Search PubMed⌕ Search

Biomedical subjects

D R Smith

Publications and source records attributed to D R Smith.

At least 73 records · Page 4Linked to original sources
PubMed2000

Single-target molecule detection with nonbleaching multicolor optical immunolabels.

We introduce and demonstrate the use of colloidal silver plasmon-resonant particles (PRPs) as optical reporters in typical biological assays. PRPs are ultrabright, nanosized optical scatterers, which scatter light elastically and can be prepared with a scattering peak at any color in the visible spectrum. PRPs are readily observed individually with a microscope configured for dark-field microscopy, with white-light illumination of typical power. Here we illustrate the use of PRPs, surface coated with standard ligands, as target-specific labels in an in situ hybridization and an immunocytology assay. We propose that PRPs can replace or complement established labels, such as those based on radioactivity, fluorescence, chemiluminescence, or enzymatic/colorimetric detection that are used routinely in biochemistry, cell biology, and medical diagnostic applications. Moreover, because PRP labels are nonbleaching and bright enough to be rapidly identified and counted, an ultrasensitive assay format based on single-target molecule detection is now practical. We also present the results of a model sandwich immunoassay for goat anti-biotin antibody, in which the number of PRP labels counted in an image constitutes the measured signal.

ATP-Binding Cassette Transporters↗
PubMed2000

Depth cue integration: stereopsis and image blur.

Depth-of-focus limitations introduce spatial blur in images of three-dimensional scenes. It is not clear how the visual system combines depth information derived from image blur with information from other depth cues. Stereoscopic disparity is the pre-eminent depth cue, so experiments were conducted to investigate interactions between image blur and stereoscopic disparity. Observers viewed two random dot stereograms (RDSs) in a 2AFC task, and were required to identify the RDS depicting the greatest depth. In control observations, all dots in both RDSs were sharply defined. In experimental observations, one RDS contained only sharply defined dots, but the other contained differential spatial blur to introduce an additional depth cue. Results showed that the addition of differential blur made only a marginal difference to apparent depth separation, and only when the blur difference was consistent with the sign of disparity. Cue combination between blur and disparity cues is thus weighted very heavily in favour of the latter. It is shown that blur and disparity cues co-vary according to geometric optics. Since the two cues are effective over different distances, the visual system is not normally called upon to integrate them, and is most likely to make use of blur cues over distances beyond the range of disparity mechanisms.

Cues↗
PubMed2000

Luminance processing in apparent motion, Vernier offset and stereoscopic depth.

We obtained (apparently) linear responses to luminance from three special displays of apparent motion, Vernier offset and stereoscopic depth. In our motion stimulus a dark and a light bar exchanged luminances repetitively on a grey surround. Motion was attributed to the bar that differed more from the surround, that is, on a dark surround the light bar appeared to jump, and on a light surround the dark bar appeared to jump. The apparent motion disappeared when the luminance of the surround lay halfway between that of the bars--on a linear, not a logarithmic scale. Similar results were obtained for special Vernier offset and stereo stimuli. These results cannot be explained if all luminances are processed within the same luminance pathway and that pathway transforms input luminance using non-linear compression. However, the apparent linearity of our results could arise from opposite and equal non-linearities cancelling out within separate ON- and OFF-spatial luminance pathways. A second set of experiments presented one bar separately into each eye on different surrounds (dichoptic presentation of competing apparent motion signals) or manipulated the display spatially so that different surrounds were associated with different bars (binocular presentation of competing Vernier targets). Results showed that apparent motion and Vernier signals of equal Weber contrast (normalisation of linear difference to surround luminance) evoked equal-motion and equal Vernier offset strengths. Given that motion and Vernier strength followed Weber's law, we infer that the ON- and OFF-pathways transform luminance non-linearly. Our third experiment presents an example of a brightness bisection task in which we were able to influence the bisection steps, to follow either a linear or non-linear series. The benefits of parsing the visual scene so that visual information is processed within two opposite luminance pathways is discussed.

Contrast Sensitivity↗
PubMed2000

Calling the shots: immunization finance policies and practices. Executive summary of the report of the Institute of Medicine.

Federal, state, and private-sector investments in vaccine purchases and immunization programs are lagging behind emerging opportunities to reduce the risks of vaccine-preventable disease. Although federal assistance to the states for immunization programs and data collection efforts rapidly expanded in the early part of the 1990s, significant cutbacks have occurred in the last 5 years that have reduced the size of state grant awards by more than 50% from their highest point. During this same period, the vaccine delivery system for children and adults has become more complex and fragmented. This combination of new challenges and reduced resources has led to instability in the public health infrastructure that supports the U. S. immunization system. Many states have reduced the scale of their immunization programs and currently lack adequate strength in areas such as data collection among at-risk populations, strategic planning, program coordination, and assessment of immunization status in communities that are served by multiple health care providers. If unmet immunization needs are not identified and addressed, states will have difficulty in achieving the national goal of 90% coverage by the year 2010 for completion of the childhood immunization series for young children. Furthermore, state and national coverage rates, which reached record levels for vaccines in widespread use (79%, 1998), can be expected to decline and preventable disease outbreaks may occur as a result, particularly among persons who are vulnerable to vaccine-preventable disease because of their underimmunization status. The Institute of Medicine (IOM) Committee on Immunization Finance Policies and Practices has therefore concluded that a renewal and strengthening of the federal and state immunization partnership is necessary. The goal of this renewed partnership is to prevent infectious disease; to monitor, sustain, and improve vaccine coverage rates for child and adult populations within more numerous and increasingly diversified health care settings; and to respond to vaccine-safety concerns. To achieve this renewal, states require a consistent strategy, additional funds, and a multiyear finance plan that can help expedite the delivery of new vaccines; strengthen the immunization assessment, assurance, and policy development functions in each state; and adapt childhood immunization programs to serve the needs of new age groups (especially adults with chronic diseases) in different health care environments. The IOM committee recommends that federal and state governments adopt a national finance strategy that would allocate $1.5 billion in federal and state resources over the first 5 years to strengthen the infrastructure for child and adult immunization-an annual increase of $175 million over current spending levels. These resources would consist of $200 million per year in state infrastructure grants awarded by the Centers for Disease Control and Prevention (the Section 317 program) and an additional $100 million per year in increased state contributions. The committee also recommends that the Congress replace the current discretionary Section 317 grants with a formula approach for state immunization grant awards to improve the targeting and stability of federal immunization grants. The formula should provide a base level of support to all states, as well as additional amounts related to each state's need, capacity, and performance. The committee further recommends that Congress introduce a state match requirement for the receipt of increased federal funds to help strengthen and stabilize the infrastructure that supports long-term public health assessment, assurance, and policy development efforts. (ABSTRACT TRUNCATED)

Adult↗
PubMed2000

Prognostic significance of TP53 gene mutation in 995 cases of colorectal carcinoma. Influence of tumour site, stage, adjuvant chemotherapy and type of mutation.

Previous studies on the prognostic significance of TP53 gene alterations in colorectal cancer (CRC) have led to conflicting results. The present study investigated the prognostic significance of TP53 gene mutation in a very large series of 995 Dukes' B and C CRC patients, the majority of whom did not receive chemotherapy. Mutations were found in 385 (39%) cases and were not associated with tumour stage, histological grade, patient age or sex. Significantly more mutations were found in tumours from the left-sided colon compared with those from the right side (43% versus 34%, P=0.006). TP53 gene mutation had no prognostic value in the overall series or in different site or stage subgroups. None of the different types of TP53 gene mutation showed prognostic value. A trend for association with worse survival was observed in the patient subgroup that received adjuvant chemotherapy (Hazard Ratio (HR) 1.4, 95% confidence interval (CI) 0.89-2.21, P=0.15). These results indicate that mutation of the TP53 gene is not a useful prognostic marker for CRC patients who do not receive adjuvant chemotherapy. Further study is required to determine whether different types of TP53 mutation might be of value in predicting the response of CRC patients to chemotherapy.

Adult↗
PubMed2000

Meningiomas in Singapore: demographic and biological characteristics.

We sought to determine the relative incidence of meningiomas compared to other central nervous system tumours in an Asian surgical series, as well as the demographic and biological characteristics of these meningiomas. A review of 655 consecutive cases of central nervous system tumours from 583 patients representing the last five years admissions to one hospital in Singapore was undertaken. A total of 33 malignant/atypical tumours from 19 patients and 196 benign meningiomas from 187 patients were identified. Twenty malignant/atypical and 20 benign tumours were selected at random and subjected to histochemical and immunohistochemical analysis using antibodies directed against p53, bax and 3'-DNA hydroxy groups (TUNEL). Meningiomas comprised some 35.2% of all central nervous system tumours with malignant/atypical meningiomas representing 9.2% of meningiomas. Histochemically, necrosis was the predominant finding. However, peri-necrotic areas displayed p53 positivity in 10% of cases and bax positivity in 25% of cases. Apoptotic cells were detected in the peri-necrotic areas in 90% of benign and 75% of malignant/atypical meningiomas. Meningiomas represent the predominant form of central nervous system tumour in the Singaporean population, and aberration of p53 expression is not associated with tumour formation or progression. There was a slight but non-significant reduction in apoptosis in the progression from benign to malignant meningioma, suggesting that in contrast to many other tumour types disruption of cellular apoptosis is not a predominant driving force in Asian meningioma tumourigenesis.

Apoptosis↗
PubMed2000

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy.

Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,alpha)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as the boron delivery agent relative to BPA. The compound biological effectiveness (CBE) factor for BSH was estimated at 0.29 +/- 0.02. This compares with a previously published CBE factor for BPA of 4.87 +/- 0.16. It was concluded that variations in the microdistribution profile of 10B, using the two boron delivery agents, had a significant effect on the response of oral mucosa to BNC irradiation. From a clinical perspective, based on the findings of the present study, it is probable that potential radiation-induced oral mucositis will be restricted to BNCT protocols involving BPA. However, a thorough high resolution analysis of 10B microdistribution in human oral mucosal tissue, using a technique such as ion microscopy, is a prerequisite for the use of experimentally derived CBE factors in clinical BNCT.

Animals↗
PubMed2000

Prostate tumours from an Asian population: examination of bax, bcl-2, p53 and ras and identification of bax as a prognostic marker.

Molecular studies have suggested that ethnicity may play a significant role in prostate tumorigenesis, but no information exists for groups other than Caucasian or Japanese patients. We examined 62 archival samples of prostate tumours from Asians of non-Japanese origin for the over-expression of p53, for the possible presence of mutated ras genes, for the overexpression of the bcl-2 and bax proteins, as well as directly for the presence of apoptotic cells by the TUNEL methodology. Gene lesions of both ras (0%) and p53 (3%) were rare. While bcl-2 expression was not observed in any sample, bax expression was noted in 76% of samples and was associated with a significantly worse patient prognosis both overall (P< 0.005) and specifically in Chinese patients (P< 0.02). Apoptotic cells were found in 61% of samples, and were significantly associated with the presence of bax expression (P = 0.002), but not patient survival. These results suggest that prostate tumours from non-Japanese Asians are genetically distinct from prostate tumour found in both Japanese and Caucasian patients, and that treatment modalities may need to be tailored for specific population groups.

Aged↗
PubMed2000

Succimer and the urinary excretion of essential elements in a primate model of childhood lead exposure.

Succimer is considered to be a safe and effective treatment for lead (Pb) poisoning, since it reduces body Pb levels without an apparent diuresis of other essential elements. However, while existing clinical data indicate that succimer does not significantly increase the excretion of non-target elements, those studies have also reported a wide range of outcomes. Therefore, we investigated whether succimer treatment measurably increased the urinary excretion of essential elements in a primate model of childhood Pb exposure. Infant rhesus monkeys (Macaca mulatta) were exposed to Pb from birth through one year of age, and presented blood Pb levels of approximately 40-50 microg/dL at the start of treatment. Subsequently, they were treated with succimer (30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days, n = 15) or vehicle (n = 14) for 19 days. Complete urine samples were collected over the first 5 days of treatment, and were analyzed for levels of calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), nickel (Ni), and zinc (Zn), using trace metal-clean techniques and magnetic sector-ICP-MS. Succimer treatment significantly (p < 0.05) reduced blood Pb levels when compared to the vehicle group over the treatment period, and concomitantly produced a significant >4-fold increase in urinary Pb excretion. Succimer treatment also significantly (p < 0.05, multivariate ANOVA) increased the urinary excretion of essential elements, but only when the cumulative total excretion over treatment days 1-5 for all elements were considered. None of these relative increases reached statistical significance for any particular element x day, although increases in Zn (day 3) excretion were only marginally non-significant (0.1 > p > 0.05). Multivariate analyses of a subset of elements (Cu, Fe, Mn, Zn) similarly indicated no significant effect of succimer treatment overall, although the urinary excretion of Mn was significantly increased on day 3 of treatment. Collectively, these data indicate that succimer does contribute to an increase in the urinary excretion of essential elements, although not significantly for any single element considered here. This may be important in Pb-exposed children, who can possess reduced trace element reserves due to nutritional deficiencies.

Animals↗
PubMed2000

Apoptosis occurs after cerebral contusions in humans.

OBJECTIVE: Animal model systems have shown that head trauma can induce cell death in regions of the brain away from the site of the impact via a process of apoptosis. We sought to determine whether there was evidence of cellular apoptosis in clinically collected materials from human head trauma patients, as well as to attempt to determine the pathway by which it may occur. METHODS: Thirty-one sequential specimens of brain tissue excised during emergency craniotomy for evacuation of cerebral contusions with mass effect were examined. Non-necrotic pericontusional tissues were detected in 11 samples. These were examined for the presence of apoptotic cells by the terminal deoxynucleotide transferase-mediated nick end labeling method as well as by immunohistochemistry to detect possible expression of the apoptosis-related genes p53, bcl-2, and bax. RESULTS: Bax expression was detected in all patients, whereas bcl-2 expression was noted in six patients. Terminal deoxynucleotide transferase-mediated nick end labeling-positive cells were noted in eight patients. One instance of p53-positive immunostaining was observed. Patients with bcl-2 expression had a better survival rate than patients in whom no bcl-2 expression was noted (P = 0.01). CONCLUSION: Although necrosis seemed to be the main finding in cerebral contusions, these results support the hypothesis that apoptosis does occur in patients after traumatic brain injury, and this may contribute to the secondary injury processes that are seen with head injury. Patients in whom anti-apoptotic bcl-2 is induced seem to have a better prognosis. This may have important clinical significance in the development of bcl-2 homologs or bax inhibitors to prevent apoptosis.

Adult↗
PubMed2000

Apoptosis and apoptosis related gene expression in normal conjunctiva and pterygium.

BACKGROUND: Pterygium is a relatively common eye disease in the tropics whose aetiology and pathogenesis remain uncertain. As such, interest has focused on understanding the underlying mechanism of pterygia development. METHODS: 15 specimens of pterygia from 15 eyes were examined, together with normal conjunctival tissue from the same eyes for the pattern of gene expression of genes associated with the induction or repression of apoptosis (p53, bcl-2, and bax). In addition, the samples directly for apoptotic cells were examined by the terminal deoxynucleotide transferase (TdT) mediated nick end labelling (TUNEL) methodology. RESULTS: In pterygia specimens apoptotic cells were found mainly confined to the basal layer of cells of the epithelial layer, situated immediately adjacent to the fibrovascular support layer. These cells were shown to express significant levels of p53 and bax, as well as the apoptosis inhibiting protein bcl-2. In contrast, normal conjunctival specimens displayed no bcl-2 expression and apoptotic cells were seen throughout the entire width of the epithelial layer, coupled with high levels of bax expression. CONCLUSION: These results support a model whereby pterygia development is a result of disruption of the normal process of apoptosis occurring in the conjunctiva.

Apoptosis↗
PubMed2000

Lead isotopes as a supplementary tool in the routine evaluation of household lead hazards.

The advent of magnetic sector inductively coupled plasma-mass spectrometry (ICP-MS) allows rapid, accurate, and precise measurement of lead isotopes in environmental and biological samples at a lower cost than traditional methods. This may increase the feasibility of including lead isotope measurements as a routine tool to identify household sources of lead exposure to children. Here, we present three household case studies to illustrate how lead hazard evaluations by an environmental specialist could be supplemented with routine lead isotope analyses of potential lead sources and blood. Sampling for lead isotopes was undertaken following the U.S. Department of Housing and Urban Development regulatory guidelines for the evaluation of lead hazards in housing, and with the consideration of minimizing the additional costs associated with lead isotope measurements. The range of isotopic ratios within a single residence was large enough to allow the characterization of different lead sources, particularly when both major (e.g., (207)Pb/(206)Pb) and minor (e.g., (206)Pb/(204)Pb) isotope ratios were considered. These cases illustrate the utility of the lead isotope method to identify main source(s) of lead exposure to the child; discard unlikely sources of exposure to the child; point to sources of lead to dust; and substantiate or refine the environmental assessment based exclusively on lead concentrations and loadings. Thus, a more effective evaluation of household lead hazards would likely benefit from considering a) lead concentrations and loadings in and around the household environment; b) all isotopic ratios of potential lead sources within that environment; and c) information about behavioral habits, as well as an evaluation of viable pathways of exposure to the child.

Blood Chemical Analysis↗
PubMed2000

Prognostic significance of mutations to different structural and functional regions of the p53 gene in breast cancer.

Alteration to the p53 tumor suppressor gene is associated with more aggressive disease in breast cancer, as evidenced by the shortened survival of patients with mutation. Data obtained from in vitro experiments suggest that mutations to different structural and functional domains of p53 may give rise to different effects on its biological activities, notably transactivational and apoptotic properties. We evaluated the prognostic significance of various types of p53 mutation in a series of 178 tumors identified by PCR-single-strand conformational polymorphism screening as containing a mutant gene. Mutations within exon 4 were associated with particularly poor prognosis, possibly relating to the importance of this region in apoptosis. Mutations that caused denaturation of the protein structure were also associated with poor survival, again perhaps because of effects on apoptosis. In contrast, patients with mutations in the DNA contact region showed similar survival to that of patients with normal p53, suggesting a less important role for p53-mediated transactivation in determining tumor aggressiveness. Other mutation groups associated with poor prognosis were single-base substitutions and transversion mutations. Mutations in exon 6, exon 7, or the "hotspot" codons (175, 245, 248, 273) were associated with only a small reduction in patient survival compared with normal p53. These results allow some insight to be gained into the functional importance of various p53 domains in terms of their influence on overall patient survival. Further work is required to determine whether these domains are also important in influencing the response of breast tumors to adjuvant therapies.

Amino Acid Substitution↗
PubMed1999

Efficacy of succimer chelation for reducing brain lead in a primate model of human lead exposure.

The extent to which succimer (meso-2,3-dimercaptosuccinic acid [DMSA], Chemet) reduces brain lead (Pb) levels may be a primary consideration in evaluating its efficacy for reducing neurotoxicity. Clinical research in this area has been hampered by the need to use blood Pb levels as the index of treatment efficacy, despite the fact that brain Pb level is the exposure parameter of greater relevance to cognitive outcomes. Here, a nonhuman primate model of human Pb exposure was used to determine: (1) The efficacy of oral succimer for reducing brain Pb derived from chronic or recent exposures, and (2) The extent to which blood Pb levels reflect brain Pb prior to and following chelation. Adult rhesus monkeys were chronically exposed to Pb orally for 5 weeks to reach and maintain a target blood Pb level of 35-40 microg/dL. Chelation of Pb from recent exposures was assessed using a stable (204)Pb isotope tracer administered over 4 days prior to treatment. Immediately prior to chelation, a prefrontal cortex (PFC) biopsy was collected to determine pretreatment brain Pb levels. Subsequently, monkeys were assigned to vehicle (n = 5) or succimer (n = 6, 30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days) groups. Blood and brain PFC, frontal lobe (FL), hippocampus (H), and striatum (S) were analyzed for total Pb and (204)Pb tracer concentrations by magnetic sector inductively coupled plasma-mass spectrometry. There were no measurable differences in brain Pb concentrations between the succimer and vehicle groups, indicating that succimer treatment was not efficacious in reducing brain Pb levels. In contrast, the cessation of Pb exposure significantly reduced brain (PFC) Pb ( approximately 34%) when compared to pretreatment levels (succimer and vehicle groups). Pb concentrations also varied among brain regions (PFC > FL approximately H > S). Finally, pretreatment PFC Pb concentrations were significantly correlated with the integrated blood Pb level (AUC) over the Pb exposure period, but not with the single pretreatment blood Pb collected concurrently with the PFC biopsy. Following treatment, blood Pb levels correlated only with Pb in the PFC, and not the other brain regions measured (FL, H, S). These data indicate that, under the conditions of this study, succimer treatment did not reduce brain Pb levels beyond the cessation of Pb exposure alone. Moreover, a single blood Pb measurement may be a poor predictor of brain Pb levels, reflecting limitations in the use of blood Pb level as an indicator of treatment efficacy.

Animals↗
PubMed1999

The effects of CaNa(2)EDTA on brain lead mobilization in rodents determined using a stable lead isotope tracer.

Studies have demonstrated the efficacy of CaNa(2)EDTA for reducing lead (Pb) levels in blood and soft tissues, including brain. However, a concern remains that a single dose of CaNa(2)EDTA may cause a significant increase in brain Pb levels due to a redistribution of endogenous Pb. Here we utilized a rodent model of Pb exposure in combination with a sensitive stable Pb isotope tracer methodology to assess the effects of CaNa(2)EDTA chelation treatment on the redistribution of Pb in brain, blood, kidney, and bone tissues. Thirty-two adult female albino rats (n = 6-7 animals/group) were exposed to 100 microg Pb/mL in drinking water for 4 weeks. Stable (204)Pb tracer was administered via i.p. injection over 2 days prior to chelation. CaNa(2)EDTA was administered i.p. at a dose of 150 mg/kg/day for 1 to 5 days. Statistical differences were evaluated with univariate ANOVA. Under the Pb exposure and chelation treatment regimens utilized here, there was no evidence of a measurable redistribution of endogenous Pb (as total Pb or labile (204)Pb tracer) into the brain after a single CaNa(2)EDTA dose. Further, CaNa(2)EDTA was not efficacious in measurably reducing brain or bone Pb levels, although brain levels of labile (204)Pb tracer were significantly reduced after 5 days of chelation. CaNa(2)EDTA treatment was effective in significantly reducing both blood and kidney Pb levels. Overall, these data substantiate the efficacy of CaNa(2)EDTA for reducing soft tissue Pb levels, but not total brain Pb, and they do not support concern for a transient increase in brain Pb levels with treatment.

Animals↗
PubMed1999

Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori.

Helicobacter pylori, one of the most common bacterial pathogens of humans, colonizes the gastric mucosa, where it appears to persist throughout the host's life unless the patient is treated. Colonization induces chronic gastric inflammation which can progress to a variety of diseases, ranging in severity from superficial gastritis and peptic ulcer to gastric cancer and mucosal-associated lymphoma. Strain-specific genetic diversity has been proposed to be involved in the organism's ability to cause different diseases or even be beneficial to the infected host and to participate in the lifelong chronicity of infection. Here we compare the complete genomic sequences of two unrelated H. pylori isolates. This is, to our knowledge, the first such genomic comparison. H. pylori was believed to exhibit a large degree of genomic and allelic diversity, but we find that the overall genomic organization, gene order and predicted proteomes (sets of proteins encoded by the genomes) of the two strains are quite similar. Between 6 to 7% of the genes are specific to each strain, with almost half of these genes being clustered in a single hypervariable region.

Duodenal Ulcer↗