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Biomedical subjects

H M Lee

Publications and source records attributed to H M Lee.

At least 55 records · Page 3Linked to original sources
PubMed2001

The lipophilicity, pharmacokinetics, and cellular uptake of different chemically-modified tetracyclines (CMTs).

CMTs are analogs of tetracyclines, which are chemically modified to eliminate their antimicrobial efficacy but which retain their inhibitory activity against matrix metalloproteinases. These compounds have been found to inhibit connective tissue breakdown in animal models of diseases such as periodontitis, arthritis and cancer. Because CMTs exhibit different in vivo efficacy in these various models of disease, the current study compared their pharmacokinetics and other properties as follows: Adult male Sprague-Dawley rats were administered by oral gavage a single dose of 5mg of different CMTs suspended in 1 ml 2% carboxymethyl-cellulose, and blood samples were collected from 1-48 hours after dosing. The sera were extracted, then analyzed by HPLC using a C-18 reverse-phase column. The results showed that the peak concentrations (C(max)) in rat sera 1-12 hours after oral administration of CMTs -1, -2,-3, -4,-5,-6,-7,-8 and doxycycline were 5.5, 0.7, 4.6, 6.2, 0.8, 0.7, 9.0 (note: the 3 peaks detected for CMT-7 were combined), 15.0 and 0.9 microg/ml, respectively. Their in vivo half-lives (t(1/2)) were 11, 5, 22, 11, 32, 15, 37, 38, and 17 hours, respectively. Of the anticollagenase CMTs tested, CMT-8 showed the greatest C(max) and t(1/2)values, followed by CMTs-3, -1, -4, and perhaps -7; CMTs-2, -5, and -6 exhibited much lower levels in serum. The relative lipophilicities of the 8 CMTs and doxycycline were tested by examining their extractability in octanol. The results showed that CMT-2, -5, and -6 had the lowest partition coefficients using this organic solvent, while CMT-3 was the most lipophilic. The lipophilicity of the different CMTs was also positively correlated (r(2)=0.767, P<0.05) to peak serum concentrations (C(max)), but not to their serum half-lives (r(2)=0.25,P=0.49). This property of the different CMTs was also found to be positively correlated to their ability to enter into human whole blood cells in vitro (r2=0.95, P<0.001). Since CMT-8, as well as CMTs-3 and -1, consistently exhibited the greatest in vivo efficacy in animal models of tissue breakdown, this may reflect, at least in part, their favorable pharmacokinetics and tissue uptake.

Administration, Oral↗
PubMed2001

Inhibition of tumor cell invasiveness by chemically modified tetracyclines.

COLO 205 is a cell line derived from a human colon carcinoma with high degradative activity towards extracellular matrix (ECM). It has been shown that COLO 205 cells produce matrix metalloproteinases (MMPs). MMPs are a family of enzymes known to degrade components of the ECM and have been implicated in tumor invasion. In the present study, we have analyzed the multiple effects of chemically modified tetracyclines (CMTs) on the expression and activity of MMPs secreted by COLO 205 cells in vitro with the aim of evaluating these compounds for potential use in management of invasive tumors. Because COLO 205 cells can degrade an interstitial ECM in serum-free medium in vitro, we have been able to compare the effects of the tetracyclines on this measure of invasive activity with their effects on proteinase expression and activity. We demonstrate here that one of the chemically modified tetracyclines, 6-deoxy-6-demethyl-4-de(dimethylamino)tetracycline (CMT-3) can effectively inhibit ECM degradation mediated by COLO 205 cells or their conditioned medium. Gelatin zymography and immunoblots show that CMT-3 has the ability to inhibit release of MMP-2 into conditioned medium as well as to inhibit MMP-2 gelatinolytic activity, which correlates with the results from ECM degradation assays. On the basis of our findings with COLO 205 cells we have expanded our evaluation of the tetracyclines to include effects on a genetically engineered line of MDA-MB-231 breast tumor cells overexpressing MMP-9 at levels over tenfold those of the parent cell line, and on three human prostate tumor cell lines, LNCaP, DU-145, and PC-3. We show here that CMT-3 displays multiple modes of action: inhibiting MMP activity, reducing levels of MMP expression, and exhibiting selective cytotoxicity towards some of the tumor cell lines.

Antineoplastic Agents↗
PubMed2001

CMT-3, a non-antimicrobial tetracycline (TC), inhibits MT1-MMP activity: relevance to cancer.

Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases. Enhanced matrix metalloproteinase-2 (MMP-2; gelatinase A) activity has been correlated to cancer invasiveness, and membrane type MMP (MT1-MMP) expressed by tumor cells is involved in localizing and activating pro-MMP-2, a pathway believed to mediate cancer induced tissue breakdown. CMT-3 (6-demethyl, 6-deoxy, 4-dedimethylamino TC) has been shown to experimentally suppress prostate cancer, colon adenocarcinoma and melanoma invasiveness in cell culture and to inhibit tumor growth and metastasis in vivo and was used in the current in vitro study. Confluent MT1-MMP transfected COS-1 cells were harvested, washed thoroughly, subjected to N(2) cavitation and cell membrane enriched fractions were isolated by sequential centrifugations. This MT1-MMP preparation exhibited (i) pro-MMP-2 activating activity as shown by molecular weight shift of this gelatinase from 72 kDa to 62 kDa using gelatin zymography, and (ii) the ability to degrade both [(3)H-methyl] gelatin and casein at 37 degrees C. Adding CMT-3 at final concentrations of 5--20microM inhibited MT1-MMP gelatinolytic and caseinolytic activity, blocked MT1-MMP activation of pro-MMP-2, and decreased invasiveness (using the Matrigel system) of HT-1080 fibrosarcoma cells. The inhibition of MT1-MMP by CMT-3 may partially explain the inhibition of cancer cell -mediated tissue breakdown and invasiveness by this non-antimicrobial tetracycline analog.

Animals↗
PubMed2001

Comparison between posterolateral fusion with pedicle screw fixation and anterior interbody fusion with pedicle screw fixation in adult spondylolytic spondylolisthesis.

There have been many reports regarding various operative methods for spondylolytic spondylolisthesis. However, there have been no reports regarding the comparison between posterolateral fusion (PLF) with pedicle screw fixation (PSF) and anterior lumbar interbody fusion (ALIF) with PSF. The purpose of the current study was to compare the clinical outcomes of PLF with PSF and ALIF with PSF, and to help in the selection of treatment options. Fifty-six patients with spondylolytic spondylolisthesis who underwent PLF with PSF (group 1, 35 patients) or who underwent ALIF with PSF (group 2, 21 patients) were studied. Minimum follow-up was 2 years. Demographic variables and disease state were similar for the two groups. We studied operating time, amount of blood loss, duration of hospital stay, clinical outcomes, complications, time at which fusion was complete, fusion rate, and radiological measurements. There were no significant differences between the two groups in terms of the amount of blood loss, duration of hospital stay, back pain, radiating pain, fusion rate, or complication rate. However, in group 2, the operation time and the time at which fusion became complete was longer, and in group 1 there was significant radiological reduction loss. In conclusion, PLF with PSF was just as effective as ALIF with PSF in terms of clinical outcomes, but ALIF with PSF was superior to PLF with PSF in terms of the prevention of reduction loss. Anterior support would be helpful for preventing reduction loss in cases of spondylolytic spondylolisthesis of the lumbar spine.

Adolescent↗
PubMed2001

Effect of early exposure on the integration of dental implants: Part 2--Clinical findings at 6 months postloading.

Implant exposure during initial healing after placement has been considered important in both implant integration and postloading effects. This study evaluated the effect of early implant exposure on the clinical findings prerestoration and 6 months postrestoration. Forty-eight implants (24 CPTi and 24 Ti-13-13) were placed in maxillary and mandibular posterior sites in six baboons. Implant exposure was evaluated for 24 of the submerged implants at placement and at each weekly visit for 3 weeks after implant placement. The crestal bone level at maxillary posterior sites was measured at 6-month uncovering, and mandibular sites were measured at 3-month uncovering. All sites were again measured 6 months after restoration placement. Periotest readings were recorded at implant uncovering and again 6 months postloading. Arbitrary groupings of the Periotest values were assigned as good = -7 to -1; guarded = 0 to +2; and poor = +3 to +27. At 6 months postloading, there were no statistical differences between CPTi and Ti-13-13 for change in crestal bone height in either arch. The mean change in maxillary crestal bone height varied from a 0.59- to 1.35-mm loss. The differences between the mean exposed and nonexposed changes were not statistically significant The mean change in mandibular crestal bone height varied from a 0.25- to 0.88-mm loss. Changes in crestal bone height for nonexposed sites from 3-month implant uncovering to 6 months postloading were statistically significant at the mesial, buccal, and lingual aspects. The mean change for the nonexposed distal aspect approached significance. The differences between the mean exposed and nonexposed changes were not statistically significant. The overall percentage of maxillary implants in the good category for nonexposed sites decreased by 41% from uncovering to 6 months after loading, while no change occurred for exposed sites; the percentage of implants in the good category was comparable for early exposed and nonexposed sites (57% and 59%, respectively). At 6 months after loading, the percentage of implants in the good category was more favorable for early exposed (88%) than nonexposed sites (50%). A one-stage implant approach should provide similar postloading clinical results as the two-stage surgical approach.

Alveolar Bone Loss↗
PubMed2001

Evidence of increased matrix metalloproteinase-9 concentration in patients following cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response, which can result in acute lung injury known as "postperfusion syndrome." Neutrophil activation with concomitant serine protease release has been implicated in the pathogenesis of "postperfusion syndrome." Increased plasma levels of neutrophil elastase (NE) have been demonstrated in patients undergoing CPB, and it is well documented that both NE and matrix metalloproteinase-9 (MMP-9) have a synergistic role in pulmonary injury. We, therefore, hypothesized that plasma levels of MMP-9 would be elevated in patients after CPB. Human plasma was obtained after informed consent from eight patients undergoing CPB. Plasma was collected at the start of CPB, 5 minutes after the initiation of CPB, and at the termination of CPB (156 +/- 17 min). All samples were analyzed by both standard enzyme-linked immunosorbent assay (ELISA) and gelatin zymography for MMP-9 (free and total enzyme) concentration. Data were expressed as means +/-SE and assessed by analysis of variance (ANOVA). Plasma MMP-9 concentration was significantly increased at the end of CPB (191 +/- 30.4 ng/mL; p <.05) as compared to both the start of CPB (28.3 +/- 13.2 ng/mL) and 5 minutes after the initiation of CPB (44.3 +/- 15.4 ng/mL). Patients undergoing CPB show an increase in serum MMP-9 levels. Prior studies utilizing an animal model of "postperfusion syndrome" have shown that inhibition of MMP-9 and NE prevented pulmonary injury following CPB. The results of the current study suggest that such an approach may also have merit in the clinical setting of cardiopulmonary bypass.

Adult↗
PubMed2000

Sexual dysfunction in men with paraparesis in lumbar burst fractures.

STUDY DESIGN: A retrospective follow-up study. OBJECTIVES: To review and analyze the sexual function of patients who have sustained lumbar fractures with incomplete paraparesis. SUMMARY OF BACKGROUND DATA: As a result of advances in surgical techniques, most patients with lumbar fractures have significant recovery of neurologic status. Because motor functions are important to patients, most of the studies have concentrated their analyses on motor recovery. Many patients who have almost completely recovered motor function, however, may have sexual dysfunction, especially men. METHODS: Forty-three patients with lumbar fractures that resulted in incomplete paraparesis were analyzed. American Spinal Injury Association motor index points were determined for each patient before and after surgery and used for comparison between American Spinal Injury Association motor index and international index of erectile function score. Eleven male patients who reported sexual dysfunction were evaluated by using Rigiscan. RESULTS: During the follow-up period, 42 patients showed neurologic recovery. Average improvement of American Spinal Injury Association motor score was 13. 1 and average international index of erectile function score was 45. Average improvement of American Spinal Injury Association motor score for patients who had not reported sexual dysfunction was 12.5, and average international index of erectile function score was 52. For 11 patients in the sexual dysfunction group, preoperative motor score was 28.0, and average improvement of score was 14.9. Nocturnal penile tumescence monitoring results were abnormal in four cases. Averaged international index of erectile function score was 15. There was a statistically significant difference between the sexually healthy and dysfunctional groups in international index of erectile function score (P < 0.05), whereas no difference was noted in American Spinal Injury Association motor score. CONCLUSIONS: Neurologic recovery after lumbar fractures was improved. Regardless of neurologic recovery, most patients reported some disability, usually caused by pain and occasionally sexual dysfunction. Impairment of sexual function was present in four patients (9.3%). Although these patients may preserve psychiatric erection potential, they usually experienced sexual problems.

Adult↗
PubMed2000

Reliability of magnetic resonance imaging in detecting posterior ligament complex injury in thoracolumbar spinal fractures.

STUDY DESIGN: Prospective study of 34 patients with thoracolumbar spinal fractures. OBJECTIVES: To assess the reliability of magnetic resonance imaging (MRI) for posterior ligament complex injury in thoracolumbar spinal fractures. SUMMARY OF BACKGROUND DATA: Some researchers have studied posterior ligament complex injury in spinal fracture using MRI. However, most did not evaluate the findings of MRI compared with the operative findings. METHODS: Thirty-four patients with thoracolumbar spinal fracture were evaluated by palpation of the interspinous gap, plain radiography, and MRI before operation. In addition to conventional MRI sequences, a fat-suppressed T2-weighted sagittal sequence was performed. Surgery was performed by a posterior approach. During the operation, posterior ligament complex injury was carefully examined. RESULTS: A wide interspinous gap was palpated in 14 patients and was found in 21 patients on plain radiography. Magnetic resonance imaging raised suspicion of injury to the posterior ligament complex in 30 patients. According to interpretation of MRI, injury to the supraspinous ligament was suspected in 27 patients, the interspinous ligament in 30 patients, and the ligamentum flavum in 9 patients. There were 28 supraspinous ligament injuries, 29 interspinous ligament injuries, and 7 ligamentum flavum injuries in operative findings. There was a significant relation between MRI interpretation and operative findings. CONCLUSION: A fat-suppressed T2-weighted sagittal sequence of MRI was a highly sensitive, specific, and accurate method of evaluating posterior ligament complex injury. Based on the results of this study, a fat-suppressed T2-weighted sagittal sequence of MRIs is recommended for the accurate evaluation of posterior ligament complex injury and would be helpful in the selection of treatment options.

Adolescent↗
PubMed2000

Effects of mutation at a conserved N-glycosylation site in the bovine retinal cyclic nucleotide-gated ion channel.

Bovine retinal cyclic nucleotide-gated (CNG) ion channel contains an evolutionary conserved N-glycosylation site in the external loop between the fifth transmembrane segment and the pore-forming region. The effect of tunicamycin treatment and the site-specific mutation suggested that the channel is glycosylated when expressed in Xenopus oocytes. To test the role of glycosylation in this channel, N-glycosylation was abolished by mutation, and the detailed permeation and the gating characteristics of the mutant channel were investigated. The charge contribution turned out to be detectable, although the mutation of the N-glycosylation site did not affect expression and functionality of the CNG channel in oocytes.

Amino Acid Sequence↗
PubMed2000

Deep vein thrombosis after major spinal surgery: incidence in an East Asian population.

STUDY DESIGN: A prospective study of 313 patients who underwent major spinal surgery. OBJECTIVES: To determine the incidence of deep vein thrombosis after major spinal surgery in an east Asian population without antithrombotic prophylaxis. SUMMARY OF BACKGROUND DATA: Spinal surgery has been associated with few thrombotic complications (2-14%) compared with other reconstructive surgeries (20-70%). It has also been well documented that the incidence of deep vein thrombosis in east Asians (10%) is lower than in westerners (20-70%) in total joint replacements. There has been no previous report on the incidence of deep vein thrombosis after reconstructive spinal surgery in east Asians. METHODS: Three hundred thirteen patients who underwent major spinal surgery were evaluated prospectively. All patients were examined with duplex ultrasonography assessments of both lower extremities. No specific antithrombotic prophylaxis were used in any patients before or after surgery. RESULTS: There were four patients with positive findings of deep vein thrombosis on duplex ultrasonography, and there was only one with clinically symptomatic deep vein thrombosis. The overall incidence of thrombotic complications was 1.3%, and the incidence of symptomatic deep vein thrombosis was 0.3%. CONCLUSION: Considering the low rate of deep vein thrombosis, routine screening and prophylaxis for deep vein thrombosis appears unwarranted in east Asians before or after major spinal surgery.

Adolescent↗
PubMed2000

Unilateral versus bilateral pedicle screw fixation in lumbar spinal fusion.

STUDY DESIGN: A prospective study of 87 patients who underwent unilateral or bilateral pedicle screw fixation. OBJECTIVES: To determine whether unilateral pedicle screw fixation is comparable with bilateral fixation in one- or two-segment lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Clinical results for unilateral variable screw placement instrumentation in isolated L4-L5 fusion have been reported to be as good as those for bilateral instrumentation. However, unilateral instrumentation may not be recommended for multilevel fusion. METHODS: Eighty-seven patients were assigned to either unilateral (n = 47) or bilateral (n = 40) pedicle screw instrumentation groups. Two kinds of pedicle screw system (Moss Miami, DePuy, Warsaw, IN, and Steffee VSP, AcroMed, Cleveland, OH) were used. Operating time, blood loss, duration of hospital stay, clinical outcomes, fusion rates, complication rates, and medical expenses were studied and tested with independent sample t test and chi2 test. RESULTS: There were no significant differences between the two groups in blood loss, clinically satisfactory results, fusion rate, and complication rate. There were significant differences in duration of operating time, duration of hospital stay, and medical expenses. The number of fusion segments or kinds of instrumentation did not affect the fusion rate or clinical outcomes. CONCLUSIONS: Unilateral pedicle screw fixation was as effective as bilateral pedicle screw fixation in lumbar spinal fusion independent of the number of fusion segments (one or two segments) or pedicle screw systems. Based on the results of this study, unilateral fixation could be used in two-segment lumbar spinal fusion.

Adult↗
PubMed2000

Effects of aging on expression of genes involved in regulation of proliferation and apoptosis in the colonic epithelium.

The purpose of this study was to characterize the effects of aging on colonic messenger ribonucleic acid (mRNA) and protein levels of genes involved in the regulation of cell proliferation and apoptosis, and epithelial morphology in male Fischer 344 rats. Our study shows that, with aging, colonic expression of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) is significantly increased and decreased, respectively. Colonic Bax protein levels are increased significantly with aging. Immunohistochemical localization of Bax protein shows a greatly increased expression in colonic crypts, especially in the upper portion of crypts. p53 expression is unchanged with aging. No significant change in proliferation of colonic crypt cells is observed by bromodeoxyuridine (BrdU) labeling, although the increased colonic expression of IGF-1 and the decreased expression of IGFBP-3 with aging may result in an increased colonic IGF-1 bioactivity. The age-related changes in Bax and IGFBP-3 appear to be independent of p53. The finding of an unchanged colonic epithelium with aging in the face of a greatly increased Bax protein levels may suggest that the elevated Bax protein levels function to render colonic epithelial cells more sensitive to apoptotic stimuli.

Aging↗
PubMed2000

Mitochondrial DNA damage and a hypoxic response are induced by CoCl(2) in rat neuronal PC12 cells.

Generation of reactive oxygen species (ROS) and activation of a transcriptional program that mimics the hypoxic response have been documented in cultured cells in the presence of cobalt chloride. We found that in the presence of hypoxia-mimicking concentrations of CoCl(2), mitochondrial but not nuclear DNA damage is induced in rat neuronal, PC12 cells. To our knowledge, this is the first documentation of induction of mitochondrial DNA (mtDNA) damage under these conditions. Likewise, we provide the first evidence for elevation of MYH, the mammalian homolog of the Escherichia coli MutY DNA glycosylase, in mammalian cells. Recently, the human MYH was implicated in repair of oxidative DNA damage and shown to carry a mitochondrial localization sequence. Here, an induction of mtDNA damage and a time-dependent increase in the MYH level were detected with exposure of cells to 100 microM CoCl(2). In addition, the levels of proteins involved in cellular responses to hypoxia, ROS and nuclear DNA damage; hypoxia-inducible factor 1alpha(HIF-1alpha), p53, p21 and PCNA were also modulated temporally. Earlier studies suggested that the mtDNA is a primary target for oxidative damage. Our findings extend these observations and suggest that activation of DNA repair processes is associated with the presence of mtDNA damage.

Animals↗
PubMed2000

Resistance to lysis by cytotoxic T cells: a dominant effect in metastatic mouse prostate cancer cells.

Better understanding of the immunology of prostate cancer is needed for the development of new therapeutic approaches that can be used in conjunction with current treatment methods. The present study was designed to compare the immunological properties of a genetically matched pair of primary tumor- and metastasis-derived prostate cancer cell lines generated from the mouse prostate reconstitution (MPR) model. Only the primary prostate cancer cells were immunogenic in that prior immunization with irradiated primary but not the metastatic prostate cancer cells delayed the growth of subsequently injected live cancer cells. The lack of immunogenicity of the metastatic cells was not attributable to their inability to induce antitumor cytotoxic T cells. Both primary and metastatic cells induced antitumor CTLs in syngeneic hosts, but unlike the primary cells, the metastatic cells were resistant to CTL lysis. Differential resistance to cytolysis in metastatic versus primary prostate cancer cells was not attributable to the differential expression of molecules such as transporter associated with antigen processing (TAP)-1, TAP-2, low molecular weight protein of the proteasome complex (LMP)-2, and LMP-7 that contribute to antigen presentation by class I MHC. IFN-gamma induced surface class I MHC expression, as well as gene expression of TAP-1, TAP-2, LMP-2, and LMP-7 in the metastatic cells, yet the cells remained resistant to cell lysis induced by CTLs. Interestingly, although in comparison to the primary cells the metastatic cells were resistant to cytolysis, both cell types were susceptible to DNA fragmentation induced by CTLs. Cell fusion between primary and metastatic cancer cells resulted in hybrids that also resisted the cytolytic activity of CTLs. Therefore, there is a dominant factor(s) in the metastatic prostate cancer cells that confers specific protection against CTL cytolysis in this model system.

Animals↗
PubMed2000

Mutations in the putative H-channel in the cytochrome c oxidase from Rhodobacter sphaeroides show that this channel is not important for proton conduction but reveal modulation of the properties of heme a.

As the final electron acceptor in the respiratory chain of eukaryotic and many prokaryotic organisms, cytochrome c oxidase catalyzes the reduction of oxygen to water, concomitantly generating a proton gradient. X-ray structures of two cytochrome c oxidases have been reported, and in each structure three possible pathways for proton translocation are indicated: the D-, K-, and H-channels. The putative H-channel is most clearly delineated in the bovine heart oxidase and has been proposed to be functionally important for the translocation of pumped protons in the mammalian oxidase [Yoshikawa et al. (1998) Science 280, 1723-1729]. In the present work, the functional importance of residues lining the putative H-channel in the oxidase from Rhodobacter sphaeroides are examined by site-directed mutagenesis. Mutants were generated in eight different sites and the enzymes have been purified and characterized. The results suggest that the H-channel is not functionally important in the prokaryotic oxidase, in agreement with the conclusion from previous work with the oxidase from Paracoccus denitrificans [Pfitzner et al. (1998) J. Biomembr. Bioenerg. 30, 89-93]. Each of the mutants in R. sphaeroides, with an exception at only one position, is enzymatically active and pumps protons in reconstituted proteoliposomes. This includes H456A, where in the P. denitrificans oxidase a leucine residue substituted for the corresponding residue resulted in inactive enzyme. The only mutations that result in completely inactive enzyme in the set examined in the R. sphaeroides oxidase are in R52, a residue that, along with Q471, appears to be hydrogen-bonded to the formyl group of heme a in the X-ray structures. To characterize the interactions between this residue and the heme group, resonance Raman spectra of the R52 mutants were obtained. The frequency of the heme a formyl stretching mode in the R52A mutant is characteristic of that seen in non-hydrogen-bonded model heme a complexes. Thus the data confirm the presence of hydrogen bonding between the heme a formyl group and the R52 side chain, as suggested from crystallographic data. In the R52K mutant, this hydrogen bonding is maintained by the lysine residue, and this mutant enzyme retains near wild-type activity. The heme a formyl frequency is also affected by mutation of Q471, confirming the X-ray models that show this residue also has hydrogen-bonding interactions with the formyl group. Unlike R52, however, Q471 does not appear to be critical for the enzyme function.

Alanine↗
PubMed2000

Epithelial-myoepithelial carcinoma of the nasal cavity.

A 22-year-old male presented with a 1-year history of nasal obstruction due to a polypoid mass in the right nasal cavity. Histopathologic examination revealed the tumor to consist of a mixture of a trabecular structure with a double-layered arrangement of inner dark cells and outer clear cells. Immunohistochemical examination showed the clear cells to be positive for alpha-smooth muscle actin and S-100 protein. Ultrastructural examination confirmed the myoepithelial cell origin. The tumor was excised and no recurrence or metastasis was found 40 months after surgery. We describe here a rare case of epithelial-myoepithelial carcinoma arising from the nasal cavity, one of the most unusual locations.

Actins↗
PubMed2000

Primary localized conjunctival amyloidosis presenting with recurrence of subconjunctival hemorrhage.

PURPOSE: To report the ocular presentation and histopathology of a patient with primary localized conjunctival amyloidosis. METHODS: A 38-year-old woman presented with a recurrence of episodes of severe bilateral subconjunctival hemorrhage. Ocular examination revealed yellowish, marked folding and redundancy of the conjunctiva in the inferior cul-de-sac of each eye. RESULTS: After two initial conjunctival biopsies that showed only chronic inflammation, a third biopsy revealed the presence of amyloid in the substantia propria of the conjunctiva. CONCLUSION: Primary localized conjunctival amyloidosis is rare and usually diagnosed histologically instead of clinically. Recurrence of subconjunctival hemorrhage may be the initial presentation. Evaluation for systemic diseases is advised, though the results of the examination are almost always negative.

Adult↗