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Biomedical subjects

C B Park

Publications and source records attributed to C B Park.

At least 37 records · Page 2Linked to original sources
PubMed1999

Structural and functional implications of a proline residue in the antimicrobial peptide gaegurin.

Although it is commonly known as a helix breaker, proline residues have been found in the alpha-helical regions of many peptides and proteins. The antimicrobial peptide gaegurin displays alpha-helical structure and has a central proline residue (P14). The structure and activity of gaegurin and its alanine derivative (P14A) were determined by various spectroscopic methods, restrained molecular dynamics, and biological assays. Both P14 and P14A exhibited cooperative helix formation in solution, but the helical stability of P14 was reduced substantially when compared to that of P14A. Chemical-shift analysis indicated that both of the peptides formed curved helices and that P14 showed diminished stability in the region around the central proline. However, hydrogen-exchange data revealed remarkable differences in the location of stable amide protons. P14 showed a stable region in the concave side of the curved helix, while P14A exhibited a stable region in the central turn of the helix. The model structure of P14 exhibited a pronounced kink, in contrast to the uniform helix of P14A. Both peptides showed comparable binding affinities for negatively charged lipids, while P14 had a considerably reduced affinity for a neutral lipid. With its destabilized alpha-helix, P14 exhibited greater antibacterial activity than did P14A. Hence, electrostatic interaction between helical peptides and lipid membranes is believed to be the dominant factor for antibacterial activity. Moreover, helical stability can modulate peptide binding to membranes that is driven by electrostatic interactions. The observation that P14 is a more potent antibacterial agent than P14A implies that the helical kink of P14 plays an important role in the disruption of bacterial membranes.

Amides↗
PubMed1999

Cross-country comparisons of colon and rectal cancer mortality suggest the existence of differences in risk factors in eastern and western Europe.

A comparison of relative mortality rates from colon and rectal cancers in World Health Organization data for various countries in Europe was undertaken to determine whether the two sites demonstrate a direct link. A significant correlation between figures for colon and rectal cancers was found throughout Europe but limited to males and only at the p < 0.05 level. Cluster analysis revealed marked differences between countries of the former west and east European blocks, the latter having much higher values for rectal cancers. Separation of countries on this basis gave rise to significant correlation between the two sites for both sexes (p < 0.05 and p < 0.001, respectively, for western and eastern males; and p < 0.05 and p < 0.001 for females). In order to assess the possible contribution of factors associated with squamous cell cancers (SCCs), data for buccal and cervical cancers, both more prevalent in eastern than in western Europe, were also compared. Whereas a significant correlation was evident between female rectal and cervical cancers overall and in the western countries (p < 0.05) this was not the case for the eastern countries. The results suggest that the observed excess of rectal cancer mortality in eastern European countries may not be simply due to factors contributing to SCCs, but that country level comparisons of individual harmful and beneficial influences, alone and in combination, might allow the underlying reasons to be explained.

Analysis of Variance↗
PubMed1999

European registry comparisons provide evidence of shared risk factors for renal, colon and gallbladder cancer development.

In order to assess links between renal cell cancer (RCCs) and transitional cell cancers (TCCs) of the kidney and cancer development in other organs of the abdominal cavity, incidence data from the Cancer Incidence in Five Continents (Vol VII) were compared between various cancer registries in Europe. Significant correlations which persisted on partial analysis were observed between RCCs and carcinomas of the colon and gallbladder, as well as between the latter themselves. Kidney TCCs, in contrast, were associated with tumours of the urinary bladder. In addition, significant correlations between hepatocellular, but not cholangiocellular carcinomas, and gallbladder and colon cancers were observed. Data for pancreas and gallbladder neoplasms also correlated. Prostate cancer incidences, while positively linked to RCCs, negatively correlated with gallbladder rates. The results point to shared risk factors for RCCs and adenocarcinomas in a number of organs, suggesting a role for humoral agents. The present findings also underline the necessity of distinguishing between tumour types within organs in epidemiological investigations of causal influences.

Adenocarcinoma↗
PubMed1998

Parasin I, an antimicrobial peptide derived from histone H2A in the catfish, Parasilurus asotus.

In response to epidermal injury, Parasilurus asotus, a catfish, secreted a strong antimicrobial peptide into the epithelial mucosal layer. The molecular mass of the antimicrobial peptide, named parasin I, was 2000.4 Da, as determined by matrix-associated laser desorption ionization mass spectrometry. The complete amino acid sequence of parasin I, which was determined by automated Edman degradation, was Lys-Gly-Arg-Gly-Lys-Gln-Gly-Gly-Lys-Val-Arg-Ala-Lys-Ala-Lys-Thr-Arg-Ser- Ser. Eighteen of the 19 residues in parasin I were identical to the N-terminal of buforin I, a 39-residue antimicrobial peptide derived from the N-terminal of toad histone H2A [Kim et al. (1996) Biochem. Biophys. Res. Commun. 229, 381-387], which implies that parasin I was cleaved off from the N-terminal of catfish histone H2A. Parasin I showed strong antimicrobial activity, about 12-100 times more potent than magainin 2, against a wide spectrum of microorganisms, without any hemolytic activity. Circular dichroism spectra of parasin I indicated a structural content of 11% alpha-helix, 33% beta-sheet, and 56% random coils. The beta-sheet axial projection diagram of parasin I showed an amphipathic structure. Our results indicate that the catfish may produce parasin I from its histone H2A by a specific protease upon injury to protect against invasion by microorganisms.

Amino Acid Sequence↗
PubMed1998

Lumbricin I, a novel proline-rich antimicrobial peptide from the earthworm: purification, cDNA cloning and molecular characterization.

A novel antimicrobial peptide was isolated and characterized from the earthworm, Lumbricus rubellus. The antimicrobial peptide was purified to homogeneity by a heparin-affinity column and C18 reverse-phase HPLC, and named lumbricin I. Lumbricin I was a proline-rich antimicrobial peptide of 62 amino acids (15% proline in molar ratio; molecular mass, 7231 Da), whose complete sequence was determined by a combination of peptide sequence and cDNA analysis. The peptide and cDNA sequence analysis revealed that lumbricin I was produced as a precursor form consisting of 76 amino acids, with 14 residues in a presegment and 62 residues in mature lumbricin I. Lumbricin I showed antimicrobial activity in vitro against a broad spectrum of microorganisms without hemolytic activity. In addition, a 29-amino acid peptide, named lumbricin I(6-34), which was derived from residues 6-34 of lumbricin I, showed marginally stronger antimicrobial activity than lumbricin I. Northern blot analysis on total RNA revealed that expression of lumbricin I gene was not induced by bacterial infection, but was constitutively expressed. Furthermore, the expression of lumbricin I gene was specific in adult L. rubellus: Lumbricin I mRNA was detected only in adult L. rubellus, but not in eggs and young L. rubellus.

Amino Acid Sequence↗
PubMed1998

Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions.

The mechanism of action of buforin II, which is a 21-amino acid peptide with a potent antimicrobial activity against a broad range of microorganisms, was studied using fluorescein isothiocyanate (FITC)-labeled buforin II and a gel-retardation experiment. Its mechanism of action was compared with that of the well-characterized magainin 2, which has a pore-forming activity on the cell membrane. Buforin II killed Esche-richia coli without lysing the cell membrane even at 5 times minimal inhibitory concentration (MIC) at which buforin II reduced the viable cell numbers by 6 orders of magnitude. However, magainin 2 lysed the cell to death under the same condition. FITC-labeled buforin II was found to penetrate the cell membrane and accumulate inside E. coli even below its MIC, whereas FITC-labeled magainin 2 remained outside or on the cell wall even at its MIC. The gel-retardation experiment showed that buforin II bound to DNA and RNA of the cells over 20 times strongly than magainin 2. All these results indicate that buforin II inhibits the cellular functions by binding to DNA and RNA of cells after penetrating the cell membranes, resulting in the rapid cell death, which is quite different from that of magainin 2 even though they are structurally similar: a linear amphipathic alpha-helical peptide.

Anti-Bacterial Agents↗
PubMed1998

Acidic peptide-mediated expression of the antimicrobial peptide buforin II as tandem repeats in Escherichia coli.

Antimicrobial peptides have received increasing attention as a new pharmaceutical substance, because of their broad spectrum of antimicrobial activities and the rapid development of multidrug-resistant pathogenic microorganisms. The main obstacle to the wide application of antimicrobial peptides has been the lack of a cost-effective, mass-production method. A novel mass-production method for an antimicrobial peptide of 21 amino acids, buforin II, which was isolated from the stomach of the amphibian Bufo bufo gargarizans, has been developed. This method is based on the neutralization of the positive charges of buforin II by fusing to an acidic peptide to avoid the lethal effect of the expressed antimicrobial peptide on the host cells. The fusion peptide was expressed in Escherichia coli as tandem repeats to increase the product yield. Multimers of the acidic peptide-buforin II fusion peptide were expressed at high levels without causing damage to the cells. The presence of cysteine residues in the acidic peptide was critical for the high level expression of the fusion peptide multimers. Multimers of this fusion peptide were expressed as inclusion bodies, and about 107 mg of pure buforin II was obtained from 1 L of E. coli culture by cleaving the multimers with CNBr. Recombinant buforin II had an antimicrobial activity identical to that of natural buforin II. These results may lead to a general, cost-effective solution to the mass production of antimicrobial peptides and other basic peptides which are lethal to the host strain.

Amino Acid Sequence↗
PubMed1998

Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation.

The present study was carried out to examine the chemopreventive effects of carotenoids such as fucoxanthin, lycopene and lutein as well as curcumin and its derivative, tetrahydrocurcumin (THC), on development of putative preneoplastic aberrant crypt foci (ACF) in colons of mice initiated with 1,2-dimethylhydrazine dihydrochloride (DMH). Influence on proliferation of colonic crypt epithelial cells was also assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Five-week-old B6C3F1 male mice were divided into three groups, groups 1 and 2 being given DMH (20 mg/kg body wt, s.c.) twice a week for 3 weeks. Animals of group 1 were then treated with one of the test compounds, lycopene (0.005% and 0.0025%) or fucoxanthin (0.01%) in the drinking water and lutein (0.05%), curcumin (0.5%) or THC (0.5% and 0.2%) in the diet from weeks 5-12. Group 2 served as a carcinogen alone control and group 3 mice were given test compounds alone. All animals were killed at week 12. Numbers of ACF/mouse in the group 1 treated with fucoxanthin (47.1 +/- 13.7), lutein (42.6 +/- 19.6) or 0.5% THC (46.6 +/- 17.7) were significantly decreased as compared to the control group 2 value (63.3 +/- 19.4) (P < 0.01). Numbers of aberrant crypts (ACs)/mouse were also significantly lower after treatment with lutein (79.9 +/- 34.7) or 0.5% THC (81.8 +/- 32.5) than in the control group (115.1 +/- 37.1) (P < 0.01). BrdU labeling indices (LI) in mice treated with lutein and 0.5% THC were significantly decreased in both upper and lower half compartments of colonic crypts as compared to the controls (P < 0.05 and 0.01, respectively), especially the upper half data corresponding to reduction of ACs/mouse. The results thus suggest that fucoxanthin, lutein, and THC may have potential as chemopreventive agents against colon carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1998

Physical exercise: a pillar for cancer prevention?

Both epidemiological and experimental studies have shown that physical exercise deserves particular attention in any consideration of approaches to the prevention of neoplasia, especially since it also exerts consistent beneficial effects on the other major chronic diseases prevalent in the Western world, atherosclerosis and non-insulin dependent diabetes mellitus (NIDDM). The organ sites for which strong evidence has been gained for a protective influence of exercise or an elevated risk with a sedentary existence include the colon, prostate, breast and endometrium. The underlying mechanisms appear to centre on the hormones insulin and oestrogen, serum elevation of both of these endocrine factors being associated with increased risk of neoplastic development. The immense potential benefit of an increased level of exercise in the general population suggests that commensurate measures should be taken in the field of cancer education.

Chronic Disease↗
PubMed1998

European country comparisons provide evidence of a link between colon cancer and adenocarcinoma development in the lung but not the oesophagus.

Relative incidence rates of lung cancers demonstrate marked international variation in values for the different histological sub-types. In order to determine whether adenocarcinomas (ACs) in this site might share risk factors with other ACs, for example, in the breast, prostate, oesophagus and colon, a comparison of data in the IARC/WHO Cancer Incidence in Five Continents (Volume VII) was made for selected registries in Europe. Significant correlations were found between lung AC incidences/100,000 population and prostate and colon cancers in males (P < 0.005 and P < 0.05, respectively) and for breast and colon in females (P < 0.05 for both). Partial correlation coefficients were significant for lung and colon (P < 0.001) and prostate and colon (P < 0.005) in men, and for breast and colon in women (P < 0.005). A significant negative correlation with prostate cancer was noted for lung ACs in men. The results provide support for shared risk factors between lung Acs and colon cancers but do not indicate any link with AC development in the oesophagus. Data from registries in the UK and Italy were remarkable for high incidences of oesophageal and lung ACs, respectively, pointing to major differences in environmental risk factor or beneficial influence acting on these sites between the two countries.

Adenocarcinoma↗
PubMed1998

Implications of the hyperinsulinaemia-diabetes-cancer link for preventive efforts.

Recent epidemiological evidence points to a link between non-insulin dependent diabetes mellitus type II (NIDDM) and cancer of the colon, liver, pancreas, breast and endometrium. This appears to be due to the long period of hyperinsulinaemia which precedes the clinical phase of NIDDM, insulin promoting colon tumour development as well as acting as a hepatocarcinogen. Indeed, the hormone could play a central role in neoplasia, and its influence could explain the observed enhancing effects of obesity and a high fat diet, as well as the inhibition associated with physical exercise, dehydroepiandrosterone administration and high soluble fibre intake. Measures to decrease insulin levels, including lifestyle improvement and supplementation with agents known to decrease insulin resistance may therefore offer a general approach to prevention of cancer in a wide variety of organ sites of major clinical importance.

Diabetes Mellitus, Type 2↗
PubMed1997

A novel antimicrobial peptide from the loach, Misgurnus anguillicaudatus.

A novel antimicrobial peptide, named misgurin, was isolated and characterized from the loach (mudfish), Misgurnus anguillicaudatus. The 21-amino-acid peptide with a molecular mass of 2502 Da was purified to homogeneity using a heparin-affinity column and C18 reverse-phase and gel-permeation high-performance liquid chromatography. The complete amino acid sequence of misgurin, which was determined by an automated amino acid sequencer, was Arg-Gln-Arg-Val-Glu-Glu-Leu-Ser-Lys-Phe-Ser-Lys-Lys-Gly-Ala-Ala-Ala-Arg- Arg-Arg-Lys. Misgurin is a strongly basic peptide which has 5 arginine and 4 lysine residues. Comparison of the amino acid sequence with those of other known antimicrobial peptides revealed that misgurin was a novel antimicrobial peptide. Misgurin showed a strong antimicrobial activity in vitro against a broad spectrum of microorganisms without significant hemolytic activity and was about 6 times more potent than magainin 2. Scanning electron microscopy confirmed that the peptide caused damage to the cell membrane by a pore-forming mechanism similar to that of magainin 2. This damage occurred at the minimal inhibition concentration (MIC), but at higher concentration than MIC it lysed the cell.

Amino Acid Sequence↗
PubMed1996

cDNA cloning and characterization of buforin I, an antimicrobial peptide: a cleavage product of histone H2A.

A cDNA containing coding information for buforin I, the toad stomach antimicrobial peptide, was identified by PCR. The cloned cDNA encoded a protein of 129 amino acids whose 39-amino-acid N-terminus was identical to buforin I. Nucleotide sequence analysis of the cloned cDNA revealed that it had over 90% amino acid homology with histone H2A, the replication-dependent protein. Both Northern and Southern blot analysis of the toad genome suggested that histone H2A and buforin I were encoded by the same gene. A specific protease responsible for the generation of buforin I from histone H2A was found to be present in the crude extracts of the toad stomach. These results suggest that there exists a specific regulation mechanism which converts the toad histone H2A to the antimicrobial peptide buforin I.

Amino Acid Sequence↗
PubMed1996

Solution structure of an antimicrobial peptide buforin II.

The structure of 21-residue antimicrobial peptide buforin II has been determined by using NMR spectroscopy and restrained molecular dynamics. Buforin II adopts a flexible random structure in H2O. In trifluoroethanol (TFE)/H2O (1:1, v/v) mixture, however, buforin II assumes a regular alpha-helix between residues Val12 and Arg20 and a distorted helical structure between residues Gly7 and Pro11. The model structure obtained shows an amphipathic character in the region from Arg5 to the C-terminus, Lys21. Like other known cationic antimicrobial peptides, the amphipathic structure might be the key factor for antimicrobial activity of buforin II.

Amino Acid Sequence↗
PubMed1996

A novel antimicrobial peptide from Bufo bufo gargarizans.

A potent and structurally novel antimicrobial peptide was isolated and characterized from the stomach tissue of Bufo bufo gargarizans, an Asian toad. The 39-amino acid peptide, named buforin I, was purified to homogeneity by heparin-affinity column and reverse-phase HPLC. The amino acid sequence of buforin I was identical in 37 of 39 amino-terminal residues of Xenopus histone H2A. The buforin I showed strong antimicrobial activities in vitro against a broad-spectrum of microorganisms and was found to be more potent than magainin 2. In addition, a 21-amino acid peptide, named buforin II, which was derived from buforin I, showed more potent antimicrobial activities than buforin I.

Amino Acid Sequence↗
PubMed1996

Case-control study of idiopathic Parkinson's disease and dietary vitamin E intake.

A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD, these preliminary data do not conclusively document a beneficial effect of dietary vitamin E on PD occurrence.

Aged↗