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Biomedical subjects

K H Shin

Publications and source records attributed to K H Shin.

At least 55 records · Page 3Linked to original sources

Correlation of laminated MR appearance of articular cartilage with histology, ascertained by artificial landmarks on the cartilage.

The object of this study was to correlate the laminae of articular cartilage on magnetic resonance (MR) imaging with histologic layers. T1- and fast spin-echo T2-weighted images of articular cartilage with artificial landmarks were obtained under high gradient echo strength (25 mT/m) conditions and a voxel size of 78 x 156 x 2000 microm. Images were also obtained with a) changed frequency-encoding directions; b) changed readout gradient strength; and c) a varied number of phase-encoding steps. T2 mapping was performed with angular variations. Artificial landmarks allowed accurate comparison between the laminae on MR images and the histologic zones. No alterations of the laminae were noted by changing the frequency gradient direction. Altering readout gradient strengths did not show a difference in the thickness of the laminae, and increasing the phase-encoding steps resulted in a more distinct laminated appearance, ruling out chemical shift, susceptibility, and truncation artifacts. The T2 mapping profile showed an anisotropic angular dependency from the magic angle effect. In conclusion, the laminated appearance of articular cartilage on spin-echo and fast spin-echo MR images correlated with the histologic zones rather than MR artifacts.

Animals↗

Germline mutations in a polycytosine repeat of the hMSH6 gene in Korean hereditary nonpolyposis colorectal cancer.

Somatic mutations within a mononucleotide repeat sequence present in the hMSH6 and hMSH3 coding regions have been frequently observed in various human cancer tissues and cell lines showing genomic instability. However, relatively few germline mutations of the repeat sequence have been identified. Two germline mutations in the hMSH6 region have been reported in hereditary nonpolyposis colorectal cancer (HNPCC); however, no germline mutations in the hMSH3 gene have been reported yet. To investigate genetic alterations within an 8 bp polycytosine repeat of the hMSH6 gene and an 8-bp polyadenine repeat of the hMSH3 gene, we amplified the mononucleotide repeat sequences of 35 HNPCC patients, 44 patients suspected of having HNPCC who did not fulfill the criteria of the International Collaborative Group on HNPCC, and 45 patients with sporadic early-onset colorectal cancer who developed colorectal cancer before the age of 40 years without any family history of colorectal cancer. Genetic alteration of the repeat sequence of the hMSH3 gene was not observed, whereas germline frame-shift mutations (one C insertion) in the hMSH6 gene were found in two of the 44 suspected HNPCC patient in whom germline mutations of hMSH2 or hMLH1 had not been detected. An identical frameshift mutation was also observed in another affected member of a suspected HNPCC family. These results suggest that the mutation of hMSH6 is responsible for tumorigenesis in minor groups of suspected HNPCC patients.

Adult↗

Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses.

Hereditary multiple exostoses (EXT) is an autosomal dominantly inherited disease characterized by the formation of cartilage-capped prominences (exostoses) that develop from the juxtaepiphyseal regions of the long bones. Recently, EXT1 and EXT2 genes were cloned and germline mutations of EXT1 and EXT2 were identified in EXT families. In this study, we performed a mutational analysis of EXT1 and EXT2 genes in eight unrelated Korean EXT families by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing. As a result, we were able to identify one family (SNU-OC3) with the EXT1 mutation and another family (SNU-OC15) with the EXT2 mutation. The EXT1 mutation was a 10-bp deletion at the 3' end of exon 5 (CTAATTTAGg) including the splice site of this exon. The EXT2 mutation identified in the SNU-OC15 family was a missense mutation at codon 85 of exon 2 (TGC-->CGC), resulting in an amino acid change from cysteine to arginine. This missense mutation cosegregated with the disease phenotype in this family, suggesting that it is the disease-causing mutation. These two mutations identified in EXT1 and EXT2 are novel ones.

Child, Preschool↗

Eradication of Helicobacter pylori infection did not lead to cure of duodenal mucosa-associated lymphoid tissue lymphoma.

Duodenal mucosa-associated lymphoid tissue (MALT) lymphoma is very rare, and little is known about its clinical course or association with Helicobacter pylori infection. This report describes the case of a 76-year-old man with a polypoid mass in the duodenal bulb, diagnosed as low-grade MALT lymphoma. H. pylori infection in the duodenal mucosa was confirmed by histology with silver stain. Endoscopic examination showed that the gross lesion regressed after the eradication of H. pylori despite its histopathologic persistence. Ten months later, however, cervical and intraperitoneal lymphadenopathy and bone marrow involvement was observed, and the pathologic diagnosis of the cervical lymph node was identical with that of the duodenal lesion.

Aged↗

The role of radiotherapy in the treatment of aggressive fibromatosis.

Aggressive fibromatosis is a rare benign soft tissue tumor that is difficult to cure because of its infiltrative nature and high tendency to recur locally. The authors retrospectively analyzed 20 patients with histologically-confirmed fibromatosis. All patients underwent surgery with a wide or marginal margin. Five (25%) cases with histologically-negative margins had recurred. External beam radiotherapy was administered to patients whose margins were positive or who had local recurrence. However, out of concern for safety, radiotherapy was not given to two babies and a reproductive-aged woman. The average dose was 5,020 cGy. During the follow-up (mean 32.6 months), all the patients undergoing radiotherapy showed no evidence of local recurrence. A wide local excision has traditionally been the treatment of choice. However, postoperative radiotherapy could be an effective measure for preventing local recurrence in patients with a histologically-positive surgical margin and recurrence independent of any signs of relapse.

Adolescent↗

Chemical sulfonation and anticoagulant activity of acharan sulfate.

Acharan sulfate is a glycosaminoglycan prepared from the giant African snail, Achatina fulica. This polysaccharide has a repeating disaccharide structure of -->4)-2-deoxy-2-acetamido-alpha-D-glucopyranose (1-->4)-2-sulfo-alpha-L-idopyranosyluronic acid (1-->). Its structure is related to heparin and heparan sulfate but is distinctly different from all known members of these classes of glycosaminoglycans. Because of its structural similarities to heparin, chemically modified acharan sulfate was studied to understand the chemical structure effected its anticoagulant activity. After de-N-acetylation, acharan sulfate was N-sulfonated using either chlorosulfonic acid-pyridine or sulfur trioxide-trimethylamine complex. The sulfate level in these products ranged from 22 to 24%(w/w), significantly less than that of heparin at 36%. The molecular weight of both N-sulfoacharan sulfates were comparable with that of heparin. In vitro anticoagulant activity assays showed that N-sulfoacharan sulfate derivatives were moderately active for the inhibition of thrombin and neither product showed any measurable anti-factor Xa activity. The differences in the activities of N-sulfoacharan sulfates produced by these two methods are probably ascribable to a small level of concomitant O-sulfonation obtained when using chlorosulfonic acid-pyridine.

Animals↗

Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG #77-06, a phase III study for T1BN0M0 (A2) and T2N0M0 (B) prostate carcinoma.

PURPOSE: To evaluate survival and time to metastatic disease in patients treated for localized prostatic carcinoma in a Phase III radiotherapy (RT) protocol, Radiation Therapy Oncology Group (RTOG) 77-06. Patients with T18N0M0 (A2) or T2N0M0 (B) disease after lymphangiogram (LAG) or staging laparotomy (SL) were randomized between prophylactic radiation to the pelvic lymph nodes and prostatic bed vs. prostatic bed alone. The outcome of both treatment arms, as well as a comparison of the LAG group, to that of the SL group, are updated. METHODS AND MATERIALS: A total of 449 eligible males were entered into RTOG protocol 7706 between 1978 and 1983. Lymph node staging was mandatory but at the physician's discretion; 117 (26%) patients had SL, while 332 (74%) had LAG. Follow-up was a median of 12 years and a maximum of 16 years. For those randomized to receive prophylactic pelvic lymph nodal irradiation, 45 Gy of megavoltage RT was delivered via multiple portals in 4.5-5 weeks, while all patients received 65 Gy in 6.5-8 weeks to the prostatic bed. RESULTS: There was no significant difference in survival whether treatment was administered to the prostate or prostate and pelvic lymph nodes. The SL group had greater 12-year survival than the LAG group (48% vs. 38%, p = 0.02). Disease-free survival was statistically significant, with 38% for the SL group vs. 26% for the LAG group (p = 0.003). Bone metastasis was less common in the SL group (14%) than the LAG group (27%) (p = 0.003). CONCLUSION: At 12-year median follow-up, there still was no survival difference in those patients treated prophylactically to the pelvic nodes and prostatic bed vs. the prostatic bed alone. Those patients not surgically staged with only LAG for lymph node evaluation were less accurately staged, as reflected by a statistically significant reduced survival and earlier metastases.

Aged↗

Degradation of acharan sulfate and heparin by Bacteroides stercoris HJ-15, a human intestinal bacterium.

When glycosaminoglycan (GAG)-degrading enzymes were measured in normal human stool suspensions, all 5 tested different stools degraded titrable heparin and acharan sulfate. GAG-degrading bacteria were screened from the isolates of human stools. Among them, HJ-15 had the most potent activities of heparinases (GAGs-degrading enzymes). However, HJ-15 produced the enzyme even if in the media without heparin. Acharan sulfate lyase was induced by acharan sulfate and heparin. Heparinase production was also induced by these GAGs. These enzymes, acharan sulfate lyase and heparinase, were produced in exponential and stationary phase of HJ-15 growth, respectively. Optimal pHs of the acharan sulfate lyase and heparinase activities were 7.2 and 7.5, respectively. The biochemical properties of HJ-15 was similar to those of B. stercoris. However, difference from B. stercoris was utilization of raffinose. This HJ-15 also degraded chondroitin sulfates A and C.

Bacteroides↗

Screening and isolation of antibiotic resistance inhibitors from herb materials-resistance inhibition of volatile components of Korean aromatic herbs.

The resistance inhibitory activities of 54 odorant mixtures (essential oil) from 41 Korean aromatic herbs were tested against multi-drug resistant Staphylococcus aureus SA2, which has resistances to 10 usual antibiotics including chloramphenicol. As results, combinations of 28 kinds of samples from 21 herbs and chloramphenicol have resistance inhibitory activities in dose dependent manner.

Chloramphenicol Resistance↗

Absence or decreased levels of the hMLH1 protein in human gastric carcinoma cell lines: implication of hMLH1 in alkylation tolerance.

Defective hMLH1 function has been increasingly associated with acquired cellular resistance to DNA alkylation damage in human colorectal and endometrial cancer cells. To investigate the relationship between the DNA alkylation tolerance and the hMLH1 status in human gastric carcinoma cells, we determined the cellular response to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the mutational changes, and the expression of hMLH1 in 11 human gastric carcinoma cell lines. Of 11 cell lines, 4 (SNU-5, -16, -620, and -719) were sensitive, whereas 7 (SNU-1, -216, -484, -520, -601, -638, and -668) were resistant to the cytotoxic effect of MNNG. As determined by Western analysis, it was evident that all the MNNG-resistant cell lines except one (SNU-601) produced very low or undetectable levels of hMLH1 protein compared to the MNNG-sensitive cell lines. A homozygous non-sense mutation that resulted in truncated protein was found in one MNNG-resistant cell line (SNU-1). Therefore, to determine whether the sensitivity of cells to MNNG can be restored by exogenous expression of hMLH1 protein, wild-type hMLH1 cDNA was introduced into the MNNG-resistant cells (SNU-1). The cytotoxicity test showed that expression of exogenous wild-type hMLH1 protein caused an increase in sensitivity to the cytotoxic effect of MNNG. This restoration was confirmed by an increase in the cell population containing less than the G1 amount of DNA (cell death) in the wild-type hMLH1-transfected cells, as determined by flow cytometry analysis. Together our results suggest that (1) the absence or decreased level of wild-type hMLH1 protein may be a frequent event in the human gastric carcinoma cell lines, (2) such alterations in the hMLH1 protein are closely associated with the MNNG tolerance in the human gastric carcinoma cell lines, and (3) the hMLH1 protein participates not only in the repair of DNA mismatches but also in the mechanism of escape from the cytotoxic effects of DNA alkylation damage.

Adaptor Proteins, Signal Transducing↗

Characterization of a Bacteroides species from human intestine that degrades glycosaminoglycans.

Polysaccharide lyases that can degrade glycosaminoglycans (GAGs) were identified in an anaerobic strain living in the human intestine. The strain was isolated from the stool of a healthy male and identified as Bacteroides sp. strain HJ-15. A detailed taxonomical study indicated the species is a strain of Bacteroides stercoris. The isolate was cultured and the polysaccharide lyase activity was partially purified. This enzyme preparation could act on GAGs containing either glucosamine or galactosamine suggesting the presence of both heparinases and chondroitinases. Various GAGs were incubated with the partially purified enzyme and the products formed were analyzed by strong anion-exchange high performance liquid chromatography and proton nuclear magnetic resonance spectroscopy. These studies demonstrated the presence of at least two types of polysaccharide lyases: heparin lyase and chondroitin sulfate lyase. The eliminative mechanism of these lyase enzymes was confirmed through the isolation of unsaturated disaccharide products. The heparin lyase acted on both heparin and acharan sulfate, a GAG recently isolated from Achatina fulica. The Bacteroides chondroitin lyase, acted on chondroitin sulfates A, B (dermatan sulfate), and C, resembling chondroitin lyase ABC. The presence of a GAG-degrading organism in human intestine may pose problems for the effective oral administration of GAG drugs.

Anaerobiosis↗

Minimizing artifacts caused by metallic implants at MR imaging: experimental and clinical studies.

OBJECTIVE: The purpose of this study was to investigate the effect of metallic implant positioning on MR imaging artifacts, to determine the optimal imaging conditions for minimizing artifacts, and to show the usefulness of artifact-minimizing methods in imaging of the knee. MATERIALS AND METHODS: Using MR images of experimental phantoms (titanium alloy and stainless steel screws), we compared the magnitude of metal-induced artifacts for various pulse sequences, different imaging parameters for the fast spin-echo sequence, and different imaging parameters for several incremental angles between the long axis of the screw and the direction of the main magnetic field. In clinical MR imaging of knees with metallic implants (n = 19), we assessed geometric distortion of anatomic structures to compare the influence of different pulse sequences (n = 19), frequency-encoding directions (n = 7), and knee positions (n = 15). RESULTS: Titanium alloy screws consistently produced smaller artifacts than did stainless steel screws. In experimental MR studies, artifacts were reduced with fast spin-echo sequences, with a screw orientation as closely parallel to the main magnetic field as possible, and, particularly, with smaller voxels that correlated positively with artifact size (R2 = .88, p < .01). In clinical MR studies, fast spin-echo MR imaging obscured articular structures less than did spin-echo imaging (8/19 patients). In particular, the anterior-posterior frequency-encoding direction (3/7 patients) and the flexion position of the knee (5/15 patients) were effective in reducing artifacts. CONCLUSION: MR artifacts can be minimized by optimally positioning in the magnet subjects with metallic implants and by choosing fast spin-echo sequences with an anterior-posterior frequency-encoding direction and the smallest voxel size.

Adult↗

Nocardia osteomyelitis in a pachymeningitis patient: an example of a difficult case to treat with antimicrobial agents.

Antimicrobial agents played a miraculous role in the treatment of bacterial infections until resistant bacteria became widespread. Besides antimicrobial-resistant bacteria, many factors can influence the cure of infection. Nocardia infection may be a good example which is difficult to cure with antimicrobial agents alone. A 66-year-old man developed soft tissue infection of the right buttock and thigh. He was given prednisolone and azathioprine for pachymeningitis 3 months prior to admission. Despite surgical and antimicrobial treatment (sulfamethoxazole-trimethoprim), the infection spread to the femur and osteomyelitis developed. The case showed that treatment of bacterial infection is not always as successful as was once thought because recent isolates of bacteria are more often resistant to various antimicrobial agents, intracellular parasites are difficult to eliminate even with the active drug in vitro, and infections in some sites such as bone are refractory to treatment especially when the patient is in a compromised state. In conclusion, for the treatment of infections, clinicians need to rely on laboratory tests more than before and have to consider the influence of various host factors.

Aged↗

Growth suppression mediated by transfection of wild-type hMLH1 in human cancer cells expressing endogenous truncated hMLH1 protein.

Many genes that are frequently mutated in human cancer are known to be involved in the control of normal cellular proliferation. One of the genes involved in DNA mismatch repair is hMLH1, defective mutations of which are found in some familial and various sporadic cancers. Although the DNA mismatch repair activity of hMLH1 has been identified, other biological functions of hMLH1 have not been well investigated. To investigate the effect of wild-type hMLH1 in cellular proliferation, wild-type hMLH1 cDNA was introduced into human colorectal carcinoma cell line HCT116 and human gastric carcinoma cell line SNU-1, each containing a homozygous non-sense mutation at codon 252 and 226 in hMLH1, repectively. The hMLH1-transfected stable clones showed mRNA and protein expression of transfected hMLH1. Three in vitro cell growth experiments demonstrated that compared with parental and vector-transfected control counterparts, both hMLH1-transfected HCT116 and SNU-1 clones displayed: i) decreased cellular proliferation; ii) a significant decrease in the rate of DNA synthesis and iii) a dramatic reduction of anchorage-independence and the size of colonies in semisolid medium. In addition to DNA repair activity, these results suggest that hMLH1 may play a role in the negative regulation of HCT116 and SNU-1 cell growth.

Adaptor Proteins, Signal Transducing↗

Multiple neurilemomas. A case report.

Multiple neurilemomas in diverse locations of the body developed in a 53-year-old woman. The patient had multiple neurilemomas which occurred in the thoracic spine, lumbar spine, retroperitoneal sympathetic chain, sacral nerve root, femoral nerve, both sciatic nerves, radial nerve, and ulnar nerve without evidence of Von Recklinghausen's disease. This is the first well documented report on multiple neurilemomas with whole body distribution.

Bone Neoplasms↗

If you 'watch and wait,' prostate cancer may progress dramatically.

PURPOSE: Observation has been proposed as an option for localized prostate cancer. However, most series reporting on 'watch and wait' include patients treated by TUR or hormones that may affect results. We retrospectively reviewed the natural history of truly untreated prostate cancer and report the outcome for these patients. METHODS AND MATERIALS: From 1976 to 1992, 34 patients of median age 70 years (range 56-88) with biopsy proven localized adenocarcinoma of the prostate refused therapy. All had negative bone scan and none underwent TUR or hormone treatment. No patient was lost to follow-up (median 76 months). Failure patterns and survival were analyzed. RESULTS: At diagnosis 27 patients had palpable nodules (T2), of which 13 were well differentiated and 14 moderately differentiated. Seven had moderately differentiated T3 lesions. Mild prostatitis including nocturia, hesistancy, and urgency were reported in 16 T2 and 6 T3 patients. Within 36 months, local progression requiring therapy occurred in all T3, all T2 moderate and 5 of 13 T2 well-differentiated patients. Systemic progression occurred in 6 of 7 T3, 9 of 14 T2 (mod), and 2 of 13 T2 (well) patients. Overall 59% are alive, 26% succumbed to prostate carcinoma and 15% to other causes. CONCLUSION: Observation results in a high rate of local progression requiring intervention (77%) and excessive systemic disease development (50%) for patients with clinically palpable disease. Perhaps this strategy is viable for earlier stage lesions detected by PSA but it must be tested in a rigorous fashion before accepted.

Adenocarcinoma↗