A statistical model for activation of Factor C by binding to LPS aggregates.

Published data on Factor C activity at various LPS and Lipid A concentrations (Nakamura et al. in Eur J Biochem 176:89, 1988; Kobayashi et al. in J Biol Chem 37:25987, 2014) were rearranged to show that Factor C exhibited its maximum activity at a specific concentration of LPS. A statistical model was proposed for examining whether a single LPS molecule binding activates Factor C (monomeric activation) or dimerization of Factor C is necessary for the activation (dimeric activation). In the monomeric activation model the plots of the relative activity of Factor C against the molar ratio of LPS to Factor C were different from those in the published data. The plots in the dimeric activation model lie on a bell-shaped curve, whatever the Factor C concentration, matching the published data and indicating the appropriateness of that model. We suggest that Factor C is activated by multiple molecular interactions of Factor C with LPS aggregates on which it dimerises and that this explains why larger aggregates are less effective at activating Factor C than smaller ones.

Wnt3a signaling induces murine dental follicle cells to differentiate into cementoblastic/osteoblastic cells via an osterix-dependent pathway.

BACKGROUND AND OBJECTIVE: Dental follicle cells, putative progenitor cells for cementoblasts, osteoblasts and periodontal ligament cells, interplay with Hertwig's epithelial root sheath (HERS) cells during tooth root formation, in which HERS is considered to have an inductive role in initiating cementogenesis by epithelial-mesenchymal interaction. However, the specific mechanisms controlling the cementoblast/osteoblast differentiation of dental follicle cells are not fully understood. Canonical Wnt signaling has been implicated in increased bone formation by controlling mesenchymal stem cell or osteoblastic cell functions. This study examined the possible expression of canonical Wnt ligand in HERS and the role of Wnt signaling during the cementoblast/osteoblast differentiation of dental follicle cells. MATERIAL AND METHODS: The expression of Wnt3a, a representative canonical Wnt ligand, in HERS was assessed by immunohistochemistry. The differentiation and function of immortalized murine dental follicle cells were evaluated by measuring alkaline phosphatase (ALP, Alpl) activity and osteogenic gene expression. RESULTS: We identified the expression of Wnt3a in HERS during mouse tooth root development by immunohistochemistry as well as in cultured human epithelial rest cells of Malassez by real-time polymerase chain reaction, while no expression of Wnt3a was detected in cultured dental mesenchymal cells. Exposure of immortalized murine dental follicle cells to Wnt3a-induced ALP activity as well as expression of the Alpl gene. Pretreatment of cells with Dickkopf-1, a potent canonical Wnt antagonist, markedly attenuated the effect of Wnt3a on ALP expression. Furthermore, Wnt3a induced transcriptional activity of runt-related transcription factor 2 (Runx2) and expression of osterix at gene and/or protein levels. Treatment with osterix-small interfering RNA significantly inhibited Wnt3a-induced ALP expression at gene and protein levels. CONCLUSION: These findings suggest that HERS has a potential role in stimulating cementoblast/osteoblast differentiation of dental follicle cells via the Wnt/ß-catenin signaling pathway.

Levobupivacaine-dextran mixture for transversus abdominis plane block and rectus sheath block in patients undergoing laparoscopic colectomy: a randomised controlled trial.

We performed a randomised controlled double-blinded study of patients having laparoscopic colectomy with bilateral transversus abdominis plane block plus rectus sheath block, comparing a control group receiving 80 ml levobupivacaine 0.2% in saline with a dextran group receiving 80 ml levobupivacaine 0.2% in 8% low-molecular weight dextran. Twenty-seven patients were studied in each group. The mean (SD) maximum plasma concentration of levobupivacaine in the control group (1410 (322) ng.ml(-1) ) was higher than the dextran group (1141 (287) ng.ml(-1) ; p = 0.004), and was reached more quickly (50.6 (30.2) min vs 73.2 (24.6) min; p = 0.006). The area under the plasma concentration-time curve from 0 min to 240 min in the control group (229,124 (87,254) ng.min.ml(-1) ) was larger than in the dextran group (172,484 (50,502) ng.min.ml(-1) ; p = 0.007). The median (IQR [range]) of the summated numerical pain rating score at rest during the first postoperative 24 h in the control group (16 (9-20 [3-31]) was higher than in the dextran group (8 (2-11 [0-18]); p = 0.0001). In this study, adding dextran to levobupivacaine decreased the risk of levobupivacaine toxicity while providing better analgesia.

Early optimization of antimicrobial therapy improves clinical outcomes of patients administered agents targeting methicillin-resistant Staphylococcus aureus.

WHAT IS KNOWN AND OBJECTIVE: Antimicrobial stewardship is required to ensure the appropriate use of antimicrobials. However, no reports have been published on clinical outcomes of implementation of antimicrobial stewardship in patients receiving pathogen-specific antibiotics. METHOD: To evaluate the clinical outcomes of patients who received drugs, we conducted a single-centre, retrospective study of the effects of an antimicrobial stewardship programme targeting methicillin-resistant Staphylococcus aureus (MRSA). RESULTS: The time to administer effective antimicrobials was significantly (median number of days, 3 before vs. 0 after, P < 0·001) shortened, and the rate of de-escalation was significantly elevated (47·1% vs. 96·2%, P < 0·001) after implementation of daily review. The 60-day clinical failure associated with Gram-positive bacterial infection was significantly reduced (33·3% vs. 17·6%, P = 0·007) after intervention. WHAT IS NEW AND CONCLUSIONS: Daily review of administration of antimicrobials targeting MRSA was highly effective in improving clinical outcomes by optimizing early antimicrobial therapy.

Bone marrow lesions, subchondral bone cysts and subchondral bone attrition are associated with histological synovitis in patients with end-stage knee osteoarthritis: a cross-sectional study.

OBJECTIVE: The aim of this study was to examine the osteoarthritis (OA)-related structural changes associated with histological synovitis in end-stage knee OA patients. METHODS: Forty end-stage knee OA patients (female: 88%, mean age: 71.8 y) were enrolled. All participants underwent 3.0-T MRI. The structural changes, such as cartilage morphology, subchondral bone marrow lesion (BML), subchondral bone cyst (SBC), subchondral bone attrition (SBA), osteophytes, meniscal lesion and synovitis, were scored using the whole-organ MRI scoring (WORMS) method. Synovial samples were obtained from five regions of interest (ROIs) of the knee joint during total joint replacement surgery. The associations between the histological synovitis score (HSS) and WORMS or the synovial expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1ß, IL-6 and transforming growth factor (TGF)-ß were examined using Spearman's correlation coefficient. RESULTS: Among the seven OA-related structural changes, the BML, SBC, SBA and synovitis were significantly associated with the HSS (r = 0.33, 0.35, 0.48 and 0.36, respectively), while other morphological changes were not. Although synovial COX-2, IL-1ß or IL-6 expression levels were not associated with the HSS, the synovial TGF-ß expression levels were associated with the HSS. CONCLUSION: The presence of BML, SBC and SBA was associated with histological synovitis in end-stage knee OA patients.

Expression of umami-taste-related genes in the tongue: a pilot study for genetic taste diagnosis.

OBJECTIVE: Expression of taste-related genes in the tongue was analysed to develop a technique for genetic diagnosis of umami taste disorders. MATERIALS AND METHODS: Tissue samples were collected from healthy volunteers by scraping the foliate papillae of the tongue. Immunocytochemistry staining of gustducin, a taste-cell-specific G protein, and gene expression analysis by real-time polymerase chain reaction of ß-actin, gustducin (GNAT3) and umami receptors (T1R1, T1R3 and mGluR1) were performed. Changes in umami receptor expression following application of umami substances onto the tongue were analysed. RESULTS: Gustducin-positive cells were observed in the samples, indicating the presence of taste cells. Gene expression of ß-actin, GNAT3, T1R1 and T1R3 was detected in all seven samples tested, while that of mGluR1 was detected in four samples. Sequence analysis by NCBI Blast showed that each polymerase chain reaction product had a 99% rate of identification of its target sequence. Stimulation of the tongue with monosodium glutamate significantly upregulated the gene expression levels of T1R1 and T1R3, indicating that this method can detect alterations in umami-related gene expression. CONCLUSION: Evaluation of the expression of the umami receptor genes, T1R1 and T1R3, in the tongue may be clinically useful for objective genetic diagnosis of umami taste disorders.

The factors associated with pain severity in patients with knee osteoarthritis vary according to the radiographic disease severity: a cross-sectional study.

OBJECTIVES: Knee osteoarthritis (OA) pain is suggested to be associated with inflammation and detrimental mechanical loading across the joint. In this cross-sectional study, we simultaneously examined the inflammation and alignment of the lower limb and examined how the pain components varied depending on the disease progression. DESIGN: One-hundred sixty female medial type of early- [n = 74 in Kellgren-Lawrence (K/L) 2] to advanced-stage (n = 96 in K/L >2) knee OA subjects (70.5 years on average) were enrolled. Knee pain was evaluated using a pain visual analog scale (VAS) and the pain-related subcategory of the Japanese Knee Osteoarthritis Measure (JKOM-pain). The serum interleukin (sIL)-6 level reflecting synovitis, and the high sensitivity C-reactive protein (hs-CRP) level were measured to evaluate the severity of inflammation. The anatomical axis angle (AAA) was measured as an alignment index. The ß-coefficient was estimated after adjusting for age and the body mass index (BMI) using a multiple linear regression analysis. RESULTS: Multiple linear regression analyses showed that the sIL-6 levels, but not AAA, associated with the pain VAS [ß = 10.77 (95% confidence interval (CI): 4.14-17.40), P < 0.01] and JKOM-pain scores [ß = 3.19 (95% CI: 1.93-4.44), P < 0.001] in the early stage. Conversely, AAA, but not the sIL-6 levels, was found to be associated with the pain VAS [ß = -1.29 (95% CI: -2.51 to -0.08), P < 0.05] and JKOM-pain scores [ß = -0.49 (95% CI: -0.82 to -0.16), P < 0.01] in the advanced stage. CONCLUSIONS: The presence of a higher level of sIL-6 and the varus alignment of the joint is associated with pain in early- and advanced-stage knee OA patients, respectively.

Coexistence of fibrotic and chondrogenic process in the capsule of idiopathic frozen shoulders.

OBJECTIVE: To analyze changes in the capsule from idiopathic frozen shoulders and clarify their etiology. MATERIALS AND METHODS: Samples (the rotator interval capsule, middle glenohumeral ligament (MGHL), and inferior glenohumeral ligament (IGHL)) were collected from 12 idiopathic frozen shoulders with severe stiffness and 18 shoulders with rotator cuff tears as a control. The number of cells was counted and the tissue elasticity of the samples was calculated by scanning acoustic microscopy (SAM). The amount of glycosaminoglycan content was assessed by alcian blue staining. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Furthermore, the total genes of the two groups were compared by DNA microarray analysis. RESULTS: The number of cells was significantly higher and the capsular tissue was significantly stiffer in idiopathic frozen shoulders compared with shoulders with rotator cuff tears. Staining intensity of alcian blue was significantly stronger in idiopathic frozen shoulders. Gene expressions related to fibrosis, inflammation, and chondrogenesis were significantly higher in idiopathic frozen shoulders compared with shoulders with rotator cuff tears assessed by both qPCR and DNA microarray analysis. CONCLUSION: In addition to fibrosis and inflammation, which used to be considered the main pathology of frozen shoulders, chondrogenesis is likely to have a critical role in pathogenesis of idiopathic frozen shoulders.

Is the 7/2(1)- isomer state of 43S spherical?

We report on the spectroscopic quadrupole moment measurement of the 7/2(1)(-) isomeric state in (16)(43)S(27) [E*=320.5(5) keV, T(1/2)=415(3) ns], using the time dependent perturbed angular distribution technique at the RIKEN RIBF facility. Our value, |Q(s)|=23(3) efm(2), is larger than that expected for a single-particle state. Shell model calculations using the modern SDPF-U interaction for this mass region reproduce remarkably well the measured |Q(s)|, and show that non-negligible correlations drive the isomeric state away from a purely spherical shape.

Endotoxin activity and leukocytic STAT3 mRNA alterations differ according to age in lipopolysaccharide-challenged calves.

The objective of this study was to investigate the age difference in the response to endotoxin in calves related to the plasma endotoxin activity and mRNA expression of cytokines. Fifteen calves were divided into three groups: control (191 ± 21 days), weaning (162.4 ± 17.5 days), and calf (22.4 ± 8.2 days). The weaning and calf groups received 2.5 µg/kg of ultrapure O111:B4 LPS in 10 mL of each autologous serum, whereas the control calves received a similar volume of saline. Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 h. Liver samples were collected by ultrasound-guided liver biopsy at 0, 2, 4, and 24 h. Plasma endotoxin activity was measured by the limulus amebocyte lysate kinetic turbidimetric assay. The mRNA expression level of GAPDH, TLR-4, NF-κB2, TNF-α, IL-6, and STAT3 in leukocytes and the liver was measured by real-time PCR. Following LPS challenge, the maximal plasma endotoxin activity, and leukocytic expression of TLR4, NF-κB2, TNF-α, and STAT3 were reached at 0.5, 4, 2-4, 2-4, and 4 h, respectively, in weaning and calf groups. The endotoxin activity in calf remained high until 2 h. Furthermore, the expression of leukocytic STAT3 mRNA in calf was not significantly different from the pre-value. In contrast, STAT3 mRNA in weaning markedly increased at 2 and 4 h. Therefore, this study provides new information to the literature of immune and inflammatory responses in calves.

Imaging of electrostatic field vector distribution.

This paper reports on the visualization of a two-dimensional distribution of electrostatic field vectors around an electrified object using the electric field imager (EFIM) device. The EFIM device is made of a virtually connected pair of plate electrodes in parallel and in proximity, between which an electronic circuit for detection and optical indication is embedded. The EFIM device is not only accurately sensitive to the electrostatic field but also possessed of agility and mobility together with directivity and noninvasiveness. It was successfully demonstrated that electrostatic field vectors were visualized quantitatively, and their spatial distributions were mapped in combination with rather simple, mobile, and low-cost equipment. The advantages and disadvantages of the EFIM visualization scheme are discussed together with the future prospect of the EFIM device.

Pleth variability index predicts hypotension during anesthesia induction.

BACKGROUND: The pleth variability index (PVI) is a new algorithm used for automatic estimation of respiratory variations in pulse oximeter waveform amplitude, which might predict fluid responsiveness. Because anesthesia-induced hypotension may be partly related to patient volume status, we speculated that pre-anesthesia PVI would be able to identify high-risk patients for significant blood pressure decrease during anesthesia induction. METHODS: We measured the PVI, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in 76 adult healthy patients under light sedation with fentanyl to obtain pre-anesthesia control values. Anesthesia was induced with bolus administrations of 1.8 mg/kg propofol and 0.6 mg/kg rocuronium. During the 3-min period from the start of propofol administration, HR, SBP, DBP, and MAP were measured at 30-s intervals. RESULTS: HR, SBP, DBP, and MAP were significantly decreased after propofol administration by 8.5%, 33%, 23%, and 26%, respectively, as compared with the pre-anesthesia control values. Linear regression analysis that compared pre-anesthesia PVI with the decrease in MAP yielded an r value of -0.73. Decreases in SBP and DBP were moderately correlated with pre-anesthesia PVI, while HR was not. By classifying PVI >15 as positive, a MAP decrease >25 mmHg could be predicted, with sensitivity, specificity, positive predictive, and negative predictive values of 0.79, 0.71, 0.73, and 0.77, respectively. CONCLUSION: Pre-anesthesia PVI can predict a decrease in MAP during anesthesia induction with propofol. Its measurement may be useful to identify high-risk patients for developing severe hypotension during anesthesia induction.

Help-seeking patterns in Chinese women with symptoms of breast disease: a qualitative study.

BACKGROUND: Prompt utilization of health services on detecting breast symptoms can improve breast cancer (BC) survival. Little is known about Chinese women's help-seeking behaviour. Our aim was to determine patterns of self-referral among Hong Kong Chinese women with self-detected breast symptoms. METHODS: We recruited 37 women awaiting their first consultation at public hospitals for breast symptoms. Interviews were transcribed and analysed based on the grounded theory approaches. RESULTS: A two-stage help-seeking model provided the best interpretation of the data. Symptom recognition was triggered by symptom interpretation, symptom progression and social messages. Painful lumps were seen as symptomatic, but atypical symptoms were often dismissed as benign as they responded to dietary change. Symptom intensification and discussions with someone who had faced BC prompted consultation. Service utilization involved fear of consequences, confirmation need, symptom distress, lay referral, media prompts and opportunistic presentation. Fearing cancer as incurable delayed consultation. Utilization barriers included cost, uncertainty about referral pathways, competing priorities and embarrassment. CONCLUSIONS: Atypical and painless presentation was more common among women delaying presentation. Barriers included cost, access, time and embarrassment. Education should emphasize atypical symptoms, the high-cure rate and the need for early presentation. Reduced cost and improved access to clinics would enhance early consultation.

An exploration of unmet information needs among breast cancer patients in Japan: a qualitative study.

Informational need assessment has become an important part of health care in order to provide information effectively in clinical settings. Literature on information needs in the West suggests that breast cancer (BC) patients needed more information than doctors had provided, and information that fully met their needs was associated with patients' long-term well-being. Since few studies on this issue have been conducted in Japan, where the general consultation style is less open and more indirect, compared with that in the West, the application of the findings in the West is questionable. The purpose of this qualitative study was to explore perceived information needs among female BC patients in Japan. Twelve Japanese women with BC participated in semi-structured face-to-face interviews. Grounded theory using verbatim transcripts extracted two main themes: information needed to minimize physical and psychological impacts of treatment and information needed for the resumption of normal life. These were closely related at two time points. Physical support after discharge was perceived as relatively insufficient, especially by women experiencing post-operative arm complications. More open and direct communication was preferred between patients and doctors/family members in the recovery phase. Unmet needs for information may lead to patients' distress.

Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma.

Epigenetic alterations like DNA methylation and the resulting inactivation of cancer-related genes often contribute to the development of various cancers. To identify the genes that are silenced by aberrant methylation in renal cell carcinoma (RCC), we subjected two RCC lines to methylated CpG island amplification/representational difference analysis. This identified 27 CpG islands. Combined bisulfite restriction analysis of these CpG islands in primary RCC cases revealed that four were methylated in a tumor-specific manner. One of these was identified as the human homeo-box gene B13 (HOXB13) gene, but the remaining three CpG islands were not associated with known genes. The methylation frequencies of HOXB13 in primary RCC samples and lines were 30 and 73%, respectively. The methylation status of HOXB13 correlated with the loss of its expression both in RCC lines and primary tumors, and methyltransferase inhibitor treatment induced the recovery of its expression. Exogenous expression of HOXB13 in RCC cells that lacked endogenous HOXB13 expression suppressed colony formation and induced apoptotic features. Furthermore, HOXB13 methylation correlated positively with tumor grade and microvessel invasion. These results suggest that HOXB13 is a novel candidate tumor suppressor gene in RCC and that its inactivation may play an important role in both RCC tumorigenesis and progression.

Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes.

The interaction of mucosal lymphocytes and intestinal epithelial cells is thought to be important in regulating immune response in the intestinal mucosa, but conclusive evidence is limited. Here we demonstrate the expression of IL-7 mRNA in human intestinal mucosa by combined reverse transcription PCR and Southern blot hybridization. Immunohistochemistry and in situ hybridization confirm the presence of IL-7 in intestinal epithelial cells, especially in epithelial goblet cells. Moreover, IL-7 receptor expression in mucosal lymphocytes is demonstrated by immunohistochemistry and in situ hybridization, as well as by Southern blot and flow cytometric analysis of freshly isolated lamina propria lymphocytes. In contrast, IL-7 receptor could not be detected in the cell surface of freshly isolated PBLs. The functional activity of IL-7 receptor is demonstrated by the utility of recombinant IL-7 to stimulate the growth of lamina propria lymphocytes, and conversely inhibit CD3-dependent proliferation of these cells. In contrast, IL-7 caused no significant increase in DNA synthesis and cell numbers when added to PBLs. These findings suggest that human intestinal epithelial cells and epithelial goblet cells produce IL-7, and locally produced IL-7 may serve as a potent regulatory factor for intestinal mucosal lymphocytes.

Prostaglandin E1 abrogates early reductive stress and zone-specific paradoxical oxidative injury in hypoperfused rat liver.

This study was designed to investigate the effects of prostaglandin E1 on reductive stress and the subsequent oxidative cell injury in hypoperfused rat liver. The intralobular heterogeneity of hepatocellular redox state, mitochondrial dysfunction, and intracellular hydroperoxide formation were visually monitored by digital microfluorography of pyridine nucleotide autofluorescence, rhodamine 123, and dichlorofluorescein fluorescence, respectively. Under the 25% low flow perfusion, pyridine nucleotide autofluorescence increased time-dependently and reached a steady state at 10 min among the entire lobules. The decrease in mitochondrial membrane potential was > 20 mV in all portions of the lobules at 60 min. The onset of hydroperoxide formation was observed at 40 min in the marginally oxygenated proximal portion of anoxic pericentral regions and the oxidative impact reached a maximum level at 60 min. Sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazo [1,5-a]-1,3,5-triazine-4-olate monohydrate (BOF 4272), a novel xanthine oxidase inhibitor, suppressed the zone-specific oxidative changes without attenuating the increase in pyridine nucleotide autofluorescence and mitochondrial dysfunction. Pretreatment with prostaglandin E1 not only abrogated an early increase in pyridine nucleotide fluorescence and mitochondrial dysfunction induced by hypoperfusion but also diminished the subsequent midzonal oxidative injury. Since prostaglandin E1 has no oxyradical-scavenging action, the preventive effect of this reagent on the hypoxia-induced oxidative cell injury is attributable to the attenuation of mitochondrial dysfunction. These results suggest that, in low flow hypoxia, early reductive stress plays a key role in the initiation of xanthine oxidase-mediated midzonal oxidative changes, which may lead to subsequent centrilobular necrosis.

Origin, splicing, and expression of rodent amelogenin exon 8.

Amelogenin RNA transcripts undergo extensive alternative splicing, and MMP-20 processes the isoforms following their secretion. Since amelogenins have been ascribed cell-signaling activities, we asked if a lack of proteolytic processing by MMP-20 affects amelogenin signaling and consequently alters amelogenin splice site selection. RT-PCR analyses of amelogenin mRNA between control and Mmp20(-/-)mice revealed no differences in the splicing pattern. We characterized 3 previously unidentified amelogenin alternatively spliced transcripts and demonstrated that exon-8-encoded amelogenin isoforms are processed by MMP-20. Transcripts with exon 8 were expressed approximately five-fold less than those with exon 7. Analyses of the mouse and rat amelogenin gene structures confirmed that exon 8 arose in a duplication of exons 4 through 5, with translocation of the copy downstream of exon 7. No downstream genomic sequences homologous to exons 4-5 were present in the bovine or human amelogenin genes, suggesting that this translocation occurred only in rodents.

Specific immunodiagnosis of hepatoma by tube leukocyte adherence inhibition assay and a modified method of repeated tube leukocyte adherence inhibition assay.

Tube leukocyte adherence inhibition (LAI) assays were performed with normal liver extract as nonspecific antigen and with hepatoma extract as specific antigen in patients with hepatoma. Titration experiments revealed that the optimal extract concentration was 400 micrograms/ml when expressing the results in terms of a nonadherence index. The results of tube LAI assays were positive in 26 of 40 cases (65%) of hepatoma. The results were negative in all cases of other liver diseases and other cancers. The tube LAI assay was repeated after discarding the non-adherent cells in the initial tube LAI assay with normal liver extract. The nonadherence index of the repeated tube LAI assay we devised was significantly higher than that of the original tube LAI assay (p less than 0.001) in patients with hepatoma. Ten of 12 patients with hepatoma in whom the results of the original tube LAI assay were negative showed positive results in the repeated tube LAI assay. The present study suggests that the problem of false-negative results in tube LAI assay can be solved by repeating the tube LAI assay.

Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth.

The mouse PM-1 monoclonal antibody binds to the human interleukin 6 receptor, inhibits IL-6 functions, and shows strong antitumor cell activity against multiple myeloma cells. In order to be effective as a therapeutic agent administered to human patients in repeated doses, reshaped human PM-1 antibodies consisting of human REI-based light chain and NEW-based heavy chain variable regions were designed and constructed with the assistance of a structural model of the mouse PM-1 variable regions. The best reshaped human PM-1 antibody is equivalent to mouse or chimeric PM-1 antibody in terms of antigen binding and growth inhibition against multiple myeloma cells. Only a few minor changes in the human framework regions were required to recreate the mouse PM-1 antigen-binding site within a human antibody. The reshaped human PM-1 antibody, therefore, could be efficacious in human multiple myeloma patients.