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Biomedical subjects

J Sohn

Publications and source records attributed to J Sohn.

At least 37 records · Page 2Linked to original sources
PubMed2000

Depletion of intracellular zinc induces macromolecule synthesis- and caspase-dependent apoptosis of cultured retinal cells.

Although zinc deficiency may contribute to age-related macular degeneration (ARMD), the pathogenic mechanism is as yet uncertain. In light of evidence that cellular zinc depletion induces apoptosis in cortical neurons and thymocytes, in the present study, we examined the possibility that the same phenomenon occurs also in retinal cells. Exposure of primary retinal cell cultures to 1-3 microM of a cell membrane-permeant zinc chelator TPEN for 24 h induced concentration-dependent death of neurons, photoreceptor cells, and astrocytes. Addition of zinc or copper reversed TPEN toxicity to all cell components, indicating the particular involvement of zinc chelation in cell death. Consistent with apoptosis, oligonucleosomal DNA fragmentation and chromatin condensation accompanied, and the protein synthesis inhibitor cycloheximide blocked the TPEN-induced retinal cell death. During TPEN-induced retinal cell apoptosis, cleavage/activation of procaspase-1, but little of procaspase-3, was observed. Consistent with this finding, a broad-spectrum caspase inhibitor (zVAD-fmk) was significantly more protective than a caspase-3-selective inhibitor (DEVD-fmk). The present study has demonstrated that depletion of intracellular zinc is sufficient to induce macromolecule synthesis- and caspase-dependent apoptosis of cultured retinal cells. In light of the possibility that zinc depletion may contribute to the pathogenesis of ARMD, the current culture model may be a useful tool for the investigation of the mechanism of zinc depletion-induced retinal cell death.

Age Factors↗
PubMed2000

Induction of G(1) cell cycle arrest and p27(KIP1) increase by panaxydol isolated from Panax ginseng.

Polyacetylenic compounds of Panax ginseng roots have been shown to inhibit growth of several human malignant tumor cell lines. Panaxydol is known to be one of the cytotoxic polyacetylenic compounds of P. ginseng. In this study, we first showed that panaxydol decreased markedly the proliferation, and to a lesser extent, the number of cells in a human melanoma cell line, SK-MEL-1. Next, the effect of panaxydol on cell cycle progression and its mechanism of action were investigated. Cell cycle analysis revealed that panaxydol inhibited cell cycle progression of a human malignant melanoma cell line, SK-MEL-1, at G(1)-S transition. At the same time, panaxydol increased the protein expression of p27(KIP1) as early as 1 hr after treatment. Cyclin-dependent kinase 2 (Cdk2) activity was decreased in a dose-dependent manner after 24 hr of panaxydol treatment. Protein levels of p21(WAF1), p16(INK4a), p53, pRb (retinoblastoma protein), and E2F-1 were not changed. It was also found that cycloheximide reversed the growth inhibition induced by panaxydol and partially abrogated the increase in p27(KIP1) expression. These results indicate that panaxydol induces G(1) cell cycle arrest by decreasing Cdk2 activity and up-regulating p27(KIP1) protein expression.

Alkynes↗
PubMed2000

Cross-linking of CD4 induces cytoskeletal association of CD4 and p56lck.

A membrane glycoprotein CD4 functions as a co-receptor of a T lymphocyte. The co-receptor function has been attributed to a protein tyrosine kinase, p56lck, which is activated upon CD4 binding to MHC molecule. In this study, we present evidences that one of the pathways through which CD4 transmits its signal is cytoskeleton association of p56lck tyrosine kinase as well as CD4 itself. Cytoskeletal association of both proteins is inhibited by a tyrosine kinase inhibitor, genistein, indicating that tyrosine protein kinase activation is important for cytoskeletal association of CD4 and p56lck. Cytoskeletal association of these proteins by CD4 cross-linking is not affected by inhibitors of protein kinase C nor PI3-kinase. Taken together, these results suggest that CD4 cross-linking activates a tyrosine kinase which then induces the simultaneous association of CD4 and p56lck with cytoskeleton.

CD4 Antigens↗
PubMed2000

Regulation of bcl-2 family in hydrogen peroxide-induced apoptosis in human leukemia HL-60 cells.

Numerous types of cells have been shown to undergo apoptosis when exposed to oxidant agent such as hydrogen peroxide. In order to understand the functional relationship between the anti- and pro-apoptotic regulatory proteins in the cells under oxidant stress, we have studied the level of expression of apoptosis regulatory proteins, bcl-2 and bax, in human leukemia HL-60 cells. The exposure of HL-60 cells to different concentrations of H2O2 for 6 h resulted in a typical apoptosis of the cells as characterized by flow cytometry, cell cycle analysis, and DNA fragmantation. There was a block in G1 to S transition and apoptotic cells were mainly derived from S and G2 cells. Kinetic study demonstrated that the levels of both bcl-2-mRNA and -protein expression were decreased with the progression of cellular apoptosis whereas the level of bax-mRNA was unchanged but the expressed bax-protein was not detectable. Cycloheximide, a nonspecific translation inhibitor, did not prevent the hydrogen peroxide-mediated apoptosis in HL-60 cells. These results suggest that the regulation of bcl-2, but not of bax are important factor in the oxidative stress-induced apoptosis in HL-60 cells.

Apoptosis↗
PubMed2000

High level activation of vitamin B1 biosynthesis genes in haustoria of the rust fungus Uromyces fabae.

In the rust fungus Uromyces fabae, the transition from the early stages of host plant invasion toward parasitic growth is accompanied by the activation of many genes (PIGs = in planta induced genes). Two of them, PIG1 (= THI1) and PIG4 (= THI2), were found to be highly transcribed in haustoria, and are homologous to genes involved in thiamine (vitamin B1) biosynthesis in yeast. Their functional identity was confirmed by complementation of Schizosaccharomyces pombe thiamine auxotrophic thi3 (nmt1) and thi2 (nmt2) mutants, respectively. In contrast to thiamine biosynthesis genes of other fungi that are completely suppressed by thiamine, THI1 and THI2 expression was not affected by the addition of thiamine to rust hyphae grown either in vitro or in planta. Immunoblot analysis revealed decreasing amounts of THI1p in extracts from spores, germlings, and in vitro-grown infection structures with increasing time after inoculation. Immunofluorescence microscopy of rust-infected leaves detected high concentrations of THI1p in haustoria, and only low amounts in intercellular hyphae. In the sporulating mycelium, THI1p was found in the basal hyphae of the uredia, but not in the pedicels and only at very low levels in uredospores. These data indicate that the haustorium is an essential structure of the biotrophic rust mycelium not only for nutrient uptake but also for the biosynthesis of metabolites such as thiamine.

Amino Acid Sequence↗
PubMed1999

Reducing scatter radiation to the contralateral breast with a mobile, conformal shield during breast cancer radiotherapy.

During a standard course of breast radiotherapy, the contralateral breast generally receives approximately 2.5 to 6.0 Gy of scattered radiation. Although most studies have not found an overall increase in metachronous contralateral breast cancers in patients undergoing radiotherapy, a cohort of younger women may be genetically more susceptible to radiation-induced breast cancers and may thus be adversely affected by the scattered radiation. We are attempting to develop a simple, convenient, effective mechanism for minimizing the scattered radiation to the contralateral breast during the process of clinical breast radiotherapy. We therefore designed a conformal, platform-based breast shield consisting of 2.5 cm of molded lead in a mobile counterweighted polystyrene casing. This shield was intended to serve as a physical barrier to prevent both low and high energy scattered photons from the medial and lateral tangential fields. We conducted a prospective trial of 20 women, each woman serving as her own control. Each woman received breast radiotherapy with and without shield, and an array of thermoluminescent dosimeters was positioned across the contralateral breast to evaluate the in vivo dosimetry and the impact of the breast shield on surface absorption of scattered radiation. We found that the use of the breast shield reduced the median dose of scattered radiation by approximately 60% (p < 0.0001). This represented a median dose reduction of approximately 300 cGy at the nipple. The shield was easily positioned and added < 1 min to daily setup time. We conclude that the use of this sort of surface barrier shielding technique was feasible, effective, and practical for clinical use. The degree of scatter reduction accomplished through the use of this breast shield may be biologically significant, especially for those patients with biologic or epidemiologic risk factors that may predispose them to the development of radiogenic breast cancers.

Breast Neoplasms↗
PubMed1999

An unusual type of cancer-associated retinopathy in a patient with ovarian cancer.

We studied a case of unusual retinopathy in a 35-year-old woman who presented with bilateral visual deterioration due to retinal pigmentary mottling and serous elevation in the posterior pole. Two years before, she had undergone hysterectomy and bilateral salphingo-oophorectomy for ovarian cancer. Her electroretinogram became subnormal, and her fluorescein angiogram exhibited multiple deep retinal pigment epithelial leakages and subretinal dye pooling in both eyes. Corticosteroid therapy failed to prevent visual loss. She was found to possess antibodies against retinal 45 kd protein. This led to a diagnosis of cancer-associated retinopathy with atypical protein profile. We report a rare variety of cancer-associated retinopathy in a patient with-ovarian cancer.

Adenocarcinoma↗
PubMed1998

Effect of petroleum ether extract of Panax ginseng roots on proliferation and cell cycle progression of human renal cell carcinoma cells.

Panax ginseng roots have long been used as a medicinal herb in oriental countries. We have investigated anti-proliferative effects of lipid soluble Panax ginseng components on human renal cancer cell lines. Petroleum ether extract of Panax ginseng roots (GX-PE) or its partially purified preparation (7:3 GX) was added to cultures of three human renal cell carcinoma (RCC) cell lines, A498, Caki-1, and CURC II. Proliferation of RCC cells was estimated by a [3H]thymidine incorporation assay and cell cycle distribution was analyzed by flow cytometry. GX-PE, 7:3 GX, panaxydol and panaxynol inhibited proliferation of all three RCC cell lines in a dose dependent manner in vitro with an order of potency, 7:3 GX > panaxydol > panaxynol = GX-PE. Additive effect of interleukin 4 was also demonstrated, most prominently in Caki-1 which responded poorly to GX-PE alone. Analysis of cell cycle in CURC II and Caki-1 treated with GX-PE demonstrated increase in G1 phase population and corresponding decrease in S phase population. The present study demonstrated that proliferation of human RCC cell lines were inhibited by lipid soluble components of Panax ginseng roots by blocking cell cycle progression at G1 to S phase transition.

Alkanes↗
PubMed1998

Effect of Chagas' disease on nitric oxide-containing neurons in severely affected and unaffected intestine.

PURPOSE: The pathophysiology of Chagas' disease is incompletely understood. Neuronal nitric oxide has been cited as a candidate neurotransmitter responsible for relaxation of the internal anal sphincter. Neuronal nicotinamide adenine dinucleotide phosphate diaphorase can be used as a marker for neuronal nitric oxide synthase. This study was designed to examine the alterations of the nitric oxide-containing neurons in the enteric nervous system of the colon of patients who underwent resections for advanced megacolon and to compare these specimens with small-bowel specimens from the same patients and with specimens from control subjects. METHODS: Specimens from resected rectum and extramucosal small-bowel biopsy specimens from 11 patients with Chagas megacolon but no apparent small-bowel clinical involvement were compared with the uninvolved colon and jejunum of 10 control patients with colon cancer. Tissues were fixed in Zamboni solution and evaluated by histochemistry for nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Reactivity was evaluated on a 0 to 4 scale in the longitudinal muscle, myenteric plexus, circular muscle, submucosal plexus, and mucosa. RESULTS: Specimens from control patients showed well-stained myenteric and submucosal neurons and an abundant network of terminal nerve fibers in the muscle layers. Chagasic specimens had decreased staining in all layers of the gut. Overall there was a statistically significant decrease in nicotinamide adenine dinucleotide phosphate diaphorase-containing neurons. Biopsy specimens from clinically uninvolved small bowel of patients with Chagas' disease also showed decreased reactivity, but to a lesser degree. CONCLUSIONS: Nicotinamide adenine dinucleotide phosphate diaphorase activity is decreased in patients with advanced megacolon. The alterations are more relevant in the myenteric plexus and the circular muscle. Reactivity is also diminished in the clinically uninvolved small bowel, but to a lesser extent.

Adult↗
PubMed1998

Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels.

OBJECTIVE: To evaluate the survival and function of hepatocytes (HCs) on a novel three-dimensional (3D) synthetic biodegradable polymer scaffold with an intrinsic network of interconnected channels under continuous flow conditions. SUMMARY BACKGROUND DATA: The authors' laboratory has investigated HC transplantation using 3D biodegradable polymers as scaffolding as an alternative approach to treatment of end-stage liver disease. Previous studies have demonstrated survival of HCs transplanted on polymer discs in peripheral tissue sites and partial correction of single enzyme liver defects. One of the major limitations has been the insufficient survival of an adequate mass of transplanted cells; this is thought to be caused by inadequate oxygen diffusion. METHODS: HCs and nonparenchymal liver cells from Lewis rats were seeded onto 3D biodegradable polymer scaffolds. Microporous 3D polymers were created using 3D printing on copolymers of polylactide-coglycolide. The cell/polymer constructs were placed in static culture or continuous flow conditions. The devices were retrieved after 2 days and examined by scanning electron microscopy and histology. Culture medium was analyzed for albumin by enzyme-linked immunosorbent assay (ELISA). Differences in culture parameters including pH, PCO2, PO2, glucose, lactate, and HCO3 were examined. RESULTS: Scanning electron microscopy revealed successful attachment of HCs on the 3D polymer in both static and flow conditions. Histology demonstrated viable HCs in both conditions. ELISA demonstrated a significantly higher mean concentration of albumin in flow conditions than in static conditions. Culture parameter analysis revealed a significantly higher PO2 and glucose level, and a more physiologic pH in flow conditions than in static conditions. CONCLUSIONS: HCs cocultured with nonparenchymal cells can attach to and survive on the 3D polymer scaffolds in both static and flow conditions in the size and configuration used in this study. Flow conditions may provide a more conducive environment for HC metabolism and albumin synthesis than static conditions. The authors hypothesize that flow through directed channels will be necessary for the transfer of large masses of cells when implantation studies are initiated.

Animals↗
PubMed1998

Iron-induced cytotoxicity in cultured rat retinal neurons.

Oxidative stress has been proposed as a major injury mechanism in the central nervous system including the retina. In this study, as an initial attempt to study the mechanism of oxidative injury in the retina, we developed a cell culture model by utilizing the iron exposure paradigm. Exposure of rat retinal cultures for 24 hours to 10-40 MicroM ferrous or ferric chloride induced a concentration-dependent death of retinal neurons but not of photoreceptors or astrocytes. An antioxidant, trolox effectively attenuated the iron-induced death of neurons and photoreceptors in a dose-dependent manner whereas neither glutamate receptor antagonists nor cycloheximide were protective. Of retinal interneurons, GABAergic neurons were more vulnerable to the iron toxicity than calbindin (+) horizontal neurons. These findings show that iron exposure induces anti-oxidant-sensitive neuronal injury in retinal culture, independent of the excitotoxic or the apoptotic mechanisms. Of retinal neurons, different cell types exhibit differential vulnerabilities to the iron-induced oxidative injury. This simplified culture model system may be useful in elucidating mechanisms of oxidative injury in the retina.

Animals↗
PubMed1997

Percutaneous management of a bladder-drained pancreas transplant pseudocyst by a transcystic approach.

BACKGROUND: We describe a 35-year-old male type 1 diabetic who underwent a cadaveric combined kidney-bladder-drained pancreas transplant with a duodenocystostomy for exocrine drainage who developed a large pelvic pseudocyst associated with a dilated pancreatic duct and an elevated serum amylase level. METHODS: Due to the risk of surgical revision and the possibility of creating a cutaneous fistula with conventional percutaneous drainage, a pseudocyst-to-bladder drainage was performed. After the procedure, the catheter was capped to allow drainage of the pancreatic secretions into the bladder. RESULTS: After drainage, the patient's serum amylase and lipase normalized along with resolution of the pseudocyst. The tube was removed after 19 weeks with no evidence of a recurrent pseudocyst and a normal serum amylase level. CONCLUSION: The percutaneous pseudocyst-cystostomy obviated the need for surgical revision of the exocrine gland drainage and thus eliminated the morbidity and the potential risk of graft loss associated with such surgery.

Adult↗
PubMed1997

[Diagnosis of blood flow in breast tumors with increased blood pressure. New possibility in tumor field diagnosis].

On the assumption that the architecture of blood vessels of malignant tumors, formed by neoangiogenesis, shows characteristics that are different from those of blood vessels of benign tumors or physiological findings, we have tried in the present study to investigate the behavior of these different vessels under increased blood pressure. Using a special stand, the same sonographic section could be stably maintained during an examination time of approx. 4 minutes. Using a new computer program, the color pixels of the employed Angio color technique were quantified and recorded as a function of the measured blood pressure. To increase blood pressure, the patient had to press a hand grip, which practically always caused a systolic blood pressure elevation of more than 15-20 mmHg. Seventy patients with sonographically detected breast tumors were examined; 54 (14 benign and 40 malignant tumors) could be included in the evaluation. We found four typical types of curves: Curve type 1 is associated with an instantaneous increase in blood flow with increased blood pressure, followed by a drop in the blood pressure, with a slow decrease in blood flow as the blood pressure drops (with 29 malignant and 3 benign tumors). Curve type 2 shows a continuous increase in blood flow-though somewhat delayed with respect to the rise in blood pressure-which is also observed when the blood pressure drops (exclusively benign tumors). In curve type 3, maximum blood flow is reached after the blood pressure maximum, and then the blood flow decreases (1 benign and 3 malignant tumors). Curve type 4 features decreased blood flow in spite of increased blood pressure (3 benign and 5 malignant tumors). The described quantification method, in combination with the stand, permits for the first time analysis of a tumor under increased blood pressure as to its blood flow behavior over time in an examination using a challenge test. Here one can find two distinctive curve types (types 1 and 2) that correlate mostly with malignant (type 1) or benign (type 2) breast tumors. Should this tendency be substantiated by additional large-scale studies, it would seem that a new ultrasonic possibility for differential diagnosis has been found.

Adult↗
PubMed1996

Inhibitory effects of interleukin-4 on human renal cell carcinoma cells in vitro: in combination with interferon-alpha, tumor necrosis factor-alpha or interleukin-2.

BACKGROUND: Immune cytokines have been shown to play important roles in regulating the growth of neoplastic cells, as well as the function of immune cells. The present study assessed the effects of interleukin (IL)-4 alone, and in combination with recombinant interferon (IFN)-alpha 2b, or with IL-2, or with tumor necrosis factor (TNF)-alpha on the in vitro proliferation of human renal cell carcinoma (RCC) cell-lines. METHODS: Growth-inhibitory effects of IL-4 alone, and in combination with other cytokines, on three human RCC cell-lines, Caki-1, CURC-II, and A-498, were measured by the [3H]thymidine incorporation assay. RESULTS: IL-4 inhibited proliferation of all three human RCC cell-lines (P < 0.001). The maximum growth inhibition of RCC cell-lines by IL-4 alone was observed at the concentration of 1 to 3 ng/mL, depending on the cell-line. Antihuman IL-4 antisera was able to reverse the growth-inhibitory effects of IL-4 on Caki-1 in a dose-dependent manner, proving that the growth inhibition was mediated by IL-4 itself. When other cytokines were added in combination with IL-4, only IFN-alpha 2b resulted in significant additional growth inhibition (P < 0.005). However, when the proliferation was compared to that of RCC cells that were not treated with any cytokine, all combinations produced marked growth inhibition. CONCLUSION: Our data suggest that IL-4 alone, or in combination with IFN-alpha 2b, can be used to develop new strategies for treatment of human RCC.

Antibody Specificity↗
PubMed1995

Regulatory regions 3' of the immunoglobulin heavy chain intronic enhancer differentially affect expression of a heavy chain transgene in resting and activated B cells.

We have compared the expression patterns of three Ig heavy chain transgenes. The three constructs differ only by deletion of J-C intron sequences located downstream of the Emu enhancer region. When stably transfected into a myeloma cell line, all three constructs are expressed at comparable levels. However, transgenic mice carrying each construct show dramatic differences in transgene expression. Our results indicate that, in addition to the Emu enhancer, at least two regions, RegA and RegS, within the J-C intron influence transgene expression. RegA, located directly downstream of the core Emu enhancer, is involved in up-regulation of transgene expression after LPS activation of splenocytes. RegS, located within or downstream of the Smu switch region, is important for normal levels of transgene expression in splenocytes of heavy chain transgenic mice.

Animals↗
PubMed1995

Helicobacter pylori gastritis: radiographic findings.

PURPOSE: To determine whether there are useful radiographic criteria for diagnosing Helicobacter pylori. MATERIALS AND METHODS: Radiographs from double-contrast upper gastrointestinal examinations of 88 patients with H pylori and 41 control subjects were blindly reviewed. The results were analyzed by means of receiver operating characteristic (ROC) curves. RESULTS: Thickened gastric folds were detected in 39 patients with H pylori (44%) and nine control subjects (22%). The area under the ROC curve was 0.62 (standard deviation [SD] = 0.05, P < .01). Among the 48 subjects with thickened gastric folds, polypoid gastritis with thickened, lobulated folds was detected in 24 patients with H pylori (62%) and four control subjects (44%). The area under the ROC curve was 0.59 (SD = 0.05, P < .01). No substantial differences were observed in the frequencies of gastric ulcers, erosive gastritis, gastric narrowing, duodenal ulcers, duodenitis, and duodenal narrowing in patients with and without H pylori. CONCLUSION: The presence of thickened gastric folds was the best radiographic criterion for differentiating subjects with from those without H pylori.

Adult↗
PubMed1994

Photoastigmatic refractive keratectomy in 168 eyes: six-month results.

Using a 193 nm excimer laser, we performed elliptical astigmatic and spherical corneal ablation on 168 eyes with compound myopic astigmatism and analyzed the three- and six-month postoperative results. Mean preoperative astigmatism was 1.51 +/- 0.81 diopters (D). Mean three- and six-month postoperative astigmatism was 0.70 +/- 0.58 D and 0.67 +/- 0.60 D, respectively. Six months after surgery, eyes with less than 1.00 D preoperative astigmatism improved 4.8%. The improvement was 53.5% and 59.1% for eyes with a preoperative astigmatism of 1.00 D to 2.00 D and above 3.00 D, respectively. Overall, astigmatism improved 55.6%. There was a wide distribution from overcorrection to undercorrection. Astigmatism six months after surgery was within 10 degrees of the preoperative axis in 46.1% of eyes.

Adult↗