Occlusion of the hepatic artery in man.
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Biomedical subjects
Publications and source records attributed to D K Kim.
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BACKGROUND: Efficient and stable transfer of therapeutic DNA into injured myocardium would be an initial step towards a genetic treatment aimed at myocardial repair after myocardial infarction. Proliferating cardiac fibroblasts in the healing myocardium could be a compelling target for retroviral infection. We evaluated the feasibility of direct in vivo gene transfer into injured myocardium using a high-titer, stable retroviral vector. METHODS: Using the TE-FLY-A-based MFG retroviral vector harboring nlsLacZ reporter, the gene transfer efficiency was assessed first in vitro in rat cardiac fibroblasts, followed by in vivo evaluation in healing rat myocardium after local freeze-thaw injury. A total of 2.5 x 10(7) infectious units of retrovirus were injected into the injured region of a beating rat heart. The transduced cells were identified by X-gal staining and immunohistochemistry. RESULTS: Highly efficient transduction of cardiac fibroblasts was observed in vitro with 98% of the cells transduced with single infection. The cell proliferation index in the cardiac granulation tissue appeared maximal 3 days after cryoinjury. Retroviral injection into the injured beating heart induced gene expression localized to the wound repair region. One week after retrovirus injection, 14% of the cells in the reparative tissue were beta-gal-positive, while 4% were beta-gal-positive after 4 weeks. The transduced cells were mostly myofibroblasts. CONCLUSIONS: Local gene transfer to the healing rat heart is feasible by retrovirus in vivo. This observation may serve as a useful guide for the development of gene therapy aimed at myocardial repair after myocardial infarction.
In this paper statistical methods are proposed to estimate the distribution of a CD4 T-cell number at the time of a clinical AIDS endpoint from serial measurements of CD4 T-cell values in a cohort study. The statistical formulation of the problem is that of survival analysis with interval censored data, but in which the endpoints are obtained with measurement error. A measurement error likelihood is developed, assuming normality of the CD4 distribution at AIDS. A maximum likelihood estimation procedure and a Gibbs sampling approach are implemented.
We investigated the variables related to electrodermal nonresponsiveness in male chronic schizophrenics. In a comparison of 31 male chronic schizophrenics and 20 male normal controls, the schizophrenics showed a much higher incidence of nonresponders in phasic electrodermal responsiveness, and fewer spontaneous fluctuations (SFs) in tonic electrodermal activity. Among the schizophrenics, nonresponders showed fewer SFs and lower tonic skin conductance level (SCL). They also had more neuropsychological abnormalities of cognitive function and more severe symptoms (both positive and negative). Furthermore, patients with structural abnormality of the brain revealed by computerized tomographic measurements (increased ventricular brain ratio and maximum diameter of third ventricle) were overrepresented among electrodermal nonresponding schizophrenics. These findings suggest that electrodermal nonresponsiveness in chronic schizophrenic illness might be considered as a functional index associated with greater neuropsychological abnormalities and more severe symptoms.
PURPOSE: This study evaluates the efficacy of endoscopic laser-assisted dacryocystorhinostomy (LADCR) in the treatment of epiphora and chronic dacryocystitis. PATIENTS AND METHODS: Treatment results were prospectively reviewed for 17 patients undergoing 19 LADCR procedures of which 12 were primary and 7 were revision cases. Silastic intubation tubing was removed after surgery at a mean of 76.5 days in the primary cases and 184 days in the revision cases. Patients were followed-up for a mean of 15.6 months (range, 5 to 25 months). RESULTS: LADCR was successful in 100% of primary cases and 60% of revision procedures. The only complications were 2 conjunctival fistula, which closed without sequela. CONCLUSION: The efficacy of primary LADCR is comparable to reported external approaches. The success of revision LADCR is less favorable, yet the number of cases reported here is too small to reach a conclusion.
Generalized eruptive histiocytoma (GEH) is a rare, benign, papular, self-healing histiocytosis characterized by recurrent crops of small, firm, tan to reddish papules that appear in a symmetrical fashion on the face, trunk and arms, affecting mainly adults. Approximately 31 cases have been described, of which 8 were in children. A new concept unifying the confusing potpourri of non-Langerhans cell histiocytosis has recently been described in which GEH has been considered to represent an early undifferentiated stage of various histiocytic disorders. We describe a 9-year-old boy who had all the features of GEH and emphasize the importance of clinical, histologic, immunohistochemical, and ultrastructural examination in the diagnosis of histiocytic disorders. On the basis of the increasing numbers of similar reported cases showing overlap in clinical and histologic features and in accordance with the new unifying concept of non-Langerhans cell histiocytosis, we presume that this group of disorders may represent a continuous spectrum of a single disease rather than a collection of separate disorders.
OBJECTIVE: The aim of this study was to demonstrate the MR characteristics of non-Hodgkin lymphoma of the skull base to help in the differential diagnosis of this neoplasm from other conditions. MATERIALS AND METHODS: MR of five patients, 7-64 years old, with pathologically proved lymphomas of the skull base were reviewed. Three cases had primary skull base lesions involving the sphenoid bone and the cavernous sinus. One case with a nasal cavity lesion involving the skull base and one with a relapsing skull base lesion of previously treated tonsillar lymphoma were included. RESULTS: The lesions had signal intensities that were similar to that of gray matter of brain on both T1- and T2-weighted imaging. Bilateral cavernous sinuses were involved with encasement of internal carotid arteries in every case. Postcontrast MR showed homogeneous enhancement of the tumor with dural infiltration along the planum sphenoidale, clivus, or tentorium. The clivus was destroyed or replaced by tumors in adult cases but in two children the clivus was preserved with intact sphenooccipital synchondrosis. In one case the tumor extended to the extracranial portion through the jugular foramen. CONCLUSION: The MR findings of a permeative lesion of the skull base, invasion of the cavernous sinus without arterial narrowing, infiltration along the dural surface, and an iso- or hypointensity with brain on T2-weighted imaging should suggest lymphoma.
OBJECTIVE: Lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, stimulates proliferation of vascular smooth muscle cells (VSMC). We investigated the direct impact of 17beta-estradiol (E2) on the proliferation of VSMC from rat aorta. RESULTS: VSMC derived from both female and male rats expressed estrogen receptors alpha and beta. Treatments with 1% fetal bovine serum or 5 microM lysoPC increased the incorporation of [3H]-thymidine in VSMC obtained from female rats. 17Beta-E2 did not alter the response to fetal bovine serum, but significantly suppressed the enhanced deoxyribonucleic acid synthesis which had been induced by lysoPC in a dose-dependent manner (10(-4)-10(-6) M). Estrogen also inhibited the proliferation of VSMC from male animals. ICI 182,780, a specific estrogen receptor antagonist, and 17alpha-E2, an inactive form of estradiol, also decreased the mitogenic response to lysoPC in VSMC. In addition, N-acetyl-L-cysteine, a potent antioxidant, inhibited the lysoPC effect. Flow cytometric analysis using the oxidation-sensitive probe 2',7'-dichlorofluorescin diacetate revealed that elevated intracellular formation of reactive oxygen species elicited with lysoPC was depressed significantly by 17beta-E2, ICI 182,780, or 17alpha-E2 as well as by N-acetyl-L-cysteine. CONCLUSION: 17Beta-E2 inhibits in vitro VSMC proliferation induced by lysoPC via a nongenomic antioxidant mechanism.
The incidence of severe neurological complications associated with measles or rubella vaccination is low. A 9-year-old girl developed urinary retention and lower limb paralysis 16 days after measles and rubella vaccination. Her illness was diagnosed as transverse myelitis. Clinical, laboratory and magnetic resonance image findings were consistent with her diagnosis. She was treated with steroids and discharged with only mild lower limb weakness.
Rat neonatal and neointimal vascular smooth muscle cells differ dramatically from adult medical vascular smooth muscle cells in their growth properties, with the neonatal and neointimal cells exhibiting growth in the absence of exogenously added growth factors. Since it has been hypothesized that extra-cellular matrix proteoglycans may influence the growth and differentiation of vascular smooth muscle cells, we examined the ability of matrix derived from these cells to influence vascular smooth muscle cell proliferation. To produce test matrices, cells were grown to confluence and removed by brief alkali treatment. Test cells were seeded onto these matrices and the rates of growth in a growth-factor-deficient medium determined. Compared to plastic wells, matrix from neonatal or neointimal cells stimulated the growth of vascular smooth muscle cells. Interestingly, matrix from adult cells was less efficient at promoting growth. Enzymatic digestion of extracellular matrix heparan sulfate, but not of other glycosaminoglycans, further increased the growth-stimulatory effect of extracellular matrix, suggesting that matrix heparan sulfate acts as a growth inhibitor. Consistent with this, biochemical analysis showed that the adult matrix contained a higher percentage of heparan sulfate compared with neonatal or neointimal matrix. These results suggest that autocrine production of heparan sulfate proteoglycans may play an important role in growth regulation of vascular smooth muscle cells during normal vascular development and differentiation as well as in pathological response to injury.
Tumor associated lymphocytes (TAL) isolated from malignant ascites cultured in media containing interleukin-2 show antitumor responses. These antitumor responses are mediated by cytotoxic T lymphocytes (CTL) which recognize antigen in the context of MHC molecules using T cell receptors. CD8+ CTL recognize peptide epitopes processed from cellular proteins in the context of MHC class I molecules. These peptides have a restricted length of 8-11 amino acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian and 20-50% of breast cancers. We recently found that FBP is the source of antigenic peptides recognized by a number of these CTL-TAL. This indicated that FBP peptides are antigenic in vivo for ovarian and breast CTL-TAL. To define FBP immunogenicity, a peptide defining the epitope E39 (FBP, 191-199) was presented by PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulation of ovarian and breast CTL-TAL by E39 pulsed DC (DC-E39), in the presence of IL-2, rapidly enhanced or induced E39 specific CTL activity. This E39-responder population consisted of cells expressing TCR V beta 9, V beta 13, and V beta 17 families, based on the increase in the percentages of these families in DC-E39 versus DC-NP stimulated TAL. Characterization of immunogenic tumor antigens and of cytokine requirements for induction of functional antitumor effectors may be important for future cancer vaccine developments.
BACKGROUND: The growth rate of a tumor is dependent on both cell proliferation and cell loss. We have established subpopulations of human colon cancer cells with different in vivo growth rates by selecting the cells according to their adhesiveness to laminin-1 in vitro. MATERIALS AND METHODS: Laminin-1-adhesion selected colon cancer cells were injected into the cecal wall of nude mice. The tumors were examined 30 days later. Cell proliferation was assessed by proliferating cell nuclear antigen (PCNA) index and apoptotic cells were labeled by digoxigenin-11-dUTP using terminal deoxynucleotidyl transferase. RESULTS: The laminin-1-adherent cells, which formed larger tumors in vivo, showed increased proliferative activity and reduced apoptosis in comparison with the laminin-1-nonadherent cells. CONCLUSION: Laminin-1 may enhance the malignant behavior of colon cancer cells by accelerating proliferation as well as by decreasing cell loss.
The coding regions of segment A of two recent Korean very virulent (vv) infectious bursal disease virus (IBDV) isolates (KK1 and KSH) and one atypical IBDV isolate (K310) were amplified by reverse transcriptase-polymerase chain reaction, sequenced, and compared with published sequences for IBDV. The overall amino acid sequence similarity of the KK1 and KSH strains compared with foreign vvIBDV strains was between 97.43% and 98.02%. The KK1 and KSH strains, like vvIBDV strains, share unique amino acid residues at positions 222(A), 256(I), 294(I), and 299(S). The sequence of K310 strain was markedly different from other IBDV strains. The K310 strain had 12, 2, and 1 unique amino acid substitutions in the VP2 hypervariable region, VP4, and VP3 gene, respectively, and 3 of 12 substitutions in a VP2 hypervariable region were found in two hydrophilic regions known to be involved in antigenic determination. Also, the K310 strain had 222(S) and 254(S), which were found in variant IBDV strains. The SWSASGS heptapeptide is conserved in all Korean IBDV isolates. By phylogenetic analysis, KK1 and KSH were categorized in one group with foreign vvIBDV isolates, but K310 isolate was categorized in a separate group that was differentiated from the other IBDV strains compared. The K310 strain seemed to be evolved from a separate lineage of IBDV strain.
The in vitro antitumor activity of a new platinum complex, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e] platinum(II) (SKI 2053R, NSC D644591), cisplatin (CDDP) and carboplatin (CBDCA) was determined against two human lung cancer (PC-9 and PC-14) and two human stomach cancer (MKN-45 and KATO III) cell lines by human tumor clonogenic assay. The activity of SKI 2053R was compared with those of CDDP and CBDCA in terms of relative antitumor activity (RAA, peak plasma concentration/IC50). Mean IC50 values (microgram/ml) of SKI 2053R, CDDP and CBDCA were 6.4 +/- 0.8, 1.8 +/- 0.7 and 20.6 +/- 12.2, respectively. The RAAs of SKI 2053R, CDDP and CBDCA were 1.6 +/- 0.4, 2.0 +/- 0.8 and 1.2 +/- 0.6, respectively. The differences in these values were not statistically significant. The results, demonstrating that antitumor activity of SKI 2053R is similar to those of CDDP and CBDCA, suggest that SKI 2053R is an interesting candidate for further development as a new anticancer drug.
Atherosclerosis is the principal cause of diabetic morbidity and mortality. Diabetic dyslipidemia, obesity, and hypertension are significant contributing factors in the acceleration of the atherosclerotic process. Regardless of the type of diabetes, increased levels of very-low-density lipoprotein triglyceride, modified levels of low-density lipoprotein cholesterol, and decreased levels of high-density lipoprotein (HDL) cholesterol are the main lipoprotein abnormalities in diabetic patients. These abnormalities can be improved in part by glycemic control, but additional intervention may be needed. Diet and exercise are important elements in the management of dyslipidemia, but lipid-lowering drugs (especially fibrates and HMG-CoA reductase inhibitors) also may be necessary for the control of diabetic dyslipidemia. Based on these findings, the American Diabetes Association Consensus Panel and the revised treatment guidelines of the National Cholesterol Education Program recommend treatment of hypertriglyceridemia/low HDL cholesterol as a risk factor of coronary heart disease in diabetic and nondiabetic individuals alike. Aggressive treatment is recommended, therefore, particularly in diabetic patients and in all patients with existing vascular disease.
The in vitro cytotoxicity of a new platinum complex, cis-malonato [(4R, 5R)-4,5-bis(aminomethyl)-1,3-dioxolane 2- spiro 1' cyclo-pentane]platinum(II) (SKI 2054R) and cisplatin (CDDP) was evaluated against two human stomach adenocarcinoma cell lines (MKN-45 and KATO III) and a human lung adenocarcinoma cell line (PC-14). The in vitro 50% inhibitory concentration (IC50) values of SKI 2054R and CDDP against MKN-45, KATO III, and PC-14 were 1.21 and 0.51, 2.11 and 0.83, and 2.90 and 0.77 micrograms/ml, respectively. The pharma-cokinetic and ex vivo pharmacodynamic studies on SKI 2054R and CDDP were performed in beagle dogs. Equitoxic doses of SKI 2054R and CDDP (7.0 and 3.0 mg/kg, respectively) were administered i.v. bolus to beagle dose in a randomized crossover study. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for the two drugs declined in a biexponential fashion. The mean area under the concentration-tine curve (AUC(0)--> infinity) determined for ultrafiltrable platinum derived from SKI 2054R, as an active component was 6.61 +/- 2.34 micrograms . h/ml (mean +/- S.D.), with an initial half-life of 0.26 +/- 0.14 h, a terminal half-life of 1.57 +/- 0.71 hour, a total clearance of 17.65 +/- 4.99 ml/min/kg, and a steady-state volume of distribution of 1.46 +/- 0.11 l/kg. The ex vivo antitumor activity of SKI 2054R was assessed using the ultrafiltrable plasma against MKN-45, KATO III, and PC-14 by tetrazolium-dye (MTT) assay and was compared with that of CDDP using the antitumor index (ATI) determined from the ex vivo pharmacodynamic results of inhibition rates (%) versus time curves. The mean ATI value recorded for SKI 2054R was higher than that noted for CDDP; however, statistical difference was not observed between SKI 2054R and CDDP, suggesting that the antitumor activity of SKI 2054R is comparable to that of CDDP. These results suggest that SKI 2054R is a new platinum complex which is worth being evaluated further.