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Biomedical subjects

J K Roh

Publications and source records attributed to J K Roh.

At least 37 records · Page 2Linked to original sources

Diffusion-weighted imaging in Wallerian degeneration.

We report two patients displaying hyperintensities on diffusion-weighted imaging (DWI) in the area of Wallerian degeneration (WD) at 12 days after stroke. High signal intensities were more conspicuous on DWI than on T2-weighted images. Both patients showed decreased diffusion anisotropy resulting in elevated apparent diffusion coefficient in the area of WD. These patients illustrate that DWI may be useful in the detection of the early stage of WD.

Aged↗

Transduction effect of antisense K-ras on malignant phenotypes in gastric cancer cells.

The antitumoral effects of antisense RNA to K-ras were investigated in gastric cancer cell lines by examining the level of K-ras expression and the tumorigenicity in vitro and in vivo. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), DNA sequencing, and immunoblotting analysis revealed that YCC-1 gastric cancer cells overexpressed wild type K-ras, whereas YCC-2 cells had a homozygous mutation in codon 12 from GGT (glycine) to AGT (serine), while SNU-1 cells had a heterozygous mutation to GAT (asparagine) in the identical position. Both YCC-1 and YCC-2 cells were transduced by LNC-AS/K-ras containing the antisense 2.2 kb genomic K-ras DNA fragment covering exon 2 and exon 3 specific for K-ras. The application of antisense K-ras significantly downregulated the expression of K-ras and had no influence on the expression of either H-ras or N-ras. The antisense-transduced YCC-2 cells grew considerably slower than the control group transduced by LNCX, whereas the growth inhibition of antisense-transduced YCC-1 cells was less prominent than that of transduced YCC-2 cells. In addition, the tumorigenicity of YCC-2 cells transduced by LNC-AS/K-ras was totally lost. Therefore, our results imply that the specific inhibition of K-ras p21 protein can be accomplished by introducing the antisense covering the K-ras- specific region to gastric cancer cells with aberrant K-ras expression, resulting in a reduction of the growth rate and suppression of tumorigenicity.

Animals↗

Acute bilateral cerebellar infarcts in the territory of posterior inferior cerebellar artery.

The authors report 12 patients with acute bilateral cerebellar infarcts in posterior inferior cerebellar artery (PICA) territory. They found three topographic patterns: A) bilateral medial PICA in six patients; B) unilateral whole + contralateral medial PICA in four; and C) bilateral small multiple in two. Nine patients in Groups A and B had unilateral PICA or vertebral artery disease, and both patients in Group C had bilateral vertebral artery disease. These findings support that unilateral supply to both medial PICA territories may be the most relevant pathogenesis of this syndrome.

Aged↗

Hypoglycemia-induced cerebellar dysfunction and quantitative positron emission tomography study.

OBJECTIVE: To describe an unusual case of hypoglycemia-induced bilateral cerebellar dysfunction. BACKGROUND: The cerebellum is known to be resistant to hypoglycemia, and selective cerebellar dysfunction caused by hypoglycemia has not been reported. Previous studies showed that the ratio between the rate constants for glucose uptake and phosphorylation (K1 and k3) is reversed in the cerebellum compared with the cerebral cortex; higher K1 in the cerebellum and higher k3 in the cerebral cortex. METHODS: Quantitative dynamic PET scanning with labeled fluorodeoxyglucose (18F-FDG) was performed to prove altered glucose kinetics in the cerebellum of a patient who presented with episodic cerebellar dysfunction associated with hypoglycemia. Four control subjects underwent the same study. RESULTS: The ratio between K1 and k3 was not reversed in the cerebellum of our patient (K1 = 0.082, k3 = 0.192). On the contrary, the ratio was reversed in the control subjects (mean K1 = 0.109, mean k3 = 0.080). In addition, the patient's cerebellar metabolic rate of glucose (rCMRglu = 27.9 micromol/100 g/minute) and the rate constant of glucose egress (k2 = 0.543) were relatively increased compared with those of control subjects (mean rCMRglu = 21.9 micromol/100 g/minute, mean k2 = 0.352). CONCLUSIONS: In a case of episodic bilateral cerebellar dysfunction caused by hypoglycemia, quantitative dynamic PET study demonstrated decreased glucose uptake-to-utilization ratio and increased leak of glucose in the cerebellum. The cerebellum is not invariably resistant to hypoglycemia.

Blood Glucose↗

Correlation of tissue and blood plasminogen activation system in breast cancer.

The plasminogen activation system plays a crucial role during cancer invasion and metastasis. In the solid tumor, urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and uPA receptor (uPAR) are considered as prognostic factors. In this study, we have investigated whether secretion of the uPA, PAI-1 and uPAR from the primary breast cancer tissue can be detected in the blood of the patients using the ELISA assay. We have found that the plasminogen activation system (uPA, PAI-1, uPAR) of tumor tissue is activated from the early stage of breast cancer. However, only a number of metastatic lymph nodes was a prognostic factor in multivariate analysis for relapse. The blood level of the plasminogen activation system correlated with that of tissue in an order of uPAR (r(2)=0.61; P=0.001), uPA (r(2)=0.35; P=0.001) and PAI-1 (r(2)=0.11; P=0.001). We conclude that the total uPAR level of cancer tissue can be substituted by that which is detected in the blood for further clinical applications.

Adult↗

Scrub typhus encephalomyelitis with prominent focal neurologic signs.

BACKGROUND: Encephalomyelitis with prominent focal neurologic signs and associated neuroradiologic abnormalities has not been previously described in scrub typhus. CASE DESCRIPTION: A 22-year-old woman was admitted because of fever and an altered mental state. Neurologic examination revealed bilateral sixth and seventh nerve palsies, bilateral gaze evoked nystagmus, anarthria, dysphagia, quadriparesis, and sensory level at T1. Serum and cerebrospinal fluid samples were positive for tsutsugamushi antibody. The patient's magnetic resonance images demonstrated the lesions responsible for the neurologic dysfunctions: in the lower brainstem, cerebellar peduncles, and spinal cord. It was interesting that the gray matter of the spinal cord was predominantly involved. CONCLUSIONS: The recognition of unusual manifestations and the clinical suspicion of this treatment-responsive disease may be important, particularly in the face of increasing international and intranational travel.

Adult↗

Neoadjuvant chemotherapy and radiation for inoperable carcinoma of the maxillary antrum: a matched-control study.

A matched-control study comparing standard radiotherapy versus neoadjuvant chemotherapy and radiation was undertaken to clarify the effects of neoadjuvant systemic chemotherapy for locally advanced squamous cell carcinoma of the maxillary antrum. Thirty-four patients with inoperable maxillary cancer were treated with neoadjuvant chemotherapy and radiotherapy (Group II). Before starting radiotherapy, all patients in Group II received two or three cycles of neoadjuvant chemotherapy consisting of cisplatin and a 5-day continuous infusion of 5-fluorouracil with or without intravenous injection of vinblastine. Radiation doses ranged from 66 Gy to 75 Gy (median, 70 Gy). The response rate, patterns of failure, toxicity, and survival for Group II were compared with those for 34 stage-matched patients treated with radiation alone (Group I). Despite a higher response rate to neoadjuvant chemotherapy, the recurrence rate and patterns of treatment failure were not influenced by the addition of neoadjuvant chemotherapy. In most cases, neoadjuvant chemotherapy did not interfere with subsequent radiotherapy, and radiation-induced late complications occurred equally in both treatment groups. After a median follow-up of 48 months, there was no significant difference in 5-year actuarial survival or disease-free survival between the two treatment groups. Radiation alone for inoperable maxillary cancer was clearly suboptimal for improving local control and survival rate, but neoadjuvant chemotherapy in addition to standard radiotherapy failed to demonstrate any therapeutic advantage over radiation alone.

Adult↗

Neuronal metabolic changes in the cortical region after subcortical infarction: a proton MR spectroscopy study.

OBJECTIVES: To investigate whether proton magnetic resonance spectroscopy ((1)H MRS) can detect neuronal metabolic changes in the cortical region in patients with cortical dysfunction after subcortical infarction. METHODS: Fifteen patients with subcortical large (diameter>/=20 mm) infarcts were studied; nine patients with cortical dysfunction (group A), and six without (group B). Seven patients with lacunar infarction served as controls. Infarct volume was measured on T2 weighted images with an image analyser. (1)H MRS data were obtained in three regions; high signal intensity area on T2 weighted image, overlying cortex with a normal T2 MRI appearance, and contralateral homologous cortical region. RESULTS: Infarct volume was not different between groups A and B. N-acetylaspartate (NAA)/creatine+phosphocreatine (Cr) ratios in the cortical region overlying subcortical infarcts in group A were significantly lower than those in group B and the control group (p=0.002). The NAA/Cr ratios in the overlying cortex were significantly lower than those in the contralateral normal cortex in group A on the initial (p=0. 015) and follow up (p=0.028) (1)H MRS, but these differences were not found in group B and the control group. CONCLUSIONS: The results support the idea that the cerebral cortex is a responsible location for cortical dysfunction after subcortical infarctions. (1)H MRS can be used as a sensitive method for the detection of a neuronal metabolic damage, which is not demonstrated by conventional MRI.

Adult↗

Significance of acute multiple brain infarction on diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) is superior to conventional MRI in identification of small new ischemic lesions and discrimination of recent infarcts from old ones. Thus, this technique is useful in the detection of acute multiple brain infarcts (AMBI). We sought to determine the frequency and the topographical and etiologic patterns of AMBI detected on DWI. METHODS: We studied 329 consecutive ischemic stroke patients who underwent DWI and MRI/MR angiography within 4 days of stroke onset. AMBI was defined as noncontiguous high signal intensities on DWI in >1 vascular territory. Stroke mechanism was determined according to the criteria of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). RESULTS: We detected AMBI in 95 patients (28.9%). AMBI in anterior circulation was found in 62 cases: in 1 hemisphere in 42 (group A) and in bilateral hemispheres in 20 (group B). Twenty-two patients had AMBI in the posterior circulation (group C) and 11 in both anterior and posterior circulations (group D). The most frequent cause of stroke was large-artery atherosclerosis in groups A (33/42), B (9/20), and C (15/22) (P=0.02) and cardioembolism in group D (6/11) (P=0.02). Elevated fibrinogen or hematocrit was significantly associated with group B (P=0.01). In 9 patients in groups B and D, anatomic variations of anterior or posterior cerebral arteries or patent posterior communicating artery contributed to AMBI. CONCLUSIONS: Different topographical patterns of AMBI are associated with different vascular pathologies and stroke mechanisms. Hemorheologic abnormality or vascular anatomic variations may be contributing factors in the pathogenesis of AMBI in bilateral cerebral hemispheres or in both anterior and posterior circulations.

Acute Disease↗

Angiocentric lymphoma of the head and neck: patterns of systemic failure after radiation treatment.

PURPOSE: To investigate the patterns of systemic failure and the clinical outcome in patients with angiocentric lymphoma of the head and neck who were treated with radiation alone, and to discuss the optimal mode of treatment for these patients. PATIENTS AND METHODS: We reviewed the records of 92 patients with stage I or II angiocentric lymphoma who were treated at Yonsei Cancer Center between 1976 and 1994. All patients were treated with involved-field irradiation. Radiation doses ranged from 40 to 60 Gy (median dose, 50.4 Gy). Treatment response, patterns of treatment failure including systemic failure, and clinical outcome after radiation treatment were analyzed. RESULTS: The most frequently involved site was the nasal cavity, either alone or in conjunction with other sites. In 16 patients (17.4%), angiocentric lymphoma was accompanied by cervical lymphadenopathy. Disease was classified as stage I in 62 patients (67.4%) and stage II in 30 patients (32.6%). After completion of radiation treatment, 61 patients (66.3%) achieved a complete response and 16 (17.4%) a partial response. Half of the patients (50.0%) ultimately experienced local recurrence with or without other components of failure, whereas regional failure was relatively uncommon (10.9%). Systemic failure occurred in 25.0% of patients during follow-up. Six patients had histologic findings identical to those at the time of the original disease (group I), whereas four patients exhibited morphologic features of frank lymphomas (group II). The majority of patients with systemic relapse had the predilection sites for widespread extranodal involvement, such as the skin, brain, lung, gastrointestinal tract, or testes. In addition, seven patients died from various medical illnesses or immunologic disorders, including hemophagocytic syndrome and second primary cancers (group III). After a median follow-up of 56 months, the overall survival and disease-free survival rates for all patients were 40.1% and 37.8%, respectively. All patients except one with systemic failure died within 1 year. CONCLUSION: Treatment with radiation alone had suboptimal results, partly because of the occurrence of a variety of systemic failure with diverse clinicopathologic features. Given the frequent occurrence of systemic failure after radiation treatment, we believe that the multimodality treatment approach containing more effective chemotherapeutic agents should be incorporated in the treatment of angiocentric lymphoma confined to the head and neck.

Actuarial Analysis↗

Tissue urokinase-type plasminogen activator receptor levels in breast cancer.

Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factors such as uPAR and growth factors. Thus, we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients. Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients. The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg cytosol protein and 4.8+/-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between the T stages (p>0.05), nor in nodal stage, in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesterone receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.002) and TNM stage (p=0.0004) were significant. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.

Adult↗

Neuroprotective effects of lamotrigine enhanced by flunarizine in gerbil global ischemia.

We examined whether the anti-ischemic effect of lamotrigine (LTG), which inhibits the presynapic sodium channel, could be enhanced by the calcium channel blocker-flunarizine (FNR) in cerebral ischemia. Global ischemia was induced in Mongolian gerbils for 5 min under the monitoring of scalp temperature. LTG and FNR were administered intraperitoneally 1 h before ischemia. After 7 days, animals were killed and viable neurons in CA1 area were counted. LTG treated group showed significant protective effects compared to control group (P < 0.01). These effects were more prominent in group treated with LTG and FNR (P = 0.01). Combination of two drugs did not increase the mortality rate compared to single-treated group. These results show that a synergistic reduction of neuronal death can be achieved by combination of LTG and FNR without serious adverse reaction.

Animals↗

Pretreatment of male BALB/c mice with beta-ionone potentiates thioacetamide-induced hepatotoxicity.

A possible role of metabolic activation by cytochrome P450 (P450) in thioacetamide-induced hepatotoxicity was investigated in male BALB/c mice. The mice were pretreated with the P450 inducer, beta-ionone, subcutaneously at 600 mg/kg, 72 and 48 h prior to an intraperitoneal administration of either 100 or 200 mg/kg of thioacetamide. The elevated activities of serum alanine aminotransferase and serum aspartate aminotransferase by thioacetamide were greatly potentiated by the pretreatment with beta-ionone. Moreover, the potentiation of thioacetamide-induced hepatotoxicity was also observed in the histopathological examination of livers. The hepatic necrosis by thioacetamide was potentiated when mice were pretreated with beta-ionone. In liver microsomes, the activities of P450 2B-specific pentoxyresorufin O-depentylase and benzyloxyresorufin O-debenzylase were significantly induced by the treatment with beta-ionone. Beta-ionone also induced other P450-associated monooxygenases. Because the pretreatment with beta-ionone was not hepatotoxic at the dose inducing P450s. our present results suggest that beta-ionone may be a useful model inducer of P450 enzyme(s) in studying toxic mechanism of certain chemicals which require metabolic activation by P450s in mice.

Alanine Transaminase↗

Subregions within the supplementary motor area activated at different stages of movement preparation and execution.

Previous studies have provided evidence that the primary motor area (M1) is involved in actual execution of a motor program, while the premotor area (PreMA) and the supplementary motor area (SMA) play a role in its preparation. We have used the high temporospatial resolution of functional magnetic resonance imaging (fMRI) to study the relationship between stages of a motor program and activation of these motor-related cortical areas. Seven normal volunteers performed a delayed-motor task in which the preparation of finger movements was dissociated in time from movement execution, while event-related fMRI was obtained. The M1 and PreMA showed expected activation associated with execution and preparation stages, respectively. Within SMA, subregions with different temporal profiles of activation were identified: The anterior part became activated early in the preparation period, whereas the posterior part only with movement execution. This supports the notion that the classic SMA consists of the pre-SMA and SMA proper each with different functions.

Adult↗

Combined peripheral facial and abducens nerve palsy caused by caudal tegmental pontine infarction.

Isolated peripheral facial and abducens nerve palsy could theoretically be caused by a caudal pontine infarction, but as far as we know, there has been no published case history which has demonstrated this point. We describe the cases of two hypertensive patients who showed combined peripheral facial and abducens nerve palsy without other neurologic symptoms or signs. Other than hypertension, there was no identifiable etiology. Magnetic resonance imaging demonstrated compatible isolated ipsilateral ischemic infarction of the caudal tegmental pons. The present cases indicate that a well-placed small pontine infarction can cause isolated peripheral facial and abducens nerve palsy.

Abducens Nerve↗

Modulation of biological phenotypes for tumor growth and metastasis by target-specific biological inhibitors in gastric cancer.

For tumor progression, a cascade of linked sequential biological events is essential. We tried to test whether biological therapy can modulate specific biological phenotypes and increase the anti-tumor effect when combined with chemotherapy. Five human gastric cancer cell lines (YCC-1, YCC-2, YCC-3, YCC-7, AGS) were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor inhibitor, Tranexamic acid as a plasmin inhibitor, Lovastatin as an adhesion inhibitor and Adriamycin as a chemotherapeutic agent were selected. The effects of each drug on colony formation and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively to test direct anti-tumor effect. The expression of uPA, PAI-1 was determined by ELISA, while MMPs activity was evaluated by zymography. PPS suppressed the colony-forming activity as much as Adriamycin did, but it showed only cytostatic effects in cell proliferation assay. Migration capacity using Boyden chamber assay was more closely correlated with adhesive capacity than uPA or MMP-2 expression. The motility inhibitory effect of Tranexamic acid was observed in the YCC-7 cell line, which expressed all the required biological phenotypes for migration. In AGS, with high cell motility and adhesiveness, the adhesion was inhibited by Lovastatin and most of the inhibitory effect was recovered by Mevalonate. When PPS was combined with Adriamycin on the Adriamycin-resistant, midkine (MK) gene expressing YCC-7 cell line, the growth inhibition rate increased up to 84%, while that for a single treatment of PPS or Adriamycin was 40% and 22%, respectively (p=0.001). When we combined Tranexamic acid and Adriamycin, we observed the synergistic effect in YCC-3 and YCC-7, while no combined effect was found in YCC-1. The combination of Lovastatin and Adriamycin did not show any combined effects in any of the cell lines. In conclusion, a synergistic anti-proliferative effect (chemo-sensitization) with combined chemo-biotherapy was found in cancer cells with specific biological target, MK. The anti-motility effect was the greatest when the gastric cancer cells expressed all the specific biological phenotypes.

Anticoagulants↗

Changes of telomerase and telomere lengths in paired normal and cancer tissues of breast.

To attain the immortal phenotype, cancer cells must overcome the mitotic clock. Telomerase activity has been identified to be activated in malignant tumors including breast cancer. Telomerase activity was evaluated in 71 breast cancer tissues and paired normal tissues with the TRAP (telomerase repeat amplification protocol) assay. Telomerase activity was calculated and translated into arbitrary units by computer-assisted densitometry with the control of telomerase activity in the 293 control cell line. In 59 paired breast tissues with telomerase activity, terminal restriction fragment (TRF) lengths were measured using Southern blotting. Relative inhibition (RI), the ratio of inhibited telomerase activity in each tumor tissue compared to that of the 293 control cell line after pre-treatment with 150 microg/ml of RNAse A, was measured. Sixty-three of 71 cancer tissues showed telomerase activity (88.7%) with 75.3+/-17.9 units in densitometry, while no telomerase activity was detected in their paired normal tissues. Telomerase activity was correlated to node metastasis (p=0.02) and stage (p=0.005), but not to tumor size or the hormonal receptor status. TRF lengths were 11. 0+/-4.7 kb in 59 tumor tissues and 11.7+/-2.2 kb in paired normal tissues. TRF lengths did not correlate to any of the clinical parameters. However changes of TRF lengths in tumor tissues compared to those of normal tissues correlated to telomerase activity. RI in the tumor tissues was proportional to telomerase activity without RNAse A pre-treatment. In breast cancer, telomerase activity was specific to tumor tissues and increased with tumor progression. Telomerase activity and changes in TRF lengths can be used as guidelines in detecting candidates for the telomerase inhibitor.

Adult↗

Role of definitive radiation therapy for larynx preservation in patients with advanced laryngeal cancer.

OBJECTIVE: Recently, neoadjuvant chemotherapy (CT) and radiation therapy (RT) have been advocated as a standard treatment for laryngeal preservation in patients with locally advanced laryngeal cancer. However, it is still being debated whether adding neoadjuvant CT to conventional RT makes an effective contribution to laryngeal preservation. The current study was designed to resolve this controversy. DESIGN: Retrospective clinical study. SETTING: The Severance Hospital, Yonsei Cancer Center, Yonsei University, Seoul, Korea. METHOD: Eighty patients (stages III, IV) with squamous cell carcinoma of the larynx were divided into two groups according to treatment modalities, which consisted of RT alone (N = 40, Group 1) and neoadjuvant CT plus RT (N = 40, Group 2). Comparative analysis was undertaken to investigate the differences in the organ preservation rate and treatment results between the two groups. RESULTS: There was no significant difference in the response rate and patterns of treatment failure between the two groups. The 5-year survival rate was similar between Group 1 (24%) and Group 2 (31%) (p = .1556). In addition, the larynx was almost equally preserved in Group 1 (62%) versus Group 2 (63%). CONCLUSIONS: Radiation therapy without neoadjuvant CT seems to be a valid alternative treatment for the purpose of laryngeal preservation in locally advanced laryngeal cancer.

Adult↗