Biomedical subjects

J J Kim

Publications and source records attributed to J J Kim.

At least 109 records · Page 6Linked to original sources

PubMed2001

Crystallization and preliminary X-ray diffraction studies of the guanylate kinase-like domain of PSD-95 protein from rat.

The PSD-95 (postsynaptic density-95) protein, one of the members of the MAGUK (membrane-associated guanylate kinase) family, is composed of three PDZ domains, one SH3 domain and one guanylate kinase-like (GK) domain. The GK domain mediates the scaffolding function of PSD-95 by protein--protein interaction. Here, the GK domain was subcloned, expressed as an intein fusion protein, purified without the intein and then crystallized at room temperature by the hanging-drop vapour-diffusion method using PEG 8000 as a precipitant. The complete native data set was collected to a resolution of 2.35 A using flash-cooling. The crystals belong to the primitive tetragonal space group P4(3) (or P4(1)), with unit-cell parameters a = b = 70.03 (4), c = 37.64 (1) A.

Animals↗

PubMed2001

The effect of sildenafil on lower esophageal sphincter and body motility in normal male adults.

OBJECTIVE: Sildenafil relaxes smooth muscle by blocking type 5 phosphodiesterase, which destroys nitric oxide-stimulated cyclic guanosine monophosphate. The aim of this study is to investigate the change of lower esophageal sphincter (LES) and body motility with the lapse of time after sildenafil infusion in normal male adults. METHODS: After basal esophageal manometry in eight healthy male adult volunteers, we infused a 50-mg tablet of sildenafil dissolved in water in the stomach through the manometry catheter and observed the changes of LES and body motility with the lapse of time. We randomized the study population into two groups, and esophageal manometry was repeated in LES and body sequence in four volunteers and in body and LES sequence in the other four volunteers immediately after sildenafil infusion. RESULTS: LES resting pressure significantly decreased after sildenafil infusion. The body peristaltic amplitude gradually decreased and eventually disappeared, and the latency increased significantly after sildenafil infusion in both the proximal and distal esophagus. CONCLUSIONS: These data support that nitric oxide mediates LES relaxation and the timing of esophageal peristalsis. In the future, sildenafil can be tried in some esophageal motor disorders, which have defects in nitric oxide neuromuscular communication.

Adult↗

PubMed2001

Furazolidone- and nitrofurantoin-resistant Helicobacter pylori: prevalence and role of genes involved in metronidazole resistance.

The prevalence of furazolidone, nitrofurantoin, and metronidazole resistance among Helicobacter pylori strains was assessed with 431 clinical isolates. Fifty-two percent were metronidazole resistant, compared to 2% (7 of 431) with resistance to furazolidone and nitrofurantoin. All seven furazolidone- and nitrofurantoin-resistant isolates were also metronidazole resistant. rdxA, frxA, and fdxB knockouts did not result in furazolidone or nitrofurantoin resistance. These data suggest that furazolidone and nitrofurantoin may be good alternatives to metronidazole for treating H. pylori infection.

Anti-Infective Agents, Urinary↗

PubMed2001

DNA sequence analysis of rdxA and frxA from 12 pairs of metronidazole-sensitive and -resistant clinical Helicobacter pylori isolates.

We previously reported that inactivation of rdxA and/or frxA converted Helicobacter pylori from metronidazole sensitive to metronidazole resistant. To examine the individual roles of rdxA and frxA in the development of metronidazole resistance in H. pylori, we examined the status of rdxA and frxA from 12 pairs of metronidazole-sensitive and -resistant H. pylori isolates obtained following unsuccessful therapy containing metronidazole. Arbitrary primed fingerprinting analyses revealed that the genotypes of 11 sensitive and resistant pairs of strains were essentially identical. Amino acid sequence identities of RdxA and FrxA from the 14 metronidazole-sensitive isolates ranged from 92 to 98% and 95 to 98%, respectively, compared to that of H. pylori J99 (MIC, 1 microg/ml). All strains with high-level metronidazole resistance (MICs, 128 microg/ml) contained premature truncation of both RdxA and FrxA caused by nonsense and/or frameshift mutations. Strains with intermediate resistance to metronidazole (MICs, 32 to 64 microg/ml) contained a single premature truncation and/or altered RdxA and FrxA caused by nonsense, frameshift, and unique missense mutations. The low-level metronidazole-resistant strains (MICs, 8 microg/ml) contained unique missense mutations in FrxA but no specific changes in RdxA. The results demonstrate that alterations in both the rdxA and frxA genes are required for moderate and high-level metronidazole resistance and that metronidazole resistance that develops during anti-H. pylori therapy containing metronidazole is most likely to involve a single sensitive strain infection rather than a coinfection with a metronidazole-resistant strain.

Amino Acid Sequence↗

PubMed2001

Construction and analysis of photolyase mutants of Pseudomonas aeruginosa and Pseudomonas syringae: contribution of photoreactivation, nucleotide excision repair, and mutagenic DNA repair to cell survival and mutability following exposure to UV-B radiation.

Based on nucleotide sequence homology with the Escherichia coli photolyase gene (phr), the phr sequence of Pseudomonas aeruginosa PAO1 was identified from the genome sequence, amplified by PCR, cloned, and shown to complement a known phr mutation following expression in Escherichia coli SY2. Stable, insertional phr mutants containing a tetracycline resistance gene cassette were constructed in P. aeruginosa PAO1 and P. syringae pv. syringae FF5 by homologous recombination and sucrose-mediated counterselection. These mutants showed a decrease in survival compared to the wild type of as much as 19-fold after irradiation at UV-B doses of 1,000 to 1,550 J m(-2) followed by a recovery period under photoreactivating conditions. A phr uvrA mutant of P. aeruginosa PAO1 was markedly sensitive to UV-B irradiation exhibiting a decrease in survival of 6 orders of magnitude following a UV-B dose of 250 J m(-2). Complementation of the phr mutations in P. aeruginosa PAO1 and P. syringae pv. syringae FF5 using the cloned phr gene from strain PAO1 resulted in a restoration of survival following UV-B irradiation and recovery under photoreactivating conditions. The UV-B survival of the phr mutants could also be complemented by the P. syringae mutagenic DNA repair determinant rulAB. Assays for increases in the frequency of spontaneous rifampin-resistant mutants in UV-B-irradiated strains containing rulAB indicated that significant UV-B mutability (up to a 51-fold increase compared to a nonirradiated control strain) occurred even in the wild-type PAO1 background in which rulAB only enhanced the UV-B survival by 2-fold under photoreactivating conditions. The frequency of occurrence of spontaneous nalidixic acid-resistant mutants in the PAO1 uvrA and uvrA phr backgrounds complemented with rulAB were 3.8 x 10(-5) and 2.1 x 10(-3), respectively, following a UV-B dose of 1,550 J m(-2). The construction and characterization of phr mutants in the present study will facilitate the determination of the roles of light and dark repair systems in organisms exposed to solar radiation in their natural habitats.

Cloning, Molecular↗

PubMed2001

Grey matter abnormalities in obsessive-compulsive disorder: statistical parametric mapping of segmented magnetic resonance images.

BACKGROUND: Although a number of functional imaging studies are in agreement in suggesting orbitofrontal and subcortical hyperfunction in the pathophysiology of obsessive-compulsive disorder (OCD), the structural findings have been contradictory. AIMS: To investigate grey matter abnormalities in patients with OCD by employing a novel voxel-based analysis of magnetic resonance images. METHOD: Statistical parametric mapping was utilised to compare segmented grey matter images from 25 patients with OCD with those from 25 matched controls. RESULTS: Increased regional grey matter density was found in multiple cortical areas, including the left orbitofrontal cortex, and in subcortical areas, including the thalamus. On the other hand, regions of reduction were confined to posterior parts of the brain, such as the left cuneus and the left cerebellum. CONCLUSIONS: Increased grey matter density of frontal-subcortical circuits, consonant with the hypermetabolic findings from functional imaging studies, seems to exist in patients with OCD, and cerebellar dysfunction may be involved in the pathophysiology of OCD.

Adult↗

PubMed2001

Mitogenic and metabolic effects of type I IGF receptor overexpression in insulin receptor-deficient hepatocytes.

We have previously shown that hepatocytes lacking insulin receptors (Ir-/-) fail to mediate metabolic responses, such as stimulation of glycogen synthesis, while retaining the ability to proliferate in response to IGFs. In this study we have asked whether overexpression of type I IGF receptors would rescue the metabolic response of Ir-/- hepatocytes. After IGF-I stimulation, insulin receptor substrate-1 and -2 phosphorylation and PI3K activity were restored to levels similar to or greater than those seen in wild-type cells. Rates of cell proliferation in response to IGF-I increased approximately 2-fold, whereas glycogen synthesis was restored to wild-type levels, but was comparatively smaller than that elicited by overexpression of insulin receptors. In summary, overexpression of IGF-I receptors in Ir-/- hepatocytes normalized insulin receptor substrate-2 phosphorylation and glycogen synthesis to wild-type levels, whereas it increased cell proliferation above wild-type levels. Moreover, stimulation of glycogen synthesis was submaximal compared with the effect of insulin receptor overexpression. We conclude that IGF-I receptors are more efficiently coupled to cell proliferation than insulin receptors, but are less potent than insulin receptors in stimulating glycogen synthesis. The data are consistent with the possibility that there exist intrinsic signaling differences between insulin and IGF-I receptors.

Animals↗

PubMed2001

Molecular authentication of Panax ginseng species by RAPD analysis and PCR-RFLP.

In order to develop convenient and reproducible methods for the identification of ginseng drugs at a DNA level, randomly amplified polymorphic DNA (RAPD) and PCR-restriction fragment length polymorphism (PCR-RFLP) analyses were applied within Panax species. To authenticate Panax ginseng among ginseng populations, RAPD analysis was carried out using a 20 mer-random primer. The similarity coefficients among the DNA of ginseng plants analyzed were low, ranging from 0.197 to 0.491. In addition, by using PCR-RFLP analysis, very different fingerprints were obtained within Korean ginseng plants. These results suggest that these methods are able to authenticate the concerned Panax species. Broader application of this approach to authenticate other morphologically similar medicinal materials is rationalized.

DNA, Plant↗

PubMed2001

Polymorphism of the angiotensin-converting enzyme gene in patients with cerebral infarction in Koreans.

The relationship between cerebrovascular disease and an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is still being debated. The frequency of the DD genotype of the ACE gene was significantly higher in subjects with than those without cerebral infarction in Japan. The aim of the present study was to assess the relationship between ACE gene polymorphism and the development of cerebral infarction in a population from Korea. We examined its possible role as a risk factor in patients with cerebral infarction. The association between ACE gene polymorphism and cerebral infarction was examined in 106 patients with cerebral infarction and 498 controls without cerebral infarction. Frequencies of the genotypes and alleles of the ACE gene were investigated. The ACE genotype was analyzed by the polymerase chain reaction (PCR). The frequency of D allele was 37.7% in patients and 39.1% in controls (chi2 = 0.128, p = 0.720). The frequencies of the genotypes of the ACE gene were II: 39.6%, ID: 45.3%, and DD: 15.1% in patients, and II: 37.1%, ID: 47.6%, and DD: 15.3% in controls (chi2 = 0.127, p = 0.721). There was no significant difference in the frequency of the DD genotype of the ACE gene, and we did not find any association between ACE polymorphism and cerebral infarction. These results indicate that ACE polymorphism is not a risk factor for the development of cerebral infarction in a Korean population.

Adult↗

PubMed2001

Clinical characteristics of constrictive pericarditis diagnosed by echo-Doppler technique in Korea.

A retrospective analysis of clinical data of 71 patients with constrictive pericarditis (CP) diagnosed by echo-Doppler technique (mean age, 49+/-17) was done. In 27 patients (38%), the etiology was unknown, and the three most frequent identifiable causes were tuberculosis (23/71, 32%), cardiac surgery (8/71, 11%), and mediastinal irradiation (6/71, 9%). Pericardiectomy was performed in 35 patients (49%) with a surgical mortality of 6% (2/35), and 11 patients (15%, 11/ 71) showed complete resolution of constrictive physiology with medical treatment. Patients with transient CP were characterized by absence of pericardial calcification, shorter symptom duration, and higher incidence of fever, weight loss, and tuberculosis. The 5-yr survival rates of patients with transient CP and those undergoing pericardiectomy were 100% and 85+/-6%, respectively, which were significantly higher than that of patients without undergoing pericardiectomy (33+/-17%, p=0.0083). Mediastinal irradiation, higher functional class, low voltage in ECG, low serum albumin, and old age were the independent variables associated with a higher mortality. Tuberculosis is still the most important etiology of CP in Korea, and not infrequently, it may cause transient CP. Early diagnosis and decision-making using follow-up echocardiography are crucial to improve the prognosis of patients with CP.

Adult↗

PubMed2001

Predicting the rotationally neutral state of the femur by comparing the shape of the contralateral lesser trochanter.

The rotationally neutral state of the femur was measured by comparing the shape of the contralateral lesser trochanter in 100 adults. Three observers predicted a position presumed to be neutral by comparing the shape of the neutrally positioned contralateral lesser trochanter previously recorded by C-arm image intensification. The mean (SD) angular discrepancy between the neutral point and the predicted angle was 3.4 degrees (+/- 2.4) without interobserver variation (P = .87). Seventy-seven percent indicated the value within 4 degrees, and none of the observations exceeded 15 degrees. These findings suggest the outline of the contralateral lesser trochanter may be a useful reference during surgical treatment of femoral fractures to minimize rotational deformity.

Adult↗

PubMed2001

Bidirectional incremental parsing for automatic pathway identification with combinatory categorial grammar.

As the importance of automatically extracting and analyzing various natural language assertions about protein-protein interactions in biomedical publications is recognized, many uses of natural language processing techniques are proposed in the literature. However, most proposals to date make rather simplifying assumptions about the syntactic aspects of natural language due to various reasons including efficiency. In this paper, we describe an implemented system that utilizes combinatory categorical grammar known to be competent in modeling natural language, with a controlled mechanism for the parser to operate bidirectionally and incrementally. We discuss the performance of the system on a large set of abstracts in Medline with quite encouraging results.

Data Interpretation, Statistical↗

PubMed2001

Engineering enhancement of immune responses to DNA-based vaccines in a prostate cancer model in rhesus macaques through the use of cytokine gene adjuvants.

DNA immunization is an important vaccination technique that is being explored as an immunotherapeutic strategy against a variety of infectious diseases as well as cancer. We have been investigating the utility of DNA-based vaccine strategy against prostate cancer. We have developed a DNA vaccine construct that encodes for the human prostate specific antigen (PSA) gene. PSA expression is limited to prostate cells, and the level of PSA expression is substantially increased in prostate cancer cells. This tissue specificity makes PSA a potential target for the development of immunotherapies against prostate cancer. A DNA-based PSA vaccine was used to elicit PSA-specific host immune responses in rodent and nonhuman primate models. In an effort to enhance the clinical utility of the DNA-based PSA vaccine, we also examined the use of cytokine gene adjuvants to modulate vaccine-induced immune responses in these animal models. We observed that pCPSA vaccine-induced humoral and cellular immune responses can be modulated through the coimmunization with cytokine genes in mice, and these enhancement effects on the PSA-specific cellular responses were extended in macaques. More specifically, coimmunization with interleukin (IL)-2 cDNA construct resulted in a significant enhancement of PSA-specific antibody responses in both mice and macaque models. In contrast, coinjection of IL-12 resulted in reduction of antibody responses in both models. In mice, the groups coimmunized with IL-2, IL-12, or IL-18 showed a dramatic increase in T helper cell proliferation over the results with pCPSA alone. These results support that further evaluation of this vaccination strategy to treat prostate cancer is warranted.

Animals↗

PubMed2001

Fear conditioning to tone, but not to context, is attenuated by lesions of the insular cortex and posterior extension of the intralaminar complex in rats.

C. Shi and M. Davis (1999) recently reported that combined lesions of the posterior extension of the intralaminar complex (PINT) and caudal insular cortex (INS) block acquisition but not expression of fear-potentiated startle to discrete conditioned stimuli (CSs) and a footshock unconditioned stimulus (US) and proposed that PINT-INS projections to the amygdala constitute the essential US pathways involved in fear conditioning. The present study further tested this hypothesis by examining whether PINT-INS lesions block fear conditioning (as measured by freezing) to diffuse-context and discrete-tone CSs, and whether posttraining lesions with continued CS-US training result in extinction to the CSs. Posttraining lesions resulted in a selective attenuation of tone conditioning, but context conditioning was unaffected by pre- and posttraining lesions. These results do not support the view that the PINT-INS represent the essential US pathway in fear conditioning.

Amygdala↗

PubMed2000

Comparison of two immunization schedules for a Pseudomonas aeruginosa outer membrane proteins vaccine in burn patients.

The aim of the present study was to compare two immunization schedules for a Pseudomonas aeruginosa outer membrane proteins (OMPs) vaccine in burn patients. In a double-blind, randomized and placebo-controlled clinical trial, 95 adult patients with burn injuries in 10% or greater of total body surface area were randomly allocated to either placebo or immunization groups. Three doses of the vaccine (0.5 or 1.0 mg) were administered intramuscularly at either 3- or 7-day intervals. The vaccine was well tolerated, and no severe adverse reactions were observed in any of the vaccinees. After three immunizations, 88 patients were available for evaluation of serum antibody titers. Elevation of OMPs-specific antibody titers in the immunization groups was significantly higher as compared with the placebo group, and the highest antibody response was obtained by immunization with 1.0-mg doses at 3-day intervals. Conventional blood culture, tissue culture of wound biopsy specimens and a nested polymerase chain reaction (PCR) assay of blood specimens were performed to determine the protective efficacy. The results of the nested PCR indicated that the overall detection rate of P. aeruginosa in blood was significantly lower among immunized patients than placebo patients (6.1 vs. 40.0%, P<0.001). Based on these results, we concluded that the P. aeruginosa OMPs vaccine is safe and highly immunogenic in burn patients, especially with 1.0-mg doses at 3-day intervals, and may be effective in conferring protection against P. aeruginosa bacteremia in burn patients.

Adult↗

PubMed2000

Long-term outcomes of minor dissection at the edge of stents detected with intravascular ultrasound.

We evaluated the influences of minor edge dissections on late angiographic in-stent restenosis in 327 patients with 348 lesions (281 lesions without edge dissection and 67 lesions [19.3%] with edge dissection); the angiographic restenosis rate was 29.9% in the lesions with edge dissections versus 25.3% without edge dissections (p = 0.540). The minor non-flow-limiting dissections at the edge of stents may not be associated with the development of late angiographic in-stent restenosis.

Coronary Angiography↗

PubMed2000

The C termini of constitutive nitric-oxide synthases control electron flow through the flavin and heme domains and affect modulation by calmodulin.

The sequences of nitric-oxide synthase flavin domains closely resemble that of NADPH-cytochrome P450 reductase (CPR). However, all nitric-oxide synthase (NOS) isoforms are 20-40 residues longer in the C terminus, forming a "tail" that is absent in CPR. To investigate its function, we removed the 33 and 42 residue C termini from neuronal NOS (nNOS) and endothelial NOS (eNOS), respectively. Both truncated enzymes exhibited cytochrome c reductase activities without calmodulin that were 7-21-fold higher than the nontruncated forms. With calmodulin, the truncated and wild-type enzymes reduced cytochrome c at approximately equal rates. Therefore, calmodulin functioned as a nonessential activator of the wild-type enzymes and a partial noncompetitive inhibitor of the truncated mutants. Truncated nNOS and eNOS plus calmodulin catalyzed NO formation at rates that were 45 and 33%, respectively, those of their intact forms. Without calmodulin, truncated nNOS and eNOS synthesized NO at rates 14 and 20%, respectively, those with calmodulin. By using stopped-flow spectrophotometry, we demonstrated that electron transfer into and between the two flavins is faster in the absence of the C terminus. Although both CPR and intact NOS can exist in a stable, one-electron-reduced semiquinone form, neither of the truncated enzymes do so. We propose negative modulation of FAD-FMN interaction by the C termini of both constitutive NOSs.

Amino Acid Sequence↗

PubMed2000

Effects of cilostazol on angiographic restenosis after coronary stent placement.

This study evaluates the impact of cilostazol on post-stenting restenosis. Cilostazol is a potent antiplatelet agent with antiproliferative properties. Few data are available about the effect of cilostazol on poststenting restenosis. Four hundred nine patients (494 lesions) who were scheduled for elective stenting were randomized to receive aspirin plus ticlopidine (group I, n = 201, 240 lesions) or aspirin plus cilostazol (group II, n = 208, 254 lesions), starting 2 days before stenting. Ticlopidine was given for 1 month and cilostazol for 6 months. Follow-up angiography was performed at 6 months, and clinical evaluation at regular intervals. Baseline characteristics were similar between the 2 groups. The procedural success rate was 99.6% in group I and 100% in group II. There were no cases of stent thrombosis after stenting. Angiographic follow-up was performed in 380 of the 494 eligible lesions and the angiographic restenosis rate was 27% in group I and 22.9% in group II (p = NS). However, diffuse type in-stent restenosis was more common in group I than in group II (54.2% vs 26.8%, respectively, p <0.05). In diabetic patients, the angiographic restenosis rate was 50% in group I and 21.7% in group II (p <0.05). Clinical events during follow-up did not differ between the 2 groups. In conclusion, aspirin plus cilostazol seems to be an effective antithrombotic regimen with comparable results to aspirin plus ticlopidine, but it does not reduce the overall angiographic restenosis rate after elective coronary stenting.

Angioplasty, Balloon, Coronary↗