A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain

BACKGROUND & AIMS: Currently available Helicobacter pylori models show variable and, in some instances, poor colonization. There is a need for a strain with high colonizing ability to act as a standard for animal studies. METHODS: After screening a range of fresh clinical isolates and long-term adaptation in mice, a strain of H. pylon has been isolated with a very good colonizing ability. RESULTS: This strain, named the Sydney strain of H. pylori (strain SS1), is cagA and vacA positive. High levels of colonization (10(6)-10(7) colony-forming units/g tissue) were achieved consistently in C57BL/6 mice. Colonization levels varied depending on the mouse strain used with BALB/c, DBA/2, and C3H/He, all being colonized but in lower numbers. In all strains of mice, bacteria were clearly visible at the junctional zone between the antrum and the body. The phenotype was stable with colonizing ability remaining after 20 subcultures in vitro. The bacterium attached firmly to gastric epithelium. During 8 months, a chronic active gastritis slowly developed, progressing to severe atrophy in both C57BL/6 and BALB/c mice. CONCLUSIONS: The Sydney strain of H. pylori is available to all and will provide a standardized mouse model for vaccine development, compound screening, and studies in pathogenesis.     

Mortality studies of machining fluid exposure in the automobile industry. V: A case-control study of pancreatic cancer

MANOVA and repeated measures ANOVA approaches have provided evidence of a number of limitations in several event-related potential (ERP) studies due to violations of their statistical assumptions and the typically moderate size of the available sample. Alternative, computer-intensive methods based on permutation principles have recently been developed. Up to now this methodology has focused mostly on magnitude differences between scalp distributions as measured by t statistics. In this paper the scope of permutation techniques in ERP analysis was widened. A new statistic (D statistic) is introduced to compare the shapes of scalp distributions of ERPs. Additionally a general non-parametric combinatory technique is introduced to evaluate, by means of multivariate permutation tests, several time points and/or recording sites in ERP data. The methodology described here was used to test if two ERP components elicited during word-pair matching tasks to semantic or phonological incongruences had different scalp distributions.     

CT and MRI features of cavernous haemangioma of internal auditory canal

A left internal auditory canal (IAC) cavernous haemangioma is reported in a 45-year-old Saudi male. The lesion was associated with rapidly deteriorating hearing loss and facial nerve dysfunction. CT showed a calcified enhanced IAC lesion while T1 weighted MRI showed an isointense contrast enhancing lesion bulging into the porus acousticus. The imaging features of the three usual IAC lesions--meningioma, acoustic neuroma and cavernous haemangioma--were compared. Calcification/ossification appear more commonly in cavernous haemangioma than in the other two lesions while facial nerve dysfunction is a clinical hallmark of IAC cavernous haemangioma.     

Resistance of actin to cleavage during apoptosis

When Proteus mirabilis was cultured anaerobically in the presence of nitrate as terminal electron acceptor, a dramatic reduction of glutathione transferase production occurred. The analysis of the glutathione affinity purified materials in terms of substrate specificity, SDS-PAGE pattern, IEF pattern and immunoblotting revealed that a significantly different glutathione transferase pattern also occurred: two new glutathione transferase forms with an isoelectric point at pH 4.8 and 5.0 appeared. Their N-terminal amino acid sequence analysis as well as the ability to bind to a glutathione affinity column indicate that major differences between anaerobic and aerobic glutathione transferase forms are mainly located in the C-terminal region of the primary structure. In contrast, no significant changes occurred in the production of glutathione transferase isoenzymes when P. mirabilis was grown anaerobically in the absence of a terminal electron acceptor. These results support the idea that bacterial glutathione transferase expression is not strictly related to the absence of oxygen stress.     

Loss of analgesic effect of morphine due to coadministration of rifampin

The nature of weak selection differs between coding and non-coding regions. Coding regions contain genetic information, whereas most non-coding regions do not have any information. Genetic information may be regarded as interaction systems, and the NK model of Kauffman was analysed. This model assumes that each amino acid makes a fitness contribution that depends on the amino acid and on K other amino acids among the N that make the protein. Through simulations, it was found that there are numerous nearly-neutral mutations under this model. Therefore, evolution is rapid in small populations, and slow in large populations. The variance of the evolutionary rate is not quite as large as data indicate under the model, and additional factors, such as environmental change or population-size fluctuation, need to be considered. Weak selection at non-coding regions may come from chromosome organization, and may be regional in character, which differs from that at coding regions. The problem of genetic load is thought to disappear in these circumstances.     

Culture-positive tuberculosis in human immunodeficiency virus type 1-infected children

BACKGROUND: Adults infected by HIV have increased susceptibility to Mycobacterium tuberculosis and progress more rapidly to disease. HIV and tuberculosis (TB) coinfection in children has been reported but often lacks bacterial confirmation. We report on the clinical picture, special investigations, clinical course and outcome of 14 children with HIV infection and culture-confirmed TB from a developing country. METHODS: The clinical records of all children, from 1992 to 1997, with HIV infection and culture-proved TB were reviewed. RESULTS: Fourteen (10.4%) of 135 children with vertically transmitted HIV infection, 93% <2 years of age, fit the criteria. Nonresolving pneumonia (4) and otorrhoea (6) were common complaints. A Mantoux test was positive (> or =15 mm) in 6 of 11 children. Extrapulmonary TB was present in 5 cases. Ear swabs were the source of M. tuberculosis culture in 3. Chest radiographs were abnormal in all with hilar and paratracheal lymphadenopathy present in 7. A source case with pulmonary TB was identified for 10. Susceptibility tests were done on 9 strains of which 1 was drug-resistant. Four children were culture-positive 4 to 10 months after initiation of TB treatment. Mortality was 21% and 3 were lost to follow-up. CONCLUSIONS: In HIV-infected children the Mantoux skin test remains useful and culture specimens should be obtained from all sources. Response to treatment is unpredictable, and for this reason repeated cultures should be taken during treatment and a 9-month course of treatment considered.     

Vav regulates peptide-specific apoptosis in thymocytes

Homologies between vertebrate forebrain subdivisions are still uncertain. In particular the identification of homologs of the mammalian neocortex or the dorsal ventricular ridge (DVR) of birds and reptiles is still a matter of dispute. To get insight about the organization of the primordia of the main telencephalic subdivisions along the anteroposterior axis of the neural tube, a fate map of the dorsal prosencephalon was obtained in avian chimeras at the 8- to 9-somite stage. At this stage, the primordia of the pallium, DVR and striatum were located on the dorsal aspect of the prosencephalon and ordered caudorostrally along the longitudinal axis of the brain. Expression of homeobox-containing genes of the Emx, Dlx and Pax families were used as markers of anteroposterior developmental subdivisions of the forebrain in mouse, chick, turtle and frog. Their expression domains delineated three main telencephalic subdivisions in all species at the onset of neurogenesis: the pallial, intermediate and striatal neuroepithelial domains. The fate of the intermediate subdivisions diverged, however, between species at later stages of development. Homologies between forebrain subdivisions are proposed based on the conservation and divergence of these gene expression patterns.     

The impact of true partnership between a university Level I trauma center and a community Level II trauma center on patient transfer practices

OBJECTIVE: To examine the effect of a clinical and administrative partnership with an academic urban Level I trauma center on the patient transfer practices at a suburban/rural Level II center. METHODS: Data for 2 years before affiliation (PRE) abstracted from inpatient charts and the trauma registry were compared with that for 2 years after (POST). The following data were collected: number of, reason for, and destination and demographics of transfers. Chi(2) test and t test analyses were used; p < 0.05 defined significance; data are mean +/- SEM. RESULTS: Transfer rate increased from 4% PRE to 6.9% (p = 0.001) POST with no significant difference in age, Glasgow Coma Scale score, Injury Severity Score, or Revised Trauma Score. Repatriation occurred in 12.8% POST (none PRE). The current Level I facility accepted 1.8% of all transfers PRE and 36.4% POST (p = 0.0001). PRE/POST rates by reason are as follows: pediatric, 14.6%/9.0% (p = 0.04); intensive care unit, 0.4%/1.7% (p = 0.13); complex orthopedic, 100%/0% (p = 0.005); vascular, 50%/0% (p = 0.008); spinal cord injury, 100%/100%; and ophthalmologic, 0%/100% (p = 0.005). CONCLUSIONS: In this experience of Level I/II partnership (1) transfer patterns were altered, (2) select patient cohort transfers decreased (pediatric, complex orthopedic, vascular), whereas others increased (aortic work-up), and (3) repatriation rates were low.     

Insulin-like growth factor I (IGF-I)-stimulated pancreatic beta-cell growth is glucose-dependent. Synergistic activation of insulin receptor substrate-mediated signal transduction pathways by glucose and IGF-I in INS-1 cells

Nutrients and certain growth factors stimulate pancreatic beta-cell mitogenesis, however, the appropriate mitogenic signal transduction pathways have not been defined. In the glucose-sensitive pancreatic beta-cell line, INS-1, it was found that glucose (6-18 mM) independently increased INS-1 cell proliferation (>20-fold at 15 mM glucose). Insulin-like growth factor I (IGF-I)-induced INS-1 cell proliferation was glucose-dependent only in the physiologically relevant concentration range (6-18 mM glucose). The combination of IGF-I and glucose was synergistic, increasing INS-1 cell proliferation >50-fold at 15 mM glucose + 10 nM IGF-I. Glucose metabolism and phosphatidylinositol 3'-kinase (PI 3'-kinase) activation were necessary for both glucose and IGF-I-stimulated INS-1 cell proliferation. IGF-I and 15 mM glucose increased tyrosine phosphorylation mediated recruitment of Grb2/mSOS and PI 3'-kinase to IRS-2 and pp60. Glucose and IGF-I also induced Shc association with Grb2/mSOS. Glucose (3-18 mM) and IGF-I, independently of glucose, activated mitogen-activated protein kinase but this did not correlate with IGF-I-induced beta-cell proliferation. In contrast, p70(S6K) was activated with increasing glucose concentration (between 6 and 18 mM), and potentiated by IGF-I in the same glucose concentration range which correlated with INS-1 cell proliferation rate. Thus, glucose and IGF-I-induced beta-cell proliferation were mediated via a signaling mechanism that was facilitated by mitogen-activated protein kinase but dependent on IRS-mediated induction of PI 3'-kinase activity and downstream activation of p70(S6K). The glucose dependence of IGF-I mediated INS-1 cell proliferation emphasizes beta-cell signaling mechanisms are rather unique in being tightly linked to glycolytic metabolic flux.     

The effect of season and latitude on in vitro vitamin D formation by sunlight in South Africa

AIMS: To assess the effect of season and latitude on the in vitro formation of previtamin D3 and vitamin D3 from 7-dehydrocholesterol (7-DHC) by sunlight in two cities in South Africa, Cape Town and Johannesburg. METHODS: An in vitro study utilising vials containing 7-DHC, which were exposed to sunlight for a period of 1 hour between 8:00 and 17:00 on 1 day a month for a year. Previtamin D3 and vitamin D3 were separated from 7-DHC by high-performance liquid chromatography, and the amounts formed were calculated with the use of external standards. RESULTS: A marked seasonal variation in vitamin D3 production was noted in Cape Town, with very little being formed during the winter months of April through September. In Johannesburg, in vitro formation changed little throughout the year, and was similar to that found in Cape Town during the summer. During sunlit hours, vitamin D3 production was maximal at midday and small quantities were still being formed between 8:00 and 9:00, and between 16:00 and 17:00 during the summer. During winter in Cape Town, peak formation at midday was less than one-third of that in Johannesburg, and negligible amounts were formed before 10:00 and after 15:00. CONCLUSIONS: The previously documented seasonal variation in serum 25-hydroxyvitamin D recorded in patients in Johannesburg is probably a consequence of the increased clothing worn and the decreased time spent out of doors during winter, rather than decreased ultraviolet radiation reaching the earth. The limited in vitro formation of vitamin D3 during winter in Cape Town may have clinical implications insofar as the management of metabolic bone diseases like rickets and osteoporosis is concerned. Breast-fed infants resident in the area are likely to suffer from vitamin D deficiency rickets unless vitamin D supplements are provided, or the mothers are encouraged to take their children out of doors.