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Biomedical subjects

R A Feldman

Publications and source records attributed to R A Feldman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Multi-laboratory comparison of eight commercially available Helicobacter pylori serology kits. Helicobacter pylori Serology Study Group.

The performance of eight commercially available EIA kits in detecting antibody to Helicobacter pylori was evaluated by a panel of 17 laboratories using serum from 59 patients selected from endoscopy clinics in Belgium, Ireland, Italy, the Netherlands and Switzerland. Each laboratory received a randomly numbered set of sera and was ignorant of the culture results of the patients. The performance of the kits was assessed in terms of diagnostic accuracy compared to culture (measured by sensitivity and specificity), the inter-laboratory variability in diagnostic accuracy and the number of laboratories that experienced problems in using the kits. Grey zone results, which are routinely used to highlight the uncertain interpretation of results that lie near the cut-off point between positive and negative diagnoses, were accounted for in the analysis. Laboratories experienced practical problems in using some kits, whilst other kits were found to have high inter-laboratory variation or low diagnostic accuracy. There was no single kit that performed better on every criterion than the others. The Orion kit was a good all-round performer, whilst the Roche kit was excellent at detecting positive results, although it had a slightly raised false-positive rate.

Evaluation Studies as Topic↗
PubMed1995

Prevention of Helicobacter pylori infection.

A gastroenterologist, treating a patient with H. pylori, must decide whether the unit of treatment is only the ill individual, or the family, perhaps including close contacts. If it is the family and close contacts, is it all family members and contacts, or are there some ages, relationships, or clinical characteristics that increase the risk of transmission to the patient after successful treatment of their infection? In preventing reinfection, the available data suggest: the natural infectious dose has not been determined infection may occur from oral or faecal shedding children are more infectious than adults socio-economic factors are important in any comparison of infection rates food and water seem unlikely vehicles in the developed world travel in the third world may increase risk of infection seropositivity in adults predominantly reflects exposure in childhood infection is frequently with more than one strain reinfections are not more frequent in families with other members infected reinfections are infrequent with strains different from the original strain reinfection might be more frequent in developing countries no need for all family members to be treated to reduce reinfection rates. In considering vaccine, the available data suggest: breast milk IgA can reduce infection rate antibodies induced by vaccine may reduce infection in animals late benefit of childhood vaccination in developed countries probable early benefit of childhood vaccination in developing countries vaccination of already infected adults would have cost-benefit.

Adult↗
PubMed1995

Migration and Helicobacter pylori seroprevalence: Bangladeshi migrants in the U.K.

Helicobacter pylori, an infectious agent of worldwide public health importance, has higher seroprevalence in developing countries than in developed countries. We investigated whether Bangladeshi women, born in Bangladesh, have a greater H. pylori seroprevalence than Bangladeshi women born in the U.K. and, in addition, whether there is an association between H. pylori seropositivity and age of migration to the U.K. amongst Bangladeshi women. Women attending antenatal clinics at the Royal London Hospital were screened using ELISA for anti-H. pylori IgG. In Bangladeshi individuals born in the U.K., 13/16 (81%, 95% confidence interval (CI) 54%-96%) and, in Bangladeshi individuals born in Bangladesh 91/137 (66%, 95% CI 59%-74%) had antibodies to H. pylori. No significant association was found between H. pylori seropositivity and country of birth, or age at migration to the U.K. Public health strategies concerning H. pylori should consider migrant populations with high seroprevalence of H. pylori.

Adolescent↗
PubMed1995

A PCR test for avian malaria in Hawaiian birds.

The decline of native Hawaiian forest birds since European contact is attributed to factors ranging from habitat destruction to interactions with introduced species. Remaining populations of Hawaiian honeycreepers (Fringillidae: Drepanidinae) are most abundant and diverse in high elevation refuges above the normal range of disease-carrying mosquitoes. Challenge experiments suggest that honeycreepers are highly susceptible to avian malaria (Plasmodium sp.) but resistance exists in some species. In order to detect low levels of malarial infection and quantify prevalence of Plasmodium in high elevation natural populations of Hawaiian birds, a polymerase chain reaction (PCR) based diagnostic test was developed that identifies rRNA genes of Plasmodium in avian blood samples. Quantitative competitive PCR (QC-PCR) experiments indicate that the detection limit of our test is an order of magnitude greater than that reported for human malaria DNA blot tests. Compared with standard histological methods, the PCR test detected a higher prevalence of diseased birds at mid-elevations. Malaria was detected in three species of native birds living in a high elevation wildlife refuge on the island of Hawaii and in four species from Maui. Our results show that avian malaria is more widespread in Hawaiian forests than previously thought, a finding that has important conservation implications for these threatened species.

Animals↗
PubMed1995

Helicobacter pylori infection in dentists--a case-control study.

To test the null hypothesis that frequent and multiple salivary exposure is not a risk factor for developing H. pylori infection, serum anti-H. pylori IgG from 179 dentists and dental students and 179 age-, sex- and socioeconomic-matched controls were assayed using an ELISA. Seroprevalence in dentists was 16% (11/70); clinical dental students 6% (3/47); and pre-clinical dental students 10% (6/62). There were no differences in H. pylori seropositivity between cases and controls. There was an increase in H. pylori seropositivity with age (chi (trend)2 9.04, p = 0.003). These data provide evidence that adults are not at high risk of developing H. pylori infection as a result of exposures to saliva from multiple sources.

Adolescent↗
PubMed1995

Accuracy of diagnostic methods used for epidemiological studies of Helicobacter pylori.

Epidemiological studies involve groups of individuals, or whole populations, many or most of whom are not ill. Clinical investigation has an individual perspective and precise statements need to be made about the individual alone. Serological methods are most commonly used for population-based epidemiological studies. Non-invasive epidemiological methods, using breath tests or the study of saliva or urine, are increasing in use. All methods depend on accuracy in identifying presently infected or non-infected persons, and accuracy in defining a previously infected person. The performance of serological methods varies with the antigens chosen, the population from which reference sera are drawn, age, ethnicity, and homologous and heterologous infection rates in the population being studied. Much of the standardization of epidemiological assays has been done in adults, which means that for children there is still uncertainty concerning standards and cut-off values. Because of differences in strains of H. pylori in different geographical areas, antigen selection is important when geographical comparisons are made. The sensitivity and specificity of a test is not strongly affected by the prevalence of infection. However, as the prevalence rises in the tested populations, the reported positive predictive value rises, and the negative predictive value falls. Depending on the patient population studied, accuracy varies with changes in the prevalence, and its magnitude depends both on the sensitivity and specificity. Accuracy is therefore not a very useful measure. It is better to look at the sensitivity and specificity, and the prevalence in the study, where they are measured. An alternative to separating test results into two or three categories is to report likelihood ratios, which report the probability of a person with a particular result being truly positive compared with the probability of a person with that result being truly negative. A receiver operating characteristic (ROC) curve, which describes the effect of varying the cut-off value on the performance of a test, can be useful in comparing the performance of two or more different tests. The use of multiple tests to augment positive culture as a 'gold standard', has been aided by use of polymerase chain reactions and other molecular biological methods. However, this augmentation has its limitations, since each of the additional methods may produce false positives. For example, polymerase chain reactions can be falsely positive if instruments are contaminated. There are people with more than one strain of Helicobacter pylori in the stomach, and, without molecular biological efforts, or serological typing tests, the 'gold standard' does not deal with multiple infections.

Helicobacter Infections↗
PubMed1994

Prospective study of bacterial meningitis in North East Thames region, 1991-3, during introduction of Haemophilus influenzae vaccine.

OBJECTIVE: To describe the epidemiology of primary bacterial meningitis in the North East Thames region over a three year period before and during the introduction of the vaccine for Haemophilus influenzae type b. DESIGN: Analysis of information on cases of primary bacterial meningitis identified by microbiology laboratories in the region, with collection of case data by questionnaire. MAIN OUTCOME MEASURES: Annual incidence rates for types of meningitis according to age and ethnic group. RESULTS: The annual incidence rates for the three major causes of bacterial meningitis in the general population were 1.9/100,000 for Neisseria meningitidis, 1.6/100,000 for Haemophilus influenzae before vaccination, and 1.0/100,000 for Streptococcus pneumoniae. Higher rates of H influenzae meningitis were found in Asians compared with white people (3.6/100,000 v 1.5/100,000, P = 0.01). As a result of the vaccine programme introduced in October 1992 the number of cases of H influenzae meningitis in children under 5 years has fallen by 87%. CONCLUSIONS: Bacterial meningitis is a serious problem especially in preschool children. There are differences in the incidence of some causes of bacterial meningitis in different ethnic groups; with H influenzae type b being significantly more common among black and Asian people than among white people. The immunisation programme for H influenzae type b in the North East Thames region has been successful in reducing the incidence of this type of meningitis in Asian and white populations. The numbers were too small to evaluate in the black population.

Adolescent↗
PubMed1994

Interaction of the c-fes proto-oncogene product with the interleukin-4 receptor.

Interleukin-4 (IL-4) regulates proliferation and differentiation of a variety of hematopoietic cell lineages through binding to the IL-4 receptor (IL-4R). Recently, we have demonstrated that IL-4 induces tyrosine phosphorylation of several proteins including the IL-4R and also induces association of phosphatidylinositol-3 kinase with the IL-4R. Since IL-4 induces tyrosine phosphorylation, we speculated that some tyrosine kinase may associate with the IL-4R. In this study, we demonstrate that IL-4 induces tyrosine phosphorylation of a protein closely related to, or identical to the c-fes protooncogene-encoded protein tyrosine kinase (FES). Furthermore, tyrosine phosphorylated FES or the closely related protein is found associated with the IL-4R. We also demonstrate that FES associates with the IL-4R in COS7 cells transfected with cDNA expression plasmids encoding these two proteins and in transfected COS7 cells IL-4 augments association of FES with the IL-4R and tyrosine phosphorylation of both FES and the IL-4R. Through a deletion analysis of the IL-4R we have identified a putative FES-binding site in the cytoplasmic domain of the IL-4R.

Animals↗
PubMed1994

The frequency of culturing stools from adults with diarrhoea in Great Britain.

Utilizing the Office of Population Censuses and Surveys (OPCS) Omnibus Survey, it was possible to measure the frequency with which a stool culture was obtained following episodes of diarrhoea in adults. Interviewing over 8000 adults, over a 4-month period between October 1992 and January 1993, 633 persons (7.9%) reported one episode of diarrhoea in the previous month, and 5.4% of these individuals with diarrhoea reported that a stool had been requested for examination. No significant regional differences were observed with the sample size available. The estimate of the rate of diarrhoea in adults was just under one episode per person per year.

Adolescent↗
PubMed1994

Functional specificity of cytoplasmic and transmembrane tyrosine kinases: identification of 130- and 75-kilodalton substrates of c-fps/fes tyrosine kinase in macrophages.

c-fps/fes encodes a 92-kDa protein-tyrosine kinase (NCP92) that is expressed at the highest levels in macrophages. To determine if c-fps/fes can mediate the action of the colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) and to identify potential targets of c-fps/fes in macrophages, we have overexpressed c-fps/fes in a CSF-1-dependent macrophage cell line. A 30- to 50-fold overexpression of c-fps/fes partially released these cells from their factor dependence by a nonautocrine mechanism, and this correlated with the tyrosine phosphorylation of two proteins of 130 and 75 kDa (P130 and P75). c-fps/fes did not cause tyrosine phosphorylation or activation of CSF-1 dependent targets, including CSF-1R, Shc, and phosphatidylinositol 3-kinase, and conversely, CSF-1 did not induce tyrosine phosphorylation of P130 and P75. P75 appears to be a novel phosphotyrosyl protein, whereas P130 cross-reacts with a known substrate of v-src. P130 and P75 may be direct substrates of c-fps/fes: P130 was tightly associated with NCP92, and the src homology 2 domain of NCP92 specifically bound phosphorylated P130 and P75 but not the CSF-1-induced phosphotyrosyl proteins, consistent with the possibility that P130 and P75 are physiological targets of c-fps/fes. We conclude that although c-fps/fes can functionally substitute for CSF-1R to a certain extent, these tyrosine kinases act largely independently of each other and that P130 and P75 are novel targets whose mechanisms of action may be unrelated to the signalling pathways utilized by receptor tyrosine kinases.

Animals↗
PubMed1994

High prevalence of Helicobacter pylori metronidazole resistance in migrants to east London: relation with previous nitroimidazole exposure and gastroduodenal disease.

A high prevalence of metronidazole resistance in Helicobacter pylori is reported in developing countries. This study examined whether migrants referred for diagnostic gastroscopy at a United Kingdom centre (n = 54), had a higher prevalence of metronidazole resistance than subjects born in the United Kingdom attending endoscopy (n = 46). Records of nitroimidazole treatment prescribed in the United Kingdom was obtained in 83 patients to find out if there was an association between H pylori metronidazole resistance and previous ingestion of either metronidazole or tinidazole. The prevalence of metronidazole resistant isolates varied according to country of birth: Bangladesh (90%, 27 of 30), other countries (67%, 16 of 24), and United Kingdom (37%, 17 of 46) (p < 0.001). Among those born in the United Kingdom, women were more likely to harbour resistant H pylori than men (54% v 18% respectively, p = 0.01) and more likely to have a history of previous nitroimidazole ingestion (41% v 11% respectively, p = 0.02). Patients previously exposed to either metronidazole or tinidazole were more likely to harbour resistant strains (84% (27 of 32) v 41% (21 or 51), p < 0.0001). The distribution of gastroduodenal disease, assessed endoscopically, was not affected by metronidazole resistance status.

Adult↗
PubMed1993

Ligand-dependent transformation by the receptor for human granulocyte/macrophage colony-stimulating factor and tyrosine phosphorylation of the receptor beta subunit.

The receptor for human granulocyte/macrophage colony-stimulating factor (hGMR) is composed of two subunits, alpha and beta, which are both required for high-affinity binding of the ligand. To examine the transforming potential of hGMR, we have transfected cDNAs encoding the receptor alpha and beta subunits into NIH 3T3 cells, which normally do not express GMRs. Introduction of the receptor subunits into these cells resulted in focal transformation, which was dependent on the presence of human granulocyte/macrophage colony-stimulating factor (hGM-CSF) in the culture medium. No transformation was observed when hGM-CSF was replaced with other growth factors such as human epidermal growth factor or human interleukin 3 or when cells were transfected with the alpha or beta subunit alone. Individual conditional transformants isolated after transfection expressed functional hGMRs, were susceptible to transformation by picomolar levels of the ligand, and were capable of anchorage-independent growth in soft agar in the presence but not in the absence of hGM-CSF. Biochemical analysis showed that treatment of these cells with hGM-CSF caused a rapid phosphorylation of the beta subunit and other cellular proteins on tyrosine residues, recapitulating some of the events that take place during GM-CSF signaling in myeloid cells. We conclude that coexpression of the alpha and beta subunits of hGMR in established murine fibroblasts is sufficient to reconstitute a functional receptor, which is capable of causing ligand-dependent transformation. The oncogenic potential of hGMR lends support to the hypothesis that its deregulated or abnormal expression may play a role in leukemogenesis.

3T3 Cells↗
PubMed1993

The cohort effect and Helicobacter pylori.

A total of 631 serum samples collected in 1969, 1979, and 1989 from adults and children were screened for Helicobacter pylori by Western blot analysis. Results showed that H. pylori seroprevalence has become less frequent over the 20-year period. By studying seropositivity by year of birth, the magnitude of a cohort effect of H. pylori seropositivity was estimated. The odds of being seropositive decreased by 26% per decade, P = .008 (95% confidence interval, 8%-41%). Estimates of seroprevalence adjusted for both age-specific variation and the cohort effect suggest that most seropositivity in adults occurs by the age of 15 years. The implication of these findings is that H. pylori infection is becoming less frequent and is predominantly acquired in childhood.

Adolescent↗
PubMed1992

Hepatitis E virus (HEV): strain variation in the nonstructural gene region encoding consensus motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site.

Hepatitis is transmitted by a number of infectious agents. The epidemiological characterization of waterborne or enterically transmitted non-A, non-B hepatitis (ET-NANBH) is unique when compared with other known hepatitides. We have reported on the molecular cloning of a cDNA clone derived from the etiologic agent associated with ET-NANBH, the hepatitis E virus (HEV). The complete sequence of these first molecular clones, isolated from an HEV-infected human after passage in Macaca fascicularis (cynomolgus macaques), illustrates a distant relationship to other known positive-strand RNA viruses of plants and animals. The translated major open reading frame (ORF-1) from these clones indicates that this portion of the genome encodes a polyprotein with consensus sequences found in RNA-dependent RNA polymerase and ATP/GTP binding domains. The latter activity has been associated with putative helicases of positive-strand RNA viruses. These viral-encoded enzymatic activities identify this region and ORF-1 as containing at least two different nonstructural genes involved in HEV replication. Molecular clones obtained from two other geographically distinct HEV isolates demonstrated sequence heterogeneity in this nonstructural gene region. Further study will be required to elucidate the pathogenic significance (if any) of this observed divergence in the nonstructural region.

Adenosine Triphosphate↗
PubMed1992

Diagnosis and treatment of Ogilvie's syndrome after lumbar spinal surgery. Report of three cases.

Three patients who developed Ogilvie's syndrome following lumbar spinal surgery are described. Ogilvie's syndrome, also known as pseudo-obstruction of the colon, is characterized by massive cecal distention without mechanical obstruction. If this condition is not recognized and not promptly treated, it may be complicated by cecal perforation, a life-threatening hazard. The etiology, diagnosis, management, and potential relationship between lumbar spinal surgery and Ogilvie's syndrome are discussed.

Adult↗
PubMed1990

Isolation and DNA sequence of a gene encoding alpha-trichosanthin, a type I ribosome-inactivating protein.

alpha-Trichosanthin (alpha-TCS) is a ribosome-inactivating protein that has recently been shown to inhibit the replication of human immunodeficiency virus. We have isolated a gene encoding alpha-TCS and have determined its DNA sequence. The data indicate that alpha-TCS is synthesized as a preproprotein consisting of 289 amino acids, the first 23 residues of which comprise a putative secretory signal peptide. The last 19 residues comprise a carboxyl extension that has not been reported to be associated with the mature protein and that may be processed in the endoplasmic reticulum or Golgi apparatus of cells producing alpha-TCS. The mature protein consists of 247 amino acids. The sequence predicted by translation of the DNA sequence agrees with and confirms the primary sequence determined recently on the protein. The molecular clone for alpha-TCS will facilitate directed mutational analyses that may provide information on how this peptide, and other ribosome-inactivating proteins, function. These studies may also lead to the development of therapeutic agents with altered activities and/or improved properties for in vivo use.

Amino Acid Sequence↗
PubMed1990

Selective potentiation of c-fps/fes transforming activity by a phosphatase inhibitor.

Human c-fps/fes when expressed at sufficiently high levels in NIH 3T3 cells can induce cellular transformation. To probe the mechanism of action of the c-fps/fes product NCP92, we have examined the biological and biochemical consequences of stabilizing phosphotyrosine in cells that overexpress NCP92. In this study we report that when cells expressing c-fps/fes are incubated with low concentrations of sodium vanadate, a tyrosine phosphatase inhibitor, the transforming activity of c-fps/fes can be potentiated by nearly two orders of magnitude. This effect was associated with a threefold increase in the level of phosphotyrosine in NCP92 and its major cellular substrates. Unlike c-src, NCP92 had a single tyrosine phosphorylation site, and vanadate treatment induced its phosphorylation in vivo. This was found to have a positive effect on NCP92 kinase specific activity, but at the low concentrations of vanadate that were used, this effect was very small. The results are consistent with the hypothesis that potentiation was a consequence of the stabilization of phosphotyrosine in critical targets of transformation of NCP92, rather than from a direct effect of vanadate on NCP92 kinase. The potentiating effect of vanadate was relatively specific for c-fps/fes; this reagent did not affect the high transforming activity of gag-v-fps/fes, nor did it enhance the less active c-ras, c-src, or EGF receptor genes, although the latter two genes encode tyrosine kinases. The specificity of the biological response of c-fps/fes to the stabilization of phosphotyrosine suggests that this molecule has a distinct mode of regulation and mechanism of action.

Animals↗