Showing papers by "Saint Louis University published in 1997"

The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma

Abstract: Background It has been hypothesized that asthma-related health problems are most severe among children in inner-city areas who are allergic to a specific allergen and also exposed to high levels of that allergen in bedroom dust. Methods From November 1992 through October 1993, we recruited 476 children with asthma (age, four to nine years) from eight inner-city areas in the United States. Immediate hypersensitivity to cockroach, house-dust-mite, and cat allergens was measured by skin testing. We then measured major allergens of cockroach (Bla g 1), dust mites (Der p 1 and Der f 1), and cat dander (Fel d 1) in household dust using monoclonal-antibody–based enzyme-linked immunosorbent assays. High levels of exposure were defined according to proposed thresholds for causing disease. Data on morbidity due to asthma were collected at base line and over a one-year period. Results Of the children, 36.8 percent were allergic to cockroach allergen, 34.9 percent to dust-mite allergen, and 22.7 percent to cat allerg...

Testosterone Replacement in Older Hypogonadal Men: A 12-Month Randomized Controlled Trial

Abstract: A decline in testicular function is recognized as a common occurrence in older men However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines This study was undertaken to examine the year-long effects of testosterone administration in this patient population Fifteen hypogonadal men (mean age 68 ± 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65± 7 yr) were randomly assigned to receive testosterone Hypogonadism was defined as a bioavailable testosterone <60 ng/dL The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months The main outcomes measured included grip strength, hemoglobin, prostate-specific antigen, leptin, and memory Testosterone improved bilateral grip strength (P < 005 by ANOVA) and increased hemoglobin (P < 0001 by ANOVA) The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean ± sem: −20 ± 09 ng/dL vs

Prospective study of blunt aortic injury: Multicenter trial of the American Association for the Surgery of Trauma

Abstract: Background: Blunt aortic injury is a major cause of death from blunt trauma. Evolution of diagnostic techniques and methods of operative repair have altered the management and posed new questions in recent years. Methods: This study was a prospectively conducted multicenter trial involving 50 trauma centers in North America under the direction of the Multi-institutional Trial Committee of the American Association for the Surgery of Trauma. Results: There were 274 blunt aortic injury cases studied over 2.5 years, of which 81% were caused by automobile crashes. Chest computed tomography and transesophageal echocardiography were applied in 88 and 30 cases, respectively, and were 75 and 80% diagnostic, respectively. Two hundred seven stable patients underwent planned thoracotomy and repair. Clamp and sew technique was used in 73 (35%) and bypass techniques in 134 (65%). Overall mortality was 31%, with 63% of deaths being attributable to aortic rupture; mortality was not affected by method of repair. Paraplegia occurred postoperatively in 8.7%. Logistic regression analysis demonstrated clamp and sew (p = 0.002) and aortic cross clamp time of 30 minutes (p = 0.01) to be associated with development of postoperative paraplegia. Conclusions: Rupture after hospital admission remains a major problem. Although newer diagnostic techniques are being applied, at this time aortography remains the diagnostic standard. Aortic cross clamp time beyond 30 minutes was associated with paraplegia; bypass techniques, which provide distal aortic perfusion, produced significantly lower paraplegia rates than the clamp and sew approach.

Sustained activation of extracellular-signal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G1 phase

Abstract: In Chinese hamster embryo fibroblasts (IIC9 cells), platelet-derived growth factor (PDGF) stimulated mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAP kinase/ERK) activity, but not that of c-jun N-terminal kinase (JNK), and induced G1 phase progression. ERK1 activation was biphasic and was sustained throughout the G1 phase of the cell cycle. PDGF induced cyclin D1 protein and mRNA levels in a time-dependent manner. Inhibition of PDGF-induced ERK1 activity by the addition of a selective inhibitor of MEK1 (MAP kinase kinase/ERK kinase 1) activation, PD98059, or transfection with a dominant-negative ERK1 (dnERK-) was correlated with growth arrest. In contrast, growth was unaffected by expression of dominant-negative JNK (dnJNK-). Interestingly, addition of PD98059 or dnERK-, but not dnJNK-, resulted in a dramatic decrease in cyclin D1 protein and mRNA levels, concomitant with a decrease in cyclin D1-cyclin-dependent kinase activity. To investigate the importance of sustained ERK1 activation, ERK1 activity was blocked by the addition of PD98059 throughout G1. Addition of PD98059 up to 4 h after PDGF treatment decreased ERK1 activity to the levels found in growth-arrested IIC9 cells. Loss of cyclin D1 mRNA and protein expression was observed within 1 h after inhibition of the second sustained phase of ERK1 activity. Disruption of sustained ERK1 activity also resulted in G1 growth arrest. These data provide evidence for a role for sustained ERK activity in controlling G1 progression through positive regulation of the continued expression of cyclin D1, a protein known to positively regulate G1 progression.

Hereditary hemochromatosis: Effects of C282Y and H63D mutations on association with β2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells

Abstract: Hereditary hemochromatosis (HH) is the most common autosomal recessive disorder known in humans. A candidate gene for HH called HFE has recently been cloned that encodes a novel member of the major histocompatibility complex class I family. Most HH patients are homozygous for a Cys-282→Tyr (C282Y) mutation in HFE gene, which has been shown to disrupt interaction with β2-microglobulin; a second mutation, His-63→Asp (H63D), is enriched in HH patients who are heterozygous for C282Y mutation. The aims of this study were to determine the effects of the C282Y and H63D mutations on the cellular trafficking and degradation of the HFE protein in transfected COS-7 cells. The results indicate that, while the wild-type and H63D HFE proteins associate with β2-microglobulin and are expressed on the cell surface of COS-7 cells, these capabilities are lost by the C282Y HFE protein. We present biochemical and immunofluorescence data that indicate that the C282Y mutant protein: (i) is retained in the endoplasmic reticulum and middle Golgi compartment, (ii) fails to undergo late Golgi processing, and (iii) is subject to accelerated degradation. The block in intracellular transport, accelerated turnover, and failure of the C282Y protein to be presented normally on the cell surface provide a possible basis for impaired function of this mutant protein in HH.

Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis

Abstract: Hereditary hemochromatosis (HH) is a common autosomal recessive disease associated with loss of regulation of dietary iron absorption and excessive iron deposition in major organs of the body. Recently, a candidate gene for HH (also called HFE) was identified that encodes a novel MHC class I-like protein. Most patients with HH are homozygous for the same mutation in the HFE gene, resulting in a C282Y change in the HFE protein. Studies in cultured cells show that the C282Y mutation abrogates the binding of the recombinant HFE protein to β2-microglobulin (β2M) and disrupts its transport to the cell surface. The HFE protein was shown by immunohistochemistry to be expressed in certain epithelial cells throughout the human alimentary tract and to have a unique localization in the cryptal cells of small intestine, where signals to regulate iron absorption are received from the body. In the studies presented here, we demonstrate by immunohistochemistry that the HFE protein is expressed in human placenta in the apical plasma membrane of the syncytiotrophoblasts, where the transferrin-bound iron is normally transported to the fetus via receptor-mediated endocytosis. Western blot analyses show that the HFE protein is associated with β2M in placental membranes. Unexpectedly, the transferrin receptor was also found to be associated with the HFE protein/β2M complex. These studies place the normal HFE protein at the site of contact with the maternal circulation where its association with transferrin receptor raises the possibility that the HFE protein plays some role in determining maternal/fetal iron homeostasis. These findings also raise the question of whether mutations in the HFE gene can disrupt this association and thereby contribute to some forms of neonatal iron overload.

Expression of Neuregulins and their Putative Receptors, ErbB2 and ErbB3, Is Induced during Wallerian Degeneration

Abstract: Schwann cell dedifferentiation and proliferation is a prerequisite to axonal regeneration in the injured peripheral nervous system. The neuregulin (NRG) family of growth and differentiation factors may play a particularly important role in this process, because these axon-associated molecules are potent Schwann cell mitogens and differentiation factors in vitro . We have examined Schwann cell DNA synthesis and the expression of NRGs and their receptors, the erbB membrane tyrosine kinases, in rat sciatic nerve, sensory ganglia, and spinal cord 0–30 d postaxotomy. Analysis of NRG cDNAs from these tissues revealed several novel splice variants and showed that cells endogenous to injured nerve express NRG mRNAs. A selective induction of mRNAs encoding the glial growth factor (GGF) subfamily of NRGs occurs in nerve beginning 3 d postaxotomy and thus coincides with the onset of Schwann cell DNA synthesis. In later stages of Wallerian degeneration, however, Schwann cell mitogenesis markedly decreases, whereas elevated GGF expression persists. Of the four known erbB kinases, Schwann cells express both erbB2 and erbB3 receptors over the entire interval studied. Expression of erbB2 and erbB3 is coordinately induced in response to axotomy, indicating that Schwann cell responses to NRGs may be modulated by changes in receptor density. Neuregulin (including transmembrane precursors) and erbB protein are associated with Schwann cells postaxotomy. Thus, in contrast to the concept of NRGs as axon-associated mitogens, our findings suggest that NRGs produced by Schwann cells themselves may be partially responsible for Schwann cell proliferation during Wallerian degeneration, probably acting via autocrine or paracrine mechanisms.

Outcomes of Long-Term Testosterone Replacement in Older Hypogonadal Males: A Retrospective Analysis

Abstract: To determine the complications, toxicities, and compliance of long term testosterone replacement in hypogonadal males, we retrospectively assessed 45 elderly hypogonadal men receiving testosterone replacement therapy and 27 hypogonadal men taking testosterone. Hypogonadism was defined as a bioavailable testosterone serum concentration of 72 ng/dL or less. Both groups received baseline physical examinations and blood tests. The testosterone-treated group received 200 mg testosterone enanthate or cypionate im every 2 weeks, and follow-up examinations and blood samplings were performed every 3 months. The control group had a single follow-up blood test and physical examination. There was no significant difference in the initial blood tests in the two groups. At 2 yr follow-up, only the hematocrit showed a statistically significant increase in the testosterone-treated group compared to the control group (P < 0.001). A decrease in the urea nitrogen to creatinine ratio and an increase in the prostate-specific a...

Evidence for the anorexia of aging : gastrointestinal transit and hunger in healthy elderly vs. young adults

Abstract: Animal studies suggest that aging is associated with anorexia and disordered gastrointestinal transit. To determine whether there is a relationship between the effects of aging on appetite and gastrointestinal transit in humans, 19 young (age 23-50 yr) and 14 elderly (age 70-84 yr) normal volunteers underwent measurements of 1) desire to eat, hunger, and fullness (visual analog scales); 2) gastric emptying (scintigraphy); 3) orocecal transit (breath hydrogen); 4) total gut transit (radiopaque markers); and 5) autonomic nerve function (cardiovascular reflexes). We found that, postprandially, elderly subjects had less desire to eat (P < 0.05) and less hunger (P < 0.05), but not a significantly greater fullness than younger subjects. Gastric emptying (50% emptying time) for solid (182 +/- 26 vs. 127 +/- 13 min, P < 0.05) and liquid (47 +/- 4 vs. 35 +/- 3 min, P < 0.05) meal components was slower in elderly subjects. Postprandial hunger was inversely related (r = -0.39, P < 0.05) to solid gastric emptying. There were no significant differences in orocecal and total gut transit times between the two groups. Autonomic nerve function was abnormal in 11 elderly but none of the young subjects (P < 0.01). We conclude that aging is associated with 1) diminished desire to eat and hunger, 2) slowing of solid and liquid gastric emptying, 3 no change in orocecal and total gut transit, and 4) autonomic nerve dysfunction. The slowing of gastric emptying may contribute to anorexia in aging subjects.

Orthodontic bracketing system and method therefor

Abstract: From a negative impression of a patient's teeth, a positive hard duplicate pattern such as a stone model of the teeth is made. A digitized three dimensional coded image of the teeth is then generated by means of a coordinate measuring machine or by laser scanning. The central axis of each tooth is then displayed in an exploded image of the set of teeth and each tooth is moved in virtual space to a desired position and orientation using torque, tip and angulation values as well as in/out position information provided by the selected orthodontic bracket system. The optimum position of each tooth-mounted orthodontic appliance bracket and its attachment point to its associated tooth for moving the tooth to a desired orientation and position is then determined using the digitized coded images of each tooth including its central axis in its initial and final desired position and orientation. Using this bracket attachment information for each tooth, the shape and contour of a bracket attachment jig is determined for each tooth and this information in digital form is used to fabricate a plurality of such jigs under computer control such as by using a computer numeric control (CNC) milling machine for attaching an off-the-shelf, conventional orthodontic bracket to each tooth. Conventional archwires attached to the upper and lower optimally positioned brackets urge each tooth to its respective desired position and orientation with minimal subsequent manipulation and adjustment of the archwires by the orthodontist.

Early fetal development of lung vasculature.

Abstract: Despite its relevance to a variety of congenital anomalies, the earliest stages of lung vascular development are poorly understood. In other organs, two processes have been identified: vasculogenesis, the development of blood lakes in mesenchyme, and angiogenesis, the branching of new vessels from preexisting ones. In the present study we established the events in the development of the lung's vasculature in Swiss-Weber mouse fetuses between 9 and 20 days gestation, using light microscopy (LM), transmission electron microscopy (TEM), barium-gelatin angiograms, and scanning electron microscopy (SEM) of Mercox (methyl methacrylate) vascular casts. Three features were identified: (1) central sprouting or angiogenesis for up to approximately seven generations (counting the artery to each lung as first generation); (2) the formation of peripheral lakes by vasculogenesis; and (3) the development of communications between the central and peripheral systems. At 9 days gestation, intercellular spaces were apparent in the lung mesenchyme; these were formed by discharge of vesicles from mesenchymal cells, which then regrouped to provide "endothelial" cells lining the spaces. The isolated lakes coalesced to form sinusoidal spaces of irregular profile. At 12 days gestation, the earliest time at which were able to make a cast, sprouting of arteries and veins from the central pulmonary vascular trunks was apparent. Between 13 and 14 days gestation the earliest connection between the peripheral and central spaces was identified. Such connections became more numerous and dense by term. Similar images seen on examination of human fetal lung sections by LM indicated that similar processes occur in the vascular development of the human lung.

Lower gastrointestinal bleeding

Abstract: BACKGROUND: Lower gastrointestinal bleeding can be a confusing clinical conundrum, the satisfactory evaluation and management of which requires a disciplined and orderly approach. Diagnosis and management has evolved with the development of new technology such as selective mesenteric angiography and colonoscopy. PURPOSE: This study was undertaken to review the available data in the literature and to determine the current optimum method of evaluation and management of lower gastrointestinal hemorrhage most likely to result in a successful outcome. METHODS: Data available on the topic of lower gastrointestinal bleeding in the English literature were obtainedviaMEDLINE search and were reviewed and analyzed. RESULTS: The colonic origin of lower gastrointestinal hemorrhage in order of decreasing incidence is diverticulosis, inflammatory bowel disease, including ischemic and infectious colitis, colonic neoplasia, benign anorectal disease, and arteriovenous malformations. Approximately 10 to 15 percent of all cases of rectal bleeding are attributable to a cause that is proximal to the ligament of Treitz. Small intestinal sources such as arteriovenous malformations, diverticula, and neoplasia account for between 3 and 5 percent of all cases. Colonoscopy successfully identified an origin in severe hematochezia in 74 to 82 percent of cases. Mesenteric angiography has a sensitivity of 42 to 86 percent. The best method of management depends on whether hemorrhage persists, the severity of continued hemorrhage, the cumulative transfusion requirement, and the specific origin of bleeding. CONCLUSION: Lower gastrointestinal hemorrhage is a complex clinical problem that requires disciplined and sophisticated evaluation for successful management. Diverticulosis is the most common cause. Colonoscopy is the diagnostic procedure of choice both for its accuracy in localization and its therapeutic capability. Selective mesenteric angiography should be reserved for those patients in whom colonoscopy is not practical. Precise identification of the bleeding source is crucial for a successful outcome. Specific directed therapy, such as segmental colonic resection for bleeding diverticulosis, is associated with the highest success rate and the lowest morbidity. A complete review of lower gastrointestinal bleeding is contained herein.

Genetic and environmental contributions to smoking

Abstract: We estimate the magnitude of genetic and shared environmental contributions to risk of initiation and maintenance of smoking. Genetic models were fitted to data from 2,204 male-male monozygotic and 1,793 male-male dizygotic twin pairs from the Vietnam Era Twin Registry who responded to smoking questions on a 1987 mail and telephone survey. The best fitting model allowed for both genetic and shared environmental effects on smoking initiation, accounting for 50% and 30% of the variance in risk, but allowed for only genetic effects, (accounting for 70% of the variance in risk), on persistence in smoking among those who had become regular smokers. This finding of a major genetic influence on smoking persistence confirms similar results from studies in Scandinavia and Australia. The role of heritable traits such as nicotine sensitivity should be addressed in smoking prevention and cessation efforts.

Infant cancer in the U.S.: histology-specific incidence and trends, 1973 to 1992

Abstract: Background Many cancers in infants demonstrate unique epidemiologic, clinical, and genetic characteristics compared with cancers in older children. Few epidemiologic reports, however, have focused on this important age group. Methods Population-based data from the Surveillance, Epidemiology, and End Results (SEER) program were used to estimate relative frequency, incidence rates, and average annual percentage change of rates among children in their first year of life (infants) who were diagnosed with a malignant neoplasm from 1973 to 1992 (N = 1461). Results The greatest proportion of cases (12%) was diagnosed during the first month of life, with extracranial neuroblastoma accounting for 35% of this total. Overall, the average annual incidence rate was 223/1,000,000 infants. Extracranial neuroblastoma was the most common infant malignancy (58/1,000,000 infants per year), followed by leukemias (37/1,000,000), brain and central nervous system (CNS) tumors (34/1,000,000), and retinoblastoma (27/1,000,000). White infants had a 32% higher incidence rate than black infants. The average annual percentage increase in rates for all cancer from 1973 to 1992 was 2.9% (95% CI: 1.9%, 3.8%). For neoplasms with at least 100 cases, increasing trends were greatest for retinoblastoma (4.6%), CNS (4.1%), and extracranial neuroblastoma (3.4%). Conclusions Incidence rates increased notably over the study period. Future studies should consider the unique presentation of infants with cancer when developing new hypotheses related to cancer etiology and gene-environment interactions.

Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract.

Abstract: Hereditary hemochromatosis (HH) is a common autosomal recessive disorder of iron metabolism that leads to excessive iron storage in the liver and other organs. Recently, between 83 and 100% of HH patients have been found to be homozygous for the same mutation in a novel major histocompatibility complex class I-like gene, called the HLA-H gene. The Cys-282 → Tyr mutation in HH patients would be expected to disrupt the function of the HLA-H gene product by altering a critical disulfide bridge. As a first step in understanding the function of the HLA-H gene product, we generated an antibody to a C-terminal peptide and used it for immunolocalization of the HLA-H protein in the gastrointestinal tract of Finnish and American subjects presumed not to have HH. Although staining for the HLA-H protein was seen in some epithelial cells in every segment of the alimentary canal, its cellular and subcellular expression in the small intestine were quite distinct from those seen in other segments. In contrast to the stomach and colon, where staining was polarized and restricted to the basolateral surfaces, and in contrast to the epithelial cells of the esophagus and submucosal leukocytes, which showed nonpolarized staining around the entire plasma membrane, the staining in small intestine was mainly intracellular and perinuclear, limited to cells in deep crypts. Prior genetic evidence suggested that a defective HLA-H protein is the molecular basis of HH. Here we show that the HLA-H protein not only varies in its pattern of expression along the cranial/caudal axis of the gastrointestinal tract but that it has a unique subcellular localization in the crypts of the small intestine in proximity to the presumed sites of iron absorption.

The correction of stereotactic inaccuracy caused by brain shift using an intraoperative ultrasound device

Abstract: Cranial stereotactic systems which utilize preoperative computed tomography (CT) or magnetic resonance imaging (MRI) data sets to guide surgery are subject to inaccuracy introduced by the intraoperative movement of the brain (brain shift). Although these systems allow precise navigation initially during a procedure, brain shift resulting from surgical intervention can lead to progressive degradation in accuracy, with the greatest inaccuracy occurring when deep structures are manipulated. One method of addressing this issue is with the use of an intraoperative scanning device such as CT or MRI; however, such scanners are costly and restrict surgical access. We have developed an alternative intraoperative imaging device consisting of an ultrasound unit coupled to a stereotactic system to quantify the degree of brain shift. This system determines the orientation of ultrasound images produced by the device and reformats the pre-operative CT or MRI images to match the ultrasound image. By comparing the position of specific structures on the two images, the amount of shift can be determined. Furthermore, this system is being expanded to include the aquisition of three-dimensional ultrasonic volumes.

Upper mantle velocity structure beneath the Tibetan Plateau from Pn travel time tomography

Abstract: We inverted 1510 P arrival times from regional distances (333–1600 km), in and around the Tibetan Plateau to map the lateral velocity variation within the uppermost mantle. Previous studies have placed first-order constraints on upper mantle velocities but relied on data recorded almost exclusively at stations outside of the plateau. We improve resolution by using 40 events recorded at stations within the Tibetan Plateau. We combine these data with observations obtained from the International Seismological Centre (ISC) to extend our coverage by including Pn arrivals from 85 additional plateau events, relocated in previous studies, and recorded at stations in and around the Tibetan Plateau. We use synthetic travel time data to evaluate the resolution of our data set. The observations provide good resolution to about 1° over most of the plateau and surrounding regions. Our results show average Pn velocities that are about 3% lower in the northern plateau relative to the southern plateau. These variations correlate well with major tectonic features and previous geophysical observations. In the Qiangtang terrane of the northern plateau, an area known to be inefficient for Sn propagation, Pn is slow relative to both the plateau south of the Banggong-Nujiang suture and the tectonically stable Tarim basin north of the plateau. This is strong evidence for the existence of partial melt within the uppermost mantle beneath the northern Tibetan Plateau. However, when laboratory estimates of relationships between temperature, velocity, and attenuation are applied, a relatively small temperature variation (240° to 370°C) is required to explain our Pn velocity observations. When combined with geochemical constraints from volcanics in the northern plateau, our results strongly suggest that the mantle lid is intact beneath the northern plateau. This result would preclude tectonic models involving wholesale delamination of the mantle lithosphere in the northern Tibetan Plateau.