected shrimp. The size of the virions was 375 x 167 nm and the nucleocapsid was 290 x 75 nm. The agent which caused ectodermal and mesodermal necrosis in penaeid shrimp in Korea resembled white spot syndrome virus (WSSV) found in Taiwan with respect to gross signs, histological changes and viral morphology. Its viral morphology differed from that of the rod-shaped nuclear virus of Penaeus japonicus (RV-PJ) found in Japan. However, a 643 bp PCR product with an identical sequence to that from RV-PJ was detected. The results suggested that the Korean agent combined characters described for WSSV and RV-PJ.

Animals↗
PubMed1998

Serum antioxidant vitamins and risk of lung and stomach cancers in Shenyang, China.

In a hospital-based case control study, we measured serum concentrations of vitamin A, beta-carotene and vitamin E for subjects with cancer (58 cases of lung cancer and 22 cases of stomach cancer) and 63 matched controls in Shenyang, China. Lung cancer patients had significantly (P < 0.01) lower mean serum levels of vitamin A, beta-carotene and vitamin E than controls, while the mean serum level of vitamin E did not differ between stomach cancer patients and the controls. Lower serum levels of vitamin A, vitamin E and beta-carotene were associated with an increased risk of lung cancer. Lower serum levels of vitamin A and beta-carotene were associated with a higher risk of stomach cancer, although the number of cases was small. An increased risk of lung cancer associated with lower serum levels of vitamin A and vitamin E was more evident among heavy smokers than among non-heavy smokers.

Adult↗
PubMed1998

N-Phenylamidines as selective inhibitors of human neuronal nitric oxide synthase: structure-activity studies and demonstration of in vivo activity.

Selective inhibition of the neuronal isoform of nitric oxide synthase (NOS) compared to the endothelial and inducible isoforms may be required for treatment of neurological disorders caused by excessive production of nitric oxide. Recently, we described N-(3-(aminomethyl)benzyl)acetamidine (13) as a slow, tight-binding inhibitor, highly selective for human inducible nitric oxide synthase (iNOS). Removal of a single methylene bridge between the amidine nitrogen and phenyl ring to give N-(3-(aminomethyl)phenyl)acetamidine (14) dramatically altered the selectivity to give a neuronal selective nitric oxide synthase (nNOS) inhibitor. Part of this large shift in selectivity was due to 14 being a rapidly reversible inhibitor of iNOS in contrast to the essentially irreversible inhibition of iNOS observed with 13. Structure-activity studies revealed that a basic amine functionality tethered to an aromatic ring and a sterically compact amidine are key pharmacophores for this class of NOS inhibitors. Maximal nNOS inhibition potency was achieved with N-(3-(aminomethyl)phenyl)-2-furanylamidine (77) (Ki-nNOS = 0.006 microM; Ki-eNOS = 0.35 microM; Ki-iNOS = 0.16 microM). Finally, alpha-fluoro-N-(3-(aminomethyl)phenyl)acetamidine (74) (Ki-nNOS = 0. 011 microM; Ki-eNOS = 1.1 microM; Ki-iNOS = 0.48 microM) had excellent brain penetration and inhibited nNOS in a rat brain slice assay as well as in the rat brain (cerebellum) in vivo. Thus, N-phenylamidines should be useful in validating the role of nNOS in neurological disorders.

Amidines↗
PubMed1998

APS kinase from Arabidopsis thaliana: genomic organization, expression, and kinetic analysis of the recombinant enzyme.

The gene encoding 5'-adenylylsulfate (APS) kinase (EC 2.7.1.25) (APK) was cloned from Arabidopsis thaliana. There is a single APK locus in A. thaliana. The coding sequence of the gene is composed of 7 exons, interrupted by 6 introns. A transcriptional initiation site was detected 120 bp 5' of the initiation codon. APK mRNA is slightly more abundant in leaves than in roots of A. thaliana and its level does not change in response to sulfur starvation. The APK protein, synthesized in vitro, is able to enter isolated intact chloroplasts. Recombinant APS kinase shows maximal activity at 10 microM APS with 5 mM ATP, but it is inhibited at APS concentrations above 10 microM. The inhibition is alleviated at higher ATP concentrations. Reciprocal plot analysis showed that the theoretical Vmax is approximately 1.2 mumol min-1 mg-1 at 25 degrees C, pH 8.0; the K(m) values are 3.6 microM APS and 1.8 mM ATP.

Arabidopsis↗
PubMed1998

Interaction between corticotropin-releasing factor and nitric oxide in mediating the response of the rat hypothalamus to immune and non-immune stimuli.

We sought to determine whether nitric oxide (NO) influences the steady-state gene expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN) of the rat hypothalamus and conversely, whether CRF alters the activity of PVN neurons containing NO synthase (NOS), the enzyme responsible for NO formation. Adult male rats exposed to a 30-min session of mild electrofootshocks displayed a significant (P<0.01) increase in mRNA levels of the immediate early gene NGFI-B in the parvocellular portion of the PVN, which contains neurons expressing CRF. This response was decreased (P<0.01) by pretreatment with l-NAME, an arginine derivative that blocks NOS activity. In contrast, the stimulatory effect of interleukin-1beta (IL-1beta), injected intracerebroventricularly (i.c.v.) 45 and 15 min earlier, on NGFI-B mRNA and CRF hnRNA levels, was not. The i.c.v. injection of CRF (1 microg) significantly upregulated transcription of the neuronal isoform of NOS in the PVN, while the ability of i.c.v. IL-1beta to stimulate this signal was not significantly altered by i.c.v. injection of CRF antagonists. These results indicate that even though CRF acts centrally to increase PVN NOS mRNA concentrations, this peptide is not required for the effect of i.c.v. IL-1beta on these transcripts. On the other hand, the ability of shocks to stimulate PVN neuronal activity depends on NO formation. It therefore appears that the functional interactions between NO and CRF-dependent pathways is a function of the type of homeostatic threat to which the organism is exposed.

Adrenocorticotropic Hormone↗
PubMed1998

Divergence in the expression of molecular markers of neuronal activation in the parvocellular paraventricular nucleus of the hypothalamus evoked by alcohol administration via different routes.

Immediate early gene (IEG) expression has been routinely used by neuroscientists as an index of neuronal activation. In the case of the hypothalamic-pituitary-adrenal axis, induction of c-fos and/or NGFI-B mRNAs in the parvocellular paraventricular nucleus (pPVN) has been documented after a variety of stimuli that increase adrenocorticotropin (ACTH) in the systemic circulation. However, the functional relationship between expression of IEGs and transcription of the genes for the ACTH secretagogues corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) is not clear. While investigating the neuroendocrine correlates of alcohol administration via different routes (intraperitoneal vs intragastric), we noted a difference in the time course of NGFI-B mRNA expression in the pPVN, despite comparable dynamics in ACTH secretion. By comparing the temporal cascade of transcriptional events in vivo after alcohol injection via either route, we sought to determine functional relationships between IEGs and the induction of CRF and AVP heteronuclear RNAs (hnRNAs). One advantage of our paradigm is the use of the same stimulus (systemic alcohol injection) in which access to the CNS does not differ between the groups to be compared. Intraperitoneal administration of the drug resulted in significant increases in c-fos mRNA, Fos protein, CRF hnRNA, and AVP hnRNA. In contrast, intragastric treatment evoked a brief, modest elevation in c-fos mRNA and Fos protein, increased AVP hnRNA, and caused no detectable change in CRF hnRNA. These data indicate that robust increases in CRF hnRNA are closely linked to full expression of c-fos mRNA and Fos protein. In addition, the expression of NGFI-B after both routes of administration is indicative of cellular activation within the pPVN in parallel with secretion of ACTH.

Animals↗
PubMed1998

Association of XK and Kell blood group proteins.

A disulfide bond links Kell and XK red cell membrane proteins. Kell, a type II membrane glycoprotein, carries over 20 blood group antigens, and XK, which spans the membrane 10 times, is lacking in rare individuals with the McLeod syndrome. Kell is classified in the neprilysin family of zinc endopeptidases, and XK has structural features that suggest it is a transport protein. Kell has 15 extracellular cysteines, and XK has one in its fifth extracellular loop. Five of the extracellular cysteine residues in Kell are not conserved in the other members of the neprilysin family, and based on the hypothesis that one of the nonconserved cysteines is linked to XK, cysteines 72 and 319 were mutated to serine. The single extracellular cysteine 347 of XK was also mutated. Co-expression of combinations of wild-type and mutant proteins in transfected COS-1 cells showed that Kell C72S did not form a Kell-XK complex with wild-type XK, while wild-type Kell and Kell C319S did. XK C347S was also unable to form a complex with wild-type Kell, indicating that Kell cysteine 72 is linked to XK cysteine 347. Kell C72S was transported to the cell surface, indicating that linkage to XK is not required. In addition, chemical cross-linking of red cell membranes with dithiobispropionimidate indicated that glyceraldehyde-3-phosphate dehydrogenase is a near neighbor of Kell.

Amino Acid Sequence↗
PubMed1998

The human hepatitis B virus transactivator X gene product regulates Sp1 mediated transcription of an insulin-like growth factor II promoter 4.

Human hepatitis B virus (HBV) is one of the causative agents of hepatocellular carcinoma (HCC). The virus encodes a 17 kDa protein, X, which is known to be a causative agent in the formation of HCC. An insulin-like growth factor-II (IGF-II) is expressed during the formation of HCC. Among the four promoters of the IGF-II gene, promoters 2, 3 and 4 become activated during the formation of HCC. The high frequency of detection of hepatitis B virus X (HBV-X) antigen in liver cells from patients with chronic hepatitis, cirrhosis, and liver cancer suggested that the expressions of HBV-X and IGF-II are associated. Studies were carried out to test the relationship between the HBV-X gene product and the activation of IGF-II promoter 4. We demonstrated that the HBV-X protein increases the endogenous IGF-II expression from promoter 3 and 4 of IGF-II gene. Analysis of the fourth promoter of IGF-II gene showed that the HBV-X gene product positively regulates transcription. Two copies of a motif are responsible for conferring HBV-X regulation on the fourth promoter of IGF-II. These motifs have been identified as Sp1 binding sites. Sp1 binding to IGF-II P4 promoter was identified by gel mobility shift assay using purified Sp1. By using a GAL4-Sp1 fusion protein it was demonstrated that HBV-X positively regulates the Spl mediated transcriptional activity of IGF-II in vivo. A protein-affinity chromatography experiment showed that HBV-X protein does not bind directly to Sp1, but HBV-X does augment the DNA binding activity of the phosphorylated form of Sp1 in HepG2 cells. Sp1 was phosphorylated by HBV-X and its DNA-binding activity was up-regulated upon HBV-X transfections. Various HBV-X mutant expression vectors were used for the demonstration of specific interactions between Sp1 and HBV-X. These results indicate that HBV-X functions as a positive regulator of transcription, and that Sp1 is a direct target for the transcriptional regulation of IGF-II. Increasing the DNA binding ability of the phosphorylated form of Sp1 by HBV-X might be an important mechanism for regulating the IGF-II gene expression and possibly promoting cell division during hepatic carcinogenesis. Our experimental results suggest that expression of HBV-X might induce the expression of IGF-II and the IGF-II might play a role in hepatitis B virus pathogenesis during the formation of HCC.

Binding Sites↗
PubMed1998

Mechanisms of hypothalamic-pituitary-adrenal axis stimulation by immune signals in the adult rat.

Immune stimulation increases the activity of the HPA axis, a phenomenon directly or indirectly mediated through cytokines. We have used two models, the peripheral administration of endotoxin (LPS) or turpentine-induced tissue injury to show that corticotropin-releasing factor (CRF) and vasopressin (VP), hypothalamic peptides released by cytokines, play a dominant role in the increased ACTH measured in these two paradigms. In turn, CRF and VP synthesis and/or release is modulated by catecholamines, prostaglandins (PGs), and nitric oxide (NO). These secretagogues are produced in the periphery and/or the central nervous system (CNS) in response to increased cytokine levels and act on CRF/VP neurons and nerve terminals. Finally, endotoxemia and local tissue inflammation may upregulate brain levels of tumor necrosis factor alpha, interleukin-1 beta, and/or interleukin-6, providing yet another mechanism through which the occurrence of systemic inflammation is conveyed to the brain. The relative importance of brain or peripheral intermediates appears to depend on the site at which cytokine levels are increased. We have shown, for example, that peripheral, but not brain, PGs are important in mediating the neuroendocrine influence of blood-borne cytokines, while PGs in the CNS play a role in situations characterized by elevated brain immune proteins. NO, on the other hand, restrains the response of the HPA axis to circulating, but not brain cytokines. These results illustrate the complexity of the mechanisms involved in the stimulation of the HPA axis and suggest that their specific involvement depends on the type, intensity, and duration of immune stimulation.

Animals↗
PubMed1998

The cDNA cloning and ontogeny of mouse alpha-synuclein.

Alpha-synuclein has been implicated in the pathogenesis of Parkinson's disease. To investigate the role of alpha-synuclein in the brain, the cDNA clone encoding the mouse cognate of the human alpha-synuclein was isolated from a mouse brain cDNA library. The open reading frame coded for 140 amino acids that share 95% identity with human alpha-synuclein. Northern blot analysis showed that alpha-synuclein mRNA was primarily expressed in brain and spleen of adult mouse. In situ hybridization histochemistry revealed the highest expression of alpha-synuclein mRNA in the hippocampal formation and neocortex of the adult mouse. alpha-Synuclein mRNA expression in the brain was first observed in the hippocampus and neocortex on postnatal day 1. Levels of alpha-synuclein mRNA in these forebrain areas were nearly maximal at postnatal day 7 and remained relatively high until the adult stage. alpha-Synuclein mRNA was expressed in the liver transiently during embryogenesis.

Amino Acid Sequence↗
PubMed1998

Importance of hydrophobic region in amphiphilic structures of alpha-helical peptides for their gene transfer-ability into cells.

It has been showned that cationic alpha-helical peptides can be useful as nucleic acid-carrier molecules for gene transfer into cells. In order to investigate the significancemake sure of importance of the hydrophobic region in amphiphilic peptides in relation to their transfection ability, we have employed five kinds of peptides with a systematically varied hydrophobic-hydrophilic balance in the amphiphilic structures, and have evaluated the relationship between the structure and the gene transfer ability of the peptides into COS-7 cells. The peptides with a large hydrophobic region took alpha-helical structures, formed large aggregates and showed high transfection efficiency. Their high efficiency can be explained on the basis of their ability to form stable aggregates which can be internalized by endocytosis and remain resistant to digestion in lysosomal vesicles. Furthermore, it was suggested that the hydrophobic region of peptides plays an important role in the disruption of the endosomal membrane, which ca prevent the degradation of DNA in lysosomal vesicles. When peptides do not have so strong membrane-disruptive activity, but form aggregates which can be incorporated by endocytosis, the transfection efficiency can be recovered by the addition of an endosome-disruptive peptide.

Amino Acid Sequence↗
PubMed1998

Coexpression of a constitutively active plasma membrane calcium pump with GFP identifies roles for intracellular calcium in controlling cell sorting during morphogenesis in Dictyostelium.

To examine the potential role of calcium in regulating Dictyostelium development, we reduced free cytosolic and total cell Ca2+ in Dictyostelium cells by expressing a constitutively active form of a human erythrocyte plasma membrane calcium pump. The pump-expressing cells lacked a thapsigargin-mediated increase in cytoplasmic calcium, consistent with a reduced level of total cellular Ca2+. During aggregation, the cells initially formed a large number of aggregation centers, many of which coalesced to form mounds that were smaller than those of wild-type cells, and the cells did not exhibit the normal formation of elongated aggregation streams. The majority of the mounds either arrested at this stage with the formation of small protrusions or formed very aberrant finger-like structures, indicating an essential role for cellular calcium in morphogenesis. We used pump and wild-type cells differentially labeled by expressing different wavelength (green and blue) forms of green fluorescent protein and three-dimensional (3-D) reconstruction of serial fluorescent imaging to visualize the movement of pump and wild-type cells within the aggregate. The results showed that the pump cells exhibited very aberrant cell movement and sorting within the forming mound, suggesting that the reduced cytosolic calcium affects movement required for tip formation. When allowed to form chimeric organisms with wild-type cells, pump cells preferentially localized to two bands, one at the prestalk/prespore boundary and the other in the very posterior of the organism, suggesting that pump cells are unable to properly sort. Expression of the calcium pump had little effect on the induction of prestalk- or prespore-specific genes, whereas extended treatment with EGTA blocked induction of both classes of cell-type-specific genes. Our results suggest a role for intracellular Ca2+ in controlling cell sorting and morphogenesis in Dictyostelium.

Animals↗
PubMed1998

Inhibitors of farnesyl protein transferase. 4-Amido, 4-carbamoyl, and 4-carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2-b]pyridin-11-yl)piperazine and 1-(3-bromo-8-chloro-6,11- dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine.

The synthesis of a variety of novel 4-amido, 4-carbamoyl and 4-carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl) piperazine to explore the SAR of this series of FPT inhibitors is described. This resulted in the synthesis of the 4- and 3-pyridylacetyl analogues 45a and 50a, respectively, both of which were orally active but were found to be rapidly metabolized in vivo. Identification of the principal metabolites led to the synthesis of a variety of new compounds that would be less readily metabolized, the most interesting of which were the 3- and 4-pyridylacetyl N-oxides 80a and 83a. Novel replacements for the pyridylacetyl moiety were also sought, and this resulted in the discovery of the 4-N-methyl and 4-N-carboxamidopiperidinylacetyl derivatives 135a and 160a, respectively. All of these derivatives exhibited greatly improved pharmacokinetics. The synthesis of the corresponding 3-bromo analogues resulted in the discovery of the 4-pyridylacetyl N-oxides 83b (+/-) and 85b [11S(-)] and the 4-carboxamidopiperidinylacetamido derivative 160b (+/-), all of which exhibited potent FPT inhibition in vitro. All three showed excellent oral bioavailability in vivo in nude mice and cynomolgus monkeys and exhibited excellent antitumor efficacy against a series of tumor cell lines when dosed orally in nude mice.

3T3 Cells↗
PubMed1998

The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal.

The inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene predisposes affected individuals to the human VHL cancer syndrome and is associated with sporadic renal cell carcinomas (RCC) and brain hemangioblastomas. VHL-negative 786-0 RCC cells are tumorigenic in nude mice which is suppressed by the reintroduction of VHL. Remarkably, this occurs without affecting the growth rate and cell cycle profile of these cells in culture. The 786-0 cell line, like many cancer cells, fails to exit the cell cycle upon serum withdrawal. Here, it is shown that reintroduction of the wild-type VHL gene restores the ability of VHL-negative RCC cancer cells to exit the cell cycle and enter G0/quiescence in low serum. Both VHL-positive and VHL-negative RCC cells exit the cell cycle by contact inhibition. The cyclin-dependent kinase inhibitor, p27, accumulates upon serum withdrawal, only in the presence of VHL, as a result of the stabilization of the protein. We propose that the loss of wild-type VHL gene results in a specific cellular defect in serum-dependent growth control, which may initiate tumor formation. This is corrected by the reintroduction of wild-type VHL, implicating VHL as the first tumor suppressor involved in the regulation of cell cycle exit, which is consistent with its gatekeeper function in the kidney.

Animals↗
PubMed1998

Establishment and characterization of cell lines constitutively expressing hepatitis B virus X-protein.

We prepared human hepatoma cell lines, which expressed the human hepatitis B virus-X gene product. The plasmid pMAMneo-X, containing an HBV-X gene promoter, an enhancer and a structural gene was constructed. Transfected HBV-X gene integration and expression were detected by Southern and Northern blotting, as well as by chloramphenicol acetylase transferase (CAT) assay using various kinds of promoter-CAT reporter systems. HBV-X protein expression in stable transfectants was confirmed by immunofluorescence microscopy. Transfected cell lines showed permanent expression of HBV-X proteins. The HBV-X transfectant activated its target promoters in promoter-CAT constructs as reporters. The HBV-X transfectant enhanced AP-1 transcription factor binding to its target DNA. Therefore, X-transfectants are not only stable, but also have specific biological functions. Cell cycle analysis by flow cytometry showed that the majority of the transfectant cells are arrested in the G1 or G2 phase of the cell cycle. These cell lines may be useful in analyzing the biological functions of HBV-X and its functional role in the formation of hepatocellular carcinomas.

Carcinoma, Hepatocellular↗
PubMed1998

Prothrombotic disorders in infants and children with cerebral thromboembolism.

BACKGROUND: To our knowledge, the contribution of prothrombotic conditions to cerebral thromboembolism has never been prospectively studied in a large series of pediatric patients. METHODS: The Hospital for Sick Children, Toronto, Ontario, established a program in January 1992 to diagnose and treat children (term newborn to 18 years old) with arterial ischemic stroke or sinovenous thrombosis. The routine evaluation for prothrombotic conditions included plasminogen, antithrombin, protein C, free protein S, activated protein C resistance, IgG and IgM anticardiolipin antibody, and lupus anticoagulant. We analyzed samples taken within 2 years of the event. We report results on patients seen from January 1, 1992, to January 1, 1997. RESULTS: Ninety-two patients (47 males and 45 females) entered the program during the study interval. Patients ranged from newborn to 18 years in age. Arterial ischemic stroke occurred in 78% of patients while sinovenous thrombosis occurred in 22%. All were tested for prothrombotic disorders. One or more abnormal results were present in 35 (38%) of the 92 patients. The majority (21/35) had multiple abnormal test results. The abnormal test results were anticardiolipin antibody (33%), plasminogen (9.5%), activated protein C resistance (9%), protein C (7%), antithrombin (12.5%), lupus anticoagulant (8%), and free protein S (11.5%). Male sex predicted the presence of prothrombotic abnormalities (relative risk, 1.7; 95% confidence interval, 1.2-2.5), but stroke type (relative risk, 0.8; 95% confidence interval, 0.7-1.1), age group, and presence of other risk factors did not predict abnormal testing. CONCLUSIONS: A significant proportion (38%) of children with cerebral thromboembolism had evidence of prothrombotic conditions. In particular, there was a predominance of children with anticardiolipin antibody (33%). These data support a recommendation that children with cerebral thromboembolism be evaluated for prothrombotic disorders.

Adolescent↗
PubMed1998

The use of high-density polyethylene implants in facial deformities.

OBJECTIVE: To determine the usefulness of porous high-density polyethylene implants (Medpor) in a variety of facial skeletal deformities and subcutaneous defects, excluding those associated with acute maxillofacial trauma. DESIGN: Case series. SETTING: Academic tertiary care referral center in Baltimore, Md. PATIENTS: Thirty-four patients (age range, 20-74 years) with facial deformities requiring skeletal defect reconstruction or augmentation (38 cases), treated between January 1, 1992, and January 1, 1997. Follow-up ranged from 6 months to 40 months. MAIN OUTCOME MEASURES: Age, type and origin of the deformity treated, type of treatment, and complications. RESULTS: Types of deformities and defects treated include 7 patients with orbital defects (secondary traumatic or oncologic deformities), 8 with temporal fossa defects, 8 with frontocranial defects, 4 with maxillary or malar defects, 7 with calvarial bone graft donor site defects, 2 with microtia, and 2 with chin deficiency. Forty implants were placed. Complications included implant exposure in 4 patients and inappropriate augmentation in 1 patient (chin implantation). CONCLUSIONS: High-density polyethylene implants offer an excellent alternative to autogenous and other alloplastic materials in reconstruction of many facial defects and deformities. Advantages include its versatility and relatively ideal pore size that allows for excellent soft tissue ingrowth and coverage. Disadvantages include its rigid nature and difficulty in contouring to the surface of complex skeletal structures.

Adult↗