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Biomedical subjects

J T Park

Publications and source records attributed to J T Park.

At least 19 recordsLinked to original sources

The association between CD99 and LMP-1 expression in nasopharyngeal carcinoma.

AIM: To characterize the roles of LMP-1 and CD99 in nasopharyngeal carcinogenesis, we undertook this pilot study of LMP-1 and CD99 expressions in nasopharyngeal cancer (NPC). MATERIALS AND METHOD: 40 NPC tissue samples were grouped according to the WHO classification. Immunohistochemical studies were performed using monoclonal antibodies against EBV latent membrane protein 1 (LMP-1) and CD99 protein. In addition, CD99 expression was evaluated in 10 samples of non-neoplastic nasopharyngeal epithelium. RESULTS: LMP-1 was detected in 12 of the 40 (30.0%) cases and its expression was found to be confined to epithelial tumor cells. WHO type I NPC samples were completely negative for LMP-1, whereas WHO type III NPC samples showed highest expression. Interestingly, CD99 was expressed in all of the non-neoplastic nasopharyngeal epithelium samples along the cytoplasmic border. CD99 expression was noted in NPC tumor cells (5 of the 40 cases, 12.5%) and in surrounding lymphoid stroma (23 of the 40 cases, 57.5%), but was not expressed in WHO type I NPC. In the 12 LMP-1 positive cases, 9 cases (75.0%) were CD99 negative, and 3 cases (25.5%) were CD99 positive. There was a statistical significance between LMP-1 and CD99 expression in lymphoid stroma. CONCLUSION: Our results suggest that the LMP-1 induced down-regulation of the CD99 pathway is important in nasopharyngeal carcinogenesis, and that the expression of CD99 in lymphoid stroma may regulate immune response to NPC.

12E7 Antigen↗

Geographical difference in the prevalence of isolated systolic hypertension in middle-aged men and women in Korea: the Korean Health and Genome Study.

To compare geographical difference in the prevalence of isolated systolic hypertension (ISH) in between urban (Ansan) and rural (Ansung) Korean adults aged 40-69 years, 4351 men and 4604 women enrolled in the Korean Health and Genome Study were analysed. Information was collected regarding gender, alcohol intake, smoking status, household income, occupation, and years of education by trained interviewers. Eligible subjects included untreated hypertensive and normotensive subjects. ISH was defined as a systolic blood pressure (SBP) > or = 140 mmHg and diastolic BP <90 mmHg. The overall age-adjusted prevalence of ISH was 4.1%. The prevalence of ISH in Ansung (5.7%) was higher than in Ansan (2.5%, P < 0.05). Also it increased with increments of age, from 1.0 to 12.8% in Ansung (P < 0.05) and from 0.3 to 13.0% in Ansan (P < 0.05). In those with body mass index (BMI) > or = 30.0 kg/m2 in Ansung, the prevalence of ISH in women was twice as much as in men. The prevalence of ISH in obese men and women with a waist-hip ratio > or =1.0 and > or = 0.85, respectively, was more than that of nonobese men and women in both areas. In Korea, because of industrialization, the age distribution was skewed and the Korean population in rural areas is more aged. ISH will become a truly major health problem in rural area, because ISH is related to age, BMI and waist-hip ratio. Therefore, the Korean government will be required to institute different policies in the hypertension management to target populations in rural and urban areas.

Female↗

Effects of intracoronary calcium chloride on regional oxygen balance and mechanical function in normal and stunned myocardium in dogs.

BACKGROUND: Brief myocardial ischaemia has been demonstrated to result in mechanical and coronary endothelial dysfunction, in which calcium may play a role. We examined whether the mechanical and vascular responses to calcium are altered in postischaemic, reperfused myocardium. METHODS: Regional myocardial oxygen consumption (MVO2), mechanical function and coronary blood flow (CBF) in response to calcium chloride (0.10, 0.25, 0.50 and 0.75 mg ml(-1) of CBF) directly infused into the left anterior descending (LAD) artery were determined before (normal) and 30 min after a 15-min-period of LAD occlusion (stunned) in an open-chest canine model. Percentage segment shortening (%SS) and percentage postsystolic shortening (%PSS) in the LAD territory were determined using ultrasonic crystals and CBF using a Doppler transducer. Myocardial extraction of oxygen (EO2) and lactate (Elac) was calculated. RESULTS: The infusion of calcium chloride resulted in dose-dependent increases in %SS and MVO2 but did not affect %PSS in normal myocardium. These changes were accompanied by parallel increases in CBF, resulting in no change in EO2. In stunned myocardium, the responses to calcium chloride were not significantly altered, with the exception of a reduction in %PSS. However, ischaemia and reperfusion itself significantly reduced %SS and Elac and increased %PSS. CONCLUSIONS: These data suggest that calcium chloride improves regional systolic and diastolic function both in normal and stunned myocardium. Calcium chloride is unlikely to cause direct coronary vasoconstriction or to deteriorate regional mechanical function in postischaemic myocardium.

Animals↗

Evaluation on the adsorption capabilities of new chemically modified polymeric adsorbents with protoporphyrin IX.

A chemically modified polymeric adsorbent was synthesized to evaluate the availability as an adsorbent for solid-phase extraction (SPE) of phenol and chlorophenols. Commercially available Amberlite XAD-2 and XAD-4 resins were modified with macrocyclic protoporphyrin IX (PPIX) through the ketone linkage. Adsorption isotherms were obtained by batch experiments and the data were fitted to the Freundlich equation to calculate the adsorption parameters. Breakthrough volumes were measured by column experiments. Physical properties such as surface area, average pore diameter and micropore volume of resins were measured to correlate with the adsorption characteristics. As a result, adsorption capacity was increased for the chemically modified resins and it can be concluded that the increase of pi-pi interaction due to the introduction of the porphyrin molecule is the major factor for the increase of the adsorption capacity.

Adsorption↗

Identification of a dedicated recycling pathway for anhydro-N-acetylmuramic acid and N-acetylglucosamine derived from Escherichia coli cell wall murein.

Turnover and recycling of the cell wall murein represent a major metabolic pathway of Escherichia coli. It is known that E. coli efficiently reuses, i.e., recycles, its murein tripeptide, L-alanyl-gamma-D-glutamyl-meso-diaminopimelate, to form new murein. However, the question of whether the cells also recycle the amino sugar moieties of cell wall murein has remained unanswered. It is demonstrated here that E. coli recycles the N-acetylglucosamine present in cell wall murein degradation products for de novo murein and lipopolysaccharide synthesis. Furthermore, E. coli also recycles the anhydro-N-acetylmuramic acid moiety by first converting it into N-acetylglucosamine. Based on the results obtained by studying mutants unable to recycle amino sugars, the pathway for recycling is revealed.

Acetylglucosamine↗

Is the human papillomavirus test in combination with the Papanicolaou test useful for management of patients with diagnoses of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions?

OBJECTIVE: To determine whether human papillomavirus (HPV) testing is useful in the evaluation of patients diagnosed with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) and whether the HPV test is appropriate as an alternative screening method. DESIGN: The results of Papanicolaou (Pap) tests and subsequent hybrid capture tube (HCT) II tests for high-risk-type HPV were analyzed for 457 patients. Among these tests, 208 histologic diagnoses were made and correlated with the results of Pap and HPV tests. The sensitivity and specificity of the Pap test, HPV test, and the combined method of Pap and HPV tests to detect cervical intraepithelial neoplasia (CIN) 2/3 and all CIN were also measured. RESULTS: Sixty (63.8%) of 94 women with LSIL and 31 (26.3%) of 118 women with ASCUS tested positive for high-risk HPV. The sensitivity values for Pap tests in detecting all cases of CIN and CIN 2/3 were 91.4% and 92.9%, respectively. The sensitivity values of HCT II tests using the high-risk probe for detecting all cases of CIN and CIN 2/3 were 62.6% and 88.1%, respectively. Biopsies confirmed that 10 (22.7%) of 44 LSIL patients with high-risk HPV had CIN 2/3, but only 1 (4.5%) of 22 LSIL patients without high-risk HPV had CIN 2/3. CONCLUSION: Testing for high-risk HPV with the HCT II test is useful in the detection of CIN 2/3 in LSIL groups and in the selection of patients for colposcopy in ASCUS groups, but it is not suitable for cervical cancer screening tests.

Biopsy↗

Molecular characterization of the beta-N-acetylglucosaminidase of Escherichia coli and its role in cell wall recycling.

The beta-N-acetylglucosaminidase of Escherichia coli was found to have a novel specificity and to be encoded by a gene (nagZ) that maps at 25.1 min. It corresponds to an open reading frame, ycfO, whose predicted amino acid sequence is 57% identical to that of Vibrio furnissii ExoII. NagZ hydrolyzes the beta-1,4 glycosidic bond between N-acetylglucosamine and anhydro-N-acetylmuramic acid in cell wall degradation products following their importation into the cell during the process for recycling cell wall muropeptides. From amino acid sequence comparisons, the novel beta-N-acetylglucosaminidase appears to be conserved in all 12 gram-negative bacteria whose complete or partial genome sequence data are available.

Acetylglucosaminidase↗

Microfibrillar structure of PGG-glucan in aqueous solution as triple-helix aggregates by small angle x-ray scattering.

The conformation of polysaccharide PGG-Glucan, isolated from yeast cell walls, in aqueous solution was investigated by small angle x-ray scattering (SAXS) and multidetector gel permeation chromatography coupled with postcolumn delivery (GPC/PCD) techniques in comparison with scleroglucan. It was shown that both polysaccharides exhibit a rigid rod-like conformation in aqueous solution by SAXS experiments. The mass per unit length (M/L) and radius (R) of rod cross section of PGG-Glucan were measured to be 6300 daltons/nm and 1.89 nm, while those of scleroglucan are 2300 and 0.83, respectively. Utilizing a GPC/light scattering technique, the average aggregation number of PGG-Glucan is 9, while that of scleroglucan is around 3. From the comparison of the M/L and R of the respective rod cross sections as well as their aggregation number data, it is concluded that PGG-Glucan is composed of triple helices, which tend to aggregate as triplets in solution, whereas scleroglucan is composed of a single triple helix. The aggregation number distribution of PGG-Glucan was found to range from 1 to about 25 determined by GPC/PCD. From the observation of a Debye-Scherrer ring type of peak in the macroscopic scattering cross section of PGG-Glucan by SAXS, the existence of a small amount of ordered clusters of PGG-Glucan can be deduced. The "lattice parameter" of these ordered fasces-like clusters is consistent with the radius of the individual triple-helical rods forming a microfibrillar superstructure. These results indicate that higher aggregated forms of PGG-Glucan containing up to 8 triple helices behave as ordered fasces-like clusters. We conclude that PGG-Glucan is triple-helix aggregates formed by rigid rods stacking together side by side. We propose a molecular structural model for PGG-Glucan conformations.

Carbohydrate Conformation↗

The periplasmic murein peptide-binding protein MppA is a negative regulator of multiple antibiotic resistance in Escherichia coli.

MppA is a periplasmic binding protein in Escherichia coli essential for uptake of the cell wall murein tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate. We have found serendipitously that E. coli K-12 strains carrying a null mutation in mppA exhibit increased resistance to a wide spectrum of antibiotics and to cyclohexane. Normal sensitivity of the mppA mutant to these agents is restored by mppA expressed from a plasmid. As is observed in the multiple antibiotic resistance phenotype in E. coli cells, the mppA null mutant overproduces the transcriptional activator, MarA, resulting in expression of the membrane-bound AcrAB proteins that function as a drug efflux pump. Reduced production of OmpF similar to that observed in the multiple antibiotic resistance phenotype is also seen in the mppA mutant. These and other data reported herein indicate that MppA functions upstream of MarA in a signal transduction pathway to negatively regulate the expression of marA and hence of the MarA-driven multiple antibiotic resistance. Overproduction of cytoplasmic GadA and GadB and of several unidentified cytoplasmic membrane proteins as well as reduction in the amount of the outer membrane protein, OmpP, in the mppA null mutant indicate that MppA regulates a number of genes in addition to those already known to be controlled by MarA.

ATP-Binding Cassette Transporters↗

Cerebral infarction with ICA occlusion after Gamma Knife radiosurgery for pituitary adenoma: A case report.

Cranial irradiation may lead to accelerated atherosclerotic changes to small or medium sized arteries, but stroke associated with pituitary irradiation is not frequent. A patient treated with Gamma Knife radio-surgery (GKRS) for a pituitary adenoma suffered a cerebral infarction with internal carotid artery occlusion 4 years after radiosurgery. The patient was a 35-year-old male presenting with a visual disturbance. Endocrinological tests were normal. MRI revealed a 4.3 by 4.3 cm diameter invasive macroadenoma of the pituitary, projecting toward the suprasellar region and with cavernous sinus involvement with encasement of both internal carotid arteries (ICAs). GKRS was performed for residual tumor after a transcranial resection. The maximum dose was 40 Gy and the dose to the right carotid artery was below 20 Gy. The delayed hemiparesis was accompanied by a right capsular lacunar infarct shown on MRI. The images also showed a marked reduction in tumor size. Total, right ICA occlusion was confirmed by Doppler ultrasound. The patient had no history or signs of heart disease or metabolic disorder which could predispose to cerebrovascular

Adenoma↗

Dominant-negative effect of a mutant cardiac troponin T on cardiac structure and function in transgenic mice.

Hypertrophic cardiomyopathy (HCM) is a disease of sarcomeric proteins. The mechanism by which mutant sarcomeric proteins cause HCM is unknown. The leading hypothesis proposes that mutant sarcomeric proteins exert a dominant-negative effect on myocyte structure and function. To test this, we produced transgenic mice expressing low levels of normal or mutant human cardiac troponin T (cTnT). We constructed normal (cTnT-Arg92) and mutant (cTnT-Gln92) transgenes, driven by a murine cTnT promoter, and produced three normal and five mutant transgenic lines, which were identified by PCR and Southern blotting. Expression levels of the transgene proteins, detected using a specific antibody, ranged from 1 to 10% of the total cTnT pool. M-mode and Doppler echocardiography showed normal left ventricular dimensions and systolic function, but diastolic dysfunction in the mutant mice evidenced by a 50% reduction in the E/A ratio of mitral inflow velocities. Histological examination showed cardiac myocyte disarray in the mutant mice, which amounted to 1-15% of the total myocardium, and a twofold increase in the myocardial interstitial collagen content. Thus, the mutant cTnT-Gln92, responsible for human HCM, exerted a dominant-negative effect on cardiac structure and function leading to disarray, increased collagen synthesis, and diastolic dysfunction in transgenic mice.

Animals↗

Antigen-dependent intrathecal antibody synthesis in the normal rat brain: tissue entry and local retention of antigen-specific B cells.

The intrathecal Ab response to Ag introduced into the normal brain has not been fully explored. Involvement of Ag-specific, peripheral B cells in an intrathecal response was studied using a normal rat model of Ag infusion through an indwelling cannula into defined brain sites, while maintaining a functionally intact blood-brain barrier. Specific Ab was detected in serum and cerebrospinal fluid. The intrathecal response is first detectable at day 14. Isoelectric focusing of cerebrospinal fluid reveals banding patterns consistent with local Ab production. To increase Ag-specific, circulating peripheral lymphocytes available for trafficking to Ag-stimulated brain and for enhancing intrathecal Ab synthesis, rats were preimmunized peripherally. Subsequently, Ag or saline (control) was infused through the cannula. Under this protocol, intrathecal synthesis is detectable earlier (day 5 postinfusion). Immunohistochemical studies at the infusion site assessed Ag-specific B cells, T cells, and activated APCs. Rats receiving peripheral preimmunization followed by Ag into caudate nucleus have far greater numbers of these cells, including plasma cells, within the infusion site compared with saline controls. Results confirm previous indirect evidence of intrathecal Ab synthesis in normal rat brain and provide the first direct evidence for B cell trafficking across normal brain barriers plus retention at the Ag deposition site. Our studies indicate that the normal brain microenvironment supports development of Ag-directed humoral immunity. We propose that immune privilege in normal brain is characterized by down-regulation of cell-mediated but not Ab immune responses within the central nervous system.

Animals↗

Hepatic metastases from carcinoma of the uterine cervix.

OBJECTIVE: To investigate the patterns of hepatic involvement and the outcome of patients with hepatic metastases from carcinoma of the uterine cervix. METHODS: Of 1665 patients with carcinoma of the uterine cervix, 20 patients with hepatic metastases were detected clinically during the course of the disease. Clinical presentation and detailed patterns of hepatic involvement were retrospectively reviewed for these patients. Comparative analysis between patterns of heaptic metastases and survival data was also undertaken. RESULTS: Hepatic metastasis from carcinoma of the uterine cervix were nearly always accompanied by uncontrolled locoregional diseases and/or extrahepatic metastases, whereas only 1 patient developed an isolated hepatic metastasis. Ninety percent of the hepatic metastases were metachronously detected. The median time from the appearance of primary carcinoma to detection of hepatic metastases was 39 months, but late metastases after 5 years were not uncommon. Metastatic lesion in 16 patients consisted of multiple tumors distributed in either one or both anatomical lobes, whereas only 4 patients had a solitary lesion confined to a single lobe. Patients with hepatic metastases were unlikely to survive 2 years with a median survival of 10 months. CONCLUSION: Favorable patterns of hepatic metastases in patient with carcinoma of the uterine cervix were not major determinants of favorable survival if components of extrahepatic disease were concomitantly present.

Adult↗

MppA, a periplasmic binding protein essential for import of the bacterial cell wall peptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate.

Mutants of a diaminopimelic acid (Dap)-requiring strain of Escherichia coli were isolated which failed to grow on media in which Dap was replaced by the cell wall murein tripeptide, L-alanyl-gamma-D-glutamyl-mesodiaminopimelate. In one such mutant, which is oligopeptide permease (Opp) positive, we have identified a new gene product, designated MppA (murein peptide permease A), that is about 46% identical to OppA, the periplasmic binding protein for Opp. A plasmid carrying the wild-type mppA gene allows the mutant to grow on tripeptide. Two other mutants that failed to grow on tripeptide were resistant to triornithine toxicity, indicating a defect in the opp operon. An E. coli strain whose entire opp operon was deleted but which carried the mppA locus was unable to grow on murein tripeptide unless it was provided with oppBCDF genes in trans. Our data suggest a model whereby the periplasmic MppA binds the murein tripeptide, which is then transported into the cytoplasm via membrane-bound and cytoplasmic OppBCDF. In assessing the affinity of MppA for non-cell wall peptides, we have found that proline auxotrophy can be satisfied with the peptide Pro-Phe-Lys, which utilizes either MppA or OppA in conjunction with OppBCDF for its uptake. Thus, MppA, OppA, and perhaps the third OppA paralog revealed by the E. coli genome sequence may each bind a particular family of peptides but interact with common membrane-associated components for transport of their bound ligands into the cell. As to the physiological function of MppA, the possibility that it may be involved in signal transduction pathway(s) is discussed.

ATP-Binding Cassette Transporters↗

A promoter for the first nine genes of the Escherichia coli mra cluster of cell division and cell envelope biosynthesis genes, including ftsI and ftsW.

We constructed a null allele of the ftsI gene encoding penicillin-binding protein 3 of Escherichia coli. It caused blockage of septation and loss of viability when expression of an extrachromosomal copy of ftsI was repressed, providing a final proof that ftsI is an essential cell division gene. In order to complement this null allele, the ftsI gene cloned on a single-copy mini-F plasmid required a region 1.9 kb upstream, which was found to contain a promoter sequence that could direct expression of a promoterless lacZ gene on a mini-F plasmid. This promoter sequence lies at the beginning of the mra cluster in the 2 min region of the E. coli chromosome, a cluster of 16 genes which, except for the first 2, are known to be involved in cell division and cell envelope biosynthesis. Disruption of this promoter, named the mra promoter, on the chromosome by inserting the lac promoter led to cell lysis in the absence of a lac inducer. The defect was complemented by a plasmid carrying a chromosomal fragment ranging from the mra promoter to ftsW, the fifth gene downstream of ftsI, but not by a plasmid lacking ftsW. Although several potential promoter sequences in this region of the mra cluster have been reported, we conclude that the promoter identified in this study is required for the first nine genes of the cluster to be fully expressed.

Bacterial Proteins↗

The convergence of murein recycling research with beta-lactamase research.

The story of how investigation of Escherichia coli cell wall elongation evolved into a study of murein recycling and how this led to the discovery that ampG and ampD were required for both murein recycling and beta-lactamase regulation is chronicled. Preliminary information on two other genes believed to be involved in recycling, nagZ, the structural gene for beta-N-acetylglucosaminidase, and tpl, the presumed structural gene for the hypothetical tripeptide-adding enzyme, is presented. The possibility that recycling of murein fragments serves a signaling function is discussed.

Escherichia coli↗

Identification of the mpl gene encoding UDP-N-acetylmuramate: L-alanyl-gamma-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan.

A gene, mpl, encoding UDP-N-acetylmuramate:L-alanyl-gamma-D-glutamyl-meso-diaminopimelat e ligase was recognized by its amino acid sequence homology with murC as the open reading frame yjfG present at 96 min on the Escherichia coli map. The existence of such an enzymatic activity was predicted from studies indicating that reutilization of the intact tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate occurred and accounted for well over 30% of new cell wall synthesis. Murein tripeptide ligase activity could be demonstrated in crude extracts, and greatly increased activity was produced when the gene was cloned and expressed under control of the trc promoter. A null mutant totally lacked activity but was viable, showing that the enzyme is not essential for growth.

Acetylmuramyl-Alanyl-Isoglutamine↗