Involvement of Interleukin (IL) 8 receptor in negative regulation of myeloid progenitor cells in vivo: evidence from mice lacking the murine IL-8 receptor homologue.

Expansion of mature neutrophils has been observed in mice lacking the murine interleukin (IL) 8 receptor homolog [mIL-8Rh(-/-)], and human (hu) IL-8 suppresses proliferation of primitive myeloid cells in vitro and in vivo. To evaluate involvement and relevance of murine IL-8 receptor homolog (mIL-8Rh) in negative regulation of myelopoiesis, we studied mIL-8Rh(-/-) and (+/+) mice raised in a normal or germ-free environment. Immature myeloid progenitors from mIL-8Rh(+/+) mice bred under normal or germ-free conditions were significantly suppressed in vitro by recombinant huIL-8, macrophage inflammatory protein (MIP)-1 alpha, platelet factor (PF) 4, interferon inducible protein (IP) 10, monocyte chemotactic peptide (MCP) 1, and H-ferritin. In contrast, progenitors from mIL-8Rh(-/-) mice were insensitive to inhibition by IL-8, but not to these other chemokines and H-ferritin. Mouse MIP-2, a ligand for mIL-8Rh, suppressed progenitors from normal but not mIL-8Rh(-/-) mice. Under normal environmental conditions, enhanced numbers of myeloid progenitors were found in femur, spleen, and blood of mIL-8Rh(-/-) compared with mIL-8Rh(+/+) mice. Numbers of myeloid progenitors were greatly decreased in mIL-8Rh(-/-)and (+/+) mice in germ-free conditions, and were either not significantly enhanced in mIL-8Rh(-/-) mice compared with (+/+) mice or were only moderately so. Differences in progenitors/organ between a germ-free and normal environment were greater for the mIL-8Rh(-/-) mice. These results document selective insensitivity of myeloid progenitor cells from mIL-8Rh(-/-) mice to inhibition by huIL-8 and mouse MIP-2 and a large expansion of myeloid progenitors in these mice, the latter effect being environmentally inducible. This provides strong support for a negative myeloid regulatory role played by the mIL-8Rh in vivo, whose active ligand may be MIP-2.

A method of identifying and correcting miscoding, misclassification and misdiagnosis in diabetes: a pilot and validation study of routinely collected data.

AIMS: Incorrect classification, diagnosis and coding of the type of diabetes may have implications for patient management and limit our ability to measure quality. The aim of the study was to measure the accuracy of diabetes diagnostic data and explore the scope for identifying errors. METHOD: We used two sets of anonymized routinely collected computer data: the pilot used Cutting out Needless Deaths Using Information Technology (CONDUIT) study data (n = 221 958), which we then validated using 100 practices from the Quality Improvement in Chronic Kidney Disease (QICKD) study (n = 760,588). We searched for contradictory diagnostic codes and also compatibility with prescription, demographic and laboratory test data. We classified errors as: misclassified-incorrect type of diabetes; misdiagnosed-where there was no evidence of diabetes; or miscoded-cases where it was difficult to infer the type of diabetes. RESULTS: The standardized prevalence of diabetes was 5.0 and 4.0% in the CONDUIT and the QICKD data, respectively: 13.1% (n = 930) of CONDUIT and 14.8% (n = 4363) QICKD are incorrectly coded; 10.3% (n = 96) in CONDUIT and 26.2% (n = 1143) in QICKD are misclassified; nearly all of these cases are people classified with Type 1 diabetes who should be classified as Type 2. Approximately 5% of T2DM in both samples have no objective evidence to support a diagnosis of diabetes. Miscoding was present in approximately 7.8% of the CONDUIT and 6.1% of QICKD diabetes records. CONCLUSIONS: The prevalence of miscoding, misclassification and misdiagnosis of diabetes is high and there is substantial scope for further improvement in diagnosis and data quality. Algorithms which identify likely misdiagnosis, misclassification and miscoding could be used to flag cases for review.

Gluten-sensitive enteropathy. Influence of histocompatibility type on gluten sensitivity in vitro.

We previously developed an in vitro organ culture system in which gluten exerts a toxic effect on intestinal mucosa of patients with active gluten-sensitive enteropathy. Gluten generally inhibits the epithelial cell maturation of intestinal biopsy specimens that otherwise occurs if the tissue is cultured for 24-48 h in a gluten-free medium. However, small intestinal mucosa from 15-20% of patients with proven gluten-sensitive enteropathy fails to manifest the expected gluten-induced damage in vitro. In the present study, we explored the relation between in vitro gluten-induced intestinal damage and the presence of HLA-B8. We determined whether the patients' histocompatibility type (HLA-B8 positive or negative) influenced the ability of gluten protein to inhibit epithelial cell maturation of cultured intestinal biopsy specimens from patients with gluten-sensitive enteropathy. Intestinal biopsies from 21 of 24 patients with gluten-sensitive enteropathy and HLA-B8 showed gluten-induced damage in vitro. On the other hand, intestinal biopsies from only 4 of 16 patients with gluten-sensitive enteropathy but without HLA-B8 showed gluten-induced damage in vitro. The difference in the effect of gluten in vitro between these two groups was statistically significant (P < 0.01). The data show a dichotomy between gluten-induced tissue damage in vivo and in vitro in HLA-B8 negative patients, suggesting that HLA-B8 is important for gluten to manifest a cytotoxic influence in organ culture.

Application of toxins from the entomopathogenic bacterium, Xenorhabdus nematophila, for the control of insects on foliage.

Larvae of the beet armyworm, Spodoptera exigua, and the diamondback moth, Plutella xylostella, and nymphs of the desert locust, Schistocerca gregaria were controlled by the application of either cell suspensions from the bacterium, Xenorhabdus nematophila or filtrates containing cell-free toxins. Since there was no significant differences between the two treatments it was concluded that toxins produced by the bacterium were responsible for the lethal effects obtained. Cells of Xenorhabdus nematophila were recovered from the haemocoele of the treated insects indicating that the bacterium, which is normally carried into the host by the J3 of Steinernema carpocapsae, was able to enter the host in the absence of the nematode vector. The entry was rapid, cells of Xenorhabdus nematophila being detected in the larvae of P. xylostella within 15 min of application of cell suspensions to chinese cabbage leaves. The possibility of using direct application of cell suspensions of X. nematophila to foliage for insect control is discussed.

The susceptibility of onion thrips, Thrips tabaci to Heterorhabditis indicus.

The potential of the entomopathogenic nematode, Heterorhabditis indicus against Thrips tabaci was tested on foliage and in soil at three concentrations. Soil treatment was more effective than the foliar treatment. At 1.5 million nematodes/m2, nearly 70% mortality was achieved with soil application whereas a similar dose applied to the foliage gave only 55% mortality. Soil application gave better mortality of onion thrips (62 %) at 1 million/m2 compared to foliar application at 1.5 million/m2. Probably this is because the nematodes are more effective against the soil dwelling prepupae and pupae stages of the thrips. The possible explanations for the differences are discussed.

Effects of in vivo treatment with PIXY321 (GM-CSF/IL-3 fusion protein) on proliferation kinetics of bone marrow and blood myeloid progenitor cells in patients with sarcoma.

PIXY321, a stimulator of multipotent colony-forming units (CFU-GEMM), burst-forming unit-erythroid (BFU-E), and colony-forming units granulocyte/macrophage (CFU-GM) progenitor cell proliferation in vitro, is currently being assessed in phase-I/-II clinical trials. We evaluated kinetics of CFU-GEMM, BFU-E, and CFU-GM proliferation in bone marrow (BM), blood, and granulocyte (CFU-G) and macrophage (CFU-M) progenitors in BM of chemotherapy-naive patients with sarcoma-administered PIXY321 (25 to 1000 micrograms/m2/day subcutaneously for 14 days). BM and/or blood cells from three to four patients at each dosage were assessed before, during, 1 to 2 days, and 7 days following treatment with PIXY321. Cells were pulse-treated in vitro with or without high-specific activity tritiated thymidine (3H-dThr) (to assess the percentage of progenitors in S-phase of cell cycle) and cultured for immature and more mature subsets of CFU-GEMM, BFU-E, CFU-GM, and for CFU-G and CFU-M. Despite heterogeneity in baseline cycling status of progenitors in BM, administration of 125 to 500 micrograms PIXY321 to patients at least doubled (p < 0.001) cycling rates of all BM progenitors. The cycling rates of blood progenitors increased from a slow or non-cycling state to > 38% cells in cycle. Within 1 to 2 days after cessation of PIXY321 infusion, all progenitors were in a slow or noncycling phase below that of many of the pre-BM samples (immature and mature CFU-GM and mature BFU-E) or were back to background levels (CFU-G, CFU-M, CFU-GEMM, and immature BFU-E). These cycling effects were similar to those previously noted for BM CFU-GM and BFU-E in patients on clinical trial with GM-CSF. In contrast, higher dosages of PIXY321, especially 1000 micrograms, increased cycling of BM and blood progenitor cells early during treatment, but cycling rates decreased while patients were still being administered PIXY321; decreased cycling was maintained after cessation of PIXY321. PIXY321 is thus highly active in vivo as a stimulator of multipotential and more lineage-restricted progenitors. The kinetics of progenitor cell proliferation noted in this study highlight differences seen with GM-CSF and G-CSF. The effects described here could be of relevance in design of future clinical trials using PIXY321 as an adjunct treatment in patients undergoing cytoreductive therapy.

Negative inotropic and relaxant effects of cocaine on myopathic human ventricular myocardium and epicardial coronary arteries in vitro.

OBJECTIVE: Cocaine produces both vascular and myocardial effects that can lead to serious cardiovascular complications in man. Tissue catecholamine stores are known to be depleted in the advanced stages of heart failure. The effects of cocaine on cardiac and coronary smooth muscle isolated from patients with end stage heart failure was tested in order to evaluate the direct actions of this drug on human tissue. METHODS: Effects of cocaine HCl were studied on cardiac ventricular trabeculae carneae and epicardial coronary artery segments obtained at heart transplantation from patients with end stage heart failure. Muscles were placed in organ baths under physiological conditions for recording isometric tension; a subset of muscles was loaded intracellularly with the bioluminescent calcium indicator, aequorin. Cardiac muscles were stimulated with threshold pulses delivered via a punctate electrode at 0.33 Hz. Coronary segments were studied under basal conditions and after contraction with 60 mM KCl. RESULTS: In both cardiac muscle and vascular smooth muscle preparations, cocaine (10(-6)-10(-3) M) produced dose related negative inotropic and relaxant effects, respectively; positive inotropic actions and vasoconstriction were not seen. In cardiac muscle, the negative inotropic actions were associated with a simultaneous decrease in peak intracellular calcium levels. In contrast, cocaine induced relaxation of potassium contracted vascular smooth muscle was not associated with a fall in peak intracellular calcium levels, a result consistent with decreased myofilament calcium responsiveness. CONCLUSIONS: These results indicate that the depressant effects of cocaine on cardiac versus vascular smooth muscle occur by different mechanisms and suggest the need for specific therapeutic approaches to managing cardiac depression versus vasodilation when these occur in cocaine intoxicated patients.

The effects of cocaine on intracellular Ca2+ handling and myofilament Ca2+ responsiveness of ferret ventricular myocardium.

1. When ferret right ventricular papillary muscles were stimulated with threshold punctate pulses (0.33 Hz; 30 degrees C), cocaine, 10(-5) M, increased peak tension development from 815 +/- 120 to 1125 +/- 180 mg (P less than 0.05) and increased the rate of relaxation from peak tension (time to 80% decline from peak tension decreased from 155 +/- 11 to 144 +/- 11 ms; P less than 0.05). These changes in the twitch were associated with comparable changes in the amplitude and time course of the calcium transient measured with aequorin (amplitude increased from 62 +/- 4 to 90 +/- 7% (P less than 0.05) of maximal values; time to 80% decline from peak amplitude decreased from 84 +/- 8 to 64 +/- 3 ms; P less than 0.05). These effects were markedly attenuated in the presence of the beta-adrenoceptor-blocking agent, propranolol, 6 x 10(-7) M, or by maximization of catecholamine release from the adrenergic nerve endings with field pulses of suprathreshold strength, indicating that catecholamine release from the adrenergic nerve endings is responsible for the positive inotropic and lusitropic responses to low and moderate doses of cocaine (i.e., less than or equal to 10(-5) M). 2. High doses of cocaine (i.e., greater than 10(-5) M) produced negative inotropic and lusitropic effects that were associated with a decreased amplitude and prolonged duration of the calcium transient. 3. In aequorin-loaded intact fibres, cocaine 10(-5) M did not affect the force-calcium relationship unless catecholamines were present. Cocaine, 10(-5) M, significantly shifted the force-calcium relationship of saponin-skinned muscles (pCa50 = 6.14 +/- 0.05 versus 5.92 +/- 0.07; P less than 0.05), indicating reduced responsiveness of the myofilaments to calcium. F. (maximal Ca2+-activated force) was reduced to 58% of control in the presence of 10- M cocaine, while the slope of the calcium-force curve remained unchanged. These data indicate that cocaine may also decrease myofilament calcium sensitivity and maximal calciumactivated force, via mechanisms independent of catecholamines, when cellular diffusion barriers are eliminated.

Differential inotropic effects of flosequinan in ventricular muscle from normal ferrets versus patients with end-stage heart failure.

1. In right ventricular papillary muscles from control ferrets, flosequinan (10(-7)-10(-4) M) produced a concentration-dependent positive inotropic effect (10(-5) M = 153 +/- 24, 10(-4) M = 198 +/- 44% increase in isometric tension; control tension = 100%; n = 11) associated with a corresponding increase in amplitude of the intracellular Ca2+ ([Ca2+]i) transient recorded with aequorin (10(-5) M = 133 +/- 11, 10(-4) M = 187 +/- 36% increase in [Ca2+]i transient; n = 11). 2. The positive inotropic effect of flosequinan in control ferret ventricular muscle was neither blocked by propranolol (6 x 10(-7) M), nor associated with the abbreviation of the [Ca2+]i transient and contraction that is typical of catecholamines. 3. Neither flosequinan (n = 12) nor BTS 53 554, its sulphone metabolite (n = 6) produced a positive inotropic effect or altered the time course of contraction in myocardium from the hearts of patients with end-stage failure. 4. In contrast to milrinone, which produces a positive inotropic effect via phosphodiesterase inhibition, the unresponsiveness of myopathic human myocardium to flosequinan was not restored after intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were increased by prior treatment with forskolin (n = 13). 5. Taken together, these data indicate that flosequinan has a direct positive inotropic effect that is Ca(2+)-dependent, but independent of changes in intracellular cyclic AMP concentrations. 6. The positive inotropic effect may be species-dependent or altered by the presence of hypertrophy and/or heart failure. However, when used therapeutically in patients with severe heart failure, our data suggest that flosequinan should not adversely affect myocardial oxygen consumption through direct or catecholamine-mediated actions on the heart.

An efficient laboratory protocol for the sequencing of large numbers of lacI mutants recovered from Big Blue transgenic animals.

Mutational spectra provide a powerful approach to investigate both the mutagenic potential and the mechanism of action of suspected mutagens and carcinogens. Recently, transgenic techniques have made it possible to generate mutational spectra in animals. Such a spectrum may consist of 50 to 200 mutants depending on the nature of the mutations, and many spectra can be generated depending on the design of the experiment. This report describes a practical approach for the processing and sequencing of large numbers of lacI mutants recovered from Big Blue animals.

End-digit preference in blood pressure recordings of patients with ischaemic heart disease in primary care.

End-digit preference describes the disproportionate selection of specific end digits. The rounding of figures might lead to either an under- or over-recording of blood pressure (BP) and a lack of accuracy and reliability in treatment decisions. A total of 85 000 BP values taken from computerised general practice records of ischaemic heart disease patients in England between 2001 and 2003 were examined. Zero preference accounts for 64% of systolic and 59% of diastolic readings, compared with an expected frequency of 10% (P<0.000001). Even numbers are more frequently seen than odd numbers. In all, 64% of nonzero systolic recordings and 65% of diastolic recordings ended in even numbers, compared with expected proportions of 44% (P<0.0001). Among the nonzero even numbers, eight is the most frequently observed: 28% of systolic and 31% of diastolic recordings compared with an expected proportion of 25% (P<0.0001). Among the five nonzero odd numbers, five is the most frequently observed end digit, representing 59% systolic and 62% of diastolic compared with an expected level of 20% (P<0.00001). English general practice displays marked end-digit preference. This is strongly for the end-digit zero. However, there is more use of other end-digits, notably 8 and 5. This bias potentially carries important treatment consequences for this high-risk population.

Managers see the problems associated with coding clinical data as a technical issue whilst clinicians also see cultural barriers.

OBJECTIVE: In UK general practice, the coding of clinical data (Read Coding) is far from universal. This study set out to examine the barriers to recording structured information in computerised medical records; and to explore whether managers and clinicians had different perspectives in how these barriers should be overcome. METHOD: A qualitative study, using semi-structured interviews of general practitioners, primary care nurses and practice managers. The interviews were recorded verbatim, and then underwent thematic analysis; additional interviews were conducted until thematic saturation was achieved. RESULTS: For clinicians the recording of structured data within a consultation is not a neutral activity, they are highly aware of diagnostic uncertainty and sensitive to the potential impact of both a correct and incorrect diagnostic label on their relationship with their patient. Clinicians accept that data has to be coded if they are to demonstrate that appropriate evidence based care has been provided to populations; but alongside this they require free-text as a more powerful reminder of the individual human encounter. Managers felt that they could encourage clinicians to code data for re-use as part of population data or as quality target indicators rather than as an enabler of the next consultation. CONCLUSIONS: The primary care consultation is a complex social interaction, and coding of the medical diagnosis in itself imposes the bio-medical model, carries assumptions about certainty, and is perceived by clinicians to potentially jeopardise their relationships with their patient. Further research to elicit patients' views may help clarify the magnitude of this barrier.

Field Evaluation of Steinernema feltiae Against the Web-spinning Larch Sawfly Cephalcia lariciphila.

Field trials were conducted in Rheola Forest, Wales, Great Britain, to determine the effectiveness of Steinernema feltiae UK strain in controlling the web-spinning larch sawfly Cephalcia lariciphila. Foliar sprays at the rate of 5,000-20,000 nematodes/100 cm branch resulted in 3.4-29.4% infection of sawfly larvae. Soil application of 200 nematodes/cm(2) resulted in 61% infection of sawfly prepupae and 17.3% of pupae. Prepupal infection ranged from 4.8 to 14.7% 1 year after nematode application. Soil applications of this nematode show that it has potential for biological control of sawfly prepupae.

Chronic kidney disease management in the United Kingdom: NEOERICA project results.

Early identification of patients with chronic kidney disease (CKD) may allow health-care systems to implement interventions aimed at decreasing disease progression and eventual morbidity and mortality. Primary care in the United Kingdom is computerized suggesting a separate screening program for CKD may not be necessary because identifying data already populates primary care databases. Our study utilized a data set of 163 demographic, laboratory, diagnosis, and prescription variables from 130 226 adults in the regions of Kent, Manchester, and Surrey. The patients were 18 years of age and older in a 5-year study period culminating in November 2003. Estimated glomerular filtration rate was calculated from the four-variable Modification of Diet in Renal Disease equation using calibrated creatinine levels. A valid creatinine value was recorded in almost 30% of this cohort. The age-standardized prevalence of stage 3-5 CKD was 10.6% for females and 5.8% for males. In these patients, the odds ratio for hypertension was 2.1, for diabetes 1.33, and for cardiovascular disease 1.69. Only 20% of the diabetic people with stage 3-5 CKD had a blood pressure less than or equal to 130/80 mm Hg. The proportion of patients with anemia significantly rose as renal function declined. We suggest that stage 3-5 CKD is easily detected in existing computerized records. The associated comorbidity and management is readily available enabling intervention and targeting of specialist resources.

Using computers to identify non-compliant people at increased risk of osteoporotic fractures in general practice: a cross-sectional study.

BACKGROUND: National guidelines recommend bisphosphonates for secondary prevention of osteoporotic fractures; however, poor compliance may result in sub-optimal prevention. OBJECTIVE: This study reports the feasibility of using GP electronic records to identify poorly compliant post-menopausal women who may be at increased risk of fragility fractures. DESIGN: Cross-sectional study of general practice computer records. SUBJECTS: Women over 45 years, registered in 29 practices across England with a total population of approximately 200,000. METHODS: MIQUEST (Morbidity Information Query and Export Syntax) a data extraction application was used to extract prescription, diagnostic data and probable fragility fractures (hip, vertebral, wrist). All women >45 years who received a first prescription for a weekly bisphosphonate (alendronate or risedronate) at least a year before data extraction were identified. Each record was examined to determine the number of days of prescribed treatment. RESULTS: Of 97992 registered women, 44% (42734) were >45 years. Prevalence of likely fragility fractures in women over 45 was 5.1% (2195/42734). 3.0% (1286/42734, mean age 72 years) received a prescription for a bisphosphonate in the 360 day period prior to data extraction with a median duration of treatment of 267 days. 45% (584/1286) received prescriptions covering >288/360 days (Medicine Possession Ratio >80%); 13% (161/1286) collected prescriptions covering >360 days. In those prescribed bisphosphonates, 23% (294/1286) had a likely fragility fracture. CONCLUSIONS: Women >45 years with probable fragility fractures are more likely to be prescribed bisphosphonates, though less than half will be actually taking them as prescribed. GPs should use computer technology to identify poorly compliant patients who are unnecessarily at risk of fracture.

Audit-based education to reduce suboptimal management of cholesterol in primary care: a before and after study.

BACKGROUND: Statins are recommended for the secondary prevention of cardiovascular disease, although they are often used in suboptimal doses and some patients may not receive lipid-lowering therapy. The Primary Care Data Quality (PCDQ) programme is an audit-based educational intervention. OBJECTIVE: To report the PCDQ programme's effect on the cholesterol management in cardiovascular disease. Subjects and methods Anonymized general practice data from 99 practices; 5% (n = 29 915) had cardiovascular diagnoses. RESULTS: Mean cholesterol fell from 4.75 to 4.64 mmol l(-1); patients achieving cholesterol target (< 5 mmol l(-1)) rose from 45.3 to 53.2%. Coronary heart disease patients achieved better control (mean 4.57 mmol l(-1)) than those with stroke (4.87 mmol l(-1)) or peripheral vascular disease (4.93 mmol l(-1)). Statin prescribing increased from 57.5 to 62.7%. Patients with diabetes [odds ratio (OR) 2.06, 95% confidence interval (95% CI) 1.91-2.21], prior myocardial infarction (MI) (OR 1.93, 95% CI 1.80-2.07), revascularization (OR 1.52, 95% CI 1.33-1.73) and smokers (OR 1.31, 95% CI 1.23-1.39) were more likely to receive statins, whereas people aged 75+ (OR 0.48, 95% CI 0.45-0.50), females (OR 0.90, 95% CI 0.86-0.94) and non-CHD-diagnosed (OR 0.36, 95% CI 0.34-0.38) were less likely. CONCLUSIONS: Diagnostic coding and number of patients who had their cholesterol measured and treated increased. There was no significant change in dosage used or inequity between the different groups prescribed statins.

Quality and variability of osteoporosis data in general practice computer records: implications for disease registers.

OBJECTIVE: To determine the extent to which routinely collected general practitioner computer data could be used to create disease registers of patients with osteoporosis, and to report any improvement in data quality since previous studies. STUDY DESIGN: Audit using anonymized data extracted from general practice computer records from across England. METHODS: Morbidity Query Information and Export Syntax (MIQUEST) software was used to extract structured data from the 78 volunteer practices that participated in the study. The data were aggregated and analysed. RESULTS: There were 100-fold differences in the rates of recording of relevant data. Many patients receiving treatment had no diagnostic codes. Data about secondary causes of osteoporosis and fractures were more consistently recorded than data relating to falls. There were no data to indicate whether fractures were low impact. T-scores, the gold-standard measure of bone density, were very infrequently recorded. CONCLUSIONS: Sufficient data about secondary causes of osteoporosis exist, and these could be searched to identify patients at risk. Meanwhile, fracture recoding could be improved, including likely fragility fractures, and T-scores could be added to computer records. A systematic approach is needed to raise the computer records to a standard where they can be used as valid and reliable disease registers.

The susceptibility of different species of sciarid flies to entomopathogenic nematodes.

Steinernema feltiae is the most effective nematode for controlling sciarid species but S. carpocapsae does exert some control. S. feltiae is less effective at 30 degrees C than at 22 degrees C. S. anomali, S. riobravis and two Heterorhabditis spp. gave better control at the higher temperature. All six sciarid species tested were susceptible to S. feltiae but there was some variation in the level of infection. UK isolates of S. feltiae were more effective against UK sciarids than the nematode isolates from other European countries which were tested. Adult sciarids are infected by S. feltiae and can disperse nematodes to nematode-free compost.

Combined oral/nasal immunization protects mice from Sendai virus infection.

Based on the concept of a common mucosal immune system wherein mucosal associated lymphocytes traffic among the various mucous membranes, the murine gastrointestinal tract was immunized with Sendai virus antigens in order to elicit a virus-specific immune response in the respiratory tract. Multiple intragastric (oral) administration of live or killed Sendai virus induced IgA and IgG antiviral antibodies in both gastrointestinal secretions and serum. When cholera toxin as an adjuvant was included along with virus, gut IgA and IgG as well as serum IgA responses were enhanced. Antiviral antibodies induced in respiratory secretions by oral killed virus plus cholera toxin, however, were variable and protection from virus challenge was not demonstrated. Significantly higher levels of respiratory antiviral antibodies were induced if immunization with oral killed Sendai virus/cholera toxin was combined with intranasal administration of small amounts of killed virus. The combined immunization also resulted in protection of both the upper and lower respiratory tracts from virus infection. Protection of the upper respiratory tract was correlated with the presence of IgA antiviral antibodies in nasal washings. On the other hand, protection of the lower respiratory tract was correlated with IgG antiviral antibodies in bronchoalveolar lavage fluids. Immunization with intranasal killed virus alone conferred partial protection to the lower respiratory tract and no protection to the upper respiratory tract. Thus, oral immunization with killed virus antigen could prime for a protective immune response in the murine respiratory tract and this protective response included IgA antibodies.