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Biomedical subjects

J C Kim

Publications and source records attributed to J C Kim.

At least 91 records · Page 5Linked to original sources
PubMed2000

Allelic loss at SMAD4 in polyps from juvenile polyposis patients and use of fluorescence in situ hybridization to demonstrate clonal origin of the epithelium.

Juvenile polyposis syndrome (JPS; Online Mendelian Inheritance in Man2 174900) is a rare Mendelian disorder in which individuals have typical hamartomatous polyps within the gastrointestinal tract. The stromal element of the polyps has classically been thought to be the proliferative component, although epithelial malignancies (largely gastrointestinal cancers) occur more frequently than expected in JPS patients. Germ-line mutations in SMAD4 (DPC4) account for about a third of JPS cases. It has been postulated that the apparent paradox of a stromal lesion predisposing to epithelial malignancy can be resolved by the "landscaper" effect: an abnormal stromal environment affects the development of adjacent epithelial cells, and the resulting regeneration of damaged epithelium leads to an increased risk of cancer. We have found allele loss at the SMAD4 locus on 18q in polyps from JPS individuals with a germ-line SMAD4 mutation, showing that SMAD4 is acting as a tumor suppressor gene in JPS polyps, as it does in sporadic cancers of the gastrointestinal tract. Interphase fluorescence in situ hybridization showed deletion of one copy of SMAD4 in the epithelial component of JPS polyps, but not in the inflammatory infiltrate. Fluorescence in situ hybridization also suggested that a single copy of SMAD4 was present in stromal fibroblasts of JPS polyps. Thus, biallelic inactivation of SMAD4 occurs in both the epithelium and some of the stromal cells in these lesions, suggesting a common clonal origin. Epithelial malignancies almost certainly develop in juvenile polyposis through direct malignant progression of the epithelial component of the hamartomas. SMAD4/DPC4 probably acts as a "gatekeeper" tumor suppressor in juvenile polyps, and there is no need to invoke a "landscaper hypothesis."

Adenomatous Polyposis Coli↗
PubMed2000

No evidence of Peutz-Jeghers syndrome gene LKB1 involvement in left-sided colorectal carcinomas.

LKB1 serine/threonine kinase is a gene for Peutz-Jeghers cancer predisposition syndrome. Most studies have detected a low frequency of LKB1 defects in sporadic cancer. A notable exception is a recent report describing frequent, mostly missense type, LKB1 mutations in Korean distal colorectal tumors. To clarify the role of LKB1 in colon cancer, we scrutinized 50 left-sided Korean and Finnish specimens. No somatic mutations were found. The seven Korean somatic missense mutations reported previously were functionally analyzed, and five were found not to alter LKB1 kinase activity. One of these changes was found to be a germ-line polymorphism. LKB1 involvement in distal colorectal cancer is not common.

AMP-Activated Protein Kinase Kinases↗
PubMed2000

Kinetics and inhibition of cyclomaltodextrinase from alkalophilic Bacillus sp. I-5.

The cyclomaltodextrinase from alkalophilic Bacillus sp. I-5 (CDase I-5) was expressed in Escherichia coli and the purified enzyme was used for characterization of the enzyme action. The hydrolysis products were monitored by both HPLC and high-performance ion chromatography analysis that enable the kinetic analysis of the cyclomaltodextrin (CD)-degrading reaction. Analysis of the kinetics of cyclomaltodextrin hydrolysis by CDase I-5 indicated that ring-opening of the cyclomaltodextrin was the major limiting step and that CDase I-5 preferentially degraded the linear maltodextrin chain by removing the maltose unit. The substrate binding affinity of the enzyme was almost same for those of cyclomaltodextrins while the rate of ring-opening was the fastest for cyclomaltoheptaose. Acarbose and methyl 6-amino-6-deoxy-alpha-d-glucopyranoside were relatively strong competitive inhibitors with K(i) values of 1.24 x 10(-3) and 8.44 x 10(-1) mM, respectively. Both inhibitors are likely to inhibit the ring-opening step of the CD degradation reaction.

Acarbose↗
PubMed2000

Novel cell proliferation marker for identification of a growth center in the developing human cricoid.

BACKGROUND: Developmental histomorphology of the human cricoid cartilage has never been well described. Regional growth centers in the cricoid have been hypothesized, but have never been demonstrated in histological sections. OBJECTIVES: To apply Mib-1 immunostaining, a monoclonal antibody directed at a nuclear proliferation marker, in human cricoids to identify a growth center and to study the changing histomorphology of the developing cricoid. DESIGN: Immunohistochemical Mib-1 studies were performed on postmortem cricoid sections of 2 fetuses (gestational age, 18.5 and 33 weeks), 1 newborn (full term, 41 weeks), and 3 children (aged 1, 4, and 13 years, respectively). Cell counts, surface areas, and organizational patterns of the chondrocytes were studied and described in hemotoxylin-eosin-stained sections. RESULTS: Differential Mib-1 staining was found. The 18.5-week fetus showed diffuse cell proliferation throughout the cricoid. The cricoid sections of the 33-week fetus and 1-year-old child revealed a distinct ring of proliferation in the outer third of the cricoid ring. The 4- and 13-year-old exhibited no cell proliferation. Histomorphologically, with increasing age came chondrocyte hypertrophy, decreasing cell count per standard square, and increasing organization from a scattered to radial columnar pattern. CONCLUSIONS: Growth of the cricoid involves a diffuse pattern of cell proliferation throughout the cricoid in fetal tissue. At term and until age 1 year, the region of proliferation is more restricted to the outer subperichondrial surface. By age 4 years, cell proliferation has stopped. Histomorphologic changes in the developing cricoid include decreasing cell counts per standard unit area, but increasing surface area with age. The aging chondrocytes develop an increasingly organized layout to form a radially arranged columnar pattern similar to that in the growth plate of the developing limb bud.

Adolescent↗
PubMed2000

A TGF-beta-inducible cell adhesion molecule, betaig-h3, is downregulated in melorheostosis and involved in osteogenesis.

Melorheostosis is a rare bone disease characterized by linear hyperostosis and associated soft tissue abnormalities. The skin overlying the involved bone lesion is often tense, shiny, erythematous, and scleodermatous. In order to look for genes differentially expressed between the normal and involved skin, we cultured skin fibroblasts from the skin lesions of several afflicted patients, and identified differentially expressed genes by reverse dot-blot hybridization. We found that the genes human TGF-beta-induced gene product (betaig-h3), osteoblast-specific factor 2, osteonectin, fibronectin, and type I collagen were all downregulated in the affected skin fibroblasts, with betaig-h3 the most significantly affected. The expression of betaig-h3 was induced by TGF-beta in both affected and normal fibroblasts. In an effort to determine the mechanism of bone and skin abnormalities in melorheostosis, we made recombinant betaig-h3. Both immobilized and soluble recombinant betaig-h3 proteins with or without an RGD motif inhibited bone nodule formation of osteoblasts in vitro. Taken together, our results suggest that altered expression of several adhesion proteins may contribute to the development of hyperostosis and concomitant soft tissue abnormalities of melorheostosis, with betaig-h3 in particular playing an important role in osteogenesis.

Animals↗
PubMed2000

Effects of partial bladder outlet obstruction and its relief on types I and III collagen and detrusor contractility in the rat.

Bladder outlet obstruction induces a rapid hypertrophy characterized by increased bladder mass and collagen deposition. An increase in collagen is likely to reduce the contractility and compliance of bladder wall. This study was undertaken to investigate the effects of partial bladder outlet obstruction and its relief on types I and III collagen, and the relationship between detrusor contractility and collagen types. A total of 40 female rats was used for experiment and divided into one control, one obstruction, and three recovery groups. The contractility to field stimulation was recorded; total collagen and collagen concentration were quantified. The localization of types I and III collagen and the expression of pro-alpha1(I) and alpha1(III) collagen mRNA were determined by immunohistochemical staining and Northern blot hybridization, respectively. Contractile response to field stimulation was reduced after obstruction and recovered following relief. The total amount of collagen increased after obstruction and decreased after relief; however, collagen concentration decreased after obstruction and increased following relief. Contractility correlated negatively with total collagen but positively with collagen concentration. The protein deposition of types I and III collagen was localized in lamina propria and muscle bundles in all groups. The expression of types I and III collagen gene was up regulated after obstruction, but down regulated after relief. Negative correlation between contractility and gene expressions of collagen types was significant. These data suggest that the change in localization and quantity of collagen types leads to morphologic changes of bladder and can have an impact on the contractility of detrusor. Neurourol. Urodynam. 19:29-42, 2000.

Animals↗
PubMed2000

Amniotic membrane patching promotes healing and inhibits proteinase activity on wound healing following acute corneal alkali burn.

Amniotic membrane (AM) contains basement membrane components and various proteinase inhibitors. Furthermore, when used as a graft, the basement membrane of AM could block inflammatory insults to a damaged corneal surface. Thus, we evaluated whether amniotic membrane patching could promote the healing process by inhibiting proteolytic damage. Alkali wounds were inflicted on the central corneas of rabbits by applying a round filter paper, 6.0 mm in diameter, soaked in 1 N NaOH for 30 sec. Amniotic membrane patching was performed over the perilimbal sclera immediately after wounding. A total of 115 rabbits were divided into four groups: (1) immediately covered by AM with the amnion cell side down up to the perilimbal sclera (n =26); (2) covered by AM with the stromal side down up to the perilimbal sclera (n =19); (3) anchored to the fornix (n =29); and (4) uncovered as a control (n =41). AM was removed 3 days postoperatively. During follow-ups, epithelial defects, corneal thickness and its opacity of each eye were measured. Some corneas were removed for histopathologic studies and for proteinase activity assay and zymography. The epithelial healing was faster and the corneal thickness was thicker in all three AM-covered groups than in the control (P<0.05). No significant difference was found between covered and anchored groups (P>0.05). Corneal opacity was least in the amnion cell side down group. Infiltration of polymorphonuclear leukocytes (PMNs) was much less in AM-covered groups than in the control. Pathological results were associated with zymographic findings, which revealed much higher proteinase activity in uncovered group than AM-covered groups. Immediate intervention for acute alkali burns with AM as a temporary patch promotes wound healing by inhibiting proteinase activity and PMNs infiltration.

Animals↗
PubMed2000

Embryo lethality and teratogenicity of a new fluoroquinolone antibacterial DW-116 in rats.

DW-116, 1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-l-piperazinyl)-1, 4-dihydro-4-oxoquinolone-3-carboxylic acid hydrochloride, is a newly developed fluoroquinolone antibacterial. The potential of DW-116 to induce developmental toxicity was, investigated in Sprague-Dawley rats. DW-116 was administered by gavage to pregnant rats from days 6 to 16 of gestation at dose levels of 0, 31.3, 125, and 500 mg/kg per day. All dams were subjected to caesarean section on day 20 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. At 500 mg/kg, toxic effects including clinical signs of toxicity, suppressed body weight and decreased food intake were found in dams. An increase in the resorption rate, a decrease in the litter size, a reduction in the fetal weight, and a decrease in the placental weight were also seen. In addition, various types of external, visceral, and skeletal malformations occurred at an incidence of 17.9, 74.2 and 8.3%, respectively. Characteristic malformations included oedema, cleft palate, dilated cerebral ventricle, hypoplasia of lung and ventricular septum defect. A dramatic increase in the incidence of skeletal variations (55.6%) and retardations (94.4%) and a decrease in the number of ossification centres of sternebra, metacarpals, metatarsals and sacrocaudal vertebra were also observed. At 125 mg/kg, a reduction in the placental weight and an increase in the incidence of skeletal variations were found. There were no signs of maternal toxicity or embryotoxicity at 31.3 mg/kg. These results indicate that the fluoroquinolone antibacterial DW-116 is embryotoxic and teratogenic at minimally maternally toxic dose and is minimally embryotoxic at nonmaternally toxic dose in rats.

Abnormalities, Drug-Induced↗
PubMed2000

Efficiency of combined colonoscopy and computed tomography for diagnosis of colonic actinomycosis: a retrospective evaluation of eight consecutive patients.

The preoperative diagnosis of colonic actinomycosis is accurate in fewer than 20% of patients. Colonoscopy and computed tomography (CT) findings were analyzed to ascertain their diagnostic value and their role in determining therapeutic modality and outcome. Before and after treatment we retrospectively evaluated eight consecutive patients with colonic actinomycosis, all of whom were women with a previous history of intrauterine contraceptive device use. Median follow-up period was 20 months (7-57). Localized nodules were found in all cases by colonoscopy; half of these nodules included umbilication at the apex. The colonic mucosa demonstrated normal to moderate inflammation as well as hyperemia and edema. Mucosal ulceration was found in only one case. All cases showed some degree of stenosis. These findings differ from those in other inflammatory or neoplastic diseases of the colon. Abdominopelvic CT revealed extramural involvement of heterogeneous lesions all cases. Contrast enhancement also indicated severe thickening of the colonic wall (7-20 mm) with focal and dense enhancement in six cases. Seven of eight patients required surgery for diagnostic or therapeutic purposes. Complete resolution was determined using both colonoscopy and CT. As more than half of these cases could have been safely managed using an adequate antibiotic treatment, diagnostic studies indicating a high likelihood of colonic actinomycosis should be evaluated to avoid unnecessary surgeries carried out for diagnostic purposes. A combination of colonoscopy and CT appears to be important for both diagnosis and management because of their compensatory findings of mucosal and extramucosal lesions, respectively.

Actinomycosis↗
PubMed2000

Ureteroscopic endopyelotomy in the treatment of patients with ureteropelvic junction obstruction.

OBJECTIVES: To investigate the effectiveness and morbidity of ureteroscopic endopyelotomy in adults with ureteropelvic junction (UPJ) obstruction. METHODS: Twenty-two patients (13 women, 9 men) with a mean age of 44 years (range 18 to 86) underwent retrograde ureteroscopic endopyelotomy in the treatment of primary (n = 18) or secondary (n = 4) UPJ obstruction. All procedures were performed using a 6F to 8.5F semirigid ureteroscope with either a 3F electrocautery probe (n = 16) or a 365-microm holmium laser fiber (n = 6). Postoperatively, a tapered 14/7F endoureterotomy stent (n = 11) or standard 7F to 8F double pigtail stent (n = 11) was left in place for 6 to 7 weeks. Radiographic follow-up was obtained using intravenous urography or renal scintigraphy. RESULTS: With a median follow-up of 20.5 months, the success rate was 82% (18 of 22 patients). Follow-up of at least 6 and 12 months was available in 21 (95%) and 17 (77%) of 22 patients, respectively. The mean operative duration was 63 minutes, and all but 1 patient was hospitalized for less than 24 hours. No bleeding complications or other serious morbidity were encountered. No difference in treatment outcome was found on the basis of the size of the stent placed postoperatively, the incision type (cautery versus laser), or the etiology of the obstruction. CONCLUSIONS: Ureteroscopic endopyelotomy is an effective, minimally invasive treatment option for patients with primary or secondary UPJ obstruction.

Adolescent↗
PubMed2000

Germline mutations of the STK11 gene in Korean Peutz-Jeghers syndrome patients.

Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation, with an increased risk for various neoplasms, including gastrointestinal cancer. Recently, the PJS gene encoding the serine/threonine kinase STK11 (also named LKB1) was mapped to chromosome 19p13.3, and germline mutations were identified in PJS patients. We screened a total of ten Korean PJS patients (nine sporadic cases and one familial case including two patients) to investigate the germline mutations of the STK11 gene. By polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing analysis, three kinds of mis-sense mutation and a frame-shift mutation were identified: codon 232 (TCC to CCC) in exon 5, codon 256 (GAA to GCA) in exon 6, codon 324 (CCG to CTG) in exon 8, and a guanine insertion at codon 342 resulting in a premature stop codon in exon 8. These mis-sense variants were not detected in 100 control DNA samples. Furthermore, we found an intronic mutation at the dinucleotide sequence of a splice-acceptor site: a one base substitution from AG to CG in intron 1, which may cause aberrant splicing. Most reported germline mutations of the STK11 gene in PJS patients were frame-shift or non-sense mutations resulting in truncated proteins. Together, these findings indicate that germline mis-sense mutations of the STK11 gene are found in PJS patients in addition to truncating mutations. The effects of these mutations on protein function require further examination. In summary, we found germline mutations of the STK11 gene in five out of ten Korean PJS patients.

AMP-Activated Protein Kinase Kinases↗
PubMed2000

Cephalometric variables as predictors of Class II treatment outcome.

Cephalometric analysis of skeletodental features is accepted as an integral part of orthodontic diagnosis and treatment planning. This assumes that diagnostic cephalometric variables affect prognosis and thus help reduce malocclusion severity, which is the aim of orthodontic treatment. The aim of this study was to assess the predictive value of 41 commonly used cephalometric parameters with regard to pretreatment severity and treatment outcomes. Pretreatment severity was assessed by using the Peer Assessment Rating (PAR) occlusal index, an instrument that has been shown to be valid and reliable. Treatment outcomes consisted of (1) posttreatment malocclusion severity (post-PAR), (2) relative improvement (percent PAR reduction), and (3) treatment duration. Complete records, including cephalograms, of 223 treated Class II cases were analyzed by means of separate multiple linear regression models. Each of the outcome variables and the pretreatment severity served as the respective dependent variables, and the cephalometric parameters served as the independent or predictor variables. The cephalometric parameters explained 39.2% of the pretreatment severity variance, 17. 9% of posttreatment severity variance, 15.7% of relative treatment improvement variance, and 20.0% of treatment duration variance.

Analysis of Variance↗
PubMed2000

The role of nitric oxide in experimental allergic conjunctivitis.

PURPOSE: To evaluate the role of nitric oxide (NO) in the pathogenesis of allergic conjunctivitis and the effect of NO-synthase (NOS) inhibitors. METHODS: The experimental allergic conjunctivitis was provoked in rabbits and healthy human volunteers by mast cell activators (codeine phosphate, 2.5 mg/mL; compound 48/80, 50 mg/mL; and lipopolysaccharide, 10 ng/eye). NOS inhibitors (aminoguanidine [AG], 1.5%, or N(G)-nitro-L-arginine methyl ester [L-NAME], 200 microg/eye) were applied as a pretreatment. In a rabbit model, concentrations of nitrite plus nitrate in the tear were measured colorimetrically using the Griess reaction after 0.5, 1.5, 3, 6, and 9 h. Immunohistochemical study for NOS was performed. The clinical scoring was performed in human volunteers. The vascular permeability was determined by measuring the albumin content in the tear of the challenged human eyes after 1 h. RESULTS: After the instillation of mast cell activator, the NO level and clinical symptoms were markedly increased within 1.5 h. The NOS inhibitors suppressed the NO level. Vascular permeability was also increased in the activator-treated group. The NO-synthase immunoreactivity has been detected in the conjunctival subepithelial area and stroma for brain and endothelial isoform. L-NAME significantly reduces the immunoreactivity for NOS. CONCLUSION: These results suggest that the expression of NOS mainly contributes to the allergic symptoms. Therefore, NO is an important factor in the induction and progress of the allergic reaction to ocular surface. The NOS inhibitors may have a beneficial effect for allergic conjunctivitis.

Adult↗
PubMed2000

Recombinant kringle 1-3 of plasminogen inhibits rabbit corneal angiogenesis induced by angiogenin.

PURPOSE: Angiostatin is a potent angiogenesis inhibitor that has been identified as a cryptic fragment of plasminogen molecule containing the first four kringle domain. Angiogenin, a 14-kDa monomeric protein, a potent blood vessel inducer, is expressed in tumors and present in mammalian plasma. The purpose of this study was to determine whether recombinant kringle 1-3 (rKI-3) of human plasminogen could interfere with angiogenesis induced by angiogenin and to evaluate the role of angiogenin in corneal angiogenesis in rabbit. METHODS: A Hydron polymer pellet containing 2.0 microg of angiogenin was implanted intrastromally into the superior cornea of each of 44 rabbit eyes. All eyes received an intrastromal pellet and were randomized into either one group treated with 12.5 microg of rKI-3 (n = 25) or the other group treated with phosphate-buffered saline (PBS; n = 19). Both pellets were positioned in parallel at the site 1.2 mm from the superior limbus. Two masked observers kept the angiogenesis score daily, based on the number and the length of new vessels. The corneas with induced angiogenesis also were examined histologically. RESULTS: On the third day of the angiogenin pellets implantation, the eye treated with rKI-3 had less angiogenesis (mean score, 4.2 +/- 6.6) than eye treated with PBS (mean score, 16.1 +/- 17.1; p < 0.05, Mann-Whitney U test). The cornea treated with PBS also showed much more leukocyte adhesion than the cornea treated with rKI-3. CONCLUSION: Recombinant kringle 1-3 appears to inhibit angiogenin-induced angiogenesis in a rabbit corneal pocket assay. Recombinant kringle 1-3 may have therapeutic potential as an antiangiogenic agent.

Angiogenesis Inducing Agents↗
PubMed2000

Identification of a calmodulin-regulated soybean Ca(2+)-ATPase (SCA1) that is located in the plasma membrane.

Ca(2)+-ATPases are key regulators of Ca(2+) ion efflux in all eukaryotes. Animal cells have two distinct families of Ca(2+) pumps, with calmodulin-stimulated pumps (type IIB pumps) found exclusively at the plasma membrane. In plants, no equivalent type IIB pump located at the plasma membrane has been identified at the molecular level, although related isoforms have been identified in non-plasma membrane locations. Here, we identify a plant cDNA, designated SCA1 (for soybean Ca(2+)-ATPase 1), that encodes Ca(2+)-ATPase and is located at the plasma membrane. The plasma membrane localization was determined by sucrose gradient and aqueous two-phase membrane fractionations and was confirmed by the localization of SCA1p tagged with a green fluorescent protein. The Ca(2+)-ATPase activity of the SCA1p was increased approximately sixfold by calmodulin (K(1/2) approximately 10 nM). Two calmodulin binding sequences were identified in the N-terminal domain. An N-terminal truncation mutant that deletes sequence through the two calmodulin binding sites was able to complement a yeast mutant (K616) that was deficient in two endogenous Ca(2+) pumps. Our results indicate that SCA1p is structurally distinct from the plasma membrane-localized Ca(2+) pump in animal cells, belonging instead to a novel family of plant type IIB pumps found in multiple subcellular locations. In plant cells from soybean, expression of this plasma membrane pump was highly and rapidly induced by salt (NaCl) stress and a fungal elicitor but not by osmotic stress.

Amino Acid Motifs↗
PubMed2000

Analysis of genetic and phenotypic heterogeneity in juvenile polyposis.

BACKGROUND: Juvenile polyposis syndrome (JPS) is characterised by gastrointestinal (GI) hamartomatous polyposis and an increased risk of GI malignancy. Juvenile polyps also occur in the Cowden (CS), Bannayan-Ruvalcaba-Riley (BRRS) and Gorlin (GS) syndromes. Diagnosing JPS can be problematic because it relies on exclusion of CS, BRRS, and GS. Germline mutations in the PTCH, PTEN and DPC4 (SMAD4) genes can cause GS, CS/BRRS, and JPS, respectively. AIMS: To examine the contribution of mutations in PTCH, PTEN, and DPC4 (SMAD4) to JPS. METHODS: Forty seven individuals from 15 families and nine apparently sporadic cases with JPS were screened for germline mutations in DPC4, PTEN, and PTCH. RESULTS: No patient had a mutation in PTEN or PTCH. Five different germline mutations were detected in DPC4; three of these were deletions, one a single base substitution creating a stop codon, and one a missense change. None of these patients had distinguishing clinical features. CONCLUSIONS: Mutations in PTEN and PTCH are unlikely to cause juvenile polyposis in the absence of clinical features indicative of CS, BRRS, or GS. A proportion of JPS patients harbour DPC4 mutations (21% in this study) but there remains uncharacterized genetic heterogeneity in JPS.

Adenomatous Polyposis Coli↗
PubMed2000

The E-cadherin gene (CDH1) variants T340A and L599V in gastric and colorectal cancer patients in Korea.

INTRODUCTION: Germline mutations in E-cadherin (CDH1) have been reported in families with early onset, diffuse gastric cancer. More recently, mutations in CDH1 have been described in colorectal cancer cell lines. AIMS: We have investigated if germline mutations in CDH1 occur among different groups of Korean gastric and colorectal cancer patients, with and without a positive family history. METHODS: We studied 131 patients and 168 normal controls (88 Korean and 80 non-Korean). Patients were divided into five groups: group I, 20 gastric cancer patients with a family history; group II, 26 colorectal cancer patients with a family history of gastric cancer (those from familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) kindred were excluded); group III, 16 HNPCC patients without identified germline mutations in hMLH1 and hMSH2; group IV, 35 gastric cancer patients without a family history; and group V, 34 colorectal cancer patients without a family history. Polymerase chain reaction, single strand conformational polymorphism analysis, direct sequencing, and genotyping for identified variants were performed. RESULTS: Several germline changes in CDH1 were found. In addition to previously described polymorphisms, we found three novel changes, two of which were missense changes (T340A and L599V). T340A was present in one patient in group III and one in group V. L599V was present in one patient in group II, in two in group III, and in one in group IV. T340A was not found in normal controls while L599V was present in two of 88 Korean controls. Patients with these variants may appear to have a tendency to early onset cancer with a positive family history, although differences in frequencies did not reach statistical significance. Genotyping results suggest that these variants might have a common origin, particularly T340A. CONCLUSION: We have described two new missense germline variants in CDH1 in various groups of Korean gastrointestinal cancer patients. Further work is required to assess if these variants increase the risk of gastrointestinal cancer.

Adolescent↗