Biomedical subjects

B Ho

Publications and source records attributed to B Ho.

At least 37 records · Page 2Linked to original sources

PubMed2000

Interpretation of biological activity data of bacterial endotoxins by simple molecular models of mechanism of action.

Lipid A moiety has been identified as the bioactive component of bacterial endotoxins (lipopolysaccharides). However, the molecular mechanism of biological activity of lipid A is still not fully understood. This paper contributes to understanding of the molecular mechanism of action of bacterial endotoxins by comparing molecular modelling results for two possible mechanisms with the underlying experimental data. Mechanisms of action involving specific binding of lipid A to a protein receptor as well as nonspecific intercalation into phospholipid membrane of a host cell were modelled and analysed. As the cellular receptor for endotoxin has not been identified, a model of a peptidic pseudoreceptor was proposed, based on molecular structure, symmetry of the lipid A moiety and the observed character of endotoxin-binding sites in proteins. We have studied the monomeric form of lipid A from Escherichia coli and its seven synthetic analogues with varying numbers of phosphate groups and correlated them with known biological activities determined by the Limulus assay. Gibbs free energies associated with the interaction of lipid A with the pseudoreceptor model and intercalation into phospholipid membrane calculated by molecular mechanics and molecular dynamics methods were used to compare the two possible mechanisms of action. The results suggest that specific binding of lipid A analogues to the peptidic pseudoreceptor carrying an amphipathic cationic binding pattern BHPHB (B, basic; H, hydrophobic; P, polar residue, respectively) is energetically more favourable than intercalation into the phospholipid membrane. In addition, binding affinities of lipid A analogues to the best minimum binding sequence KFSFK of the pseudoreceptor correlated with the experimental Limulus activity parameter. This correlation enabled us to rationalize the observed relationship between the number and position of the phosphate groups in the lipid A moiety and its biological activity in terms of specific ligand-receptor interactions. If lipid A-receptor interaction involves formation of phosphate-ammonium ion-pair(s) with cationic amino-acid residues, the specific mechanism of action was fully consistent with the underlying experimental data. As a consequence, recognition of lipid A variants by an amphipathic binding sequence BHPHB of a host-cell protein receptor might represent the initial and/or rate-determining molecular event of the mechanism of action of lipid A (or endotoxin). The insight into the molecular mechanism of action and the structure of the lipid A-binding pattern have potential implications for rational drug design strategies of endotoxin-neutralizing agents or binding factors.

Amino Acid Motifs↗

PubMed2000

Increasing frequency of dental patients in the urban ED.

This study examined the spectrum and frequency of dental disorders presenting to an urban ED. Data were retrospectively collected on all patients presenting with dental complaints between January 1, 1987 and December 31, 1995. Data included age, date and time of presentation, diagnosis, triage acuity and disposition. Of the 3,943 charts reviewed, 1,892 (48%) patients required emergent oral surgery management and 2,051 (52%) emergency physician management only. The frequency of dental patients increased from 4.4/1,000 total ED patients in 1987 to 11.5/1,000 in 1995 (P < .05). The rate of emergent dental trauma, emergent nontraumatic dental care, and nonemergent nontraumatic dental care increased similarly during the study period. There was no significant difference by day of week, but a significantly greater number of nonemergent patients presented between 7:00 a.m. and 3:00 p.m. (72%). The incidence of dental patients presenting to the ED increased significantly between 1987 and 1995. Approximately one-half did not require specialist consultation and could potentially have been managed by a primary care dental practitioner.

Adolescent↗

PubMed2000

Expression of histo-blood group antigens by lipopolysaccharides of Helicobacter pylori strains from asian hosts: the propensity to express type 1 blood-group antigens.

Past studies have shown that the cell surface lipopolysaccharides (LPSs) of the ubiquitous human gastric pathogen Helicobacter pylori (a type 1 carcinogen) isolated from people residing in Europe and North America express predominantly type 2 Lewis x (Le(x)) and Le(y) epitopes and, infrequently, type 1 Le(a), Le(b), and Le(d) antigens. This production of Lewis blood-group structures by H. pylori LPSs, similar to those found in the surfaces of human gastric cells, allows the bacterium to mimic its human niche. In this study, LPSs of H.pylori strains extracted from patients living in China, Japan, and Singapore were chemically and serologically analyzed. When compared with Western H.pylori LPSs, these Asian strains showed a stronger tendency to produce type 1 blood groups. Of particular interest, and novel observations in H.pylori, the O-chain regions of strains F-58C and R-58A carried type 1 Le(a) without the presence of type 2 Le(x), strains R-7A and H607 were shown to have the capability of producing the type 1 blood group A antigen, and strains CA2, H507, and H428 expressed simultaneously the difucosyl isomeric antigens, type 1 Le(b) and type 2 Le(y). The apparent proclivity for the production of type 1 histo-blood group antigens in Asian H.pylori LPSs, as compared with Western strains, may be an adaptive evolutionary effect in that differences in the gastric cell surfaces of the respective hosts might be significantly dissimilar to select for the formation of different LPS structures on the resident H.pylori strain.

ABO Blood-Group System↗

PubMed2000

High-affinity LPS binding domain(s) in recombinant factor C of a horseshoe crab neutralizes LPS-induced lethality.

SSCrFCES is a biologically active, recombinant fragment of factor C, which is the endotoxin-sensitive serine protease of the LAL coagulation cascade. The approximately 38 kDa protein represents the LPS binding domain of factor C. A novel secretory signal directs the secretion of SSCrFCES into the culture supernatant of Drosophila cells, and hence it is readily purified. By differential ultrafiltration followed by preparative isoelectric membrane electrophoresis, SSCrFCES was purified as an isoelectrically homogeneous and stable monomeric protein. The ability of SSCrFCES to bind lipid A was analyzed using an ELISA-based assay as well as surface plasmon resonance. SSCrFCES exhibits high positive cooperativity of binding to two or three lipid A molecules, with a Hill's coefficient of 2.2. The 50% endotoxin-neutralizing concentration of SSCrFCES against 200 EU of endotoxin is approximately 0.069 microM, suggesting that SSCrFCES is an effective inhibitor of LAL coagulation cascade. Although partially attenuated by human serum, as little as 1 microM of SSCrFCES inhibits the LPS-induced secretion of hTNF-alpha and hIL-8 by THP-1 and human peripheral blood mononuclear cells with greater potency than polymyxin B. SSCrFCES is noncytotoxic, with a clearance rate of 4.7 ml/min. The L.D.(90) of SSCrFCES for LPS lethality is achieved at 2 microM. These results demonstrate the endotoxin-neutralizing capability of SSCrFCES in vitro and in vivo and its potential use for the treatment of endotoxin-induced septic shock.

Animals↗

PubMed2000

Definition of endotoxin binding sites in horseshoe crab factor C recombinant sushi proteins and neutralization of endotoxin by sushi peptides.

Three truncated fragments, harboring different sushi domains, namely, sushi123, sushi1, and sushi3 domains, of Factor C were produced as biologically active secreted recombinant proteins. Sushi1 and 3 each has a high-affinity LPS binding site with K:(d) of 10(-9) to 10(-10) M. Positive cooperativity in sushi123 resulted in a 1000-fold increase in K:(d)2. The core LPS binding region of sushi1 and 3 reside in two 34-mer peptides, S1 and S3. A rigidly held disulfide-bonded structure is not essential but is important for LPS binding, as confirmed by a 100- to 10000-fold decrease in affinity. Both S1 and S3 can inhibit LAL reaction and LPS-induced hTNF-alpha secretion with different potency. LAL assay revealed that at least two molecules of S1 bind cooperatively to one LPS molecule, with Hill's coefficient of 2.42. The LPS binding by S3 is independent and noncooperative. The modified SDelta1 and SDelta3 peptides exhibited increased LPS neutralization potential although its LPS binding affinities indicated only a 10-fold improvement. Hence, the structural difference of the four sushi peptides conferred different efficiencies in LPS neutralization without altering their binding affinity for LPS. Circular dichroism spectrometry revealed that the four peptides underwent conformational change in the presence of lipid A, transitioning from a random coil to either an alpha-helical or beta-sheet structure. Two factors are critical for the sensitivity of Factor C to LPS: 1) the presence of multiple binding sites for LPS on a single Factor C molecule; and 2) high positive cooperativity in LPS binding. The results showed that in the design of an improved LPS binding and neutralizing peptide, charge balance of the peptide is a critical parameter in addition to its structure.

Animals↗

PubMed2000

Isolation of a single strain of Helicobacter pylori from the antrum and body of individual patients.

OBJECTIVES: This study aimed to determine intra-patient colonization patterns of Helicobacter pylori strains based on DNA fingerprinting and antibiotic susceptibility. METHODS: Two biopsies, one from the antrum and one from the body of the stomach, were taken from 97 patients. Prior informed consent was obtained. The status of cagA gene of H. pylori strains was analysed by using the polymerase chain reaction (PCR) technique, while DNA fingerprints were generated by PCR-based, random amplified polymorphic DNA (RAPD) fingerprinting. The antibiotic susceptibility of the H. pylori isolates was examined by the disk diffusion method. RESULTS: A total of 51 pairs of H. pylori strains were isolated from both antrum and body specimens of 51 patients. This included two patients who were endoscoped twice because of treatment failure. All strains were positive for cagA gene by PCR. These 51 patients were found to harbour a single strain of H. pylori with identical or highly similar DNA profiles by PCR-based RAPD fingerprinting. In four of the 51 pairs, the DNA patterns of H. pylori from antrum and body showed minor differences, while three pairs of strains with different metronidazole sensitivities showed identical DNA fingerprints. Interestingly, the two treatment failure patients remained colonized with the strains that had the same RAPD fingerprinting patterns before and after treatment. CONCLUSION: The present study demonstrates that a single H. pylori strain colonizes a single stomach. However, this single genotypic strain may exhibit different metronidazole susceptibility in different parts of stomach.

Adult↗

PubMed2000

Association of peptic ulcer with increased expression of Lewis antigens but not cagA, iceA, and vacA in Helicobacter pylori isolates in an Asian population.

BACKGROUND: Studies in Western populations suggest that cagA, iceA, and vacA gene status in Helicobacter pylori isolates is associated with increased virulence and peptic ulcer disease. AIM: To investigate the relationship between peptic ulcer and expression of Lewis (Le) antigens as well as cagA, iceA, and vacA in H pylori isolates in Singapore. METHODS: Expression of Le antigens in H pylori isolates obtained from patients with dyspepsia was measured by enzyme linked immunosorbent assay. The cagA, iceA, and vacA status was determined by polymerase chain reaction. RESULTS: Of 108 H pylori isolates, 103 (95.4%) expressed Le(x) and/or Le(y), while Le(a) and Le(b) were expressed in 23 (21.3%) and 47 (43.5%) isolates, respectively. Expression of two or more Le antigens (Le(x), Le(y), Le(a), or Le(b)) was significantly higher in H pylori isolated from ulcer patients than in non-ulcer patients (89.6% v 73.2%, p=0.035). There were no significant differences in the prevalence of cagA or iceA1 in H pylori isolates from peptic ulcer and non-ulcer patients (86.6% v 90.2% for cagA; 70.1% v 68.3% for iceA1), and no association of peptic ulcer with any specific vacA genotype. CONCLUSIONS: The present study indicates that peptic ulcer disease is associated with increased expression of Lewis antigens but not cagA, iceA, or vacA genotype in H pylori isolates in our population. This suggests that cagA, iceA, and vacA are not universal virulence markers, and that host-pathogen interactions are important in determining clinical outcome.

Adolescent↗

PubMed2000

The status of the cagA gene does not predict Helicobacter pylori-associated peptic ulcer disease in Singapore.

Discrepancies among reports from different geographical regions worldwide on the association between the presence of cagA and peptic ulcer disease prompted this study on the predictive value of the cagA gene in Helicobacter pylori-associated gastroduodenal diseases in the Singapore population. H. pylori strains were obtained from 169 patients with a peptic ulcer, 83 with non-ulcer dyspepsia, and nine with gastric cancer. The presence of the cagA gene was evaluated by polymerase chain reaction (PCR). The expected 400 bp PCR product coding for the cagA gene was present in 232/261 (89%) H. pylori isolates. Of these, 151/169 (89%) strains from patients with peptic ulcer, 73/83 (88%) strains from patients with non-ulcer dyspepsia and 8/9 (89%) strains from cancer patients were positive for the cagA gene. There was no statistically significant difference between the prevalence of cagA-positive strains from patients with distinct clinical outcomes (p > 0.05). The prevalence of cagA-positive strains in the Singapore population is high regardless of clinical disease status. The results suggest that the cagA gene is not a universal virulence marker of H. pylori.

Adolescent↗

PubMed1999

Predominance of a single strain of Helicobacter pylori in gastric antrum.

BACKGROUND: Diversity of DNA among H. pylori strains isolated from different patients can serve as a useful marker for differentiating strains. DNA profiles of H. pylori obtained from sequential gastric biopsies were identical in most patients indicating that a given strain can persist from months to years. Patients colonized with more than two strains isolated mainly from different anatomical sites have been reported. This work examined whether the gastric antrum of patients with dyspepsia is colonized by single or multiple strains of H. pylori as well as the in vitro competition of different strains of H. pylori. MATERIALS AND METHODS: Two antral biopsy specimens from each of the 124 patients were cultured for H. pylori. DNA fingerprinting of H. pylori isolates was performed using random amplified polymorphic DNA (RAPD) analysis. To elucidate the possible interaction among H. pylori isolates, bacterial populations of two H. pylori strains cogrown in broth medium over 21 days were enumerated and DNA fingerprinting was compared. RESULTS: A total of 58 patients showed the presence of H. pylori in both antral specimens, while five patients had H. pylori in only one of the two samples. These 58 patients were shown to harbor a single strain of H. pylori as analyzed by RAPD fingerprinting. In vitro studies of bacterial interaction of two different strains of H. pylori showed growth competition resulting in the predominance of a single strain. CONCLUSIONS: The results support the concept that a single strain predominates in the gastric antrum site of patients studied.

Antibiosis↗

PubMed1999

Ventricular volume following third ventriculostomy.

OBJECT: Ventricular size often shows no obvious change following third ventriculostomy, particularly in the early postoperative period, making postoperative evaluation difficult without expensive and often invasive testing in patients with equivocal clinical responses. The authors hypothesized that performing careful volumetric measurements would show decreases in size within the first 3 weeks after surgery. METHODS: Volumetric measurements were calculated from standard 3 x 3-mm axial computerized tomography (CT) scans obtained immediately before and 3 and 21 days after surgery. Two independent investigators measured third ventricular volume in a series of 16 patients and lateral ventricular volume in 10 of the patients undergoing stereotactically guided endoscopic third ventriculostomy for noncommunicating hydrocephalus. Fifteen patients were symptomatically improved at the time the follow-up scan was obtained. Third ventricular volume decreased in all patients by a mean of 35% (range 7.8-95.1%) and lateral ventricular volume decreased in all patients by a mean of 33% (range 4.5-80.3%). The degree of change correlated with the length of preoperative symptoms (p < 0.005). The one patient who experienced no improvement showed no decrease in third ventricular volume. In seven of 10 patients, the decrease in third ventricular volume exceeded the decrease in lateral ventricular volume. Repeated measurements indicated that the 95% confidence interval for the authors' calculations varied around the mean by 2.5% for third ventricular volume and 1.2% for lateral ventricular volume. Long-term outcome was excellent, with only one case of delayed failure. The mean follow-up duration was 12 months. CONCLUSIONS: Volumetric measurements calculated from standard CT scans will show a demonstrable decrease in ventricular volume soon after successful third ventriculostomy and can be helpful in assessing patients postoperatively. Although the third ventricle may exhibit a greater decrease, the lateral ventricular measurements are more accurate. Patients with more indolent symptoms show the smallest change.

Adolescent↗

PubMed1999

2-pyridylthioureas: novel nonpeptide somatostatin agonists with SST4 selectivity.

Somatostatin [somatotropin release-inhibiting factor (SRIF)] is a cyclic tetradecapeptide that is a potent inhibitor of growth hormone (GH) secretion from the anterior pituitary. In addition to the inhibitory effects on GH-release, SRIF-14 and SRIF-28, a 28-amino acid form of SRIF extended from the N-terminal end, inhibit the release of a variety of other peptides including glucagon, insulin, and gastrin, and both peptides act as neurotransmitters and neuromodulators in the central nervous system and the periphery. SRIF exerts its potent inhibitory effects following binding to high affinity SRIF receptors (ssts) that have been identified on target tissues. The recent cloning of five ssts has confirmed that the effects of SRIF are mediated by a family of G protein-coupled receptors (sst1-5). Based on structural and pharmacological properties sst2, sst3, and sst5 belong to the SRIF1 receptor subclass, and the sst1 and sst4 subtypes comprise the SRIF2 subclass. The major difference between these two subclasses is that SRIF1 receptors bind octapeptide and hexapeptide SRIF-14 analogs with high affinity, while SRIF2 receptors bind these analogs with drastically reduced affinity. A screening program was initiated to identify a lead nonpeptide with affinity for sst1-5 receptors. The search focused on a scaffold with the following attachments: (1) a heteroaromatic nucleus to mimic the Trp8 residue, (2) a nonheteroaromatic nucleus to mimic Phe7, and (3) a primary amine or other basic group to mimic the Lys9 residue of SRIF-14. Using these criteria, a novel thiourea (NNC 26-9100, 17) was discovered as a structural lead. The key fragments in this compound are a heteroaromatic moiety (pyridine), an aromatic group, and a basic imidazole group connected through a thiourea scaffold. Compound 17 exhibited a Ki = 6 nM at sst4 receptors with a 100-fold sst4/sst2 selectivity and was shown to be a full agonist at this receptor subtype. This article will review the literature on the design and development of nonpeptide somatostatin receptor ligands and the therapeutic potential of these agents. Furthermore, our work on the development of 2-pyridylthioureas as sst4 receptor agonists will be described.

Animals↗

PubMed1999

Unchanged characteristics of Helicobacter pylori during its morphological conversion.

Helicobacter pylori strains RH 54 and NCTC 11637 were grown in brain-heart infusion broth up to 56 days, and the coccoid form was obtained during prolonged incubation. Two morphological types of coccoids were observed, one of which was electron-dense and had an intact cellular membrane and flagella, indicating that it was likely to be viable. The other coccoid form was sphaeroblast-like and weakly stained, showing features of degeneration. Catalase activity was positive for aged cultures even up to 160 days. Sodium dodecyl sulphate polyacrylamide gel electrophoresis showed that most of the protein bands appeared to be similar in both the spiral and coccoid forms. In addition, Lewis blood group antigens were detected in cultures of up to 8 weeks. Furthermore, two sets of primers for the vacA and cagA genes were used in polymerase chain reaction, and these two important genes remained conserved in both the spiral and coccoid forms. The present study shows that the coccoid form of H. pylori retained many important characteristics present in the spiral form despite the morphological conversion, and thus supports the notion that some of the coccoid forms of H. pylori are likely to be viable.

Antigens, Bacterial↗

PubMed1998

Nonpeptide somatostatin agonists with sst4 selectivity: synthesis and structure-activity relationships of thioureas.

Utilizing NNC 26-9100 (11) as a structural lead, a variety of nonpeptide derivatives of somatostatin were synthesized and evaluated for sst2 and sst4 receptor binding affinity. A novel thiourea scaffold was utilized to attach (1) a heteroaromatic nucleus to mimic the Trp8 residue, (2) a nonheteroaromatic nucleus to mimic Phe7, and (3) a primary amine or other basic group to mimic the Lys9 residue of somatostatin. Displacement studies were carried out using membranes from cell lines expressing ssts [BHK cells (sst4) and HEK 293 cells (sst2)] utilizing [125I]Tyr11-SRIF as the radioligand. Several thioureas (11, 38, 39, 41, and 42) and the urea 66 exhibited Ki values of less than 100 nM. The thioureas 11 (Ki = 6 nM) and 41 (Ki = 16 nM) and the urea 66 (Ki = 14 nM) are believed to be the most potent nonpeptide sst4 agonists known. Since the thiourea 11 and the urea 66 exhibit high sst4 selectivity, these novel nonpeptide derivatives may be useful tools for studying the sst4 receptor. Studies are currently in progress to evaluate the therapeutic potential of NNC 26-9100 (11) in the treatment of glaucoma.

Aminopyridines↗

PubMed1998

Epoxide derivatives of pipecolic acid and proline are inhibitors of pipecolate oxidase.

The cis-4,5-epoxide derivative of L-pipecolic acid (2S,4S,5R-epoxypipecolic acid, cis-3) was synthesized and found to serve as an excellent substrate for L-pipecolate oxidase (L-PO) and also to cause time-dependent, irreversible inactivation of the enzyme. Data are presented showing this compound is a mechanism-based inhibitor of L-PO, whereas 2S,3R,4S-epoxyproline acts as a reversible inhibitor.

Drug Design↗

PubMed1998

Pharmacokinetics, cortisol release, and hemodynamics after intravenous and subcutaneous injection of human corticotropin-releasing factor in humans.

OBJECTIVE: Two clinical trials investigated the pharmacokinetics of human corticotropin-releasing factor (hCRF), resulting cortisol release, and associated hemodynamic changes. METHODS: In a 3 x 3 Latin square design, subjects were randomized to receive a single dose of 5 microg x kg(-1) hCRF as a 10-minute intravenous infusion, a 180-minute infusion, and a subcutaneous injection in separate study sessions 7 days apart. Twelve additional subjects obtained a subcutaneous dose of either 300, 600, or 1200 microg hCRF on 3 consecutive days. Noncompartmental and compartmental pharmacokinetic analysis was performed. Hemodynamic response was characterized with use of pharmacodynamic models. RESULTS: The volume of distribution at steady state was 9.81 +/- 3.0 and 15.61 +/- 2.9, and the clearance was 256 +/- 40 mL x min(-1) and 345 +/- 90 mL x min(-1) for the 10-minute and 180-minute intravenous infusion, respectively (P < .05). Corresponding elimination half-life was 45 +/- 7 minutes and 37 +/- 10 minutes. Two-compartment and 1-compartment models adequately described the 10-minute and 180-minute infusions, respectively. The bioavailability of hCRF after subcutaneous administration was 67% +/- 17%. Apparent clearance remained unchanged for different subcutaneous doses. Peak plasma cortisol concentrations were similar after subcutaneous and intravenous administration of hCRF. Repetitive administration of hCRF did not result in accumulation but produced a reduced plasma cortisol response. A sigmoidal model related plasma hCRF concentrations to increase in heart rate (maximum, 39 beats x min(-1)). The relationship between the modest decrease in diastolic blood pressure and plasma hCRF concentrations was linear. CONCLUSION: The pharmacokinetics of intravenously administered hCRF were nonlinear, but apparent clearance was constant for various subcutaneous doses. An excellent bioavailability and preserved bioactivity make the subcutaneous route an attractive choice. Repetitive administration of hCRF probably caused tolerance of the cortisol response.

Adult↗

PubMed1998

Severe gastritis in guinea-pigs infected with Helicobacter pylori.

An appropriate animal model is essential to study Helicobacter pylori infection. The aim of this study was to investigate if H. pylori can colonise the guinea-pig stomach and whether the infection causes gastritis and a serological response similar to that observed in man. Guinea-pigs were infected either with fresh H. pylori isolates from human gastric biopsies or with a guinea-pig passaged strain. When the animals were killed, 3 and 7 weeks after inoculation, samples were taken for culture, histopathology and serology. H. pylori was cultured from 22 of 29 challenged animals. All culture-positive animals exhibited a specific immune response against H. pylori antigens in Western blotting and gastritis in histopathological examination. Antibody titres in enzyme immunoassay were elevated among animals challenged with H. pylori. The inflammatory response was graded as severe in most animals and consisted of both polymorphonuclear leucocytes and lymphocytes. Erosion of the gastric epithelium was found in infected animals. These results suggest that the guinea-pig is suitable for studying H. pylori-associated diseases. Moreover, guinea-pigs are probably more similar to man than any other small laboratory animal as regards gastric anatomy and physiology.

Animals↗

PubMed1998

Improving the success of culturing Helicobacter pylori from gastric biopsies.

Factors influencing the successful isolation of Helicobacter pylori from human gastric biopsies were studied. Within 24 h, each of the gastric biopsies was inoculated onto chocolate blood agar media and incubated for up to 2 weeks. Among 63 (70%) culture positive cases in 90 patients, 58 (64%) cases were culture positive for both specimens, while five (6%) cases were culture positive in only one biopsy. Of the 63 positive cultures, 51 H. pylori strains (81%) grew on both media with and without antibiotics. Eight strains (13%) grew only on medium without antibiotics, while four isolates (6%) were obtained only from medium with antibiotics. These results support the previous histological observation of patchy colonization of H. pylori in the stomach. The success rate for culture of H. pylori from gastric biopsies increased when two biopsies were taken and inoculated on chocolate blood agar media with and without antibiotics.

Helicobacter Infections↗

PubMed1998

Characterization of clinical isolates of Helicobacter pylori in Singapore.

Of the 69 Helicobacter pylori isolates analysed, 31 strains (45%) showed resistance to metronidazole, one strain (1.4%) was resistant to amoxicillin while two strains (2.9%) were resistant to clarithromycin. It was found that metronidazole resistance rates increased in Singapore from 20% to 62% between late 1995 and early 1997. By biotyping using API ZYM, a total of 80% (55/69) strains were characterized as biotype II, while the remaining 20% (14/69) strains belonged to biotype III. Interestingly, 71% (10/14) of biotype III were resistant to metronidazole compared with 38% (21/55) of biotype II. DNA profiles generated by random amplified polymorphic DNA from 69 isolates showed highly diversified DNA fingerprints allowing effective discrimination among strains. Of the 60 H. pylori isolates from peptic ulcer patients, it was found that cagA and vacA occurred in 80% (48/60) and 82% (49/60) isolates, respectively.

Amoxicillin↗