Overall safety profile and effectiveness of tramadol hydrochloride/acetaminophen in patients with chronic noncancer pain in Japanese real-world practice.

OBJECTIVE: To evaluate the overall safety profile and clinical effectiveness of tramadol hydrochloride/acetaminophen (TA) combination tablets in Japanese patients with chronic noncancer pain unrelieved by non-opioid drugs for up to 12 weeks in real-world practice. RESEARCH DESIGN AND METHODS: This survey was a multicenter, prospective, longitudinal registry on the use of TA as a newly initiated pain treatment for chronic noncancer pain incurable by non-opioid analgesics that was conducted under the Good Post Marketing Study Practice regulation controlled by the Japan Ministry of Health, Labor and Welfare. Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician's global impression (PGI) during the 12 week observation period. RESULTS: A total of 1316 patients were registered. ADRs were reported in 259 patients (20.5%); most events were nonserious (99.4%), including nausea (n = 87 [6.9%]), constipation (n = 63 [5.0%]), dizziness and somnolence (n = 29 [2.3%] each), and vomiting (n = 21 [1.7%]). No event related to drug dependence or respiratory depression was reported. In addition, 82.8% of patients showed acceptable effectiveness based on PGI at Week 4. Numerical rating scale for intensity of pain and EQ-5D utility scores were improved by -2.7 (SD 2.3) and 0.16 (SD 0.20) at Week 4, respectively, and the improvement was maintained until Week 12. CONCLUSION: This is a first report to evaluate the risk-benefit profile of TA in Japanese real-world practice using large size registry data. It is suggested that the favorable risk-benefit balance of TA was confirmed for patients with chronic noncancer pain unrelieved by non-opioid drugs in real-world practice. Limitations of this study were those inherent to open-label and non-interventional study designs. TRIAL REGISTRATION: This registry survey is registered at umin.ac.jp (identifier: UMIN000015901).

Isolation of Ralstonia solanacearum-infecting bacteriophages from tomato fields in Chiang Mai, Thailand, and their experimental use as biocontrol agents.

AIMS: To isolate and characterize novel bacteriophages infecting the phytopathogen, Ralstonia solanacearum, and to evaluate them as resources with potential uses in the biocontrol of bacterial wilt. METHODS AND RESULTS: Fourteen phages infecting R. solanacearum were isolated from soil samples collected in Chiang Mai, Thailand. The phages showed different host ranges when tested against 59 R. solanacearum strains isolated from Thailand and Japan. These phages were characterized as nine podoviruses and five myoviruses based on their morphology. Podovirus J2 in combination with another podovirus (φRSB2) lysed host cells very efficiently in contaminated soil. J2 treatment prevented wilting of tomato plants infected with a highly virulent R. solanacearum strain. CONCLUSIONS: Treatment with J2 effectively reduced the amount of the bacterial wilt pathogen in contaminated soil and prevented bacterial wilt of tomato in pot experiments. Myovirus J6 possessed jumbo phage features, giving a unique opportunity to study its utilization as a biocontrol agent. SIGNIFICANCE AND IMPACT OF THE STUDY: As exemplified by J2, the phages isolated in this study represent valuable resources with potential uses in biocontrol of bacterial wilt. A rare jumbo phage J6 served as a valuable subject to understand and utilize this new group of phages.

Development and testing of an endoscopic pseudo-viewpoint alternating system.

PURPOSE: An endoscopic system is needed that presents informative images irrespective of the surgical situation and the number of degrees of freedom in endoscopic manipulation. This goal may be achieved with a virtual reality view for a region of interest from an arbitrary viewpoint. An endoscopic pseudo-viewpoint alternation system for this purpose was developed and tested. METHOD: Surgical experts and trainees from an endoscopic surgery training course at the minimally invasive surgery training center of Kyushu University were enrolled in a trial of a virtual reality system. The initial viewpoint was positioned to approximate the horizontal view often seen in laparoscopic surgery, with [Formula: see text] between the optical axis of the endoscope and the task surface. A right-to-left suturing task with right hand, based on a task from the endoscopic surgery training course, was selected for testing. We compared task outcomes with and without use of a new virtual reality-viewing system. RESULT: There was a 0.37 mm reduction in total error ([Formula: see text]) with use of the proposed system. Error reduction was composed of 0.1 mm reduction on the y-axis and 0.27 mm reduction on the x-axis. Experts benefited more than novices from use of the proposed system. Most subjects worked at a pseudo-viewpoint of around 34[Formula: see text]. DISCUSSION: Suturing performance improved with the new virtual reality endoscopic display system. Viewpoint alternation resulted in an overview that improved depth perception and allowed subjects to better aim the marker. This suggests the proposed method offers users better visualization and control in endoscopic surgery.

Indoleamine 2,3-dioxygenase in the pathogenesis of tuberculous pleurisy.

BACKGROUND: Pleural fluid is a frequent manifestation in pulmonary diseases, such as lung cancer and infectious diseases, including pulmonary tuberculosis (TB). The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan through the kynurenine pathway, and is considered a crucial immunoregulatory molecule mediating immune tolerance. Recent studies have shown IDO activity to be a novel prognostic factor not only in cancer patients but also in those with infectious diseases, including pneumonia and pulmonary TB. However, no studies have measured and determined the clinical significance of IDO activity in pleural fluid. METHODS: We enrolled 92 patients, including 34 with tuberculous pleurisy (TBP), 36 with malignant pleuritis and 15 with parapneumonic effusions. IDO activity was evaluated using liquid chromatography/electrospray ionisation tandem mass spectrometry, and was estimated by calculating kynurenine-to-tryptophan ratio. RESULTS: Pleural fluid from patients with TBP had significantly higher kynurenine concentrations and significantly lower tryptophan concentrations, resulting in significantly higher IDO activity compared with pleural effusion or serum from non-tuberculous pleuritis (all P < 0.001). Pleural tissue from TBP showed enhanced IDO expression in epithelioid granuloma regions by immunohistochemistry. CONCLUSIONS: These results suggest that IDO is strongly involved in the pathogenesis of TBP.

Boundary condition generating large strain on breast tumor for nonlinear elasticity estimation.

We describe a robotic palpation system that determines whether a breast tumor is benign or malignant by measuring its nonlinear elasticity. Two indenters compress the breast from different directions to generate sufficient strain on the inner tumor, which simply represents clinical dynamic testing. The nonlinear elasticity of the inner tumor is estimated by correcting the reaction force data of the surrounding soft tissue. Here, we present the basic concept of our study and simulation results considering geometric conditions of the indenters using a finite element breast model. Indenters with variable width are applied to the breast at several contact positions in a simulation for comparison. Our results indicate that when the spring stiffness between the contact position of one indenter and the center of the tumor equals the spring stiffness between the contact position of the other indenter and the center of the tumor, a larger contact area (i.e., larger spring stiffness) provides larger strain acting on the inner tumor.

Algorithm for selecting appropriate transfer support equipment and a robot based on user physical ability.

In this present paper, we propose an algorithm for selecting appropriate transfer support equipment and robot based on the physical ability of the user. In addition, we describe the relationship between physical human features and the burden during standing when using a standing support robot. Although a number of care support devices have been developed, assistive robots are not yet popular because users do not know which devices are appropriate for their needs or physical abilities. In this study, we focus on a transfer support device and propose an algorithm for selecting transfer support equipment and a robot that suits the user's physical ability. We investigated the relationship between standing support equipment including a robot and the physical burden during standing, which is a basic transfer motion. Experimentally, we analyzed and calculated the knee and ankle joint moments and discussed the relationship between standing support equipment and knee and ankle joint moments during standing; we also investigated and the relationship between physical human features and the knee joint moment during standing. Our results identified standing support equipment that was appropriate to the user's physical ability. We found that it was effective to provide an up/down seat to persons having low residual ability; a standing support robot is appropriate for people having less residual ability in the knees, and a railing is suitable for people having low residual ability in the ankles.

Lysyl oxidase secreted by tumour endothelial cells promotes angiogenesis and metastasis.

BACKGROUND: Molecules that are highly expressed in tumour endothelial cells (TECs) may be candidates for specifically targeting TECs. Using DNA microarray analysis, we found that the lysyl oxidase (LOX) gene was upregulated in TECs compared with its expression in normal endothelial cells (NECs). LOX is an enzyme that enhances invasion and metastasis of tumour cells. However, there are no reports on the function of LOX in isolated TECs. METHODS: TECs and NECs were isolated to investigate LOX function in TECs. LOX inhibition of in vivo tumour growth was also assessed using ß-aminopropionitrile (BAPN). RESULTS: LOX expression was higher in TECs than in NECs. LOX knockdown inhibited cell migration and tube formation by TECs, which was associated with decreased phosphorylation of focal adhesion kinase (Tyr 397). Immunostaining showed high LOX expression in human tumour vessels in vivo. Tumour angiogenesis and micrometastasis were inhibited by BAPN in an in vivo tumour model. CONCLUSION: LOX may be a TEC marker and a possible therapeutic target for novel antiangiogenic therapy.

Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells.

BACKGROUND: We isolated tumour endothelial cells (TECs), demonstrated their abnormalities, compared gene expression profiles of TECs and normal endothelial cells (NECs) by microarray analysis and identified several genes upregulated in TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat proteoglycan. No report is available on biglycan expression or function in TECs. METHODS: The NEC and TEC were isolated. We investigated the biglycan expression and function in TECs. Western blotting analysis of biglycan was performed on sera from cancer patients. RESULTS: Biglycan expression levels were higher in TECs than in NECs. Biglycan knockdown inhibited cell migration and caused morphological changes in TECs. Furthermore, immunostaining revealed strong biglycan expression in vivo in human tumour vessels, as in mouse TECs. Biglycan was detected in the sera of cancer patients but was hardly detected in those of healthy volunteers. CONCLUSION: These findings suggested that biglycan is a novel TEC marker and a target for anti-angiogenic therapy.

Algorithm for selecting appropriate transfer support equipment based on the physical ability of the user.

In the present paper, we propose an algorithm for selecting appropriate transfer support equipment based on the physical ability of the user. In addition, we describe the relationship between features of the human body and the physical burdens during standing. Although several care support devices have been developed, assistive robots are not yet popular because users do not know which devices are suitable for their needs or appropriate for their physical abilities. In the present study, we focus on a transfer support device and propose an algorithm for selecting transfer support equipment that will be suitable to the physical ability of the user. We investigated the relationship between standing support equipment and physical burdens during standing, which is one of transfer motions. In an experiment, we calculated and analyzed the knee and ankle joint moments and discussed the relationship between standing support equipment and the knee and ankle joint moments during standing. The results indicated a difference in the relation of standing support equipments appropriate to the user's physical ability. It was found effective to provide a railing to persons having low residual ability in the ankle joints and an up/down seat to persons having low residual ability in the knee joints.

Neuropeptides and their receptors of the protochordate, Ciona intestinalis: the evolutionary origin of vertebrate neuropeptides.

Ci-TK and Ci-TK-R are authentic tachykinin (TK) and TK receptor isolated from a protochordate, Ciona intestinalis. In this study, we investigated a novel function of TK as an enhancer of oocyte growth. Ci-TK-R is expressed specifically in the Ciona vitellogenic oocytes. Moreover, administration of Ci-TK to the Ciona ovary resulted in upregulation of gene expression and enzymatic activity of several proteases. Moreover, maturation of the Ciona oocytes from the vitellogenic stage to the post-vitellogenic stage was induced in the presence of Ci-TK, which was completely blocked by addition of protease inhibitors.

Sustained swimming increases erythrocyte MCT1 during erythropoiesis and ability to regulate pH homeostasis in rat.

We investigated the effect of sustained swimming exercise on the increase in monocarboxylate transporter 1 (MCT1) concentration and its ability to regulate pH homeostasis in rat erythrocytes. Male Sprague-Dawley rats aged 9 weeks were divided into sedentary and swimming groups for both 1- and 3-week experiments. The exercise group swam for 30 - 60 min/day, 5 days/week. Before and 1 and 3 weeks after initiation of the exercise, blood was collected for lactate concentration measurement during pre-exercise rest and post-exercise recovery periods. On the last day of each experiment, venous blood and erythroid cells in bone marrow were collected to assay the capacity for erythropoiesis and MCT1 concentration. In the swimming group at 0 weeks (p < 0.05), 1 week (p < 0.01) and 3 weeks (p < 0.001), the blood lactate concentration post-exercise was significantly higher than at rest. The ratio of young erythrocytes to total erythrocytes was significantly higher in the 3-week swimming group than in the sedentary group (p < 0.05). The MCT1 concentration in erythrocytes was higher in the 3-week swimming group than in the sedentary group (18 %, p < 0.05), which was found in young erythrocytes (22 %, p < 0.05) when total erythrocytes were separated into young and old fractions. The MCT1 concentration in erythroid cells was higher in both the 1-week and 3-week swimming groups than in either of the sedentary groups (27 and 28 %, respectively, p < 0.05). The pH recovery of erythrocyte suspensions at 10, 15 and 20 seconds after addition of lactate to the suspension medium was significantly faster in the 3-week swimming group than in the sedentary group (p < 0.001). These findings suggest that erythrocyte MCT1 is increased during erythropoiesis in bone marrow and that the increase of the transporter facilitates, at least partly, lactate/proton co-transport due to sustained swimming exercise in rats.

Development of the walking support robot with the weight bearing mechanism supporting ischia--cushion for ischia and behavior of ischia during walking.

This report describes the cushion suitable for weight bearing mechanism supporting ischia and the behavior of ischia during walking. Hitachi Ltd. developed the power-assisted walking support device and the walk training machine with weight bearing mechanisms using a hip orthosis and a saddle. Because user's weight is centered on symphysis pubica, users feel sore and it is obstacle to smooth walking. Then, we propose a new weight bearing mechanism supporting ischia. Because an interface between human and robot is important, we experimented on the cushion for ischia that is the interface between human and the weight bearing mechanism supporting ischia. In the experiment, we measured seating pressure, the trajectory of the seating pressure's center, position of ischia, and force on the weight bearing arm when a user was walking while locating his hip on the cushion for ischia. The result shows that the seating cushion is suited for the interface, but it is also necessary to support separately each ischium's up down movement and rotating movement during walking.

Quinolone-photoconjugated major histocompatibility complex class II-binding peptides with lysine are antigenic for T cells mediating murine quinolone photoallergy.

Fluoroquinolone antibacterial agents cause photosensitivity dermatitis as an adverse effect and can function immunologically as photohapten. In a murine model of quinolone photoallergy, Langerhans cells are photomodified with a systemically given quinolone upon ultraviolet A irradiation of skin and thus present photohaptenic moieties to sensitize and restimulate T cells. The aim of this study is to determine the site of peptides/proteins photobound to quinolones and to assess the T cell antigenicity of quinolone-photocoupled peptides using Langerhans cells as photoadduct-presenting cells. On an amino acid composition analysis, lysine was preferentially degraded in bovine serum albumin that was ultraviolet A-conjugated with a representative quinolone ofloxacin. An affinity chromatographic study using a quinolone photoadduct-specific monoclonal antibody as ligand demonstrated preferential photocoupling of ofloxacin with a lysine-containing peptide. CD4+ T cells were purified from lymph nodes of BALB/c mice sensitized subcutaneously with ofloxacin-photomodified epidermal cells and from those sensitized epicutaneously via barrier-disrupted skin with a major histocompatibility complex class II (I-Ad)-binding, ofloxacin-photoconjugated peptide. These immune T cells proliferated in vitro in response to Langerhans cells loaded with class II-binding, lysine-containing peptides when photomodified with ofloxacin. Furthermore, epicutaneous application of the ofloxacin-photoconjugated peptide was able to prime mice for subsequent elicitation of photoallergy evoked with systemic ofloxacin and ultraviolet A light. This study suggests that lysine affords quinolone photocoupling of peptides and quinolone-photomodified peptides on class II molecules stimulate pathogenetic T cells in quinolone photoallergy.

Experimental study on the effect of antegrade cerebral perfusion on brains with old cerebral infarction.

OBJECTIVE: Patients with old cerebral infarction who undergo aortic arch operations are susceptible to postoperative neurologic dysfunction. To verify such susceptibility, we performed this experimental study. METHODS: A cerebral infarct model was created in mongrel dogs by means of injection of cylindrical silicone embolus through the internal carotid artery. The dogs that had obvious neurologic deficits 1 day later and survived for 4 weeks or more were included in the cerebral infarct model. One month after cerebral infarction was induced, deep hypothermia and selective cerebral perfusion were used in 14 mongrel dogs (infarct group, n = 7; control group, n = 7). During this procedure, serum glutamate concentration and venous-arterial lactate difference were measured. Histopathologic study of the brain was also performed. RESULTS: Changes in venous-arterial lactate difference in both groups were almost similar, except in the rewarming phase. At 32 degrees C during rewarming, the venous-arterial lactate difference in the infarct group was significantly higher than that in the control group (P =.006). Although pre-cooling concentrations of serum glutamate were similar in both groups, the values in the infarct group at the end of rewarming were significantly higher than those in the control group (P =.046). On histologic examination, the presence of old cerebral infarction with gliosis was confirmed in the infarct group, but neither new cerebral infarction nor destruction of the blood-brain barrier was found. CONCLUSION: We observed an accelerated anaerobic metabolism and an increased extracellular glutamate release in the infarct group. The brain with old cerebral infarction is more susceptible to ischemia during arch operation than noninfarcted brain.

Excretion of bikunin and its fragments in the urine of patients with renal stones.

PURPOSE: Bikunin is a Kunitz-type protease inhibitor found in serum and urine. It has been implicated in urinary stone formation. This study was designed to investigate the role of urinary bikunin in stone formation. MATERIALS AND METHODS: Urinary concentrations of bikunin were measured in 18 male formers of urinary stones 28 to 74 years old and in 77 healthy controls, including 39 males and 38 females, without urological abnormality. A sensitive competitive solid phase enzyme immunoassay was established for urinary bikunin. Bikunin was also qualitatively assessed by Western blot analysis. RESULTS: The mean urinary bikunin-to-creatinine ratio plus or minus standard deviation in stone formers was significantly elevated compared with that in healthy male and female controls (52.9 +/- 46.0 microg./mg. creatinine versus 28.0 +/- 30.4 and 26.5 +/- 21.7, p = 0.005 and 0.006, respectively). By Western blot analysis all urine samples contained authentic 40 kDa. bikunin species. However, a significantly higher proportion of patients was found to have aberrant 25 kDa. bikunin species compared with controls (10 of 18 or 55.6% versus 15 of 77 or 19.5%, p = 0.002). Experiments on de-glycosylation with chondroitinase ABC, amino acid sequencing of the aberrant bikunin species and calcium oxalate crystal growth inhibition assay demonstrated that the 25 kDa. bikunin fragment was identical to de-glycosylated bikunin and less inhibitory on calcium oxalate crystal growth. CONCLUSIONS: If urinary bikunin is important in the pathogenesis of urolithiasis, its effect is probably attributable to the concentration and degree of glycosylation.

Characterization of binding properties of urinary trypsin inhibitor to cell-associated binding sites on human chondrosarcoma cell line HCS-2/8.

Urinary trypsin inhibitor (UTI) forms membrane complexes with UTI-binding proteins (UTI-BPs) and initiates modulation of urokinase-type plasminogen activator (uPA) expression, which results in UTI-mediated suppression of cell invasiveness. It has been established that suppression of uPA expression and invasiveness by UTI is mediated through inhibition of protein kinase C-dependent signaling pathways and that human chondrosarcoma cell line HCS-2/8 expresses two types of UTI-BPs; a 40-kDa UTI-BP (UTI-BP(40)), which is identical to link protein (LP), and a 45-kDa UTI-BP (UTI-BP(45)). Here we characterize binding properties of UTI-BPs.UTI complexes in the cells. In vitro ligand blot, cell binding and competition assays, and Scatchard analyses demonstrate that both UTI-BP(40) and UTI-BP(45) bind (125)I-UTI. A deglycosylated form of UTI (NG-UTI), from which the chondroitin-sulfate side chain has been removed, binds only to UTI-BP(40). Additional experiments, using various reagents to block binding of (125)I-UTI and NG-UTI to the UTI-BP(40) and UTI-BP(45) confirm that the chondroitin sulfate side chain of UTI is required for its binding to UTI-BP(45). Analysis of binding of (125)I-UTI and NG-UTI to the cells suggests that low affinity binding sites are the UTI-BP(40) (which can bind NG-UTI), and the high affinity sites are the UTI-BP(45). In addition, UTI-induced suppression of phorbol ester stimulated up-regulation of uPA is inhibited by reagents that were shown to prevent binding of UTI to the 40- and 45-kDa proteins. We conclude that UTI must bind to both of the UTI-BPs to suppress uPA up-regulation.

Algal-lytic activities encoded by Chlorella virus CVK2.

Using a halo assay with E. coli lysates expressing Chlorella virus CVK2 genes on a cosmid contig, two different algal-lytic activities against Chlorella strain NC64A cells were found to be encoded on the CVK2 genome. The gene for vAL-1, one of the two activities, encoded a 349-aa ORF, which was homologous to PBCV-1 A215L and CVN1 CL-2. The vAL-1 gene was expressed at relatively early stages of the virus life cycle; transcripts and translation products appeared at 60 and 90 min postinfection, respectively. The vAL-1 protein was not incorporated into the viral particles but remained in the cell lysate, suggesting a role in the digestion of the cell wall before viral release at the final stage of infection. Cell wall materials isolated from Chlorella strain NC64A cells were digested by vAL-1 and degradation products were detected on TLC. In addition to Chlorella strain NC64A, vAL-1 lysed cells of four C. vulgaris strains as well as Chlorella sp. SAG-241-80.

The involvement of a cysteine proteinase in the nodule development in Chinese milk vetch infected with Mesorhizobium huakuii subsp. rengei.

Cys proteinases play important roles in plant cell development and senescence. A cDNA, AsNODf32, obtained by differential screening of a nodule cDNA library of the leguminous plant Chinese milk vetch (Astragalus sinicus), represents a nodule-specific Cys proteinase similar to that reported for the actinorhizal Alnus glutinosa-Flankia symbiosis. A characteristic feature of this proteinase is the presence of a putative vacuolar targetting signal, LQDA, within its propeptide. Expression of the AsNODf32 gene, which was studied on northern blots and in situ hybridization, showed good correlation with the onset of nodule senescence. In situ hybridization studies revealed that AsNODf32 was expressed in senescent-infected tissue at the base of the nodule, as well as in interzone II-III of the infected nodules. In addition to degrading old nodule tissues and bacteroids, AsNODf32 protein may be required as a component of tissue remodeling during nodule development.

Identification and characterization of a Kunitz-type protease inhibitor in ascites fluid from patients with ovarian carcinoma.

Urinary trypsin inhibitor (UTI; Mr 40 kDa) is a Kunitz-type protease inhibitor that efficiently inhibits cell-associated trypsin and plasmin activities. The aim of this study is to examine the expression pattern of UTI in the human ovarian carcinoma ascites fluid by Western blotting, zymography, immunoprecipitation, immunohistochemistry, biochemical and gene analyses and animal experiments. We have identified and characterized the 40 kDa immunoreactive UTI (UTI(40)) and 8 kDa degradation fragment (UTI(8)) in ascites fluid. The levels of UTI(40) and UTI(8) are elevated in ascites fluid taken from patients with ovarian carcinoma relative to paired plasma samples. The UTI(40) and UTI(8) were identified immunologically by the reactivity with 2 different anti-UTI antibodies recognizing different epitopes of the UTI molecule, functionally by its ability to bind trypsin and structurally by its apparent molecular mass with and without deglycosylation treatment. The purified polypeptides have been sequenced and were identical with sequences obtained from UTI and the carboxyl-terminal domain of UTI, respectively. However, UTI mRNA was not detected in the ovarian carcinoma tissue and ovarian carcinoma cell lines examined. Based on extravasation experiments using intravenously injected biotinylated inter-alpha-trypsin inhibitor (IalphaI; a precursor of UTI), we conclude that UTI(40) and UTI(8) found in the ascites fluid may result from (i) the extravasation of plasma proteins such as IalphaI into the peritoneal cavity via hyperpermeable vessels and (ii) the subsequent degradation of IalphaI and UTI(40) by tumor cell-associated trypsin-like enzymes.

Identity of urinary trypsin inhibitor-binding protein to link protein.

Urinary trypsin inhibitor (UTI), a Kunitz-type protease inhibitor, directly binds to some types of cells via cell-associated UTI-binding proteins (UTI-BPs). Here we report that the 40-kDa protein (UTI-BP(40)) was purified from the cultured human chondrosarcoma cell line HCS-2/8 by UTI affinity chromatography. Purified UTI-BP(40) was digested with trypsin, and the amino acid sequences of the peptide fragments were determined. The sequences of six tryptic fragments of UTI-BP(40) were identical to subsequences present in human link protein (LP). Authentic bovine LP and UTI-BP(40) displayed identical electrophoretic and chromatographic behavior. The UTI-binding properties of UTI-BP(40) and LP were indistinguishable. Direct binding and competition studies strongly demonstrated that the NH(2)-terminal fragment is the UTI-binding part of the LP molecule, that the COOH-terminal UTI fragment (HI-8) failed to bind the NH(2)-terminal subdomain of the LP molecule, and that LP and UTI-BP(40) exhibited significant hyaluronic acid binding. These results demonstrate that UTI-BP(40) is identical to LP and that the NH(2)-terminal domain of UTI is involved in the interaction with the NH(2)-terminal fragment of LP, which is bound to hyaluronic acid in the extracellular matrix.