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Showing papers by "Tufts University published in 1990"


Journal ArticleDOI
TL;DR: The validity of a self-administered diet history questionnaire has been estimated using as the reference data the mean of three 4-day diet records collected over the year prior to the administration of the questionnaire, in 1985-1986, using participants in the Women's Health Trial Feasibility Study.

1,131 citations


Journal ArticleDOI
01 Jan 1990-Blood
TL;DR: A specific radioimmunoassay was developed and used for IL-6 to compare production of this cytokine on a molar basis with that of IL-1 alpha,IL-1 beta, and tumor necrosis factor (TNF)alpha, and there was a significant correlation betweenIL-6 and IL-2 beta (r = .72) and between IL-4 and TNF ( r = .66).

1,028 citations


Journal ArticleDOI
TL;DR: The concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes is supported.
Abstract: Interleukins (IL) -1 beta and -1 alpha and tumor necrosis factor (TNF-alpha) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1 alpha levels were low (40 pg/ml) or undetectable in all situations. In 67% of the healthy subjects, plasma IL-1 beta levels were less than 70 pg/ml. Septic patients had higher plasma IL-1 beta levels (120 +/- 17 pg/ml, P = .001); those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-alpha concentrations in septic individuals were elevated (119 +/- 30 pg/ml) and correlated with severity of illness (r = .73, P = .003), but no correlation was observed between plasma IL-1 beta and TNF-alpha concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1 beta, from a baseline of 35 +/- 5 pg/ml to a maximum of 69 +/- 27 pg/ml at 180 min (P less than .05). Peak TNF-alpha levels after endotoxin infusion were 15 times higher than IL-1 beta levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1 beta levels. These data support the concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes.

783 citations


Journal ArticleDOI
09 Mar 1990-Cell
TL;DR: It is shown here that multiple members of the integrin superfamily of cell adhesion receptors bind the Y. pseudotuberculosis invasin protein prior to bacterial penetration into mammalian cells.

765 citations


Journal ArticleDOI
27 Sep 1990-Nature
TL;DR: Exposure of CFTR to cultured cystic fibrosis airway epithelial cells corrected the Cl− channel defect, demonstrating a causal relationship between mutations in the CFTR gene and defective Cl− transport which is the hallmark of the disease.
Abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique. Expression of CFTR, but not of a mutant form of CFTR (delta F508), corrected the Cl- channel defect. Correction of the phenotypic defect demonstrates a causal relationship between mutations in the CFTR gene and defective Cl- transport which is the hallmark of the disease.

706 citations


Journal ArticleDOI
TL;DR: The authors compared and contrasted semantic priming in the visual and auditory modalities using event-related brain potentials (ERPs) and behavioural measures (errors and reaction time) and found that the ERP priming effect began earlier, was larger in size, and lasted longer in the auditory modality than in visual modality.
Abstract: This study compared and contrasted semantic priming in the visual and auditory modalities using event-related brain potentials (ERPs) and behavioural measures (errors and reaction time). Subjects participated in two runs (one visual, one auditory) of a lexical decision task where stimuli were word pairs consisting of “prime” words followed by equal numbers of words semantically related to the primes, words unrelated to the primes, pseudo-words, and nonwords. Subjects made slower responses, made more errors, and their ERPs had larger negative components (N400) to unrelated words than to related words in both modalities. However, the ERP priming effect began earlier, was larger in size, and lasted longer in the auditory modality than in the visual modality. In addition, the lateral distribution of N400 over the scalp differed in the two modalities. It is suggested that there may be overlap in the priming processes that occur in each modality but that these processes are not identical. The results a...

659 citations


Journal ArticleDOI
TL;DR: The purified phosphoinositide 3-kinase preparation contained an 85-kDa protein and a protein doublet of approximately 110 kDa, which was the same protein previously shown to associate with polyoma virus middle T antigen and the platelet-derived growth factor receptor.

597 citations


Journal ArticleDOI
Dice Jf1
TL;DR: One mechanism by which proteins enter lysosomes for subsequent degradation requires that substrate proteins contain peptide sequences biochemically related to Lys-Phe-Glu-Arg-Gln (KFERQ).

590 citations


Journal ArticleDOI
TL;DR: Short-term vitamin E supplementation improves immune responsiveness in healthy elderly individuals; this effect appears to be mediated by a decrease in PGE2 and/or other lipid-peroxidation products.

551 citations


Journal ArticleDOI
TL;DR: It is reported that PI 3-kinase activity is immunoprecipitated from insulin-stimulated CHO cells by antiphosphotyrosine and anti-insulin receptor antibodies and suggested that this regulation involves a physical association between the insulin receptor and the PI 3 -kinase and tyrosyl phosphorylation.
Abstract: Insulin action appears to require the protein-tyrosine kinase domain of the beta subunit of the insulin receptor. Despite this, the identities and biochemical functions of the cellular targets of this tyrosine kinase are unknown. A phosphatidylinositol 3-kinase (PI 3-kinase) that phosphorylates the D-3 position of the inositol ring associates with several protein-tyrosine kinases. Here we report that PI 3-kinase activity is immunoprecipitated from insulin-stimulated CHO cells by antiphosphotyrosine and anti-insulin receptor antibodies. Insulin as low as 0.3 nM increased immunoprecipitable PI 3-kinase activity within 1 min. Increases in activity were much greater in CHO cells expressing the human insulin receptor (100,000 receptors per cell) than in control CHO cells (2000 receptors per cell). During insulin stimulation, various lipid products of the PI 3-kinase either appeared or increased in quantity in intact cells, suggesting that the appearance of immunoprecipitable PI 3-kinase reflects an increase in its activity in vivo. These results indicate that insulin at physiological concentrations regulates the PI 3-kinase and suggest that this regulation involves a physical association between the insulin receptor and the PI 3-kinase and tyrosyl phosphorylation.

526 citations


Journal ArticleDOI
TL;DR: The results demonstrate that introduction of an activated abl gene into the appropriate target cell, not the structure of the gene, is the major determinant in myeloid cell specificity.
Abstract: The v-abl gene in Abelson virus induces pre-B-cell lymphoma in mice while the BCR/ABL oncogene is associated with chronic myelogenous leukemia and some cases of acute lymphocytic leukemia in humans. Understanding the mechanisms by which these oncogenes affect various cell types has been hampered by a paucity of experimental systems that reproduce the range of biological effects associated with them. We have developed an experimental system in which murine hematopoietic stem cell populations are infected with either v-abl or BCR/ABL retroviruses and are used to reconstitute lethally irradiated mice. Irrespective of the form of activated abl, greater than 90% of the animals reconstituted with such cells develop tumors. About 50% of them develop a myeloproliferative syndrome that shares several features with the chronic phase of chronic myelogenous leukemia; the remaining animals succumb to pre-B-cell lymphomas. The myeloproliferative syndrome is characterized by large numbers of clonally derived, infected myeloid cells. This model will allow study of the mechanism by which activated abl genes affect hematopoietic precursors in chronic myelogenous leukemia. Furthermore, our results demonstrate that introduction of an activated abl gene into the appropriate target cell, not the structure of the gene, is the major determinant in myeloid cell specificity.

Journal ArticleDOI
TL;DR: The results indicate that the failure to find a substantial positive association between breast cancer risk and saturated fat intake cannot be explained by measurement error in fat, calories, or alcohol.
Abstract: If several risk factors for disease are considered in the same multiple logistic regression model, and some of these risk factors are measured with error, the point and interval estimates of relative risk corresponding to any of these factors may be biased either toward or away from the null value. A method is provided for correcting point and interval estimates of relative risk obtained from logistic regression for measurement error in one or more continuous variables. The method requires a separate validation study to estimate the coefficients from the multivariate linear regression model relating the surrogate variables to the vector of true risk factors. Similar methods have been suggested by other authors, but none provides a means of correcting the confidence intervals which include a component of variability due to estimation of the measurement error parameters from a validation study. An example is provided from a prospective study of dietary fat, calories, and alcohol in relation to breast cancer, and from a validation study of the questionnaire used to assess these nutrients. Before correcting for measurement error, the age-adjusted relative risk for a 25 g increment in alcohol intake was 1.33 (95% confidence interval (CI) 1.14-1.55); after correcting for measurement error, the relative risk increased to 1.62 (95% CI 1.23-2.12). Similarly, for a 10 g increment in saturated fat intake, the age-adjusted relative risk was 0.94 (95% CI 0.83-1.06); after correcting for measurement error, the relative risk was 0.84 (95% CI 0.59-1.20). These results indicate that the failure to find a substantial positive association between breast cancer risk and saturated fat intake cannot be explained by measurement error in fat, calories, or alcohol.

Journal ArticleDOI
TL;DR: It is suggested that a program which can demonstrate expertise in the area of medical consultation will have to use a judicious combination of categorical and probabilistic reasoning—the former to establish a sufficiently narrow context and the latter to make comparisons among hypotheses and eventually to recommend therapy.

Journal ArticleDOI
Bryan P. Toole1
TL;DR: Hyaluronan is a high-molecular-weight, highly anionic polysacchande found in extracellular matrices and at ceU surfaces and its unique physicochemical properties have fascinated polymer biophysicists and physiologists for decades.

Journal ArticleDOI
TL;DR: Month to years after the initial infection with B. burgdorferi, patients with Lyme disease may have chronic encephalopathy, polyneuropathy, or less commonly, leukoencephalitis, which usually improve with antibiotic therapy.
Abstract: Background and Methods. Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, is associated with a wide variety of neurologic manifestations. To define further the chronic neurologic abnormalities of Lyme disease, we studied 27 patients (age range, 25 to 72 years) with previous signs of Lyme disease, current evidence of immunity to B. burgdorferi, and chronic neurologic symptoms with no other identifiable cause. Eight of the patients had been followed prospectively for 8 to 12 years after the onset of infection. Results. Of the 27 patients, 24 (89 percent) had a mild encephalopathy that began 1 month to 14 years after the onset of the disease and was characterized by memory loss, mood changes, or sleep disturbance. Of the 24 patients, 14 had memory impairment on neuropsychological tests, and 18 had increased cerebrospinal fluid protein levels, evidence of intrathecal production of antibody to B. burgdorferi, or both. Nineteen of the 27 patients (70 percent) had polyneuropathy wi...

Journal ArticleDOI
21 Dec 1990-Science
TL;DR: The physical association between a replication protein and a transcription factor suggests that transcriptional activator proteins may function in targeting replication initiator proteins to their respective origins of replication.
Abstract: The mechanism by which transcription factors stimulate DNA replication in eukaryotes is unknown. Bovine papillomavirus DNA synthesis requires the products of the viral E1 gene and the transcriptional activator protein encoded by the E2 gene. Experimental data showed that the 68-kilodalton (kD) E1 protein formed a complex with the 48-kD E2 transcription factor. This complex bound specifically to the viral origin of replication, which contains multiple binding sites for E2. Repressor proteins encoded by the E2 open reading frame failed to complex with E1 suggesting that the 162-amino acid region of E2 that participates in transactivation contained critical determinants for interaction with E1. The physical association between a replication protein and a transcription factor suggests that transcriptional activator proteins may function in targeting replication initiator proteins to their respective origins of replication.

Journal ArticleDOI
02 Nov 1990-Cell
TL;DR: CD15, lacto-N-fucopentaose III or Lex, is a component of the PADGEM ligand on neutrophils and monocytes and is evaluated for their ability to block leukocyte-PADGem binding.

Journal ArticleDOI
TL;DR: ASCOT provides a more precise description of patient physiologic status and injury number, location, and severity than TRISS, and may be useful in relating to other important outcomes not highly correlated with TRISS or the Injury Severity Score (ISS).
Abstract: ASCOT (A Severity Characterization of Trauma) is a physiologic and anatomic characterization of injury severity which combines emergency department admission values of Glasgow Coma Scale, systolic blood pressure, respiratory rate, patient age, and AIS-85 anatomic injury scores in a way that obviates ISS shortcomings. ASCOT values are related to survival probability using the logistic function and regression weights reaffirm the importance of head injury and coma to the prediction of patient outcome. The ability of TRISS and ASCOT to discriminate survivors from non-survivors and the reliability of their predictions, as measured by the Hosmer-Lemeshow statistic, were compared using Major Trauma Outcome Study (MTOS) patient data. ASCOT performance matched or exceeded TRISS's for blunt-injured patients and for penetrating-injured patients. ASCOT performance gains were modest for blunt-injured patients. The Hosmer-Lemeshow statistics suggest that ASCOT reliably predicts patient outcome for penetrating-injured patients and nearly so for blunt-injured patients. Statistically reliable predictions were not achieved by TRISS for either set. ASCOT provides a more precise description of patient physiologic status and injury number, location, and severity than TRISS. The ASCOT patient description may be useful in relating to other important outcomes not highly correlated with TRISS or the Injury Severity Score (ISS) such as disability, length of stay, and resources required for treatment.

Journal ArticleDOI
TL;DR: This study compared the validity of two promising measures of shame and guilt proneness: revisions of the Harder Personal Feelings Questionnaire (PFQ2) and the ASGS Adapted Shame and Guilt Scale (ASGS).
Abstract: This study compared the validity of two promising measures of shame and guilt proneness: revisions of the Harder Personal Feelings Questionnaire (PFQ2; Harder & Lewis, 1987) and the Hoblitzelle Adapted Shame and Guilt Scale (ASGS; Hoblitzelle, 1982). Internal consistency, test-retest stability, factor structure, and construct validity with convergent and discriminant personality dimensions were examined for both scales. In addition to the shame and guilt measures, 63 (37 male, 26 female) mostly freshman college students completed a randomly ordered battery of personality scales theoretically relevant to shame and guilt proneness. Results support the reliability and shame/guilt factor structure of each scale. ASGS Shame correlations appeared marginally more valid with 11 external construct variables than PFQ2 Shame, whereas PFQ2 Guilt was clearly more valid than its corresponding ASGS subscale. New, potentially improved scales were constructed from the factor analyses and from item analyses. However, the r...

Journal ArticleDOI
TL;DR: It is demonstrated that IL-1 gene expression and synthesis occur early in the course of immune complex-induced colitis and are significantly elevated for 12 h before the appearance of PGE2 and LTB4; tissue levels ofIL-1 correlate with the degree of tissue inflammation and; specific blockade of IL-2 receptors reduces the inflammatory responses associated with experimental colitis.
Abstract: Interleukin 1 (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-1 alpha and beta mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-1 alpha was significantly elevated at 4 h (9.4 +/- 1.5 ng/g colon), progressively increased at 48 h (31 +/- 5.8 ng/g) and then decreased by 96 h (11.5 +/- 3.4 ng/g). IL-1 beta levels were 2.0 +/- 0.5 ng/g colon at 4 h, 5.0 +/- 1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-1 alpha levels were highly correlated with inflammation (r = 0.885, P less than 0.0001), edema (r = 0.789, P less than 0.0001) and necrosis (r = 0.752, P less than 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-1 ra) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2 +/- 0.4 to 1.4 +/- 0.3, P less than 0.02), edema (from 2.2 +/- 0.4 to 0.6 +/- 0.3, P less than 0.01) and necrosis (from 43 +/- 10% to 6.6 +/- 3.2%, P less than 0.03) compared to vehicle-matched colitis animals. These studies demonstrate that (a) IL-1 gene expression and synthesis occur early in the course of immune complex-induced colitis; (b) are significantly elevated for 12 h before the appearance of PGE2 and LTB4; (c) tissue levels of IL-1 correlate with the degree of tissue inflammation and; (d) specific blockade of IL-1 receptors reduces the inflammatory responses associated with experimental colitis.

Journal ArticleDOI
TL;DR: In this paper, the validity of the development edition of the Pediatric Evaluation of Disability Inventory (PEDI) in groups of disabled and nondisabled children was evaluated using data obtained by the Battelle Developmental Inventory Screening Test (BDIST).
Abstract: The purpose of this study was to determine the validity of the Development Edition (pilot version) of the Pediatric Evaluation of Disability Inventory (PEDI) in groups of disabled and nondisabled children. The PEDI is a new functional assessment instrument for the evaluation of disabled children aged 6 months to 7 years. The PEDI has been developed to identify functional status and change along three dimensions: 1) functional skill level, 2) caregiver assistance, and 3) modifications or adaptive equipment used. The PEDIs were administered as a parental-report questionnaire, and the results were compared with data obtained by the Battelle Developmental Inventory Screening Test (BDIST). The BDIST is a standardized assessment with developmental and adaptive content. Subjects were 20 children between the ages of 2 and 8 years with arthritic conditions and spina bifida and 20 nondisabled children matched for age and sex. All subjects' scores on the BDIST cognitive domain were no greater than 1.50 standard deviations below the mean for their age group. Concurrent validity was supported by moderately high Pearson product-moment correlations between BDIST and PEDI summary scores (r = .70-.80). Construct validity was supported by significant differences between the disabled and nondisabled groups' PEDI scores and by discriminant analysis identifying the PEDI scores as better group discriminators than the BDIST scores. Results validate the Developmental Edition of the PEDI and support the further development and standardization of the final version. Use of the PEDI in clinical pediatric physical therapy practice is discussed.

Journal ArticleDOI
TL;DR: Clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease showed racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations.
Abstract: The distribution of cerebrovascular lesions is affected by race Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease In symptomatic vascular territories, whites had more severe (≥50% stenosis) extracranial lesions, while Chinese had more severe intracranial lesions When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions When we combined symptomatic and asymptomatic temtories, whites had more extracranial lesions, while Chinese had more intracranial lesions White patients reported more transient ischemic attacks The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterol-emia, or ischemic heart disease between the groups The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations

Journal ArticleDOI
TL;DR: Particular Class II major histocompatibility genes determine a host immune response to B. burgdorferi that results in chronic arthritis and lack of response to antibiotics, and appear to act as independent, dominant markers of susceptibility.
Abstract: Background and Methods. A small percentage of patients infected with Borrelia burgdorferi have chronic Lyme arthritis that does not respond to antibiotic therapy. To learn whether genetically determined variations in the host immune response might account for such outcomes, we determined the immunogenetic profiles of 130 patients with various manifestations of Lyme disease. Results. Of the 80 patients with arthritis, 57 percent of those with chronic arthritis (12 to 48 months in duration) had the HLA-DR4 specificity; only 23 percent of those with arthritis of moderate duration (6 to 11 months) and only 9 percent of those with arthritis of short duration (1 to 5 months) had this specificity (P = 0.003). After the HLA-DR4-positive patients were excluded from each group, a secondary association was noted with HLA-DR2, which was found in 75 percent of the remaining patients with chronic arthritis and in 50 percent of those with arthritis of moderate duration, but in only 20 percent of those with arth...

Journal ArticleDOI
TL;DR: Analysis of ovarian cryosections stained with the DNA‐binding fluorochrome Hoechst 33258 indicates that sequential changes in GV chromatin occur duing folliculogenesis that result in the formation of a continuous perinucleolar chromatin sheath at the time of antrum formation.
Abstract: Changes in the organization of germinal vesicle chromatin in mouse oocytes have been analyzed by fluorescence microscopy with respect to progressive stages of follicular development and the disposition of oocyte cytoplasmic microtubules. Four discrete patterns of chromatin organization exist in germinal vesicle (GV)-stage oocytes isolated from the ovaries of 21-25-day-old gonadotropin-primed mice. Analysis of ovarian cryosections stained with the DNA-binding fluorochrome Hoechst 33258 indicates that sequential changes in GV chromatin occur during folliculogenesis that result in the formation of a continuous perinucleolar chromatin sheath at the time of antrum formation. Specific alterations in the cytoplasmic microtubule complex of GV-stage oocytes were observed that correlate with chromatin patterns. The extensive cytoplasmic microtubule complex seen in oocytes of preantral follicles initially localizes to perinuclear areas of the ooplasm. This is followed by a progressive reduction in cytoplasmic microtubules and the appearance of prominent microtubule-organizing centers at the nuclear periphery. Coordinated nuclear and microtubular alterations also occur under in vitro conditions prior to progression of meiosis to prometaphase-1. The results are discussed with respect to the ongoing differentiation of the oocyte nucleus and the microtubule cytoskeleton during folliculogenesis in preparation for the resumption of meiosis.

Journal ArticleDOI
TL;DR: Information suggests that mast cells may serve as a link between the immune, endocrine and nervous systems and could have an important role in the access of lymphocytes and pathogens to the brain.


Journal ArticleDOI
TL;DR: Patients with motor or sensorimotor peripheral neuropathy or lower motor neuron disease should be tested for anti-GM1 antibodies or anti-Gal(β1-3)GalNAc antibodies, as therapeutic reduction in antibody concentrations was reported to result in clinical improvement in some patients.
Abstract: We compared anti-GM1 IgM antibody titers in patients with various neurologic diseases and in normal subjects. We found increased titers in patients with lower motor neuron disease, sensorimotor neuropathy, or motor neuropathy with or without multifocal conduction block. In patients with other diseases, titers are similar to those in normal individuals, suggesting that anti-GM1 antibody levels are not increased nonspecifically after neural injury or inflammatory diseases. Anti-GM1 antibodies in many of the patients occur as monoclonal gammopathies, predominantly of lambda light-chain type, but the antibodies are sometimes polyclonal with normal or increased serum IgM concentrations. Most of the anti-GM1 antibodies appear to react with the Gal(beta 1-3)GalNAc epitope which is shared with asialo-GM1 and GD1b, but in some patients the antibodies are more specific for GM1 and associated with motor neuropathy. Patients with motor or sensorimotor peripheral neuropathy or lower motor neuron disease should be tested for anti-GM1 antibodies or anti-Gal(beta 1-3)GalNAc antibodies, as therapeutic reduction in antibody concentrations was reported to result in clinical improvement in some patients.

Journal ArticleDOI
TL;DR: In this article, a three-valued description of anatomic injury is presented and a logistic function model relating AP components and the Injury Severity Score (ISS) to survival probability is presented.
Abstract: A three-valued description of anatomic injury is presented. Anatomic profile (AP) components A, B, and C summarize serious injuries (greater than AIS 2) to the head/brain or spinal cord; to the thorax or front of the neck; and all remaining serious injuries. Relationships between AP components and survival rate reaffirm the seriousness of head injury. Logistic function models relating AP components and the Injury Severity Score (ISS) to survival probability were based on 20,946 Major Trauma Outcome Study (MTOS) patients (9.2% mortality rate) submitted through 1986. Model performance comparisons were based on 5,939 MTOS patients (7.8% mortality rate) submitted during 1987. The AP better discriminated survivors from nonsurvivors and provided a 31% increase in sensitivity when compared with the ISS. Neither the ISS nor the AP alone reliably predict patient outcome. The predictive power of methods for estimating patient survival probability which include physiologic indices or profiles, patient age, and an anatomic profile should be compared with current methods. The AP, which is based on the severity and location of all serious injuries, provides a more rational basis for comparing patient samples than the ISS.


Journal ArticleDOI
TL;DR: Results indicated that the carboxyl‐terminal 192 amino acids of invasin contains the integrin‐binding domain, even though this region does not contain the tripeptide sequence Arg‐Gly‐Asp.
Abstract: The invasin protein of the pathogenic Yersinia pseudotuberculosis mediates entry of the bacterium into cultured mammalian cells by binding several beta 1 chain integrins. In this study, we identified the region of invasin responsible for cell recognition. Thirty-two monoclonal antibodies directed against invasin were isolated, and of those, six blocked cell attachment to invasin. These six antibodies recognized epitopes within the last 192 amino acids of invasin. Deletion mutants of invasin and maltose-binding protein (MBP)--invasin fusion proteins were generated and tested for cell attachment. All of the invasin derivatives that carried the carboxyl-terminal 192 amino acids retained cell binding activity. One carboxyl-terminal invasin fragment and seven MBP--invasin fusion proteins were purified. The purified derivatives that retained binding activity inhibited bacterial entry into cultured mammalian cells. These results indicated that the carboxyl-terminal 192 amino acids of invasin contains the integrin-binding domain, even though this region does not contain the tripeptide sequence Arg-Gly-Asp.