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Biomedical subjects

J Kim

Publications and source records attributed to J Kim.

At least 253 records · Page 14Linked to original sources

Descartes' fly: the geometry of genomic annotation.

The completion of the Drosophila melanogaster genome marks another significant milestone in the growth of sequence information. But it also contributes to the ever-widening gap between sequence information and biological knowledge. One important approach to reducing this gap is theoretical inference through computational technologies. Many computer programs have been designed to annotate genomic sequence information with biologically relevant information. Here, I suggest that all of these methods have a common structure in which the sequence fragments are "coordinated" by some method of description such as Hidden Markov models. The key to the algorithms lies in constructing the most efficient set of coordinates that allow extrapolation and interpolation from existing knowledge. Efficient extrapolation and interpolation are produced if the sequence fragments acquire a natural geometrical structure in the coordinated description. Finding such a coordinate frame is an inductive problem with no algorithmic solution. The greater part of the problem of genomic annotation lies in biological modeling of the data rather than in algorithmic improvements.

Animals↗

Effects of cataract extraction with intraocular lens placement on scanning laser polarimetry of the peripapillary nerve fiber layer.

PURPOSE: To determine the effects of cataract extraction with intraocular lens placement on scanning laser polarimetry of the peripapillary nerve fiber layer. DESIGN: Cohort study. METHODS: Thirty-four eyes of 33 patients undergoing phacoemulsification cataract surgery with intraocular lens were imaged using the GDx Nerve Fiber Analyzer within 4 weeks before and at least 4 weeks after cataract surgery. Preoperative and postoperative mean images were compared. The effects of cataract severity and type, and intraocular lens material, were also examined. RESULTS: Comparison of preoperative and postoperative mean scanning laser polarimetry measurements revealed that eyes in which acrylic intraocular lenses (n = 11) were placed had a significant increase in scanning laser polarimetry for the total band circumference, and superior, inferior, and nasal quadrants (P < or =.041). Placement of silicone (n = 15) and polymethylmethacrylate (n = 8) intraocular lenses did not result in statistically significant changes in scanning laser polarimetry measurements. However, eight of 34 eyes (23.5%) had changes of 15% or more postoperatively in the total circumference measurement, including eyes with acrylic, silicone, and polymethylmethacrylate intraocular lenses. CONCLUSIONS: Cataract extraction with intraocular lens was associated with a statistically significant change in mean scanning laser polarimetry values in eyes that received an acrylic intraocular lens. In individual patients, clinically important changes (15% or greater) in scanning laser polarimetry measurements were not uncommon irrespective of intraocular lens type. New baseline scanning laser polarimetry measurements may be warranted in eyes that undergo cataract extraction with intraocular lens.

Acrylic Resins↗

The role of cyclic AMP response element-binding protein in testosterone-induced differentiation of granular convoluted tubule cells in the rat submandibular gland.

The postnatal development of granular convoluted tubules (GCT) in the duct system of the rodent submandibular gland is known to be androgen-dependent, but the underlying molecular mechanism is unclear. To test the possible role of the transcription factor, cyclic AMP response element-binding protein (CREB), in the androgen-induced differentiation of GCT, the effect of testosterone on the expression and localization of epidermal growth factor (EGF), a marker of GCT cells, and of CREB was examined in the submandibular glands of immature 3-week-old rats. Northern blotting demonstrated increases in both EGF and CREB mRNA 1-4 days after testosterone administration. Immunoprecipitation also indicated that CREB protein was increased in amount with testosterone administration, and that induced CREB was phosphorylated at the serine residue as in the active form of CREB. In situ hybridization demonstrated that cells with CREB mRNA signal first appeared in the distal portions of striated ducts at 1 day and had increased in number by 4 days after giving testosterone, when cells with EGF mRNA signal became evident in the same duct portions. Immunohistochemistry also showed the occurrence of CREB protein in the nuclei of duct epithelial cells before their differentiation into EGF-positive GCT cells. Finally, pieces of submandibular gland from immature rats were cultured in vitro and their expression of EGF mRNA analysed by the reverse transcriptase-polymerase chain reaction. Testosterone in the medium caused a marked enhancement of EGF expression in the gland in 1-4 days, which was attenuated by simultaneous administration of the antisense oligonucleotide for CREB as well as that for the androgen receptor. These results suggest the CREB is upregulated by androgen and has a crucial role in androgen-induced differentiation of GCT in the duct system of the rat submandibular gland.

Androgen Receptor Antagonists↗

Studies on the plasma lipid profiles, and LCAT and CETP activities according to hyperlipoproteinemia phenotypes (HLP).

Hyperlipoproteinemia phenotypes (HLP), one of genetic disorders with an estimated prevalence of 0.5-2% in the general population, is responsible for 10% of premature CHD. After first screening with the high cholesterol (>6.47 mM/l) and triglyceride (TG) (>2.6 mM/l) levels without medication, subjects were typed for HLP classification. Differential metabolic effects of HLP types on plasma lipid profiles and the reverse cholesterol transport system (RCT) were studied in 196 HLP types (91.2%) and 19 non-HLP (8.8%). A total of 45% of subjects had primary HLP and the others had NIDDM (10.7%), hypertension (9.3%) and other chronic diseases. Type IV HLP (58.6%) was most predominant and Types IIa, IIb, III and V comprised 16.7, 12.1, 2.3 and 1.4% of the HLP. Type I was not found. Plasma lipids excluding apo A-I and Lp(a) were significantly different among HLP compared to non-HLP (P<0.001). Since Type V and III impact the clearance of TG-riched lipoproteins, TG and VLDL-C levels were higher in V and III. TG and LDL-C were higher in Type II than those in the others because of defect of LDL receptors. LCAT activity, lower in Type III and Type IV and highest in Type V, was highly associated with plasma free cholesterol levels and the ratio of apoB/apoA and LDL/HDL. CETP activity was highest in Type V due to high VLDL-C and TG and low HDL-C. The ratio of LCAT/CETP was not different among HLP types but was significantly lower in HLP than in non-HLP. CETP increased 2-3 times as well as LCAT decreased among HLP patients compared to non-HLP. We conclude non-HLP subjects with high cholesterol and TG levels do not always mean high risk of CHD and the intervention effects of HLP types would lead to impose the risk of CHD by the impact of RCT.

Adult↗

Uterine artery embolization for leiomyomata.

OBJECTIVE: To determine whether uterine artery embolization is safe and effective for treating uterine leiomyomata. METHODS: We analyzed 200 consecutive patients (61 reported previously) undergoing uterine artery embolization for the treatment of uterine leiomyomata at a single institution. After treatment, follow-up data were obtained by written questionnaire mailed to the patients at intervals of 2 weeks, 3 months, 6 months, and 12 months after treatment. Follow-up imaging was obtained at 3 months and 12 months after therapy. All complications and subsequent gynecologic interventions were recorded prospectively, obtained using the patient questionnaires and physician contact. The percentages and their 95% confidence intervals (CI) were calculated to compare the symptoms at follow-up. Proportional odds models for repeated ordinal responses were used to assess the stability of symptom improvement over time. RESULTS: The mean follow-up was 21 months (minimum 12). Heavy menstrual bleeding improved in 87% (95% CI 82%, 92%) of patients at 3 months and in 90% (95% CI 86%, 95%) at 1 year after therapy. Bulk symptoms improved in 93% of patients (95% CI 88%, 96%) at 3 months and in 91% (95% CI 86%, 95%) at 1 year after treatment. Only one major periprocedural complication occurred (pulmonary embolus), which resolved with anticoagulant therapy. Subsequent gynecologic interventions occurred in 10.5% of the patients (95% CI 7.0%, 15.0%) during the follow-up period. CONCLUSION: Uterine artery embolization is safe and controls the symptoms caused by leiomyomata in most patients.

Adult↗

Regulation of secretion from mucous and serous cells in the excised ferret trachea.

Mucus hypersecretion is an important characteristic of many airway diseases. Mucin is the major component of mucus, and is secreted from surface goblet cells of the airway epithelium and mucous cells of submucosal glands. Lysozyme is an enzyme secreted by serous cells of airway submucosal glands. We hypothesized that secretagogues acting through different pathways would have different effects on tracheal mucin and lysozyme secretion. We used a sandwich enzyme-linked lectin assay (ELLA) to measure mucin-like glycoprotein secretion and a spectrophotometric method to measure lysozyme secretion from isolated ferret tracheal segments. We evaluated the secretory response to four secretagogues; prostaglandin F(2alpha) (PGF(2alpha)), adenosine triphosphate (ATP), methacholine (MCh), and human neutrophil elastase (HNE). Each agent stimulated mucin and lysozyme secretion. The relative potency was PGF(2alpha)< or =ATP<MCh<HNE for mucin and ATP< or =PGF(2alpha)<MCh<HNE for lysozyme secretion. We showed that there is an anatomic gradient for constitutive and stimulated mucin and lysozyme secretion with the distal tracheal segments secreting more mucin and lysozyme per gram of tissue than the proximal segments. This robust model system can be used to evaluate the regulation of airway mucous and serous cell secretion and to assess the effect of agents that might alter the secretory response. We confirm that on an equimolar basis, HNE is one of the most potent mucus secretagogues.

Adenosine Triphosphate↗

Reductive dechlorination of polychlorinated biphenyls as affected by sediment characteristics.

The effect of sediment sources on the selection of polychlorinated biphenyl (PCB) dechlorinating competence was investigated using sediments from two different locations, the Grasse River and Owasco Lake. These two sediments had a similar organic carbon content but different particle size distribution. The two PCB-free sediments were spiked with Aroclor 1248 and inoculated with microorganisms from the Reynolds and General Motors sites in the St. Lawrence River, which exhibited different dechlorination patterns. When each inoculum was serially transferred into fresh sediments four times (every 8-10 weeks), they still maintained the initial dechlorination patterns regardless, the source of sediments and the number of transfers, and dechlorination patterns of the two inocula in the same sediments did not converge. In a parallel approach, when the acclimated microorganisms from the Reynolds site were inoculated into fresh sediments from both sources as well as sediments enriched with organic carbon (2%, w/v), the dechlorination pattern remained unchanged after a 40-week incubation. These results suggest that the sediment characteristics or organic carbon content did not play a role in the selection of dechlorinating populations.

Biodegradation, Environmental↗

Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis.

OBJECTIVES: Elevated circulating levels of interleukin 6 (IL-6) have been associated with cancer metastasis. IL-6 binds either to membrane or to soluble IL-6 receptor (IL-6sR), which then induces homodimerization of gp130 that activates downstream signaling. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels are associated with prostate cancer stage, progression, and metastasis after radical prostatectomy. METHODS: Plasma levels of IL-6 and IL-6sR were measured in 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer, 44 healthy men without any cancer, 19 men with prostate cancer metastatic to the regional lymph nodes, and 10 men with prostate cancer metastatic to bone. RESULTS: Plasma IL-6 and IL-6sR levels were highest in patients with bone metastases (P <0.001). The preoperative IL-6 and IL-6sR levels were associated with the preoperative prostate-specific antigen (PSA) level (P </=0.041), prostatectomy tumor volume (P </=0.048), and final Gleason sum (P </=0.042). The preoperative IL-6 and IL-6sR levels and biopsy Gleason sum were independent predictors of PSA progression (P </=0.029). However, in a model that included both IL-6 and IL-6sR, only IL-6sR and the biopsy Gleason sum predicted progression (P </=0.040). In patients whose disease progressed, the preoperative IL-6 and IL-6sR levels were highest in those with presumed aggressive failure (P </=0.042). CONCLUSIONS: Plasma IL-6 and IL-6sR levels were dramatically elevated in the men with prostate cancer metastatic to bone. In patients with clinically localized prostate cancer, the preoperative plasma IL-6 and IL-6sR levels independently predicted biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.

Adult↗

Optimized protocols for the detection of porcine circovirus 2 DNA from formalin-fixed paraffin-embedded tissues using nested polymerase chain reaction and comparison of nested PCR with in situ hybridization.

Optimized DNA extraction method and nested polymerase chain reaction (PCR) were developed for the detection of porcine circovirus 2 (PCV2) from formalin-fixed, paraffin-embedded tissues. Conventional PCR, nested PCR, and in situ hybridization methods were also compared for the detection of PCV2 in archival tissues. A method based on xylene deparaffinization followed by proteinase K digestion yielded DNA of sufficient quality for PCR analyses reliably and consistently. Twenty-six (70%) of the 37 tissues examined gave positive results with conventional PCR, whereas all the 37 tissues gave positive results using the nested PCR. A distinct positive signal for PCV2 was detected in spleen and lymph node from all the 37 pigs by in situ hybridization. The nested PCR and in situ hybridization could be applied successfully to archival tissues for the detection of porcine circovirus 2 DNA.

Animals↗

Differentiation of porcine circovirus (PCV)-1 and PCV-2 in boar semen using a multiplex nested polymerase chain reaction.

A multiplex nested polymerase chain reaction (PCR) was developed for the detection of and differentiation between porcine circovirus (PCV)-1 and PCV-2 in boar semen. Eighteen (30%) and 30 (50%) out of 60 whole semen samples were found to be positive for PCV using multiplex conventional PCR and multiplex nested PCR, respectively. Of the 30 positive samples obtained using multiplex nested PCR, two were found to be positive for PCV-1 only, eight for PCV-2 only, and 20 for PCV-1 and PCV-2. When the separated fractions of PCV-contaminated semen were analyzed using multiplex nested PCR, PCV DNA was found to be present mainly in the seminal fluid and nonsperm cell fractions. When compared with the virus isolation method commonly used to detect viruses, this PCR assay was found to be more sensitive and rapid and, as such, may prove to be a good alternative method for the detection of and differentiation between PCV-1 and PCV-2 in boar semen.

Animals↗

Isolation of neuronal precursors from differentiating P19 embryonal carcinoma cells by neuronal T alpha 1-promoter-driven GFP.

The induction of pluripotent P19 embryonal carcinoma (EC) cells with retinoic acid results in their differentiation into cells that resemble neurons, glia, and fibroblasts. To isolate and enrich the developing neurons from heterogeneously differentiating P19 EC cells, we used a recently introduced protocol combining the expression of green fluorescent protein (GFP) driven by a tissue-specific promoter and fluorescence-activated cell sorting. Cells were transfected with the gene for GFP, which is under the control of the neuronal T alpha 1 tubulin promoter. After four days of retinoic acid treatment, GFP was specifically detected in cells undergoing neuronal differentiation. Sorting of fluorescent differentiating P19 EC transfectants yielded populations highly enriched in neuronal precursors and neurons. Immunoreactivity for nestin and neurofilament was observed in 80 and 25% of the sorted cell population, respectively. These results demonstrate that differentiated neuronal precursor cells can be efficiently isolated from differentiating pluripotent embryonic cells in vitro, suggesting that this method can reproducibly provide homogeneous materials for further studies on neurogenesis.

Antineoplastic Agents↗

Poly(A) binding protein II in Xenopus laevis is expressed in developing brain and pancreas.

We have isolated Xenopus homolog of poly(A) binding protein II (XPABPII) and examined its expression during early embryogenesis and embryonic gut development. XpabpII encodes a nuclear protein of 296 amino acids that contains an alpha-helical coiled-coil domain and a ribonucleoprotein-type RNA binding domain. XpabpII is expressed both maternally and zygotically. In gastrula and neurula embryos, XpabpII is expressed mainly in ectoderm, neural and epidermal. From tailbud through to tadpole stages, the neural tissue specific expression of XpabpII gradually becomes confined to the specific vesicle regions of developing brain, being detected in the eye, olfactory pit, telencephalon and mesencephalon, but being excluded from the diencephalon region. Intriguingly, XpabpII transcripts are observed in differentiating gut endoderm. XpabpII first becomes visible in the anterior part of a stage 35 embryonic gut in which prospective liver, stomach and pancreas are located. During further development, uniform expression in anterior gut gradually becomes restricted to the pancreas rudiment. At the seventh day of development, when the gut has formed a complex coiled structure in which each organ contains clearly differentiated cell type, XpabpII is detectable exclusively in the pancreas. Taken together, we suggest that XpabpII plays a specific role in the polyadenylation process of genes involved in brain and pancreas development.

Amino Acid Sequence↗

The effect of immediate and delayed word repetition on event-related potential in a continuous recognition task.

The dissociation of immediate and delayed word repetition was studied using a continuous recognition memory task and event-related potential (ERP). Among 240 stimulus words, 40 words were not repeated, 100 were immediately repeated and 100 were repeated after 5 intervening words. Words presented only once during the experiment were referred to as new words. Subjects responded faster and more accurately to words repeated immediately than to new words and to words repeated after a delay. In terms of ERP results, immediate repetition was associated with large P300 amplitude, early P300 latency and the absence of N400, while delayed repetition was associated with small P300 amplitude, late P300 latency and the presence of N400. N400 was elicited only to new words and to those repeated after intervening words. The general morphology of the waveforms was similar for two repetition conditions until around 310 ms after the onset of stimulus. These results indicate that distinct neural systems subserve the immediate and delayed repetition effect, and that the difference between the two emerges around 310 ms poststimulus. Immediate and delayed word repetition are considered in terms of template matching and memory searching, and are possibly mediated by the parietal and left medial temporal lobes, respectively.

Adult↗

N-(3-Acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives as potent vanilloid receptor agonists and analgesics.

A series of N-(3-acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives were investigated as vanilloid receptor ligands in an effort to discover a novel class of analgesics. The proposed pharmacophore model of resiniferatoxin. which includes the C20 homovanillic moiety, the C3-carbonyl and the orthoester phenyl ring as key pharmacophoric groups, was utilized as a guide for drug design. The compounds were synthesized after several steps from diethylmalonate and evaluated in vitro in a receptor binding assay and in a capsaicin-activated channel assay. Additional evaluation of analgesic activity, anti-inflammatory activity and pungency was conducted in animal models by the writhing test, the ear edema assay, and the eye-wiping test, respectively. Among the new compounds, 23 and 28 were found to be the most potent receptor agonists of the series with Ki values of 19 nM and 11 nM, respectively. Their strong in vitro potencies were also reflected by an excellent analgesic profile in animal tests with ED50 values of 0.5 microg kg for 23 and 1.0 microg/kg for 28. Relative to capsaicin these compounds appear to be ca. 600 and 300 times more potent. Both 23 and 28 were found to be less pungent than capsaicin based on the eye-wiping test. However, the compounds did not show significant anti-inflammatory activity. A molecular modeling study comparing the energy-minimized structures of resiniferatoxin and 35 demonstrated a good correlation in the spatial disposition of the corresponding key pharmacophores. The thioureas described in this investigation, which were designed as simplified resiniferatoxin surrogates, represent a novel class of potent vanilloid receptor agonists endowed with potent analgesic activity and reduced pungency.

Analgesics↗

Recovery of 18F from [18O] water by electrochemical method.

An electrochemical method for producing 18F sources for the slow positron beam was applied to the recovery of 18F from H2(18)O water. The 18F of activities 150-227 mCi (5.55-8.40 GBq) was electro-deposited on a graphite rod and then emitted into pure water. The best result of the efficiency for the electro-deposition for 5 min was 97% and that for the electro-emission for 5 min was 89%. The H2(18)O water is expected to be reused much more easily by this method than by the ion exchange resin method. The metal impurities contained in the 18F solution were considerably reduced by using this method.

Journal Article↗

Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway.

Cvt19 is specifically required for the transport of resident vacuolar hydrolases that utilize the cytoplasm-to-vacuole targeting (Cvt) pathway. Autophagy (Apg) and pexophagy, processes that use the majority of the same protein components as the Cvt pathway, do not require Cvt19. Cvt19GFP is localized to punctate structures on or near the vacuole surface. Cvt19 is a peripheral membrane protein that binds to the precursor form of the Cvt cargo protein aminopeptidase I (prAPI) and travels to the vacuole with prAPI. These results suggest that Cvt19 is a receptor protein for prAPI that allows for the selective transport of this protein by both the Cvt and Apg pathways.

Aminopeptidases↗

Pyrrolidine dithiocarbamate inhibits serum-induced NF-kappaB activation and induces apoptosis in ROS 17/2.8 osteoblasts.

Nuclear factor-kappaB (NF-kappaB) activity affects cell survival in ROS 17/2.8 osteoblasts. Preventing NF-kappaB transcription activity with a potent NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), results in apoptosis. Thus, we explored the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor-kappaB (NF-kappaB) in serum-exposed condition, on the activation of mitogen activated protein kinase (MAPK), especially, JNK/SAPK and p38 MAPK induction. PDTC transiently increased the phosphotransferase activity of c-Jun N-terminal Kinase1 (JNK1), which might in turn activates transcriptional activity of activating protein-1 (AP-1). The activation of JNK was completely decreased in dominant negative JNK1 transfected cells and the PDTC-induced cell death was attenuated in these cells. In addition, AP-1 activation was decreased in the JNK1 transfected cells, compared with vector-transfected cells. The NF-kappaB inhibitor also transiently activates p38 MAPK but SB203580, a specific p38 MAPK inhibitor, does not have any regulatory effect on PDTC-induced cell death, suggesting that the cell death is mediated by JNK not by p38 MAPK. Thus, overall, these results show that PDTC induces apoptosis and suggest that JNK/SAPK and subsequent AP-1 activation may be involved in the apoptotic pathway in ROS 17/2.8 osteoblasts.

Animals↗

Comparison of volatile components in dried scallops (Chlamys farreri and Patinopecten yessoensis) prepared by boiling and steaming methods.

Comparison of two types of dried scallops, Chlamys farreri and Patinopecten yessoensis, and effects of preparation methods (boiling and steaming) on the composition of their volatile components were carried out by simultaneous steam distillation and extraction and with analysis by gas chromatography-mass spectrometry. One hundred and seventy-two compounds were identified, three tentatively. Qualitatively, both scallops had similar components. Quantitatively, C. farreri contained more components with higher levels in aldehydes, alkanes, naphthalenes, esters, furans, miscellaneous compounds, alcohols, and ketones, whereas P. yessoensis had more components with higher levels in aromatics, pyrazines, pyridines, sulfur-containing compounds, and terpenes from both boiling and steaming methods. Comparison between methods for the same scallop showed that similar qualities of components were detected. Overall, more compounds with higher levels were detected from the boiling method.

Alcohols↗