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Biomedical subjects

J C Kim

Publications and source records attributed to J C Kim.

At least 55 records · Page 3Linked to original sources

Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes.

Juvenile polyposis syndrome (JPS) is an inherited hamartomatous-polyposis syndrome with a risk for colon cancer. JPS is a clinical diagnosis by exclusion, and, before susceptibility genes were identified, JPS could easily be confused with other inherited hamartoma syndromes, such as Bannayan-Riley-Ruvalcaba syndrome (BRRS) and Cowden syndrome (CS). Germline mutations of MADH4 (SMAD4) have been described in a variable number of probands with JPS. A series of familial and isolated European probands without MADH4 mutations were analyzed for germline mutations in BMPR1A, a member of the transforming growth-factor beta-receptor superfamily, upstream from the SMAD pathway. Overall, 10 (38%) probands were found to have germline BMPR1A mutations, 8 of which resulted in truncated receptors and 2 of which resulted in missense alterations (C124R and C376Y). Almost all available component tumors from mutation-positive cases showed loss of heterozygosity (LOH) in the BMPR1A region, whereas those from mutation-negative cases did not. One proband with CS/CS-like phenotype was also found to have a germline BMPR1A missense mutation (A338D). Thus, germline BMPR1A mutations cause a significant proportion of cases of JPS and might define a small subset of cases of CS/BRRS with specific colonic phenotype.

Abnormalities, Multiple↗

2'-Ribose-ferrocene oligonucleotides for electronic detection of nucleic acids.

We have synthesized two novel phosphoramidites with a ferrocenyl moiety at the 2'-ribose position linked through a butoxy linker. Using automated DNA/RNA synthesis techniques, oligonucleotides containing ferrocene at various positions were prepared and characterized by HPLC, MALDI-TOF mass spectrometry, and electrochemistry. Thermal stability studies of the ferrocene-modified DNA duplexes revealed that introduction of one or two ferrocenyl complexes does not result in an observed change of the T(m) values of the corresponding DNA duplexes when compared to the nonmodified hybrids. These data indicate that the introduction of a ferrocenyl group at the 2'-position of the ribose ring containing either a purine or pyrimidine base has no effect on the stability of the modified DNA. The electrochemical behavior of the ferrocene-containing DNA was examined by cyclic voltammetry. The modified 2'-ferrocene-oligonucleotides are electrochemically active and can be used as signaling probes for the electronic detection of nucleic acids on bioelectronic sensors.

Chromatography, High Pressure Liquid↗

Cloning of cDNA for a novel fibrinogen/angiopoietin-related protein, FARP.

Using a low abundant gene screening strategy in the human dermal papilla cell cDNA library, we isolated a novel cDNA, which was 1,872 bp of nucleotides in length and contained an open reading frame encoding 405 amino acids. We designated it 'fibrinogen/angiopoietin-related protein' (FARP) as it contained the characteristic coiled-coil domain and fibrinogen-like domain in the NH2- and COOH-terminal, which are conserved in angiopoietins. FARP has a highly hydrophobic region at the N-terminus that is typical of a secretory signal sequence. Recently, a very similar gene, HFARP, was cloned and they have a difference of only 18 amino acids in N-terminus. While HFARP was expressed only in the liver, northern blot analysis showed that FARP mRNA is abundantly expressed in the liver, placenta, prostate, and ovary in human adult tissues. It was also expressed in the fetal liver and lung carcinoma cell line. Further study will be needed to clarify the function of the FARP gene.

Angiopoietin-Like Protein 4↗

Activity against plant pathogenic fungi of phomalactone isolated from Nigrospora sphaerica.

Phomalactone, 5,6-dihydro-5-hydroxy-6-prop-2-enyl-2H-pyran-2-one, produced by the fungus Nigrospora sphaerica, was tested in vitro against nine plant pathogenic fungi, and specifically inhibited the mycelial growth of Phytophthora infestans, with an MIC value of 2.5 mg litre-1. Its inhibitory activities against sporangium and zoospore germination of P infestans were similar to those against Phytophthora capsici. In vivo, at 100 and 500 mg litre-1, it reduced the development of tomato late blight caused by P infestans.

Ascomycota↗

Characterization and pathogenetic role of proteinase from Acanthamoeba castellanii.

A secreted proteinase was purified from the culture supernatant of Acanthamoeba castellanii with several chromatographic steps. The purified proteinase was a chymotrypsin-like serine proteinase. Its molecular weight was approximately 12 kDa on SDS-PAGE, and its native molecular weight was 12 kDa when determined by molecular sieve chromatography. It showed a broad temperature optimum ranging 30-55 degrees C with an optimal at 55 degrees C and an optimal pH of 8.5. It could degrade various protein substrates, such as collagen, fibronectin, laminin, secretory immunoglobulin A, immunoglobulin G, plasminogen, fibrinogen, haemoglobin and rabbit corneal proteins. It showed strong cytopathic effects in cultured cells, including HEp2 and HEK cells. The corneal lesions, induced by both the purified proteinase and A. castellanii, displayed similar clinical results for both cases, in which the stromal infiltration and opacity with the epithelial defect were revealed. These results suggest that the enzyme was highly associated with the pathogenesis of Acanthamoeba. The fact that cytopathic effects and development of corneal lesions caused by the proteinase of Acanthamoeba were inhibited by the proteinase inhibitor suggest that the proteinase inhibitor might be useful as a therapeutic agent.

Acanthamoeba↗

Source of errors in the evaluation of early rectal cancer by endoluminal ultrasonography.

PURPOSE: Although preoperative evaluation of early rectal cancers can be done by endoluminal sonography and by means of colonoscopic findings, it is still controversial whether endoluminal sonography can effectively discriminate mucosal from submucosal lesions. This study was performed to verify objective causes of errors in the evaluation of early rectal cancer (T0/1) using a review of videotaped endoluminal sonography images. METHODS: Eighty-nine patients with suspected early rectal cancer on endoluminal sonography were included. Two different scanners with appropriate probes were used according to tumor location, i.e., transrectal ultrasonography was used to scan up to 8 cm of the rectum above the anal verge, whereas endoscopic ultrasonography was used to assess higher lesions. Endoluminal sonography images were correlated with histologic infiltration and were reevaluated carefully to identify sources of errors. RESULTS: Sensitivity and specificity were 83.1 and 96.5 percent, respectively, for tumor staging, whereas sensitivity was very low compared with specificity (16.7 vs. 90.2 percent) for metastatic lymph nodes. Endoluminal sonography images showed irregularity of the underlying tumor border (P < 0.01) and hypoechoic blurring or cutoff of the inner and outer hypoechoic layers (P < 0.001), all of which closely correlated with histologic infiltration of tumor cells. Overstaging occurred more than twice as often as understaging in tumor reevaluation (14 vs. 5 occurrences). In contrast to tumors, lymph nodes showed a similar amount of both overstaging (four cases) and understaging (five cases). The sources of errors were summarized as five types: false instrumentation, interpretive errors, anatomic defects, imaging failure, and inevitable errors. CONCLUSIONS: Because false instrumentation, interpretive errors, and anatomic defects were considered preventable, 23 (82.1 percent) of the 28 errors might have been avoided. Therefore, a clear image by endoluminal sonography can effectively distinguish mucosal from submucosal lesions in early rectal cancer.

Diagnosis, Differential↗

Mutations at the APC exon 15 in the colorectal neoplastic tissues of serial array.

Although the APC protein is known to participate in cellular proliferation and apoptosis, APC mutations have been thought to play a major role in the early stage of colorectal tumorigenesis. The somatic APC mutation of exon 15 was assessed to determine its impact on various stages of colorectal tumorigenesis. The colorectal neoplastic tissues of serial array studied included sporadic adenomas (group 1, n = 36), adenomas (group 2, n = 33), and carcinomas (group 3, n = 32) in the synchronous adenoma and carcinoma as well as sporadic carcinomas (group 4, n = 36). Aberrant DNA was detected by protein truncation test and confirmed by direct sequencing. The mutation prevalence was 36.1% in group 1, 45.5% in group 2, 59.4% in group 3, and 41.7% in group 4 with no differences among the groups. Among the 18 patients with synchronous adenoma and carcinoma, 9 had mutation in their adenomas and 12 in their carcinomas. The mutation loci and patterns did not differ in adenomas and carcinomas. Mutations in the mutation cluster region (MCR) were much more frequent than in the preceding region of MCR, i.e., 85.7% vs. 14.3%. The mutation prevalence of villous adenomas appeared greater than that of tubular adenoma (3/21 vs. 3/4). Predominant pathogenic mutations at MCR suggest that the APC mutation is implicated in all stages of colorectal tumorigenesis.

Adenocarcinoma↗

Sequential magnetic resonance imaging findings in hypereosinophilia-induced encephalopathy.

Hypereosiophilia-induced encephalopathy (HE) is a rare but well-described clinical syndrome. However, serial magnetic resonance imaging (MRI) findings of HE have rarely been reported. We describe serial MRI findings of three patients with HE. The patients presented with acute confusion, focal neurological deficits and/or seizures. Eosinophils in repeated blood tests were more than 3000/mm3 in all the patients. Echocardiography in two patients showed findings consistent with eosinophilic endomyocardial fibrosis or global hypokinesia. The initial MRI revealed multiple high-signal lesions on T2-weighted images with gadolinium-DTPA enhancement on T1-weighted images, which were predominantly distributed in the border zone of the middle-anterior cerebral arteries and the middle-posterior cerebral arteries. The second MRIs taken prior to the initiation of steroid therapy showed that the lesions increased in size and number in the same area. The third MRIs performed long after the therapy showed that the lesions were shrunken. A brain biopsy specimen in one patient showed reactive gliosis following infarction with abundant intravascular eosinophils. The MRI-identified lesions in the patients with HE thus develop mainly in the border zone. The lesions occasionally increase in size and number and shrink if the eosinophilia is adequately treated. Although the nature of the MRI-identified lesions remains unclear, their pathogenesis may be related to multiple embolisms associated with concomitant cardiac abnormality and hypercoagulable state.

Adult↗

A new diacylgalactolipid containing 4Z-16:1 from the marine cyanobacterium Oscillatoria sp.

A new diacylgalactolipid was isolated from the marine cyanobacterium Oscillatoria sp., and the structure was elucidated as (2S)-3-O-beta-D-galactopyranosyl-1-O-(9Z,12Z-oc-tadecadienoyl)-2-O-(4Z-hexadecenoyl)glycerol by enzymatic partial hydrolysis using lipase and physicochemical evidence, which included determining the double bond position in the hexadecenoic acid moiety.

Chemical Phenomena↗

Should laparoscopy be the standard approach used for pelvic lymph node dissection?

Involvement of the pelvic lymph nodes in patients with prostate cancer worsens the overall prognosis of this common disease entity. Prior radiographic staging techniques, including fine-needle aspiration, are limited by a poor sensitivity and are not reliable. The gold standard for the evaluation of pelvic lymph nodes in men with prostate cancer involves performing a lymphadenectomy. Historically, this procedure was performed using an open surgical technique. Unfortunately, this invasive procedure is associated with significant morbidity. In response, modern surgical technology has provided newer, less invasive techniques, including laparoscopic pelvic lymphadenectomy (LPLND). Improved detection of localized prostate cancer through the institution of screening protocols and early detection programs has decreased the number of patients presenting with lymph node involvement. Various clinical indicators, including prostate-specific antigen, grade, and stage, have been used to improve the selection of "high-risk" patients that are appropriate candidates for pelvic lymph node dissection. The technique of LPLND is a valid option in the armamentarium for staging of prostate cancer. The laparoscopic approach provides the same staging accuracy as the open surgical technique and is superior with respect to morbidity. LPLND is limited to patients who present with a high risk of advanced prostate cancer. In addition, the urologist must accept the additional training, financial expense, and "learning curve" associated with this technique.

Humans↗

Cardiac transplant outcome of patients supported on left ventricular assist device vs. intravenous inotropic therapy.

BACKGROUND: Although the left ventricular assist device (LVAD) has been increasingly used as a bridge to transplant, its effect on post-transplant outcome is uncertain. We, therefore, designed this study using the Cardiac Transplant Research Database to compare patients supported on an LVAD before transplant with those treated with intravenous inotropic medical therapy. METHODS AND RESULTS: Of the 5,880 patients transplanted between 1990 and 1997, a total of 502 received support from LVADs and 2,514 received intravenous inotropic medical therapy at the time of transplant. Kaplan-Meier analysis showed no significant difference in post-transplant survival between the LVAD and medical-therapy groups (p = 0.09). Results of a multivariate Cox regression analysis were consistent with that of the Kaplan-Meier analysis and did not identify LVAD as a significant risk factor for mortality. The percentage of patients who received LVADs as a function of total transplants increased from 2% in 1990 to 16% in 1997. Furthermore, although the number of extracorporeal LVADs remained relatively constant, the number of intracorporeal LVADs increased over time. Multivariate parametric analysis found that the risk factors for post-transplant death in the LVAD group were extracorporeal LVAD use (p = 0.0004), elevated serum creatinine (p = 0.05), older donor age (p = 0.03), increased donor ischemic time (p < 0.0001), and earlier year of transplant (p = 0.03). CONCLUSIONS: Given a limited donor supply, the intracorporeal LVAD helps the sickest patients survive to transplant and provides post-transplant outcome similar to that of patients supported on inotropic medical therapy. Therefore, patients supported on LVADs before transplant may receive the greatest marginal benefit when compared with other transplant candidates.

Cardiotonic Agents↗

A novel cold-inducible zinc finger protein from soybean, SCOF-1, enhances cold tolerance in transgenic plants.

Cold stress on plants induces changes in the transcription of cold response genes. A cDNA clone encoding C2H2-type zinc finger protein, SCOF-1, was isolated from soybean. The transcription of SCOF-1 is specifically induced by low temperature and abscisic acid (ABA) but not by dehydration or high salinity. Constitutive overexpression of SCOF-1 induced cold-regulated (COR) gene expression and enhanced cold tolerance of non-acclimated transgenic Arabidopsis and tobacco plants. SCOF-1 localized to the nucleus but did not bind directly to either C-repeat/dehydration (CRT/DRE) or ABA responsive element (ABRE), cis-acting DNA regulatory elements present in COR gene promoters. However, SCOF-1 greatly enhanced the DNA binding activity of SGBF-1, a soybean G-box binding bZIP transcription factor, to ABRE in vitro. SCOF-1 also interacted with SGBF-1 in a yeast two-hybrid system. The SGBF-1 transactivated the beta-glucuronidase reporter gene driven by the ABRE element in Arabidopsis leaf protoplasts. Furthermore, the SCOF-1 enhanced ABRE-dependent gene expression mediated by SGBF-1. These results suggest that SCOF-1 may function as a positive regulator of COR gene expression mediated by ABRE via protein-protein interaction, which in turn enhances cold tolerance of plants.

Abscisic Acid↗

Evaluation of survival rate after follicular unit transplantation using the KNU implanter.

BACKGROUND: Many hair transplant surgeons have advocated the use of micrograft megasessions for the purpose of a more natural looking end result, especially in the Oriental with higher skin/hair color contrast and darker, coarse, straight hairs. But it also has some fundamental limitations. Most important are a low graft yield and a low density after transplantation. There are several reports about the survival rate of micrografts in Caucasians, though the results are variable, but few reports about the survival rate and fate of micrografts in Orientals. OBJECTIVE: To compare the survival rate of one-hair follicular units with that of two-hair follicular units using the KNU implanter, to ascertain the average survival rate of micrografts (one- and two-hair follicular units), and to evaluate the fate of grafted hair according to time. METHODS: Two templates of 1.5 cm2 were made by tattooing on both sides of the frontoparietal recess areas in 11 patients with male pattern baldness (beyond Norwood type IIIa). The authors planted one-hair unit micrografts in the left template and two-hair unit micrografts in the right template, which were prepared by the concept of follicular unit, and counted the surviving number of follicular units at 1 and 3 months and total hairs at 6 and 12 months after transplantation. RESULTS: The mean survival rate by the number of follicular units was 47.3 and 57.4% at 1 and 3 months after transplantation, respectively. The mean survival rate by the total number of hairs was 92.0 and 90.4% at 6 and 12 months after transplantation, respectively. CONCLUSION: About 50% of the transplanted hairs fell out in 1 month, but at 6 months the survival rate of follicular unit transplantation using the KNU implanter showed a good result (92%), and there were no significant differences in the mean survival rate of follicular unit and total hairs between one-hair and two-hair units at 1, 3, 6, and 12 months after transplantation.

Adult↗

Macrophage phenotype during cholestatic injury and repair: the persistent inflammatory response.

BACKGROUND/PURPOSE: Biliary decompression for congenital or acquired obstruction (eg, biliary atresia) does not uniformly lead to liver repair, restore function, or prevent cholangitis. The authors hypothesize that failed repair is caused by altered macrophage (Mo) phenotypes central to an ongoing inflammatory and fibrogenic response. METHODS: In adult rats, biliary obstruction was performed by suspension of the common bile duct for 5 or 7 days. Decompression followed release of the loop until death during the course of liver repair. To determine Mo phenotype in the presence or absence of resident macrophages, animals were either administered gadolinium chloride or saline before injury and repair. At death, hepatic Mo were isolated, stained with MAC-1 (CD11b/CD 18) and OX-3 (MHC class II), and quantified with flow cytometry. Liver sections were immunostained for ED-1 and ED2; positive Mo were counted per square millimeter of tissue. RESULTS: Obstruction led to bile duct proliferation, fibrosis, and inflammation. Decompression relieved jaundice and ductal hyperplasia. After injury, hepatic Mo showed an 80% phenotypic conversion to MAC-1 and OX-3-positive cells. Cells isolated from livers at 9 days of repair persisted with 60% MAC-1 and 77% OX-3 expression. Gadolinium reduced Kupffer cells at all stages of repair. Recruited Mo in treated animals increased 4-fold greater than controls. CONCLUSIONS: Kupffer cells appear to limit the recruitment and persistence of a systemic macrophage phenotype in liver injury and repair. Cell surface markers for systemic macrophages appear after injury and persist during repair, despite adequate biliary decompression. After biliary decompression, this macrophage phenotype accounts for inflammatory complications such as cholangitis and ongoing fibrosis.

Animals↗

The relationship between oligohydramnios and the onset of preterm labor in preterm premature rupture of membranes.

OBJECTIVE: The objective of this study was to determine whether a reduced amniotic fluid volume was associated with the onset of preterm parturition in patients with preterm premature rupture of membranes. STUDY DESIGN: An amniotic fluid index was determined before transabdominal amniocentesis in 129 patients with preterm premature rupture of membranes (gestational age < or = 35 weeks). Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Survival techniques were used for analysis. RESULTS: Amniotic fluid index was < or = 5 cm in 29% of patients (38/129). Patients with an amniotic fluid index of < or = 5 cm had a significantly higher rate of positive amniotic fluid culture than those with an amniotic fluid index of >5 cm (42% [16/38] vs 18% [16/91]; P<.01). Spontaneous preterm delivery within 24 hours and 48 hours was more frequent among patients with an amniotic fluid index of < or = 5 cm than those with an amniotic fluid index of >5 cm (for 24 hours, 29% vs 12%; for 48 hours, 42% vs 21%; P<.05 for each). The amniocentesis-to-delivery interval was significantly shorter in patients with an amniotic fluid index of < or = 5 cm than in patients with an amniotic fluid index of >5 cm (median, 38 hours; range, 0.2-1310 hours; vs median, 100 hours; range 0.1-2917 hours; P<.01). Moreover, Cox proportional hazards model analysis indicated that an amniotic fluid index of < or = 5 cm was a significant predictor of the duration of the pregnancy after adjustment for gestational age and the results of amniotic fluid culture (odds ratio, 2.4; 95% confidence interval, 1.4-3.9; P<.001). CONCLUSION: Patients with preterm premature rupture of membranes and an amniotic fluid index of < or = 5 cm are at increased risk for a shorter interval to delivery.

Adult↗

The frequency and clinical significance of intra-amniotic inflammation in patients with a positive cervical fetal fibronectin.

OBJECTIVE: A positive fetal fibronectin result in cervicovaginal fluid is a powerful predictor of preterm delivery and is considered a marker for upper genital tract infection (ie, intrauterine infection). Treatment with antimicrobial agents is being considered in patients with a positive fetal fibronectin test of cervico/vaginal fluid. This study was undertaken to determine the frequency and clinical significance of intra-amniotic infection/inflammation in patients with a positive fetal fibronectin. STUDY DESIGN: A total of 1709 pregnant women (gestational age, 23-31 weeks) were screened for cervical fetal fibronectin. Patients with a positive fibronectin were offered amniocentesis for the diagnosis of intra-amniotic infection and treatment with antibiotics. Amniocentesis was performed in 58 patients with a positive fibronectin test (>50 ng/mL). Amniotic fluid was cultured for aerobic/anaerobic bacteria and mycoplasmas. Polymerase chain reaction assay for Ureaplasma urealyticum was performed. Interleukin-6 concentrations were measured by a specific immunoassay. Nonparametric statistics were used for analysis. RESULTS: None of the patients with a positive fibronectin had a positive amniotic fluid culture. U urealyticum was detected in 1 case (1.8%) with the polymerase chain reaction assay. Amniotic fluid IL-6 was elevated (>2.5 ng/mL) in 5.3% of patients (3/57 patients); all of these patients delivered preterm neonates. There was no relationship between amniotic fluid IL-6 and cervical fibronectin concentration (r = 0.14;P: >.1). Patients who delivered preterm (<34 weeks) had higher median amniotic fluid IL-6 and cervical fetal fibronectin concentrations than those patients who delivered after 34 weeks (IL-6: median, 2.1 ng/mL [range, 0.1-25.3 ng/mL] vs median, 0.3 ng/mL [0.03-2.4 ng/mL]; P <.05; fibronectin: median, 509 ng/mL [260->1000 ng/mL] vs median, 155 ng/mL [50-889 ng/mL]; P <.01). CONCLUSION: Intra-amniotic infection was detected in 1.8% of cases with a positive fibronectin in the cervical fluid; intra-amniotic inflammation was present in 5.3% of cases. All patients with a positive fetal fibronectin and intra-amniotic inflammation delivered preterm neonates.

Adult↗

Value of amniotic fluid neutrophil collagenase concentrations in preterm premature rupture of membranes.

OBJECTIVE: Neutrophils in amniotic fluid are thought to be of fetal origin, and therefore the detection of these cells and/or their products in amniotic fluid may reflect the fetal inflammatory status. We propose that amniotic fluid neutrophil collagenase (matrix metalloproteinase-8) is a useful parameter to predict adverse neonatal outcome, impending preterm labor/delivery, and intrauterine infection in the setting of preterm premature rupture of the membranes. STUDY DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis from 101 patients with preterm premature rupture of the membranes (gestational age, 24-36 weeks). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Amniotic fluid analysis included Gram stain, white blood cell count, and determination of interleukin-6 and matrix metalloproteinase-8 concentrations (enzyme-linked immunosorbent assay). RESULTS: Neonates with adverse neonatal outcome were born to mothers with a significantly higher median amniotic fluid matrix metalloproteinase-8 concentration than those without adverse neonatal outcome (median, 54.4 ng/mL; range, 0.82-14,500 ng/mL vs median, 28.9 ng/mL; range, 0.78-2451.8 ng/mL; P <.05, respectively). The higher the amniotic fluid matrix metalloproteinase-8 concentrations, the shorter the interval to delivery (Cox proportional hazards model adjusting for gestational age at delivery; hazard ratio, 1.9; 95% CI, 1.1-3.5; P <.03). Amniotic fluid matrix metalloproteinase-8 concentration was more sensitive than an amniotic fluid white blood cell count and interleukin-6 in the detection of microbiologically proven intra-amniotic infection. CONCLUSION: Increased concentrations of neutrophil collagenase (matrix metalloproteinase-8) in amniotic fluid are associated with intra-amniotic infection, impending preterm delivery, and adverse neonatal outcome in patients with preterm premature rupture of the membranes. Moreover, matrix metalloproteinase-8 in amniotic fluid is a stronger predictor for the duration of pregnancy and intra-amniotic inflammation than interleukin-6 and an amniotic fluid white blood cell count.

Amniotic Fluid↗