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J E Allen

Publications and source records attributed to J E Allen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Interleukin-5 is essential for vaccine-mediated immunity but not innate resistance to a filarial parasite.

The study of protective immune mechanisms effective against filarial nematodes has been hampered by the inability of these important human pathogens to infect laboratory mice. Recently, Litomosoides sigmodontis, a natural parasite of rats, has been developed as a valuable model for the study of filarial infection. BALB/c mice are fully susceptible to infection with L. sigmodontis third-stage larvae and develop patent infection. In contrast, mice on the C57BL background are resistant, and parasites undergo only a single molt and do not mature to adulthood. We used interleukin-5 (IL-5)-deficient mice on the C57BL/6 background to address the role of IL-5 and eosinophils in the innate resistance of C57BL/6 mice. We found no differences in parasite survival between IL-5-deficient and C57BL/6 mice. However, when these mice were used for the analysis of vaccine-mediated immunity, a critical role for IL-5 was elucidated. Mice genetically deficient in IL-5 were unable to generate a protective immune response when vaccinated with irradiated larvae, whereas C57BL/6 mice were fully protected from challenge infection. These studies help to clarify the highly controversial role of eosinophils in filarial infection.

Animals↗
PubMed2000

The abundant larval transcript-1 and -2 genes of Brugia malayi encode stage-specific candidate vaccine antigens for filariasis.

Lymphatic filariasis is a major tropical disease caused by the mosquito-borne nematodes Brugia and Wuchereria. About 120 million people are infected and at risk of lymphatic pathology such as acute lymphangitis and elephantiasis. Vaccines against filariasis must generate immunity to the infective mosquito-derived third-stage larva (L3) without accentuating immunopathogenic responses to lymphatic-dwelling adult parasites. We have identified two highly expressed genes, designated abundant larval transcript-1 and -2 (alt-1 and alt-2), from each of which mRNAs account for >1% of L3 cDNAs. ALT-1 and ALT-2 share 79% amino acid identity across 125 residues, including a putative signal sequence and a prominent acidic tract. Expression of alt-1 and alt-2 is initiated midway through development in the mosquito, peaking in the infective larva and declining sharply following entry into the host. Humans exposed to Brugia malayi show a high frequency of immunoglobulin G1 (IgG1) and IgG3 antibodies to ALT-1 and -2, distinguishing them from adult-stage antigens, which are targeted by the IgG4 isotype. Immunization of susceptible rodents (jirds) with ALT-1 elicited a 76% reduction in parasite survival, the highest reported for a single antigen from any filarial parasite. ALT-1 and the closely related ALT-2 are therefore strong candidates for a future vaccine against human filariasis.

Amino Acid Sequence↗
PubMed2000

Analysis of genes expressed at the infective larval stage validates utility of Litomosoides sigmodontis as a murine model for filarial vaccine development.

We used an expressed sequence tag approach to analyze genes expressed by the infective larvae of the rodent filarial parasite Litomosoides sigmodontis. One hundred fifty two new genes were identified, including several proposed as vaccine candidates in studies with human filarial parasites. Our findings have important implications for the use of L. sigmodontis as a model for filarial infection.

Amino Acid Sequence↗
PubMed1999

Comparative analysis of glycosylated and nonglycosylated filarial homologues of the 20-kilodalton retinol binding protein from Onchocerca volvulus (Ov20).

Ov20 is a structurally novel 20-kDa retinol binding protein secreted by Onchocerca volvulus. Immunological and biological investigation of this protein has been hampered by the inability to maintain O. volvulus in a laboratory setting. In an effort to find a system more amenable to laboratory investigation, we have cloned, sequenced, and expressed cDNA encoding homologues of Ov20 from two closely related filarial species, Brugia malayi (Bm20) and Acanthocheilonema viteae (Av20). Sequence comparisons have highlighted differences in glycosylation of the homologues. We present here an analysis of mouse immune responses to Ov20, Bm20, and Av20. The results suggest a strong genetic restriction in response to native Bm20 that is overcome when recombinant, nonnative material is used. Reactivity of human filarial sera to the three recombinant proteins confirmed previous specificity studies with Ov20 but highlighted important differences in the reactivity patterns of the O. volvulus and B. malayi homologues that may be due to differences in glycosylation patterns. Ov20 is a dominant antigen in infected individuals, while Bm20 is not. The availability of the B. malayi homologue enabled us to use defined murine reagents and inbred strains for genetic analysis of responsiveness in a way that is not possible for Ov20. However, the close sequence similarity between Ov20 and Av20 suggests that the A. viteae model may be more suited to the investigation of the biological functions of Ov20.

Amino Acid Sequence↗
PubMed1999

Suppressive antigen-presenting cells in Helminth infection.

Infection with filarial nematodes is commonly associated with a failure of T cells to proliferate in response to parasite antigen. We have investigated the possibility that antigen-presenting cells recruited during filarial infection are responsible for impairment of T cell function. We have found that the human filarial parasite Brugia malayi, when implanted into the peritoneal cavity of mice, recruits a population of adherent cells that actively block the proliferation of T cells. Phenotypic analysis of the recruited cells reveals large numbers of both macrophages and eosinophils and cell sorting experiments demonstrate that these antiproliferative cells are Mac-1-positive. Studies in gene-deficient mice have demonstrated that proliferative suppression is dependent on the in vivo production of IL-4 but not IL-5 or IL-10, while suppression in vitro is not mediated by any known antiproliferative factor. Our results suggest that helminth infection can lead to the development and/or recruitment of an IL-4-dependent macrophage population that mediates suppression via a novel mechanism.

Animals↗
PubMed1999

Fetal dosimetry from natural alpha-particle emitters.

The alpha-particle dose to human fetal bone marrow from natural exposure was investigated. The rate of calcification and the (210)Pb activity levels in fetal vertebrae showed that (210)Pb follows the uptake of calcium into the skeleton. Lead-210-supported (210)Po activity concentrations of up to 0.18 Bq kg(-1) were found in fetal lumbar vertebra. The mean chord length of the trabecular spaces in lumbar vertebra were 110-320 micrometer at 20- 40 weeks, in rib 130-180 micrometer at 20-35 weeks, and in sternum 190 micrometer at 35 weeks of gestation. In lumbar vertebra, up to 80% of marrow was within alpha-particle range (37 micrometer) of a bone surface. This resulted in a gestational equivalent dose to marrow from (210)Pb-supported (210)Po in bone of 8 and 24 micrometerSv when the contribution from all major natural alpha-particle-emitting radionuclides was considered. The mean distance of CD34(+) cells from the nearest bone surfaces in lumbar vertebra was 61 and 46 micrometer at mid- and late gestation, respectively. The mean cellular and nuclear diameters of CD34(+) cells were 5.5 and 3.8 micrometer respectively, and remained constant with gestational age. Few stem cells were hit by alpha particles at natural exposure; however, those that were hit received doses of up to 1.3 Gy.

Alpha Particles↗
PubMed1998

Value of the American College of Cardiology/American Heart Association stenosis morphology classification for coronary interventions in the late 1990s.

The goal of this study was to reassess the accuracy of the American College of Cardiology/American Heart Association (ACC/AHA) stenosis morphology classification for predicting coronary intervention success and complications in the era of new devices. Previous studies performed in the early part of this decade for percutaneous transluminal coronary angioplasty in patients with multivessel coronary artery disease found that these criteria were predictive of success rates but not complication rates. Data for 957 consecutive coronary interventions in 1,404 lesions from June 1994 to October 1996 were prospectively classified according to ACC/AHA guidelines and entered into a database. Ninety-one and 9/10 of coronary interventions were successful, defined as <50% residual stenosis of each vessel attempted in the absence of major in-hospital complications, including Q-wave myocardial infarction, ventricular arrhythmia, need for emergency coronary artery bypass surgery, or death. Success rates did not differ between A (186 of 193, 96.3%), B1 (211 of 221, 95.5%), and B2 (676 of 711, 95.1%) lesions, but each was more successful than C (246 of 279, 88.2%) lesions (p <0.003, p < 0.004, and p = 0.0001, respectively). The class of lesion (A, B, or C) did not predict device (atherectomy, rotablator, and stent) use but specific morphologic characteristics of lesions within these classes were predictive of which device was used. Multiple regression analysis revealed that total occlusion and vessel tortuosity were predictive of procedure failure. Lesion type (A, B, or C) was not predictive of complications, but bifurcation lesions (p = 0.0045), presence of thrombus (p = 0.0001), inability to protect a major side branch (p = 0.0468), and degenerated vein graft lesions (p = 0.0283) were predictive. Thus, the ACC/AHA grading system is predictive of successful coronary intervention outcome, particularly of C-type characteristics, but not of complications or device success rate and selection. Although lesion type (A, B, or C) was not predictive of complications, specific lesion morphologies were predictive of adverse events and device use.

Aged↗
PubMed1998

Requirement for in vivo production of IL-4, but not IL-10, in the induction of proliferative suppression by filarial parasites.

Loss of T lymphocyte proliferation and the emergence of a host response that is dominated by a Th2-type profile are well-established features of human filariasis. We have previously reported that adherent peritoneal exudate cells (PEC) from mice transplanted with adult Brugia malayi parasites suppress the proliferation of lymphocytes without blocking Ag-cytokine production in vitro. We now show that infection of mice with the infective larval (L3) stage of B. malayi generates a similar population of PEC. Suppressive cells are generated within 7 days of infection and mediate their effects through a nitric oxide-independent pathway. Both L3 and adult infection elicit high levels of host IL-4 whereas the microfilarial stage of the parasite induces IFN-gamma production and does not generate a similar form of suppression. Production of host IL-4 was necessary to allow the generation of suppressive PEC, given that IL-4-deficient mice implanted with adult parasites failed to induce proliferative block. However, IL-10-deficient mice implanted with adult parasites resulted in T cell suppression, indicating that IL-10 is not essential for the induction of hyporesponsiveness. Neither IL-4 nor IL-10 were directly responsible for ablating cellular proliferation in vitro, as the addition of neutralizing Ab to either cytokine did not reverse the proliferative block. Thus, IL-4 produced in vivo in response to filarial L3 and adult parasites is essential for the induction of proliferative suppression but is not itself the suppressive factor.

Animals↗
PubMed1998

Requirement for in vivo production of IL-4, but not IL-10, in the induction of proliferative suppression by filarial parasites.

Loss of T lymphocyte proliferation and the emergence of a host response that is dominated by a Th2-type profile are well-established features of human filariasis. We have previously reported that adherent peritoneal exudate cells (PEC) from mice transplanted with adult Brugia malayi parasites suppress the proliferation of lymphocytes without blocking Ag-cytokine production in vitro. We now show that infection of mice with the infective larval (L3) stage of B. malayi generates a similar population of PEC. Suppressive cells are generated within 7 days of infection and mediate their effects through a nitric oxide-independent pathway. Both L3 and adult infection elicit high levels of host IL-4 whereas the microfilarial stage of the parasite induces IFN-gamma production and does not generate a similar form of suppression. Production of host IL-4 was necessary to allow the generation of suppressive PEC, given that IL-4-deficient mice implanted with adult parasites failed to induce proliferative block. However, IL-10-deficient mice implanted with adult parasites resulted in T cell suppression, indicating that IL-10 is not essential for the induction of hyporesponsiveness. Neither IL-4 nor IL-10 were directly responsible for ablating cellular proliferation in vitro, as the addition of neutralizing Ab to either cytokine did not reverse the proliferative block. Thus, IL-4 produced in vivo in response to filarial L3 and adult parasites is essential for the induction of proliferative suppression but is not itself the suppressive factor.

Animals↗
PubMed1998

Money as a tool to extinguish conditioned responses to cocaine in addicts.

Classical conditioning principles offer a nondrug way to treat cocaine dependence. Eleven male subjects with the primary diagnosis of cocaine dependence were placed into one of two groups. The experimental group was asked to handle $500 cash in a mock budgetary task. The control group was asked to just imagine handling and budgeting the money. The subjects rated their craving-related feelings before and after each task. The experimental group showed significantly more craving after the money-handling task as compared to the control group, and the scores improved with time and as more tasks were completed. These data show that craving induced by handling cash is powerful and can be attenuated, at least on a short-term basis, using classical extinction procedures.

Analysis of Variance↗
PubMed1998

Impact of bicycle helmet safety legislation on children admitted to a regional pediatric trauma center.

PURPOSE: The regional pediatric trauma center in Buffalo, NY, has been active in pediatric injury prevention programs, including community education and distribution of bicycle helmets, since 1990. Since June 1, 1994, the use of bicycle safety helmets for children under 14 years of age has been mandated by a state law in New York. The authors undertook this study to assess the impact of this legislation on the frequency of helmet use in children involved in bicycle crashes presenting to the regional pediatric trauma center, and to assess the impact of helmet use on the number and severity of head injuries. METHODS: Bicycle crash victims (n = 208) admitted to a regional pediatric trauma center from 1993 to 1995 were studied retrospectively. Head injuries were classified as concussion alone, skull fractures, intracranial hemorrhages (ie, epidural, subdural, and subarachnoid), cerebral contusions, or diffuse cerebral edema alone (without any other intracranial injury). Helmeted children (HC) were compared with nonhelmeted children (NHC) using chi2 and Fisher's Exact test. P value less than .05 was considered significant. RESULTS: Only 31 children (15%) wore helmets at the time of the crash. Helmet use increased from 2%, during the period of education alone, to 26% after the legislation went into effect (P < .00001). The proportion of children suffering head injuries was similar in both groups (HC, 68%; NHC, 61%; P = NS). However, the type of head injury was different. HC were more likely to sustain concussion alone (HC, 65%; NHC, 44%; P < .03). HC were less likely to have skull fractures (HC, 0%; NHC, 13%; P < .02), and exhibited a trend toward less intracranial hemorrhages (HC, 0%; NHC, 9%; P = NS), cerebral contusions (HC, 3%; NHC, 5%; P = NS), and cerebral edema (HC, 0%; NHC, 0.6%; P = NS). Excluding the isolated concussions, head injuries were noted in only one HC, compared with 30 NHC (P < .04). None of the three children who died wore helmets at the time of the crash, and all died of multiple head injuries. CONCLUSIONS: The bicycle helmet safety law resulted in a 13-fold increase in the use of bicycle helmets among the children admitted to a regional pediatric trauma center after bicycle crashes, but the helmet use remains inadequate. Helmet use reduced the severity of head injuries, and might have prevented deaths caused by head injuries.

Bicycling↗
PubMed1998

Cervical ECMO cannula placement in infants and children: recommendations for assessment of adequate positioning and function.

BACKGROUND/PURPOSE: Cervical extracorporeal membrane oxygenation (ECMO) cannula position is often difficult to confirm by chest x-ray alone. Malposition requires a second surgery to rectify the problem. Reoperation places the patient at risk for infection, bleeding, or death. This study analyzes indications for cannula repositioning and suggests an alternative standard for intraoperative evaluation of catheter function as it relates to position. METHODS: The authors reviewed charts of 73 patients placed on arterio-venous ECMO through cervical vascular access. Reasons for repositioning of either cannula at the initial surgery or postoperatively were recorded. RESULTS: Of 73 patients, 18 (24.6%) required either arterial cannula or venous cannula repositioning. In 10 (55%) of these patients, cannula malposition was not detected by chest x-ray during the initial cannulation, and they therefore required a second cervical exploration for repositioning. CONCLUSIONS: Chest x-ray is not sensitive in demonstrating malpositioned cervical ECMO cannulae. Two-dimensional ECHO before wound closure, may be a superior, more cost effective means of assessing cannula placement and function than x-ray alone. Confirmation of cannula position and function, before wound closure, would reduce the risks involved with cervical reexploration.

Catheterization↗
PubMed1998

Profound suppression of cellular proliferation mediated by the secretions of nematodes.

Loss of T lymphocyte proliferation and the emergence of a host response that is dominated by a Th2-type profile are well-established features of human filarial infection. Down-regulation and modulation of host T cell responses during lymphatic filariasis has been investigated by implantation of parasite stages into inbred mice. Adherent peritoneal exudate cells (PEC) from mice transplanted with adult or larval Brugia malayi parasites are profoundly anti-proliferative but do not prevent antigen-specific cytokine production by T cells. We demonstrate here that the excretory/secretory (E/S) products of the adult parasite are sufficient to induce PEC that block proliferation if injected daily into mice. We have previously shown that in vivo production of host IL-4 is required for the generation of suppressive cells. Because the induction of host IL-4 is characteristic of infection with nematodes, we asked whether E/S from two other nematode parasites, Nippostrongylus braziliensis and Toxocara canis were also capable of generating a suppressor cell population. Injection of E/S from these two parasites also led to a reduction in T cell proliferation suggesting that this mechanism of down-regulating host responses is a feature common to nematode parasites.

Animals↗
PubMed1998

Diagnosis and initial management of blunt pancreatic trauma: guidelines from a multiinstitutional review.

OBJECTIVE: The authors' objective was to resolve the current controversies surrounding the diagnosis and management of blunt pancreatic trauma (BPT). SUMMARY BACKGROUND DATA: The diagnosis of BPT is notoriously difficult: serum amylase has been claimed to be neither sensitive nor specific, and recent anecdotal reports have suggested a role for computed tomography. The therapy of BPT has been controversial, with some suggesting selective observation and others advocating immediate exploration to prevent a delay-induced escalation in morbidity and death. METHODS: The authors conducted a retrospective chart review of documented BPT from six institutions, using a standardized binary data form composed of 187 items and 237 data fields. RESULTS: A significant correlation between pancreas-specific morbidity and injury to the main pancreatic duct (MPD) was noted. Patients requiring delayed surgical intervention after an unsuccessful period of observation demonstrated notably higher pancreas-specific mortality and morbidity rates, principally because of the incidence of unrecognized injuries to the MPD. Although detection of MPD injuries by computed tomography was no better than flipping a coin, endoscopic pancreatography was accurate in each of the five cases in which it was used. CONCLUSIONS: The principal cause of pancreas-specific morbidity after BPT is injury to the MPD. Parenchymal pancreatic injuries not involving the ductal system rarely result in pancreas-specific morbidity or death. Delay in recognizing MPD injury leads to increased mortality and morbidity rates. CT is unreliable in diagnosing MPD injury and should not be used to guide therapy. Initial selection of patients with isolated BPT for observation or surgery can be based on the determination of MPD integrity.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1997

Risk of hemorrhage and appropriate use of blood transfusions in pediatric blunt splenic injuries.

OBJECTIVE: To define changes in hematocrit (Hct) and the indications for blood transfusion in pediatric blunt splenic injury. DESIGN: Retrospective case series MATERIALS AND METHODS: All children with blunt splenic injuries from 1990 to 1995 were studied (n = 74). Transfusion practices were reviewed for the whole group. Thirty children with isolated splenic injuries who were not transfused were analyzed to document Hct changes (mean +/- 95% confidence intervals). MEASUREMENTS AND RESULTS: The Hct at presentation was 37 +/- 2%, which rapidly dropped to 31 +/- 2% (p < 0.05) within 24 hours. After remaining stable at that level for the next 5 days, the Hct rose to 33 +/- 4% on day 6 (p = not significant), 35 +/- 4% on day 7 (p = not significant), and 38 +/- 2% (p = not significant) on day 13 +/- 3. Fifteen children received transfusions, all but one of whom had suffered multiple injuries. The transfusion rate declined from 38% of children in 1990 to 10% in 1995. CONCLUSIONS: After the initial drop within the first 24 hours, the Hct remains stable and rises with time to reach the baseline by day 6. Transfusion rates have declined over time, and transfusions are now used almost exclusively in severely injured children with multiple injuries.

Blood Transfusion↗