Biomedical subjects
Publications and source records attributed to H M Lee.
Chronic rejection is a major cause of late graft loss, and pathogenesis of the chronic rejection is multifaceted. Further investigation of the pathogenesis is needed. Prevention and treatment include the reduction of risk factors and effective manipulation of factors involved in the pathogenesis.
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BACKGROUND: The search continues for the ideal conduit for infrageniculate arterial reconstructions when the autogenous vein is unsuitable or unavailable. Based on experimental observations in our laboratory demonstrating improvement in canine cryopreserved allograft vein patency using systemic immunosuppression (Imsup), and the remarkable clinical success achieved in older (greater than 60 years of age) solid organ transplant recipients using combination low-dose Imsup, we studied the effects of Imsup on patency of cryopreserved homograft saphenous vein (CADVEIN) used for infrageniculate arterial reconstructions. STUDY DESIGN: Under the Institutional Review Board protocol, 21 infrageniculate CADVEIN grafts were placed in 19 patients between July 1993 and August 1994 for limb salvage when autogenous veins were unavailable. An immunopharmacologic protocol consisting of low-dose cyclosporine A, azathioprine, prednisone, warfarin, aspirin, and vasodilators given orally was instituted. For various reasons, 15 patients in group 1 received Imsup; five patients never received Imsup, and one patient in group 2 received Imsup briefly. Follow-up examinations were completed using the time range of six to 18 months (mean, eight plus or minus one month). RESULTS: One patient died (5.3 percent) 30 days after emergency combined venous graft and bilateral CADVEIN bypass. The actuarial 12-month primary patency in group 1 was 59.4 percent compared with 16.7 percent in group 2 (p < 0.015, log-rank test). Cellular rejection was typically seen in explanted CADVEIN. Systemic morbidity related to Imsup was minimal. The CADVEIN morbidity rate was significant: three graft aneurysms and four early graft ruptures. Major amputations were necessary in eight of 12 patients with graft closure. CONCLUSIONS: The data suggest that Imsup significantly improves CADVEIN patency with limited systemic morbidity; however, complications related to the conduit itself occurred with greater frequency and cause greater morbidity than when the autogenous veins were used. Much has yet to be learned regarding the preservation characteristics of CADVEIN and the immunologic interactions in patients receiving CADVEIN grafts, before further clinical use of this conduit can be recommended.
The tonsillar crypt shows infiltration of lymphoid cells in the epithelium and the highly porous or discontinuous basement membrane. However, the relationship between developmental period and the significance of the disrupted epithelial basement membrane and infiltration of lymphoid cells within the human tonsillar crypt epithelium is still obscure. The present study was designed to determine the prenatal and postnatal changes of the human tonsillar crypt epithelium in 4 fetuses, 4 neonates, 1 infant, 5 children and 4 adults using immunohistochemical stains with polyclonal anti-laminin and monoclonal anti-type IV collagen antibody, and transmission electron microscope. The tonsillar crypt epithelium from all fetuses and neonates showed infiltration of many lymphoid cells and an intact basement membrane by immunohistochemistry. Transmission electron microscope revealed pores in the basement membrane through which lymphocytes passed. Tonsils from a 4-month-old infant showed focal disruption of the basement membrane by immunohistochemical staining. The tonsils from children and adults showed that there was massive disruption of the basement membrane with lymphoid cell infiltration in the tonsillar crypt epithelium by immunohistochemical staining and transmission electron microscopy. In conclusion, lymphoid cell infiltration and holes of the basement membrane of the tonsillar crypt epithelium are normal developmental findings, whereas disruption of the basement membrane of the tonsillar crypt epithelium is pathological.
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STUDY DESIGN: The anatomic dimensions of the vertebral body and spinal canal of the lumbar spine were analyzed in Koreans. OBJECTIVES: To determine the normal dimension of the lumbar spinal canal in Koreans, to determine whether there are any racial differences in the morphometry of the lumbar spinal canal, and to provide criteria for diagnosing spinal stenosis in the Far Eastern Asian. SUMMARY OF BACKGROUND DATA: Some radiologic and anatomic studies have been conducted regarding the size of the lumbar spinal canal of whites and blacks in western and African countries. METHODS: One-thousand-eight-hundred measurements were performed on the transverse and sagittal diameters of vertebral bodies and spinal canals using complete sets of 90 lumbar vertebrae. RESULTS: The mean mid-sagittal diameter of the lumbar spinal canal in the Korean population was less than that measured in white and African populations, but there was no significant differences between the Korean, white, and African populations regarding the transverse diameter of the lumbar spinal canal. CONCLUSION: The mid-sagittal diameter of the lumbar spinal canal is narrowest in the Far Eastern Asian population; the radiologic criteria of spinal stenosis should be reconsidered for these people.
Transforming growth factor beta (TGF-beta) exhibits diverse effects on growth and differentiation of a wide range of cell types. In the immune system, TGF-beta 1 is a potent inhibitor of T cell proliferation and certain T cell effector functions. However, TGF-beta 1 also enhances growth of T cells, predominantly of naive phenotype, and induces their expression of selected cytokines. We have previously demonstrated that TGF-beta 1 costimulates growth of highly purified murine CD8+ T cells activated by immobilized anti-CD3 Ab. TGF-beta 1-costimulated CD8+ T cells rapidly express a memory phenotype, lose lytic function, and express a mixed cytokine pattern with IL-2, IFN-gamma, and appreciable IL-10, as well as TGF-beta 1. The present work examines the possibility that TGF-beta 1 similarly costimulates response of murine CD8+ T cells to the microbial superantigen staphylococcal enterotoxin B (SEB) and characterizes their effector and regulatory functions. TGF-beta 1 significantly enhances CD8+ T cell proliferation to SEB in the presence of MHC class II-positive APC and TGF-beta 1-primed CD8+ T cells are enriched for SEB-reactive V beta 8+ TCR expression. TGF-beta 1 priming also up-regulates a memory-like CD45RBlowCD44highMEL-14low phenotype. TGF-beta 1 priming inhibits development of SEB-specific lytic effector function by more than 90%. However, TGF-beta 1-primed CD8+ effector T cells express elevated levels of IL-10 and TGF-beta 1, variable IFN-gamma, and undetectable IL-4. Additionally, they exhibit growth inhibitory effector function of SEB-induced proliferation of other CD4+ and CD8+ T cells. Growth inhibition by TGF-beta 1-primed CD8+ T cells is reversed in part by anti-IL-10 Ab. Thus, in the context of SEB response, TGF-beta 1 promotes the outgrowth and induces the effector function of CD8+ T cells that have the capacity to impair T cell clonal growth.
The avian skeletal alpha-actin gene was used as a template for construction of a myogenic expression vector that was utilized to direct expression of a human IGF-I cDNA in cultured muscle cells and in striated muscle of transgenic mice. The proximal promoter region, together with the first intron and 1.8 kilobases of 3'-noncoding flanking sequence of the avian skeletal alpha-actin gene directed high level expression of human insulin-like growth factor I (IGF-I) in stably transfected C2C12 myoblasts and transgenic mice. Expression of the actin/IGF-I hybrid gene in C2C12 muscle cells increased levels of myogenic basic helix-loop-helix factor and contractile protein mRNAs and enhanced myotube formation. Expression of the actin/IGF-I hybrid gene in mice elevated IGF-I concentrations in skeletal muscle 47-fold resulting in myofiber hypertrophy. IGF-I concentrations in serum and body weight were not increased by transgene expression, suggesting that the effects of transgene expression were localized. These results indicate that sustained overexpression of IGF-I in skeletal muscle elicits myofiber hypertrophy and provides the basis for manipulation of muscle physiology utilizing skeletal alpha-actin-based vectors.
We previously reported that low-dose doxycycline (DOXY) therapy reduces host-derived collagenase activity in gingival tissue of adult periodontitis (AP) patients. However, it was not clear whether this in vivo effect was direct or indirect. In the present study, inflamed human gingival tissue, obtained from AP patients during periodontal surgery, was extracted and the extracts partially purified by (NH4)2SO4 precipitation. The extracts were then analyzed for collagenase activity using SDS-PAGE/fluorography/laser densitometry, and for gelatinase activity using type I gelatin zymography as well as a new quantitative assay using biotinylated type I gelatin as substrate. DOXY was added to the incubation mixture at a final concentration of 0-1000 microM. The concentration of DOXY required to inhibit 50% of the gingival tissue collagenase (IC50) was found to be 16-18 microM in the presence or absence of 1.2 mM APMA (an optimal organomercurial activator of latent procollagenases); this IC50 for DOXY was similar to that exhibited for collagenase or matrix metalloproteinase (MMP)-8 from polymorphonuclear leukocytes (PMNs) and from gingival crevicular fluid (GCF) of AP patients. Of interest, Porphyromonas gingivalis collagenase was also inhibited by similar DOXY levels (IC50 = 15 microM), however the collagenase activity observed in the gingival tissue extracts was found to be of mammalian not bacterial origin based on the production of the specific alpha A (3/4) and alpha B (1/4) collagen degradation fragments. In contrast, the inhibition of collagenase purified from culture media of human gingival fibroblasts (MMP-1) required much greater DOXY levels (IC50 = 280 microM). The predominant molecular forms of gelatinolytic activity presented in the AP patients gingival tissue extracts were found to closely correspond to the 92 kD PMN-type gelatinase (MMP-9) although small quantities of 72 kD fibroblast-type gelatinase (MMP-2), and some other low molecular weight gelatinases, were also detected. The IC50 of DOXY versus gingival tissue gelatinolytic activity was estimated at 30-50 microM measure using either type I gelatin zymography or the biotinylated type I gelatin assay. We conclude that MMPS in inflamed gingival tissue of AP patients, like those in GCF, originate primarily from infiltrating PMNs rather than resident gingival cells (fibroblasts and epithelial cells) or monocyte/macrophages, and that their pathologically-elevated tissue-degrading activities can be directly inhibited by pharmacologic levels of doxycycline.
BACKGROUND: Dislocation of the shoulder is one of our earliest frequent injuries. Many procedures have been evaluated for treatment of the condition since the mid 1960s. The modified Bristow procedure was initially described in 1970 by May. Technically easy, the procedure is very effective in prevention of redislocation, and has gained popularity over two decades of use. METHODS: A retrospective study was done of 32 patients with recurrent anterior shoulder dislocation, who had received modified Bristow procedure during the years 1987 through 1991 in this Hospital. Average followup period was 26 months. RESULTS: At postoperative evaluation, average loss of external rotation and abduction as compared to the nonoperated side were 15 and 10 degrees, respectively. There was no limitation on daily activity, but some little restriction in extreme throwing sports was found. Postoperative complications included three patients who had bone block resorption and one patient who had superficial wound infection. There was no redislocation nor implant loosening in the study. CONCLUSIONS: This procedure is technically easy, had a low rate of complication, a high degree of patient satisfaction and very effectively prevents redislocation.
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BACKGROUND: The Lesch-Nyhan syndrome is an X-linked recessive inherited disease caused by a complete deficiency of hypoxanthine guanine phosphoribosyl-transferase (HPRT) activity. Many different mutations throughout the HPRT coding region of Lesch-Nyhan patients have been described, including single base substitutions, partial or entire gene deletions, gene insertions or endoduplication of exons. However, study of gene mutation in Chinese patients has rarely been reported in Taiwan. METHODS: Polymerase chain reaction (PCR) and nucleotide sequence analysis were used to identify the location and the nature of the mutation at the HPRT locus in two brothers affected with Lesch-Nyhan syndrome. The HPRT cDNA, amplified from total RNA of patient's peripheral blood by reverse transcription-polymerase chain reaction, was cloned into a pGEM-3Zf(-) vector and then sequenced. Family study involved initial screening using single-strand conformation polymorphism, and further confirmation by direct sequencing of the exon encompassing the mutation. RESULTS: The mutation identified in these two affected siblings was a single nucleotide substitution, from cytosine to guanine, in exon 3 of the HPRT coding region. This transversion putatively caused a single amino acid substitution from phenylalanine to leucine at codon 74 in the translated protein. This base change was further confirmed by direct sequencing of both the HPRT cDNA fragment and the exon 3 of HPRT gene amplified from genomic DNA. The family study revealed that the patient's mother was a heterozygous carrier, and the mutation seemed to have occurred de novo in a germinal cell from one of the maternal grandparents. CONCLUSIONS: This is the first family study on Chinese patients with Lesch-Nyhan syndrome identified by molecular analysis in Taiwan. The mutation described herein is a novel substitution which occurs in a suggested "hotspot" of mutation (exon 3) of the HPRT gene. The application of molecular analysis of HPRT-gene allows not only DNA diagnosis by directly detecting the mutant alleles, but also prenatal diagnosis and carrier identification within individual families affected by Lesch-Nyhan syndrome.
OBJECTIVES: The purposes of this study were to evaluate the nature of the paraspinal soft tissue mass and the location of the lesion involved using magnetic resonance imaging and to correlate these observations with surgical findings. SUMMARY OF BACKGROUND DATA: In the past, tuberculous spondylitis was diagnosed by plain radiography and since the 1970s, computed tomography has been a useful method for assessing tuberculous spondylitis. In contrast to most imaging methods, MRI has the advantages of improved contrast resolution for bone and soft tissues and versatility of direct imaging in multiple planes. METHODS: Medical records and magnetic resonance imaging studies of 22 patients with bacteriologically and/or histologically proved tuberculous spondylitis were reviewed. In each patient, the numbers of vertebrae involved were evaluated as well as which columns of vertebrae were affected and the signal intensities of lesions. In addition, an attempt was made to determine if granulation tissue differed from the abscess based on magnetic resonance imaging appearance and to compare the outcome with surgical findings. RESULTS: The average number of vertebrae involved per patient was 2.8 and T8 and T9 were the vertebrae most frequently affected. The destruction of vertebrae and discs was easily identified in both sagittal and axial planes. The peripheral margins were exclusively enhanced in all cases. Of particular interest, the posterior aspect of the vertebral body was predominantly involved. Mostly the involvement of both anterior and middle columns was noted. With the aid of intravenous administration of magnetic resonance contrast agents, magnetic resonance imaging was highly accurate in distinguishing the granulation tissue from the cold abscess. CONCLUSIONS: Magnetic resonance imaging demonstrated excellent images of bone destruction and soft tissue mass, and provided information in multiple planes, thereby delineating the extent of involvement in tuberculous spondylitis. Magnetic resonance imaging is most helpful in planning a surgical approach to tuberculous spondylitis.
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STUDY DESIGN: The shape and size of the pedicles of the human spine differs within different races. The authors studied the diameters and angles of the spine pedicle from the T1 to L5 levels in Koreans. The following measurements were made 1) transverse diameter, 2) superoinferior diameter, 3) anteroposterior pedicle angle, 4) horizontal pedicle angle, and 5) pedicle axis angle. OBJECTIVES: This study obtained indices of pedicle morphology in Koreans to use in transpedicular screw fixation and to explain the difference between other races and Koreans. SUMMARY OF BACKGROUND DATA: Internal fixators for vertebrae fixation have been developed. Knowledge of pedicle morphology is essential for pedicle screw use. The use of pedicle screws in Asians is questionable. Few reports exist regarding pedicle morphology, and in those few reports, the pedicle isthmus diameter, pedicle angles, and the depth to the anterior cortex are emphasized. METHODS: The following measurements of the diameter and length of the human cadaver pedicle were done with vernier and dial calipers: 1) transverse diameter of pedicles, 2) superoinferior diameter of pedicles, 3) anteroposterior pedicle angle, and 4) horizontal pedicle and pedicle axis angles. RESULTS: The widest transverse diameter of the pedicle was seen at the L5 level and the narrowest was at the T4 level. The widest superoinferior diameter of the pedicle was seen at the T12 level, the narrowest was at the T1 level. In the transverse plane, the angles of the pedicles of T11 and T12 were faced laterally. The anteroposterior angle increased rapidly at the T4 level, with the T1 level having the greatest. In the sagittal plane, the horizontal angle of the lumbar vertebra was almost parallel to the horizontal plane. The pedicle axis was longest at the L3 level and shortest at the T1 level. In all areas, the transverse diameter of the pedicle in males was wider than the that in the female. CONCLUSIONS: The results suggest that using 6-mm screws can violate the cortex of the pedicles in a significant number of levels of the upper lumbar spine. Using a screw longer than 40 mm is dangerous in the lower thoracic spine of a Korean. A statistical difference exists between the transverse diameter of the pedicles of Westerners and Koreans.
Massive deep venous thrombosis with marked venous outflow obstruction can result in limb loss or end-organ injury. Systemically administered drugs may not reach thrombi in therapeutic concentrations and surgical and thrombolytic strategies carry a small but real risk of pulmonary embolus--similar to the risks with anticoagulation alone. We therefore developed a strategy in which catheter-directed thrombolysis was used to deliver high concentrations of a plasminogen activator directly to the thrombus combined with placement of a downstream Greenfield filter to protect patients from pulmonary embolus. From 1984 to 1993 six patients were treated with this regimen. All had severe symptoms of less than 4 days' duration. On radiologic evaluation four patients had large iliofemoral and/or inferior vena cava thrombosis, one had subclavian/innominate vein thrombosis, and one had transplant renal vein/iliofemoral/inferior vena cava thrombosis. A Greenfield filter was first placed downstream prior to imbedding an infusion catheter in the greatest mass of thrombus for subsequent infusion of urokinase (n = 4) or streptokinase (n = 2). In four patients the catheter traversed the Greenfield filter. All patients were given bolus lytic therapy followed by maintenance infusions ranging in duration from 24 hours to 12 days. Five patients remained on heparin simultaneously. Clot lysis was achieved in all patients with hemodynamic, symptomatic, and arteriographic improvement. There were no deaths, pulmonary emboli, or complications of filter placement. One patient had minor bleeding at the puncture site and another had catheter-related infection.(ABSTRACT TRUNCATED AT 250 WORDS)