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Biomedical subjects

B L Allen

Publications and source records attributed to B L Allen.

At least 19 recordsLinked to original sources

Soil and surface runoff phosphorus relationships for five typical USA midwest soils.

Excessively high soil P can increase P loss with surface runoff. This study used indoor rainfall simulations to characterize soil and runoff P relationships for five Midwest soils (Argiudoll, Calciaquaoll, Hapludalf, and two Hapludolls). Topsoil (15-cm depth, 241-289 g clay kg(-1) and pH 6.0-8.0) was incubated with five NH4H2PO4 rates (0-600 mg P kg(-1)) for 30 d. Total soil P (TPS) and soil-test P (STP) measured with Bray-P1 (BP), Mehlich-3 (M3P), Olsen (OP), Fe-oxide-impregnated paper (FeP), and water (WP) tests were 370 to 1360, 3 to 530, 10 to 675, 4 to 640, 7 to 507, and 2 to 568 mg P kg(-1), respectively. Degree of soil P saturation (DPS) was estimated by indices based on P sorption index (PSI) and STP (DPSSTP) and P, Fe, and Al extracted by ammonium oxalate (DPSox) or Mehlich-3 (DPSM3). Soil was packed to 1.1 g cm(-3) bulk density in triplicate boxes set at 4% slope. Surface runoff was collected during 75 min of 6.5 cm h(-1) rain. Runoff bioavailable P (BAP) and dissolved reactive P (DRP) increased linearly with increased P rate, STP, DPSox, and DPSM3 but curvilinearly with DPSSTP. Correlations between DRP or BAP and soil tests or saturation indices across soils were greatest (r > or = 0.95) for FeP, OP, and WP and poorest for BP and TPS (r = 0.83-0.88). Excluding the calcareous soil (Calciaquoll) significantly improved correlations only for BP. Differences in relationships between runoff P and the soil tests were small or nonexistent among the noncalcareous soils. Routine soil P tests can estimate relationships between runoff P concentration and P application or soil P, although estimates would be improved by separate calibrations for calcareous and noncalcareous soils.

Midwestern United States↗

Failure of trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia with concurrent leucovorin use.

Pneumocystis carinii is a common cause of pneumonia in patients with AIDS, however, the incidence has dropped with the availability of effective prophylactic regimens. First-line treatment for both acute Pneumocystis pneumonia and chronic prophylaxis is trimethoprim/sulfamethoxazole (TMP/SMX). This combination can cause hypersensitivity reactions as well as myelosuppression. The simultaneous administration of leucovorin during acute treatment has been shown to reduce the incidence of neutropenia, but may interfere with the efficacy of TMP/SMX. We report a case of P. carinii pneumonia in a patient with AIDS who failed TMP/SMX prophylaxis while taking leucovorin.

AIDS-Related Opportunistic Infections↗

Role of heparan sulfate as a tissue-specific regulator of FGF-4 and FGF receptor recognition.

FGF signaling uses receptor tyrosine kinases that form high-affinity complexes with FGFs and heparan sulfate (HS) proteoglycans at the cell surface. It is hypothesized that assembly of these complexes requires simultaneous recognition of distinct sulfation patterns within the HS chain by FGF and the FGF receptor (FR), suggesting that tissue-specific HS synthesis may regulate FGF signaling. To address this, FGF-2 and FGF-4, and extracellular domain constructs of FR1-IIIc (FR1c) and FR2-IIIc (FR2c), were used to probe for tissue-specific HS in embryonic day 18 mouse embryos. Whereas FGF-2 binds HS ubiquitously, FGF-4 exhibits a restricted pattern, failing to bind HS in the heart and blood vessels and failing to activate signaling in mouse aortic endothelial cells. This suggests that FGF-4 seeks a specific HS sulfation pattern, distinct from that of FGF-2, which is not expressed in most vascular tissues. Additionally, whereas FR2c binds all FGF-4-HS complexes, FR1c fails to bind FGF-4-HS in most tissues, as well as in Raji-S1 cells expressing syndecan-1. Proliferation assays using BaF3 cells expressing either FR1c or FR2c support these results. This suggests that FGF and FR recognition of specific HS sulfation patterns is critical for the activation of FGF signaling, and that synthesis of these patterns is regulated during embryonic development.

Alkaline Phosphatase↗

Structure-based design of a bispecific receptor mimic that inhibits T cell responses to a superantigen.

Key surface proteins of pathogens and their toxins bind to the host cell receptors in a manner that is quite different from the way the natural ligands bind to the same receptors and direct normal cellular responses. Here we describe a novel strategy for "non-antibody-based" pathogen countermeasure by targeting the very same "alternative mode of host receptor binding" that the pathogen proteins exploit to cause infection and disease. We have chosen the Staphylococcus enterotoxin B (SEB) superantigen as a model pathogen protein to illustrate the principle and application of our strategy. SEB bypasses the normal route of antigen processing by binding as an intact protein to the complex formed by the MHC class II receptor on the antigen-presenting cell and the T cell receptor. This alternative mode of binding causes massive IL-2 release and T cell proliferation. A normally processed antigen requires all the domains of the receptor complex for its binding, whereas SEB requires only the alpha1 subunit (DRalpha) of the MHC class II receptor and the variable beta subunit (TCRVbeta) of the T cell receptor. This prompted us to design a bispecific chimera, DRalpha-linker-TCRVbeta, that acts as a receptor mimic and prevents the interaction of SEB with its host cell receptors. We have adopted (GSTAPPA)(2) as the linker sequence because it supports synergistic binding of DRalpha and TCRVbeta to SEB and thereby makes DRalpha-(GSTAPPA)(2)-TCRVbeta as effective an SEB binder as the native MHC class II-T cell receptor complex. Finally, we show that DRalpha-(GSTAPPA)(2)-TCRVbeta inhibits SEB-induced IL-2 release and T cell proliferation at nanomolar concentrations.

Amino Acid Sequence↗

Epiphyseal changes after proximal femoral osteotomy.

This study was conducted to evaluate the risk factors for epiphyseal changes suggestive of osteonecrosis after proximal femoral osteotomy for hip subluxation associated with cerebral palsy. Forty-eight children with 94 hips were reviewed. Two observers rated the radiographs using a written protocol on two occasions each so that reproducibility of these observations could be assured. Concomitant pelvic osteotomy proved to have the greatest association with risk of epiphyseal changes. These findings, suggestive of osteonecrosis, were present in 7 of 68 (10%) hips that had isolated femoral osteotomy, and in 12 of 26 (46%) hips that had concomitant pelvic osteotomy.

Cerebral Palsy↗

Clinical evaluation of bowed legs in children.

Early radiographic screening and/or referral to a clinical specialist are often used to distinguish between physiologic bow leg deformity and infantile tibia vara disease in young children. These practices are a consequence of the clinician's inability (based upon the clinical examination) to distinguish between the deformities associated with physiologic and pathologic bow legs. Because the great majority of these children have physiologic bowing, routine radiographic screening and referral are not cost effective and expose children to unnecessary radiation. This study describes and evaluates the efficacy of a simple clinical examination technique, the 'cover up' test, to identify young children with bow legs who are at high risk for having infantile tibia vara. The 'cover up' test qualitatively assesses the alignment of the proximal portion of the shank or lower leg relative to the thigh or upper leg. Obvious valgus alignment is considered a negative test and is indicative of physiologic bowing. Neutral or varus alignment is considered a positive test and suggests that the child is at greater risk for having infantile tibia vara. Eighteen children with infantile tibia vara, evaluated initially prior to 3 years of age, and followed to the time of surgical correction, were compared with 50 children with physiologic bowing, also evaluated initially prior to 3 years of age and followed to resolution (mean follow-up 3 years and 10 months). All of the children with infantile tibia vara had a positive 'cover up' test (sensitivity = 1.00). Eighteen of 25 children with a positive 'cover up' test actually had or developed infantile tibia vara (positive predictive value = 0.72). Forty-three of 50 children with physiologic bowing had a negative 'cover up' test (specificity = 0.86). All of the children with a negative 'cover up' test actually had physiologic bowing (negative predictive value = 1.00). We conclude that the 'cover up' test is an effective screening tool for the assessment of bow legs in children between 1 and 3 years of age. Children with a negative 'cover up' test do not require radiographic evaluation and should be followed clinically for resolution of the bowing. Children with a positive 'cover up' test should have radiographic evaluation of the lower extremities or be referred to a specialist for further evaluation and treatment.

Bone Diseases, Developmental↗

Caps on malpractice awards: update.

Tort reform for professional liability is in the best interests of not only all physicians, but for industry and the citizenry as a whole. The enormous sums of money donated by the Trial Lawyers Association, whose livelihood is at stake, makes initial passage of tort reform difficult and, once passed, brings it under constant attack. Even if a well-disposed legislature passes a professional liability law, state supreme courts are ever ready to invalidate such laws. Thus, once tort reform has been passed, the next battleground is the state supreme court. ACS chapters should be preparing their membership for educating the public as well as themselves as to the danger of a state supreme court comprised of members opposed to tort reform, and be prepared to help the election of those individuals who are more sympathetic to tort reform.

Cost Control↗

DNA recognition properties of the N-terminal DNA binding domain within the large subunit of replication factor C.

Replication Factor C (RFC) is a five-subunit protein complex required for eukaryotic DNA replication and repair. The large subunit within this complex contains a C-terminal DNA binding domain which provides specificity for PCNA loading at a primer-template and a second, N-terminal DNA binding domain of unknown function. We isolated the N-terminal DNA binding domain from Drosophila melanogaster and defined the region within this polypeptide required for DNA binding. The DNA determinants most efficiently recognized by both the Drosophila minimal DNA binding domain and the N-terminal half of the human large subunit consist of a double-stranded DNA containing a recessed 5' phosphate. DNA containing a recessed 5' phosphate was preferred 5-fold over hairpined DNA containing a recessed 3' hydroxyl. Combined with existing data, these DNA binding properties suggest a role for the N-terminal DNA binding domain in the recognition of phosphorylated DNA ends.

Amino Acid Sequence↗

A modified Harrington technique for scoliosis.

Post-Harrington techniques for adolescent idiopathic scoliosis have increased the complexity of scoliosis surgery while contributing only biomechanically more secure fixation and sagittal contour preservation. On the the basis of principles defined by Harrington, the authors developed a simplified technique that accomplishes equivalent outcomes.

Biomechanical Phenomena↗

Distraction instrumentation outcomes in scoliosis.

The short-term outcomes of a new distraction technique using a small rod spinal instrumentation system (WRIGHTLOCK) are reported for adolescent idiopathic scoliosis. No caudally directed thoracic hooks were used. Seventy-four children aged 11.7 to 17.5 years who underwent consecutive posterior instrumentations are reviewed. Their curves improved from a mean of 55.6 degrees to 22.7 degrees (average of 59.2% correction). At 2.7 years mean follow-up, coronal curves lost an average of 4.2 degrees correction. Overall, there was a mean increase of 4.4 degrees in kyphosis. Children with the most preoperative hypokyphosis were afforded the greatest gains in kyphosis. Instrumentation resulted in a mean loss of 8.2 degrees lumbar lordosis. These results compare favorably with published results for other multihook systems.

Adolescent↗

Surgical corrections in scoliosis: a meta-analysis.

A meta-analysis of the acute correction outcomes in adolescent idiopathic scoliosis is reported. Posterior instrumentation systems generally gave similar coronal plane corrections with average corrections for differing systems ranging from 48% to 67%. There was significant overlap of corrections reported for each of the systems. Anterior instrumentation gave better results with average corrections ranging from 71% to 93%. No instrumentation demonstrated a consistent ability to restore a normal thoracic kyphosis, but all seemed to maintain preoperative kyphosis measures. All systems, including newer multihook systems, showed a small loss of lumbar lordosis postoperatively. The available data demonstrates that no posterior implant produces vertebral derotation.

Humans↗

Replication factor C interacts with the C-terminal side of proliferating cell nuclear antigen.

Replication factor C (RF-C) is a heteropentameric protein essential for DNA replication and repair. It is a molecular matchmaker required for loading of proliferating cell nuclear antigen (PCNA) onto double-stranded DNA and, thus, for PCNA-dependent DNA elongation by DNA polymerases delta and epsilon. To elucidate the mode of RF-C binding to the PCNA clamp, modified forms of human PCNA were used that could be 32P-labeled in vitro either at the C or the N terminus. Using a kinase protection assay, we show that the heteropentameric calf thymus RF-C was able to protect the C-terminal region but not the N-terminal region of human PCNA from phosphorylation, suggesting that RF-C interacts with the PCNA face at which the C termini are located (C-side). A similar protection profile was obtained with the recently identified PCNA binding region (residues 478-712), but not with the DNA binding region (residues 366-477), of the human RF-C large subunit (Fotedar, R., Mossi, R., Fitzgerald, P., Rousselle, T., Maga, G., Brickner, H., Messner, H., Khastilba, S., Hübscher, U., and Fotedar, A., (1996) EMBO J., 15, 4423-4433). Furthermore, we show that the RF-C 36 kDa subunit of human RF-C could interact independently with the C-side of PCNA. The RF-C large subunit from a third species, namely Drosophila melanogaster, interacted similarly with the modified human PCNA, indicating that the interaction between RF-C and PCNA is conserved through eukaryotic evolution.

Animals↗

Comparison of neurologic deficits with atlanto-dens intervals in patients with Down syndrome.

Eighty-four patients with Down syndrome had flexion-extension lateral roentgenograms of the C1-C2 articulation for the purpose of dividing the group into subluxators (> or = 4 mm atlanto-dens interval and 2 mm translation) and nonsubluxators (those who did not meet these criteria). Neurologic examinations and chart review were carried out on all patients to ascertain those with a positive neurologic finding or history. Seventeen (20%) were defined as subluxators and 67 (80%) as nonsubluxators. Five (29%) of the subluxators were found to have positive neurologic findings and 18 (27%) of the nonsubluxators had similar types of positive neurologic findings. These percentages are not significantly different. This led us to conclude that positive neurologic findings and an abnormal atlanto-dens interval are not alone adequate criteria to judge need for surgical stabilization of the C1-C2 articulation in patients with Down syndrome.

Adolescent↗

MSCRAMM-mediated adherence of microorganisms to host tissues.

Microbial adhesion to host tissue is the initial critical event in the pathogenesis of most infections and, as such, is an attractive target for the development of new antimicrobial therapeutics. Specific microbial components (adhesins) mediate adherence to host tissues by participating in amazingly sophisticated interactions with host molecules. This review focuses on a class of cell surface adhesins that specifically interact with extracellular matrix components and which we have designated MSCRAMMs (microbial surface components recognizing adhesive matrix molecules). MSCRAMMs recognizing fibronectin-, fibrinogen-, collagen-, and heparin-related polysaccharides are discussed in terms of structural organization, ligand-binding structures, importance in host tissue colonization and invasion, and role as virulence factors.

Adhesins, Bacterial↗

Fimbriation, capsulation, and iron-scavenging systems of Klebsiella strains associated with human urinary tract infection.

Thirty-two strains of Klebsiella pneumoniae and seven strains of Klebsiella oxytoca isolated from urinary tract infections in elderly adults were analyzed for capsular antigens, iron-scavenging systems, and fimbriation. All strains were capsulated. Twenty-seven different K antigens were identified among the strains, with no particular antigen dominating. All strains produced the iron-scavenging system enterochelin as analyzed by bioassay and DNA hybridization. In contrast, the aerobactin iron-sequestering system was not detected in any of the strains. All strains caused hemagglutination of tannin-treated human erythrocytes and reacted with an anti-type 3 fimbriae antiserum as well as in DNA hybridization with a type 3 fimbria-specific probe, indicating that the Klebsiella strains possessed this fimbrial type. Possession of type 1 fimbriae was analyzed by agglutination tests and by hybridization with DNA probes from two distinct Klebsiella type 1 fimbria gene clusters. Phenotypic expression of the type 1 fimbriae was found in 29 of 32 K. pneumoniae strains, whereas 30 strains reacted with either of the two type 1 fimbrial cluster DNA probes. In K. oxytoca, however, only three of seven strains expressed type 1 fimbriae and reacted with the DNA probes. The type 3 fimbriae were found to bind to a fraction of epithelial cells exfoliated in normal human urine, whereas the type 1 fimbriae bound strongly to urinary slime. No inhibitors of type 3 fimbrial binding were detected in human urine.

Aged↗

Adherence to respiratory epithelia by recombinant Escherichia coli expressing Klebsiella pneumoniae type 3 fimbrial gene products.

We examined the role of Klebsiella fimbrial types 1 and 3 in mediating adherence to human buccal and tracheal cells and to lung tissue sections. We found that clinical isolates of Klebsiella pneumoniae producing type 3 fimbriae and Escherichia coli HB101 containing a recombinant plasmid encoding expression of Klebsiella type 3 fimbriae (pFK10) demonstrated increased adherence to tracheal cells, trypsinized buccal cells, and lung tissue sections, in contrast to nonfimbriate and to type 1 fimbriate bacteria. Adherence by type 3 fimbriate bacteria was inhibited by purified type 3 fimbriae and Fab fragments derived from type 3 fimbrial-specific polyclonal immunoglobulin G. Type 3 fimbriae mediated attachment to the basolateral surface of tracheal cells and to the basal epithelial cells and the basement membrane regions of bronchial epithelia. Using an E. coli transformant (pDC17/pFK52), which expresses nonadherent P fimbrial filaments, along with the type 3 fimbrial adhesin (MrkD), we demonstrated that type 3 fimbrial attachment to respiratory cells was attributable to the MrkD adhesin subunit. Subsequent experiments demonstrated that the epithelial target of the type 3 fimbrial adhesin was most likely a peptide molecule rather than a carbohydrate. The results of this study demonstrate that, in vitro, the Klebsiella type 3 fimbrial adhesin mediates adherence to human respiratory tissue.

Acetates↗

Design and evaluation of a posterior laminar clamp spinal fixation system.

A new spinal instrumentation system for posterior applications was designed with the intent of minimizing intrusion of hardware into the neural canal during and postinsertion. Basic biomechanical measurements of posterior pullout strength led to the establishment of a clamp as an effective mechanism for gaining purchase on the vertebral lamina. These experiments defined the appropriate instrumentation size, as well as establishing that there was no loss of strength with the spinous process removed and the posterior laminar cortex compromised. There was no statistically significant difference between the maximum pullout strength achievable, using a band around the lamina as a control, and that produced by the implant system, in the thoracic spine. Comparative testing of a prototype system in flexion, extension, lateral bending, and torsion showed that the system, in general, had stiffness greater than segmental wiring and less than or equal to Cotrel-Dubousset fixation.

Biomechanical Phenomena↗

Nucleotide sequence and functions of mrk determinants necessary for expression of type 3 fimbriae in Klebsiella pneumoniae.

The nucleotide sequence of six genes involved in the expression of type 3 fimbriae of Klebsiella pneumoniae was determined. In addition to the genes that encode the fimbrial subunit (mrkA) and adhesion (mrkD), the mrkB, mrkC, and mrkE genes appear to be involved in assembly of the fimbrial filament and regulation of type 3 fimbrial expression. The mrkF gene product is required to maintain the stability of the fimbrial filament on the cell surface.

Adhesins, Bacterial↗