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Biomedical subjects

M C Lee

Publications and source records attributed to M C Lee.

At least 145 records · Page 8Linked to original sources

Different patterns of angiogenesis in sarcomas and carcinomas.

Solid tumors depend on angiogenesis for growth and metastasis. It has been shown that blood vessel density, as determined by counting the number of capillaries in clustered bursts, is a significant prognostic factor in carcinomas. It is unclear, however, whether vessel density is a prognostic factor in sarcomas. In this study, we examined angiogenesis in sarcomas of various grades and compared their vascular patterns to those of carcinomas. Microvessels were identified by von Willebrand factor staining. The matrix of multiple sarcoma and breast carcinoma specimens were extracted and subjected to Western analysis of various angiogenic factors and inhibitors. Metalloproteinase inhibitor presence was also determined by in situ hybridization. In breast carcinomas, capillaries were clustered in bursts within the stroma of the tumor, whereas the sarcoma capillaries were homogeneously distributed in the tumor stroma. Random blood vessel density per high power field in sarcomas did not correlate with patient prognosis. The matrix of sarcomas and carcinomas contained both angiogenic stimulators and inhibitors. Tissue inhibitor of metalloproteinase-1 was found predominantly in fibroblasts and myofibroblasts in the matrix of carcinoma specimens. The difference in the pattern of angiogenesis in sarcomas and carcinomas may be attributable to the presence of fibroblasts and myofibroblasts in carcinomas, resulting in the compartmentalization of bursts of angiogenic factors. The homogeneous appearance of vessel density in sarcomas observed in the present study would be the consequence of the influence of a single compartment.

Angiogenesis Inhibitors↗

Sequencing and chromosomal localization of the RA138 gene encoding a rice allergenic protein.

A cDNA clone (RA138) encoding a rice allergenic (RA) protein has been isolated during a large-scale random sequencing of a cDNA library prepared from developing seeds. The nucleotide sequence of the RA138 gene contained an open reading frame (ORF, 477 bp) encoding a 17 kDa protein. The amino acid sequence deduced from the ORF was composed of 159 amino acid residues and was highly homologous to those from RA genes previously isolated, such as RA5 (92% identity), RA14 (73%), and RA17 (68%). The protein contained 10 cysteine residues that were conserved in the alpha-amylase/trypsin inhibitor family including RA proteins. Excluding a putative signal peptide consisting of 26 amino acid residues, the mature protein would be 14.4 kDa in size and have a pI of 7.0. DNA gel blot analysis under high stringency conditions indicated that multiple copies of the RA138 gene were present in the rice genome. The chromosomal location of the RA138 gene has been identified on chromosome 7 in a segregation analysis using a population of 164 recombinant inbred lines derived from a cross between Milyang 23 and Gihobyeo. The locus that may contain multiple copies of the RA138 was located between RFLP markers RG477A and C492 with genetic distances of 10.7 cM and 6.7 cM, respectively.

Allergens↗

Dopamine transporter density measured by [123I]beta-CIT single-photon emission computed tomography is normal in dopa-responsive dystonia.

The clinical distinction between dopa-responsive dystonia (DRD) and juvenile Parkinson's disease JPD) can pose a diagnostic challenge. Both conditions are dopa responsive. However, long-term L-dopa benefit is very different between the two. The difference in the prognosis is due to presence or absence of nigral cell loss. In JPD, there is degenerative nigral cell loss, whereas there are enzymatic defects in dopamine synthesis without cell loss in DRD. Mutations have been found in the GTP cyclohydrolase I (GCH-I) and tyrosine hydroxylase genes in DRD. As the discovered mutations are multiple and more are expected to be found, it is difficult to confirm or exclude DRD by mutation studies. Measurement of cerebrospinal fluid (CSF) neopterin will detect DRD from mutations in the GCH-I gene but not from mutations in tyrosine hydroxylase. The dopamine transporter (DAT) is a protein in the dopaminergic nerve terminals. (1R)-2beta-Carbomethoxy-3beta-(4-[123I]iodophenyl)tropane ([123I]beta-CIT) is a ligand for the DAT, and it was shown to be a useful nuclear imaging marker for neurons that degenerate in Parkinson's disease (PD). As DRD was shown to have a normal DAT without nigral cell loss in a postmortem study, we predicted that the DAT measured in vivo by nuclear imaging will be normal in DRD and will differentiate DRD from JPD. Therefore, we performed [123I]beta-CIT single-photon emission computed tomography ([123I]beta-CIT SPECT) in clinically diagnosed DRD, PD, and JPD, and examined whether DAT imaging can differentiate DRD from PD and JPD. We then examined whether DAT imaging can provide a screening tool for molecular genetic studies, by studying mutations in the candidate gene GCH-I and measuring CSF neopterin. Five females (4 from two families, and 1 sporadic) were diagnosed as DRD based on early-onset foot dystonia and progressive parkinsonism beginning at ages 7 to 12. All patients were functioning normally on L-dopa 100 to 250 mg/day for up to 8 years. SPECT imaging was obtained after intravenous injection of [123I]beta-CIT; 15 healthy volunteers served as normal control, and 6 PD and 1 JPD as disease controls. [123I]beta-CIT striatal binding was normal in DRD, whereas it was markedly decreased in PD and JPD. Gene analysis showed a novel nonsense mutation in the GCH-I gene in one family. No mutation was found in the other family or in the sporadic case. CSF neopterin was markedly decreased in the 4 tested patients. [123I]beta-CIT SPECT is a sensitive method for probing the integrity of nigrostriatal dopaminergic nerve terminals. A normal striatal DAT in a parkinsonian patient is evidence for a nondegenerative cause of parkinsonism and differentiates DRD from JPD. Finding a new mutation in one family and failure to demonstrate mutations in the putative gene in other cases supports the usefulness of DAT imaging in diagnosing DRD.

Adult↗

Proton MR spectroscopic findings in paroxysmal kinesigenic dyskinesia.

Although paroxysmal kinesigenic dyskinesia (PKD) has characteristic clinical features, the pathophysiology of PKD has remained unknown. The purpose of this study was to investigate the pathophysiology of idiopathic PKD by performing proton magnetic resonance spectroscopy (1H-MRS) in five patients with idiopathic PKD. Three patients were familial and two sporadic. Single-voxel 1H-MRS was performed on a GE 1.5-T SIGNA MR system. Localized 1H-MR spectra were obtained from the basal ganglia (n = 5), thalamus (n = 3), and supplementary motor area (SMA; n = 4) using STEAM sequence (stimulated echo acquisition mode; TR = 3.0 sec, TE = 30 msec, 64 AVG, volume = 8 mL) or PRESS (point resolved spectroscopy; TR = 3.0 sec, TE = 135 msec, volume = 4 mL). Peak ratios of Cho/Cr (Cho: choline, Cr: creatine) and mI/Cr (mI: myoinositol) were decreased significantly in the unilateral basal ganglia of two patients. In one, decreased peak ratio of mI/Cr in the unilateral basal ganglia was the only abnormality. In the remaining two, there was no significant abnormality. 1H-MR spectra obtained from the thalamus and SMA were all within normal limits. In conclusion, these results suggest that underlying pathophysiological mechanism of PKD may be at least partially associated with the dysfunction of cholinergic system in the basal ganglia.

Acetylcholine↗

Diagnostic value of positron emission tomography for detecting breast cancer.

Positron emission tomography (PET) is an imaging method that employs radionuclide and tomography techniques. PET has high sensitivity for detecting breast cancer, both the primary tumor and axillary node metastasis. From June 1995 to November 1996 a total of 27 patients underwent breast operations based on PET results at Seoul National University Hospital. Whole-body PET images were obtained beginning 60 minutes after injection of 370 MBq (10 mCi) 18F-fluorodeoxyglucose. Regional scans were also obtained with transmission images. We compared the PET results with those from the physical examination and mammography. All cases were histologically confirmed. The diagnostic accuracy of PET was excellent for the primary tumor mass (97%) compared with that of the physical examination (78%) and mammography (67%). For axillary lymph node metastasis, PET had outstanding detection accuracy (96%) compared with the physical examination and mammography (74% and 60%, respectively). Whole-body PET scans made it possible to see all of the metastatic lesions at a glance in cases of metastatic or recurrent breast cancer. There was a probable correlation between the standard uptake value (SUV) and the number of axillary lymph node metastases, but in this study statistical significance was not proved because of the small number of cases. PET also could detect breast cancer in paraffin-augmented breasts. We concluded that PET is a highly sensitive, accurate diagnostic tool for breast cancer and that SUV, after more studies, could be used as an important prognostic factor.

Breast Neoplasms↗

Early operative intervention after thrombolytic therapy for primary subclavian vein thrombosis: an effective treatment approach.

PURPOSE: Effective treatment of primary subclavian vein thrombosis focuses on restoration of venous patency, relief of intrinsic stenosis, and decompression of the thoracic inlet. The appropriate method and timing for surgery, however, have not been not well defined. We conducted a study to determine an acceptable treatment approach. METHODS: A retrospective review evaluated 11 patients seen at our institution in an 8-year period. Seven patients were male and four were female, with an average age of 30 years (range 15 to 54 years). Two patients who had symptomatic stenosis without occlusion were omitted from the study. All patients with occlusion received urokinase therapy and underwent surgical decompression within 5 days of thrombolytic therapy. Five percutaneous transluminal angioplasties were attempted before operative intervention. Eleven decompressions were performed, including nine first-rib resections and two scalenectomies. Five operative venous procedures, consisting of thrombectomy with patch closure (n = 3) and bypass (n = 2), and seven venolysis procedures were performed. All patients received coumadin for 3 to 6 months after the operation. RESULTS: Urokinase therapy established wide venous patency in nine of the 11 extremities treated, with the remaining two requiring thrombectomy for residual thrombus at the time of operation. One patient who underwent transluminal angioplasty before the operation had rethrombosis, and the remaining four showed no improvement in venous stenosis after the intervention. Eight of nine extremities treated by first-rib resection and one of two treated by scalenectomy were free of residual symptoms at follow-up. CONCLUSIONS: Preoperative use of percutaneous balloon angioplasty is ineffective and should be avoided in this setting. Surgical intervention within days of thrombolysis obviates the need for interim oral anticoagulation and enables patients to return to normal activity sooner.

Adolescent↗

A cell surface molecule, JL1; a specific target for diagnosis and treatment of leukemias.

We previously reported a novel differentiation antigen, which is specifically expressed in stage II double positive (CD4+CD8+) human cortical thymocytes (Park et al, J Exp Med 1993; 178: 1447-1451). This study was designed to investigate the expression pattern of JL1 in various types of leukemic cells from patients and normal hematopoietic cells to evaluate the possibility as a tool for diagnosis and treatment of leukemia. The expression of JL1 antigen was observed in 75.6% of leukemic cases (117 out of 154 leukemic patients tested) on flow cytometric analysis. The percentage of JL1-positive cases of T lineage acute lymphoblastic leukemia (T-ALL) (92.6%) was higher than that of other types of leukemias (75%). The presence of JL1 antigen was also confirmed by immunoblotting and immunoprecipitation. Since the JL1 antigen is selectively expressed on the surface of human leukemic cells but not on the mature human peripheral blood cells, normal bone marrow cells and various types of normal tissues, JL1 could be an excellent candidate for an immunodiagnostic and immunotherapeutic tool for hematopoietic malignancies such as leukemia.

Antibodies, Monoclonal↗

Association of parental characteristics with adverse outcomes of adolescent pregnancy.

BACKGROUND: It is well-known that pregnancy in adolescence has an increased risk of adverse reproductive outcomes. It remains unclear whether this association is due mainly to the unfavourable sociodemographic status or due solely to biological immaturity of pregnant adolescents. OBJECTIVE: The purpose of this study was to determine the association of parental sociodemographic characteristics with the adverse outcomes of adolescent pregnancy. METHOD: Data from certificates of live births in Taichung County, Taiwan in 1994 of 7994 singleton, first-born babies whose mothers were 15-34 years of age were analysed. The relative risk of having adverse pregnancy outcomes for adolescent subgroups was obtained as compared with that among mothers 20-34 years of age with the same characteristics. The adjusted relative risk of having adverse pregnancy outcomes for each covariate was calculated by a multiple logistic regression analysis. RESULTS: Of 7994 babies born to mothers of 15-34 years of age, 8.3% were born to adolescent mothers. In all age groups, the younger adolescent mothers (15-17 years of age) had the highest percentage of both infants with low birth weight (10.6%) and preterm births (7.1 %). Younger adolescent mothers in almost all sociodemographic categories had higher risks of having both low-birth-weight and preterm births than those of older adolescent mothers. Multiple logistic regression analysis showed that a younger maternal age is the only significant risk factor for having infants with low birth weight (adjusted RR = 2.5, 95% Cl 1.8-4.5 and adjusted RR = 1.7, 95% Cl 1.2-2.6 for younger and older adolescent mothers, respectively) or preterm birth (adjusted RR = 1.9, 95% Cl 1.1-3.4 and adjusted RR = 1.5, 95% Cl 1.0-2.3 for younger and older adolescent mothers, respectively). CONCLUSIONS: Adolescent pregnancy carries an increased risk of having low-birth-weight and preterm births, and a younger maternal age is causally implicated.

Adolescent↗

Trends in injury mortality among adolescents in Taiwan, 1965-94.

OBJECTIVES: To describe trends in injury mortality among adolescents in Taiwan for prioritising preventive interventions. METHODS: Adolescent injury mortality data for Taiwan were derived from official publications of vital statistics from 1965 to 1994 to determine trends by sex and cause of death. Simple linear regression was used to test the trends. RESULTS: The number of deaths due to injury among adolescents aged 10-19 years in Taiwan increased from 983 in 1965 to 1783 in 1994, an 81% increase. The injury mortality rate increased 42%, from 32.2 per 100,000 in 1965 to 45.6 per 100,000 in 1994. The proportion of injury deaths also increased, from 45.3% in 1965 to 72.8% in 1994. The trends in mortality from motor vehicle injury (MVI) among four demographic groups were all significantly positive (p < 0.001). The proportion of deaths due to MVI among injury was 14% in 1965 and increased to 63% in 1994. CONCLUSIONS: The increase in injury mortality rates among adolescents over the past three decades appears to be due largely to the increase in MVI mortality rates with males aged 15-19 years accounting for most of this increase. Priorities for adolescents in Taiwan are MVI (especially motorcyclists) and drownings.

Accidents↗

Dopamine transporter imaging with [123I]-beta-CIT demonstrates presynaptic nigrostriatal dopaminergic damage in Wilson's disease.

OBJECTIVES: The most common neurological manifestations in Wilson's disease are parkinsonism and dystonia. These are assumed to be due to striatal injury, which has been repeatedly demonstrated by pathology and CT or MRI. The substantia nigra has not been shown to be damaged in pathological studies. However, there have been clinical and imaging studies suggesting presynaptic nigrostriatal injury. (1r)-2Beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) is a specific ligand that binds to the dopamine transporter (DAT), and can examine the integrity of dopaminergic nerve terminals. Evidence for presynaptic nigrostriatal dopaminergic damage in Wilson's disease was searched for using [123I]-beta-CIT SPECT. METHODS: Six patients with Wilson's disease were studied, together with 15 healthy normal controls, and six patients with Parkinson's disease. After injection of [123I]-beta-CIT, SPECT studies were done at 18 hours. Specific striatal/occipital binding ratio (S/O ratio) was calculated as (striatal binding-occipital binding)/occipital binding. RESULTS: The specific S/O ratios were 6.22 (1.32) (mean (SD)) in normal volunteers, 3.78 (0.65) in Parkinson's disease, and 3.60 (0.49) in Wilson's disease. CONCLUSION: There was severe loss of the DAT in the striatum suggesting significant damage in presynaptic nigrostriatal dopaminergic nerve terminals. Therefore, a presynaptic lesion may contribute to neurological manifestations in Wilson's disease.

Adolescent↗