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Abstract With an interest in monitoring the patency of stents that are used to treat strictures in the bile duct, this paper reports the investigation of a wireless sensing system to interrogate a microsensor integrated into the stent. The microsensor is comprised of a 28-μm-thick magnetoelastic foil with 8.25-mm length and 1-mm width. Magnetic biasing is provided by permanent magnets attached to the foil. These elements are incorporated into a customized 3D polymeric package. The system electromagnetically excites the magnetoelastic resonant sensor and measures the resulting signal. Through shifts in resonant frequency and quality factor, the sensor is intended to provide an early indication of sludge accumulation in the stent. This work focuses on challenges associated with sensor miniaturization and placement, wireless range, drive signal feedthrough, and clinical use. A swine specimen in vivo experiment is described. Following endoscopic implantation of the sensor enabled plastic stent into the bile duct, at a range of approximately 17 cm, the signal-to-noise ratio of ~106 was observed with an interrogation time of 336 s. These are the first reported signals from a passive wireless magnetoelastic sensor implanted in a live animal.

Advanced technology used for arithmetic computing application, comprises greater number of approximatemultipliers and approximate adders. Truncation and Rounding-based Scalable ApproximateMultiplier (TRSAM) distinguish a variety of modes based on height (h) and truncation (t) as TRSAM (h, t) in the architecture. This TRSAM operation produces higher absolute error in Least Significant Bit (LSB) data shift unit. A new scalable approximate multiplier approach that uses truncation and rounding TRSAM (3, 7) is proposed to increase themultiplier accuracy. With the help of foremost one bit architecture, the proposed scalable approximate multiplier approach reduces the partial products. The proposed approximate TRSAM multiplier architecture gives better results in terms of area, delay, and power. The accuracy of 95.2% and the energy utilization of 24.6 nJ is observed in the proposed multiplier design. The proposed approach shows 0.11%, 0.23%, and 0.24% less Mean Absolute Relative Error (MARE) when compared with the existing approach for the input of 8-bit, 16-bit, and 32-bit respectively. It also shows 0.13%, 0.19%, and 0.2% less Variance of Absolute Relative Error (VARE) when compared with the existing approach for the input of 8-bit, 16-bit, and 32-bit respectively. The proposed approach is implemented with Field-Programmable Gate Array (FPGA) and shows the delay of 3.640, 6.481, 12.505, 22.572, and 36.893 ns for the input of 8-bit, 16-bit, 32-bit, 64-bit, and 128-bit respectively. The proposed approach is applied in digital filters designwhich shows the Peak-Signal-to-NoiseRatio (PSNR) of 25.05 dB and Structural Similarity Index Measure (SSIM) of 0.98 with 393 pJ energy consumptions when used in image application. The proposed approach is simulated with Xilinx and MATLAB and implemented with FPGA. [ABSTRACT FROM AUTHOR]

Background To ensure the validity and therapeutic utility of the Neck disability index (NDI) scale, translations, cultural adaptations and psychometric evidence is necessary. This study aimed to address the absence of a suitable and validated Hindi version of the NDI for the rural population. The specific objectives were to translate, adapt, and evaluate the psychometric properties of the newly developed Hindi version of the NDI. Methods Following guidelines provided by the American Association of Orthopedic Surgeons, the original English NDI scale was cross-culturally adapted into Hindi. The adaptation process included translations (forward and backward), expert committee review, pre-testing and cognitive debriefing with 30 individuals experiencing chronic non-specific neck pain. The outcome of this process was the creation of the Hindi version of the NDI, termed NDI-Hi. Subsequently, NDI-Hi was administered to 211 participants with neck pain from multiple centers for psychometric testing. The evaluation involved test-retest reliability over a 48-hour interval, factor analysis, assessment of internal reliability measures, and criterion-related validity by comparing it with the NPAD-Hindi version. Results The NDI-Hi version exhibited favorable psychometric properties, including good test-retest reliability with an intra-class correlation coefficient (ICC) of 0.87. Internal consistency of the scale was high, indicated by Cronbach’s alpha coefficient (α) of 0.96. The standard error of measurement (SEM) was determined to be 2.58, and the minimal detectable change (MDC) was calculated to be 7.15. Furthermore, the NDI-Hi showed significant correlation with the NPAD-Hindi version, with a correlation coefficient (rho) of 0.86, and a p-value of less than 0.001. Conclusions The NDI-Hi demonstrated validity and reliability as an outcome tool for assessing neck disability. It can be effectively utilized in clinical practice and research settings involving Hindi-speaking individuals with chronic non-specific neck pain. The adapted scale is particularly well-suited for the rural Northern Indian Hindi-speaking population.

Background Case reports are one of the important forms of documentation and publication of clinical physiotherapy presenting the first line of evidence in scientific literature. In order to provide a systematic and precise structure for reporting and presenting cases, the CARE guidelines were established in 2013. However, these guidelines present limitations as while reporting require items of specific specialties following the checklist. Authors from different specialities have developed CARE extensions specifying the characteristic features of corresponding fields, however, an extension dealing with physiotherapy assessment and line of management in the CARE guidelines is proposed as PhyCaRe. Method After consulting with the advisors, a draft will be prepared of the specific elements that should be included in the PhyCaRe using web Delphi methodology considering CARE statement as the source and SurveyMonkey will be used to undertake the web Delphi questionnaire. The web Delphi methodology will be assumed for three rounds and will be open to physiotherapists and others with substantial experience in reviewing case reports. Subsequently, an online consensus meeting, pilot testing, and submission of the CARE extension for physiotherapy will be conducted for publication. Dissemination The 2010 “Guidance for Developers of Health Research Reporting” and instructions from the EQUATOR Network will be followed in the preparation of PhyCaRe guidelines. The guidelines will be propagated at different platforms and journals will be requested to adopt the guidelines. Registration The reporting guideline under development is prospectively registered on the EQUATOR Network website on PhyCaRe – Reporting guideline for physiotherapy case reports.

Background: The countermovement jump (CMJ) and the squat jump (SJ) are two vertical jump (VJ) tests widely used to evaluate lower limb muscle strength and power, respectively. Biomechanical analysis of SJ and CMJ could help to predict the strength associated musculoskeletal clinical disorder which is most commonly seen among females such as patellofemoral pain syndrome, osteoarthritis etc. Therefore, the purpose of the study was to conduct and compare the biomechanical analysis of squat and countermovement jump using advanced motion analysis system and compare the changes among sedentary and active young females of the United Arab Emirates. Methodology: The experimental study was conducted at the Thumbay Physical Therapy and Rehabilitation Hospital, Gulf Medical University, Ajman, UAE. A total of 60 sedentary females, and 60 active females within age group 18-30 years were recruited under the convenience sampling method. The participants were randomly divided into two subgroups of 30 each for SJ and CMJ jump analysis respectively for sedentary and active group. Results: There was a statistically significant difference between the CMJ and SJ among the young females in UAE population (p < 0.05). The outcome variables such as jump height, and lower limb joint force were significantly reduced for SJ and CMJ in the sedentary group compared to active group. Majority of the variables showed moderate to severe effect size. Conclusion: Based on the study findings, it could be suggested that the “Sedentary Group” in the present study had poor muscle strength and ability to sustain the stress on the lower limb joints as also shown with lower mean total work. Since we have conducted the study on healthy non-athletes’ young females, the data could be used for further clinical correlation and comparison for lower limb muscle strength and power.

BackgroundLow back pain stands as a prevalent contributor to pain-related disability on a global scale. In addressing chronic low back pain (CLBP), there is a growing emphasis on incorporating psychological strategies into the management process. Among these, pain education interventions strive to reshape pain beliefs and mitigate the perceived threat of pain. This randomized controlled trial sought to assess the effects of pain education on various aspects, including pain levels, disability, quality of life, self-efficacy, and prognostic characteristics in individuals grappling with CLBP.MethodsThe clinical trial, retrospectively registered with the Clinical Trials Registry of India (CTRI/2021/08/035963), employed a two-arm parallel randomized design. Ninety-two participants with CLBP were randomly assigned to either the standard physiotherapy care with a pain education program or the control group. Both groups underwent a 6-week intervention. Assessment of pain intensity (using NPRS), disability (using RMDQ), self-efficacy (using the general self-efficacy scale), and well-being (using WHO 5I) occurred both before and after the 6-week study intervention.FindingsPost-intervention score comparisons between the groups revealed that the pain education intervention led to a significant reduction in disability compared to the usual standard care at 6 weeks (mean difference 8.2, p < 0.001, effect size Cohen d = 0.75), a decrease in pain intensity (mean difference 3.5, p < 0.001, effect size Cohen d = 0.82), and an improvement in the well-being index (mean difference 13.7, p < 0.001, effect size Cohen d = 0.58).ConclusionThe findings suggest that integrating a pain education program enhances the therapeutic benefits of standard physiotherapy care for individuals dealing with chronic LBP. In conclusion, the clinical benefits of pain education become apparent when delivered in conjunction with standard care physiotherapy during the management of chronic low back pain.

Background: Case reports are one of the important forms of documentation and publication of clinical physiotherapy presenting the first line of evidence in scientific literature. In order to provide a systematic and precise structure for reporting and presenting cases, the CARE guidelines were established in 2013. However, these guidelines present limitations as while reporting require items of specific specialties following the checklist. Authors from different specialities have developed CARE extensions specifying the characteristic features of corresponding fields, however, an extension dealing with physiotherapy assessment and line of management in the CARE guidelines is proposed as PhyCaRe. Method: After consulting with the advisors, a draft will be prepared of the specific elements that should be included in the PhyCaRe using Delphi methodology considering CARE statement as the source and SurveyMonkey will be used to undertake the Delphi questionnaire. The Delphi methodology will be assumed for three rounds and will be open to physiotherapists and others with substantial experience in reviewing case reports. Subsequently, an online consensus meeting, pilot testing, and submission of the CARE extension for physiotherapy will be conducted for publication. Dissemination: The 2010 "Guidance for Developers of Health Research Reporting" and instructions from the EQUATOR Network will be followed in the preparation of PhyCaRe guidelines. The guidelines will be propagated at different platforms and journals will be requested to adopt the guidelines. Registration: The reporting guideline under development is prospectively registered on the EQUATOR Network website on PhyCaRe – Reporting guideline for physiotherapy case reports.

Wireless magnetoelastic sensors offer significant potential for measuring the accumulation of biomass within stents—enabling early detection prior to stent occlusion—but the encapsulation of these sensors remains a critical challenge. The encapsulation must allow the sensors to navigate the curvature and accommodate the contact forces imparted during and after the implantation procedure, while also leaving the sensor open to mechanical interaction with the biomass during the extended period of deployment. This paper is focused on the encapsulation of ribbon-like magnetoelastic sensors (12.5 mm × 1 mm × 60 μm) within plastic biliary stents (inner diameter of 2.54 mm). The compromise between two polymer-based package designs—one mechanically flexible (Type F) and one mechanically stiff (Type S)—is evaluated. The primary advantage of the Type F package is the flexibility during the delivery process while that of the Type S package is in maintaining a strong signal even when the stent is in a curved bile duct. The maximum thicknesses of the Type F and S packages are 0.53 and 0.74 mm, respectively. Mechanical tests show that both types protect the sensors from forces imparted by a standard introducer, and allow the encapsulated sensors to accommodate bending with a radius of curvature as small as 3 cm. The Type F package has also been tested in situ, in the bile duct of a porcine carcass. The signal is measurable with a wireless range of ≍10 cm, at a resonant frequency of 159 kHz and a quality factor of 397. [ABSTRACT FROM AUTHOR]

Aims and Objectives: This study was conducted to compare the clinical assessment of impacted third molars of mandible with panaromic radiograph (OPG) and intraoral periapical radiograph (IOPA) and to assess the efficacy of IOPA and. Moreover, we corroborated the OPG and IOPA findings of impacted mandiblar third molar root apex to inferior alveolar canal. Materials and Methods: A total of 200 patients with pericoronitis were examined who were indicated for surgical extraction, among which 50 patients were selected for the study. All the patients underwent a radiographic survey with a digital OPG and IOPA of impacted mandibular third molars, along with clinical survey for anatomic relationship, type of impaction, space available, position in relation to second molar, number of roots, root curvature, and proximity of nerve canal. The data was subjected to statistical analysis. The Statistical Package for Social Sciences version 4.0.1 software was used for analyzing the collected data. Results: The study revealed that IOPA was more accurate in determining a majority of the factors affecting the third molar surgery, including relationship of the external oblique ridge (IOPA vs OPG = 96%:90%), anteroposterior relation with ramus (IOPA vs OPG = 70%:66%), vertical depth of impaction (IOPA vs OPG = 72%:68%), number of roots (P = 0.013), morphology of roots (IOPA vs OPG = 96%:90%); however, OPG was found to be accurate in evaluating the type of impaction (IOPA vs OPG = 88%:94%), canal relation, along with root of impacted molar (IOPA vs OPG = 74%:86%). Conclusion: To conclude, although IOPA has a marginal angle over OPG in assessing various parameters, only the number of roots have a greater accuracy (P < 0.0013) in IOPA than with OPG. However, the OPG is the better choice to be considered when the patient is associated with trismus. [ABSTRACT FROM AUTHOR]

Background: Preprogrammed reactions (PPR) appear at a latency of higher than 40 ms, but before the voluntary muscle responds (~ 120 ms) to postural perturbations. Objective: To examine the difference in magnitude of preprogrammed reactions in patients with chronic low back pain (CLBP) and without low back pain. Methods: we analyzed electromyographic Root Mean Square (RMS) amplitudes of asymptomatic (n=25) and CLBP patients (n=25) on stable and unstable surfaces during expected and unexpected perturbations for rectus abdominus and erector spinae muscles. The mean PPR and PPR-combined voluntary response RMS amplitudes (VRPPR) were compared between the two groups. To find the presence of PPR in LBP patients, a criteria was set that the obtained PPR RMS amplitude value should exceed 60% mean reflex RMS amplitude that occur within 50 ms after perturbation. Results: Fleiss' kappa revealed a good agreement ([kappa] = 0.7 to 0.9) among raters for absence of PPR in patients with CLBP and presence of PPR in asymptomatic population. The two way ANOVA revealed significantly different mean PPR and VRPPR RMS amplitudes between asymptomatic and LBP population for rectus abdominus and erector spinae muscles (p< 0.05). Conclusion: PPR responses were found absent (< 60% of Mean Reflex RMS) in patients with CLBP. Further, patients with CLBP demonstrated lower PPR amplitudes with higher peak voluntary responses compared to asymptomatic population, indicating difficulties in presetting of voluntary responses for regaining postural stability after perturbation. [ABSTRACT FROM AUTHOR]

A reply by M. Ramprasad to a letter to a editor about his article "Effect of Backpack Weight on Postural Angles in Preadolescent Children" in a 2010 issue is presented.

Goal: Implementation of an artificial intelli gence-based medical diagnosis tool for brain tumor classification, which is called the BTFSC-Net. Methods: Medical images are preprocessed using a hybrid probabilistic wiener filter (HPWF) The deep learning convolutional neural network (DLCNN) was utilized to fuse MRI and CT images with robust edge analysis (REA) properties, which are used to identify the slopes and edges of source images. Then, hybrid fuzzy c-means integrated k-means (HFCMIK) clustering is used to segment the disease affected region from the fused image. Further, hybrid features such as texture, colour, and low-level features are extracted from the fused image by using gray-level cooccurrence matrix (GLCM), redundant discrete wavelet transform (RDWT) descriptors. Finally, a deep learning based probabilistic neural network (DLPNN) is used to classify malignant and benign tumors. The BTFSC-Net attained 99.21% of segmentation accuracy and 99.46% of classification accuracy. Conclusions: The simulations showed that BTFSC-Net outperformed as compared to existing methods.

Background: Deficiency in hip girdle neuromuscular control can cause exaggerated Dynamic Knee Valgus (DKV) which afflicts the knee joint and lead to knee injuries especially ACL injury in sports. Though Kinesio taping (KT) is known to improve function, stability and proprioception, the evidence is inconclusive on its effectiveness in athletes. We hypothesized that kinesio taping could enhance neuromuscular control of the hip girdle there by causing a reduction in DKV., Aim/objective: To determine whether KT on Gluteus medius can correct exaggerated dynamic knee valgus and improves hip abductor strength when compared to sham KT., Method: 40 collegiate level athletes, aged between 18 and 28 years, of both genders with presence of dynamic knee valgus (>8° for men and >13° for women) were recruited in the study. Athletes were excluded if they had history of lower back pain, history of any injury or surgery to the lower extremities during the past year. Subjects who met the inclusion criteria were randomized into kinesio taping (KT) group and sham taping (ST) group. The Drop Jump test and the Donnatelli Drop Leg Test (DDT) were performed before, and on the third day, immediately after the application of KT on them and documented., Results: There was a significant reduction in DKV among male [4.0° (95% CI 3.5-4.5); p < 0.001] and female [4.3° (95% CI 3.5-5.2); p < 0.002] immediately after application of taping but not on the third day after application of KT. There was a significant rise in DDT immediately and on the third day after application of KT between KT group and SC group., Conclusion: There was a reduction in DKV immediately after the application of KT. However, there was no significant difference between KT group and SC group on the third day. Meanwhile, gluteus medius strength also showed significant improvement immediately after taping and it was maintained even on the third day., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Thyroid disorders are common in pregnancy and the most common disorder is subclinical hypothyroidism. Due to the complex hormonal changes during pregnancy, it is important to remember that thyroxine requirements are higher in pregnancy. According to recent American Thyroid Association (ATA) guidelines, the recommended reference ranges for TSH are 0.1 to 2.5 mIU/L in the first trimester, 0.2 to 3.0 mIU/L in the second trimester, and 0.3 to 3.0 mIU/L in the third trimester. Maternal hypothyroidism is an easily treatable condition that has been associated with increased risk of low birth weight, fetal distress, and impaired neuropsychological development. Hyperthyroidism in pregnancy is less common as conception is a problem. Majority of them are due to Graves' disease, though gestational hyperthyroidism is to be excluded. Preferred drug is propylthiouracil (PTU) with the target to maintain free T4 in upper normal range. Doses can be reduced in third trimester due to the immune-suppressant effects of pregnancy. Early and effective treatment of thyroid disorder ensures a safe pregnancy with minimal maternal and neonatal complications.

Macrosialin, the mouse homolog of human CD68, is a heavily glycosylated transmembrane protein found almost exclusively in macrophages. Its function remains uncertain. It has a high affinity for oxidized low-density lipoprotein (LDL) in ligand blots and antibodies against the human homolog, CD68, inhibit the binding of oxidized LDL to a human monocyte-derived cell line (THP-1). However, there is still controversy as to whether macrosialin, found predominantly in late endosomes, is expressed at all on the plasma membrane. The present studies, done in thioglycollate-elicited peritoneal macrophages, confirm that macrosialin is predominantly intracellular but show clearly that 10-15% of it is expressed on the cell surface. Exchange with intracellular pools occurs at an extremely high rate. The results are compatible with a surface function, including internalization of bound ligands or adhesion to surfaces.

Two human monocyte-macrophage (HMM) membrane binding proteins, (MBP) 200 and 235, are receptor candidates that bind to the apolipoprotein (apo)B-48 domain in triglyceride-rich lipoproteins for uptake independent of apoE. Microsequence analysis of the purified reduced MBP 200R characterized tryptic peptides of MBP 200R. A synthetic peptide mimicking a unique, unambiguous 10-residue sequence (AEGLMVTGGR) induced antipeptide antibodies that specifically recognized MBP 200, 235 and 200R, in 1- and 2-dimensional analyses, indicating 1) the ligand binding protein was sequenced and 2) MBP 200 and 235 yielded MBP 200R upon reduction. These antibodies identified the MBPs in human blood-borne, THP-1, U937 MMs, and endothelial cells (EC) but not in human fibroblasts or Chinese hamster ovary (CHO) cells. Fluorescence activated cell sorting (FACS) analysis located the MBPs on the MM surface as necessary for receptor function. The 10-residue, unambiguous MBP 200-derived sequence is unique, with no matches in extant protein databases. Antipeptide antibodies bind to the MBPs in reticuloendothelial cells that have this receptor activity, but not to proteins in cells that lack this receptor activity. These studies provide the first direct protein sequence and immunochemical data that a new, unique apoB receptor for triglyceride-rich lipoproteins exists in human monocytes, macrophages, and endothelial cells.

Studies in animals and humans have demonstrated uptake of plasma chylomicrons (triglyceride-rich lipoprotein [TGRLP] of Sf>400) by accessible macrophages in vivo. One potential mechanism is via a unique receptor pathway we previously identified in human blood and THP-1 monocytes and macrophages for the lipoprotein lipase (LpL)- and apolipoprotein (apo) E-independent, high-affinity, specific binding of plasma chylomicrons and hypertriglyceridemic VLDL (HTG-VLDL) to cell-surface membrane-binding proteins (MBP 200, 235; apparent Mr 200, 235 kD on SDS-PAGE) that leads to lipid accumulation in vitro. Competitive binding studies reported here demonstrate that anti-apoB antibodies specifically block the high-affinity binding of TGRLP to this receptor on THP-1 cells and on ligand blots. LpL, which binds to an N-terminal domain of apoB, also inhibits TGRLP binding both to this site on THP-1s and to MBP 200, 235 by binding to apoB. Chylomicrons of Sf>1100 that contain apoB-48, but not apoB-100, bind specifically to MBP 200, 235, and this binding is blocked by anti-apoB IgG. In contrast, lactoferrin and heparin do not inhibit TGRLP binding. We conclude that the receptor-binding domain is within apoB-48 (or an equivalent in apoB-100) near the LpL-binding domain, but not a heparin-binding domain. Uptake of TGRLP by this mechanism could provide essential nutrients or, in HTG, cause excess lipid accumulation and foam cell formation.

We have previously identified a 94- to 97-kDa oxidized low density lipoprotein (LDL)-binding protein in mouse macrophages as macrosialin (MS), a member of the lamp family. Earlier immunostaining studies have shown that MS and its human homolog, CD68, are predominantly intracellular proteins. However, using sensitive techniques such as flow cytometry (FACS) and cell-surface-specific biotinylation, we now show that there is significant surface expression of these proteins. FACS analysis of intact cells using mAb FA/11 showed small but definite surface expression of MS in resident mouse peritoneal macrophages but this was greatly enhanced with thioglycollate elicitation. Biotinylation of intact cells and detergent-solubilized cell preparations followed by immunoprecipitation revealed 10-15% of the total MS content of elicited macrophages on the plasma membrane. Similar results were obtained with untreated RAW 264.7 cells. FACS analysis of intact THP-1 monocytic cells showed minimal surface expression of CD68 on unactivated cells (4% of total cell content). Stimulation with phorbol 12-myristate 13-acetate increased both surface and total CD68 expression considerably. Furthermore, the specific binding at 4 degrees C and uptake at 37 degrees C of 125I-labeled oxidized LDL by activated THP-1 cells was inhibited by 30-50% by CD68 mAbs KP-1 and EBM-11. Thus, although the surface expression of MS/CD68 at steady-state represents only a small percentage of their total cellular content, these proteins can play a significant role in oxidized LDL uptake by activated macrophages in vitro and could contribute to foam cell formation in atherosclerotic lesions.

We have previously reported the partial purification of a 94- to 97-kDa plasma membrane protein from mouse peritoneal macrophages that binds oxidatively modified low density lipoprotein (OxLDL) and phosphatidylserine-rich liposomes. We have now identified that protein as macrosialin, a previously cloned macrophage-restricted membrane protein in the lysosomal-associated membrane protein family (mouse homologue of human CD68). Early in the course of purification of the 94- to 97-kDa protein, a new OxLDL-binding band at 190-200 kDa appeared and copurified with the 94- to 97-kDa protein. The HPLC pattern of tryptic peptides from this higher molecular mass ligand-binding band closely matched that derived from the 94- to 97-kDa band. Specifically, the same three macrosialin-derived tryptic peptides (9, 9, and 15 residues) were present in the purified 94- to 97-kDa band and in the 190- to 200-kDa band and antisera raised against peptide sequences in macrosialin recognized both bands. An antiserum against macrosialin precipitated most of the 94- to 97-kDa OxLDL-binding material. We conclude that the binding of OxLDL to mouse macrophage membranes is in part attributable to macrosialin. Our previous studies show that OxLDL competes with oxidized red blood cells and with apoptotic thymocytes for binding to mouse peritoneal macrophages. Whether macrosialin plays a role in recognition of OxLDL and oxidatively damaged cells by intact macrophages remains uncertain.

An apolipoprotein (apo) E- and lipoprotein lipase-independent, high affinity, saturable and specific binding site and pathway for uptake of certain triglyceride-rich lipoproteins (TGRLP) by human monocyte-macrophages that leads to lipid accumulation and foam cell formation in vitro has been reported; two membrane binding activities were identified as receptor candidates with apparent molecular masses of 200 and 235 kDa [Gianturco et al. (1994) J. Lipid Res. 35, 1674-1687]. Here we present new evidence that these activities are TGRLP receptors with unique biochemical properties which distinguish them from other lipoprotein receptors. Protease and heparinase susceptibility studies demonstrate that (1) these activities have essential protein, but not heparan sulfate proteoglycan (HSPG) components; (2) the membrane binding proteins (MBPs) are located on the cell surface; (3) HSPGs do not facilitate TGRLP binding to this specific cellular site. Upon reduction, MBP 200 and 235 are both converted into a single, new binding activity of intermediate mobility (MBP 200R); all MBP forms displayed high affinity, saturable TGRLP binding with similar Kds (1.4-2.2 micrograms/mL). Notably, MBP 200R retained the combined ligand binding capacity of MBP 200 and 235 prior to reduction, demonstrating that, unlike members of the LDL receptor or the scavenger receptor families, disulfide bonds are not critical for activity. At 65 degrees C, MBP 235 was converted into MBP 200 without loss of total binding activity, suggesting heat dissociates a small subunit not required for binding from a common large protein subunit that binds TGRLP. Since the MBPs are found on the cell surface, are themselves functionally and structurally related, have distinctly different biochemical properties from members of the LDL receptor and scavenger receptor families, and share all critical characteristics with the cellular binding site, we hypothesize that they represent a new and unique receptor family for apoE- and lipoprotein lipase-independent uptake of TGRLP by human monocyte-macrophages.

Previously we reported that human blood-borne and THP-1 monocyte-macrophages have an apolipoprotein E- and lipoprotein lipase-independent, high affinity, specific binding site for the uptake and degradation of hypertriglyceridemic VLDL and plasma chylomicrons distinct from the LDL receptor gene family and the acetyl LDL receptor (Gianturco et al., J. Lipid Res. 35:1674-1687, 1994). Ligand blot analyses identified two cell-surface, structurally related membrane binding proteins as receptor candidates of M(r) approximately 200 kDa and M(r) approximately 235 kDa which are converted into a single ligand binding species of intermediate mobility upon reduction. We now report a approximately 1200-fold purification of the reduced candidate receptor protein from cultured THP-1 monocytes.

The binding and uptake of oxidatively modified low density lipoprotein (OxLDL) by mouse peritoneal macrophages occurs, in part, via the well characterized acetyl LDL receptor. However, several lines of evidence indicate that as much as 30-70% of the uptake can occur via a distinct receptor that recognizes OxLDL with a higher affinity than it recognizes acetyl LDL. We describe the partial purification and characterization of a 94- to 97-kDa plasma membrane protein from mouse peritoneal macrophages that specifically binds OxLDL. This receptor is shown to be distinct from the acetyl LDL receptor as well as from two other macrophage proteins that also bind OxLDL--the Fc gamma RII receptor and CD36. We suggest that this OxLDL-binding membrane protein participates in uptake of OxLDL by murine macrophages and also represents a receptor responsible for macrophage binding and phagocytosis of oxidatively damaged cells.

Autoimmune diseases are characterized by the presence of autoantibodies often restricted to host proteins exhibiting charge rich domains. Charged polypeptides elicit strong immune responses, and cationized bovine serum albumin and other cationic proteins are significantly more immunogenic than their less charged counterparts. These phenomena may involve enhanced protein uptake by macrophages, resulting in greater processing and presentation of antigenic peptide-MHC complexes to T-cells. We compared macrophage cell-surface binding and uptake of native and cationized bovine serum albumin. Specific binding of [125I]cationized bovine serum albumin to THP-1 macrophages in vitro was 11-16 fold greater than for native albumin. Half-maximal inhibition of [125I]cationized albumin binding was observed at 10-7M ligand. The specificity of [125I]cationized bovine serum albumin binding and uptake was further studied in terms of competitive inhibition of proteolysis by proteins of varying charge content. Cationized bovine serum albumin, but not native albumin, inhibited proteolysis of [125I]cBSA. Calf thymus histones also inhibited cBSA degradation. High concentration of myelin basic protein was moderately effective at blocking cBSA degradation, while myoglobin and beta lactalbumin showed no inhibition. These results indicate that specific cell-surface binding sites which occur on macrophages may mediate selective uptake of certain proteins with highly charged domains including some autoantigens.