Ten-year fracture risk by FRAX and osteoporotic fractures in patients with systemic autoimmune diseases.

The Fracture Risk Assessment Tool (FRAX) has been used universally for the purpose of fracture risk assessment. However, the predictive capacity of FRAX for autoimmune diseases remains inconclusive. This study aimed to compare the applicability of FRAX for autoimmune disease patients. This retrospective study recruited rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS) patients with bone mineral density (BMD) tests. Patients with any osteoporotic fractures were identified. Taiwan-specific FRAX with and without BMD were then calculated. In total, 802 patients (451 RA, 233 SLE and 118 pSS) were enrolled in this study. The cumulative incidences of osteoporotic fractures in the RA, SLE and pSS patients were 43.0%, 29.2% and 33.1%, respectively. For those with a previous osteoporotic fracture, T-scores were classified as low bone mass. Overall, the patients' 10-year probability of major fracture risk by FRAX without BMD was 15.8%, which then increased to 20.3% after incorporation of BMD measurement. When analyzed by disease group, the fracture risk in RA patients was accurately predicted by FRAX. In contrast, current FRAX, either with or without BMD measurement, underestimated the fracture risk both in SLE and pSS patients, even after stratification by age and glucocorticoid treatment. For pSS patients with major osteoporotic fractures, FRAX risks imputed by RA were comparable to major osteoporotic fracture risks of RA patients. Current FRAX accurately predicted fracture probability in RA patients, but not in SLE and pSS patients. RA-imputed FRAX risk scores could be used as a temporary substitute for SLE and pSS patients.

Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study.

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12-1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29-3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07-1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06-1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01-19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41-24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.

[Management strategies of granulation in tracheal post-tracheostomy caused by prolonged mechanical ventilation].

Objective:To analyze the effect and safety of treatment in patients with airway stenosis caused by tracheotomy for mechanical ventilation. Method: We treated the patients with airway stenosis caused by granulation tissue. The patients with grade Ⅰ,Ⅱ airway stenosis were treated with adjustable flange tracheostomy tube, and the holmium laser under a fibro-laryngoscope were applied for the patients with grade Ⅲ airway stenosis.Two hundred and sixteen patients were enrolled in this study. Forty-four patients had been found tracheal stenosis caused by granulomatous hyperplasia, accounting for 20.4% of all patients, including 12 cases of gradeⅠ, 18 cases of grade Ⅱ, and 14 cases of grade Ⅲ.Result:Thirty patients with grade Ⅰ and Ⅱ were replaced with adjustable flange tracheostomy cannula. Fourteen cases of grade Ⅲ airway stenosis were treated with Ho:YAG laser under a fibro laryngoscope. All cases were completed operation successfully. None of cases bleeding, perforated and asphyxia during operation. The clinical symptoms disappeared after operation, and endoscopy showed that airways of patients were smooth. No recurrence were found after operation.Conclusion: Replacement of adjustable flange tracheostomy tube and Ho:YAG laser can safely and effectively treat airway obstruction caused by tracheal granulation tissue hyperplasia after tracheotomy.

[Photochemical induced vestibular ischemiawith icy water test in guinea pigs].

Objective:To ascertain the effects of a new method of photochemical reaction in vestibular function in guinea pigs.Method:Local photochemical reaction was initiated by systemic injection of rose bengal(20mg), photoillumination of the vestibule through medial wall of epitympanum for 30 minutes was started immediately after the injection of rose bengal, with a optic fiber connected to a xenon light (wavelength, 540nm; photointense, 500-600 mW/cm ²). There were 20 guinea pigs divided random equally into 2 groups. Group 1 was injected with rose bengal. Group 2 was control, injected with physiological saline solution. The ice caloric tests were performed on the second day.Result:The test group (7 ears) and the control group (6 ears) with test nystagmus showed mean frequencies were（2.0±0.33）times/s and（3.7±0.33）times/s,the mean amplitude were (3.1±0.39)mm and (3.5±0.54)mm,and the mean duration were (44.7±17.22)s and (62.0±7.22)s respectively.The nystagmus frequency difference was statistically significant, but the amplitude and the duration of the nystagmus were not significantly different. There was no obvious spontaneous nystagmus in the two groups, and there were negative results of ice water test (3 ears in the test group and 4 ears in the control group).Conclusion:Photochemical reaction can induce the ischemic state of the vestibule system in guinea pig, and produce an acute vestibular dysfunction, and ice water test shows that the frequency of nystagmus is reduced.

[The clinical features and efficacy of patients with geotropic direction-changing positional nystagmus].

Objective: The purpose of this study was to observe the clinical characteristics of two types of geotropic direction-changing positional nystagmus, the transient(nystagmus time <1 min) and the persistent(nystagmus time > 1 min), and to evaluate the efficacy of the barbecue roll maneuver. Methods: A total of 105 cases diagnosed by supine roll test were studied, which including 35 males and 70 females and the average age was (56.9±14.6)years. There were 70 transient geotropic DCPN and 35 persistent geotropic DCPN. The clinical characteristics and the immediate and one-week efficacy of the barbecue roll maneuver were discussed. Results: The nystagmus disappeared at the null-point position and the nystagmus in supine position were opposite to the bowing (90° nose-down) position in persistent geotropic DCPN cases. While to the transient geotropic DCPN cases, there were no NP and no nystagmus in prone position. The ratio of the first onset of the two groups was 28.6% (persistent) and 72.9% (transient) respectively, and the difference was statistically significant (P<0.05). The immediate and one-week efficacy after barbecue roll maneuver were 91.4% and 80.0% in transient geotropic DCPN cases, and 0% and 42.9% in persistent geotropic DCPN cases, which were statistically significant different(P<0.05). Conclusions: The light cupula hypothesis can mainly explain the clinical features of persistent geotropic DCPN cases; the barbecue roll maneuver is invalid to persistent geotropic DCPN cases which can be self-healing.

[Relative analysis of endolymphatic imaging and clinical manifestations in Meniere's patients].

Objective:The research aimed to study the relationship between endolymphatic imaging and clinical manifestations(duration of last attack period to MRI scan) of Meniere's patients.Method:Twenty-six Meniere's patients and 29 affected ears were enrolled in this research. According to clinical manifestations, when performing MRI scan, patients who were not in attack period and the duration of last attach period to MRI scan was longer than 14 days were divided to Group A; and patients who were in attack period or the duration of last attach period to MRI scan was shorter than or equal to 14 days were divided to Group B. Administrate gadolinium to mid-ear affected by MD via non-invasive method through Eustachian tube, and then perform 3D-FLAIR MRI scan the next day. After measurement and calculation, compare RV and RC (area of endolymphatic space divided by total lymphatic space in vestibule and cochlea, respectively) of the two groups. Result:Twenty-nine affected ears of 26 patients were administrated successfully.The endolymphatic spaces were distinct from perilymphatic spaces in vestibule and cochlea in 26 ears. In the images of B6, B12, B14, the cochlea and semicircular canals were enhanced, but the vestibules were not enhanced. For Group A ,the average of RV was 0.37±0.06; the average of RC was 0.15±0.04. As to Group B ,the average of RV was 0.52±0.26; the average of RC was 0.18±0.06. According to ANOVA test,RV of the two groups had significant difference（P<0.05）, RC had no significant difference（P>0.05）. The positive RC and RV in Group A were 7.1% and 42.9% respectively. The positive RC and RV in Group B were 13.3% and 66.7%, respectively. As to 4 patients who were during attack period in Group B, the positive RC and RV were 50% and 100%, respectively. The positive RV of Group B was higher than that of Group A. Conclusion:The clinical manifestations(duration of last attack period to MRI scan) of Meniere's patients had relationship with positive rate of MRI scan. The possibility of positive RV was higher when the duration of attack period to MRI scan was shorter.

Normal esophageal high-resolution manometry and impedance values in the supine and sitting positions in the population of Northern China.

The aim of this study was to investigate the normal high-resolution manometry and impedance (HRiM) values in the supine and sitting positions in the population of Northern China, and to investigate the influence of different body positions and bolus consistency on esophageal HRiM findings. In this study, healthy volunteers in the supine position underwent esophageal HRiM examination of 10 swallows of 5 mL normal saline solution and 10 swallows of 5 mL synthetic gel of known viscosity, and in the sitting position of an additional five swallows of a synthetic gel of known viscosity. Total bolus transit time (TBTT), complete bolus transit rate (CBTR), distal contractile integral (DCI), distal esophageal amplitude (DEA), and integrated relaxation pressure (IRP) were measured. Sixty-two healthy volunteers were examined in the supine position and 45 of these performed additional swallows of the viscous gel in the sitting position. In the supine position, normal values for swallowing the liquid and viscous boli were as follows: TBTT 6.9 ± 0.9 and 8.0 ± 1.2 s (P < 0.001), CBTR 90.3 ± 14.0 and 77.9 ± 20.3% (P < 0.001), DCI 1891.5 ± 1131.9 and 1967.8 ± 1140.1 mmHg.s.cm (P = 0.227), DEA 95.3 ± 35.4 and 98.7 ± 37.5 mmHg (P = 0.148), and IRP 10.4 ± 4.9 and 9.0 ± 4.2 mmHg (P < 0.001), respectively. For swallows of the viscous boli in the sitting position, TBTT, DCI, DEA, and IRP were significantly decreased, while CBTR was unchanged (P = 0.075). Normal HRiM values of the population of Northern China were established. Esophageal transit times of viscous boli were significantly slower, more often incomplete and produced less normal peristalsis in the supine position than swallows of liquid boli. Independent reference values for different manometric systems, body positions, and population need to be established before clinical application.

[Preliminary analysis of influencing factors on source of snoring sound].

Objective:To investigate the main factors affecting the source of snoring sound of snoring patients.Method:Seventy-three patients with either simple snoring or obstructive sleep apnea-hypopnea syndrom(AHI≤40) underwent routine ENT examination,CT scanning(in awake condition) and drug-induced sleep endoscopy.The sources of snoring sound were observed.The neck circumference,body mass index and CT data were measured.Result:The sources of snoring sound of the 73 cases were divided into three types in general: palatal fluttering based group(Group Ⅰ),lateral wall vibration based group(Group Ⅱ) and palatal fluttering together with vibration of lateral wall based group(Group Ⅲ).The minimum lateral caliber of retropalatal region and retroglossal region,the ratio of minimum anteroposterior/ lateral caliber of the two regions,the thickness of pharyngeal lateral wall had statistical differences.The main influencing factors on the source of snoring sound between Group Ⅱ and Group Ⅰ were the ratio of minimum anteroposterior/lateral caliber of retropalatal region and the mean thickness of pharyngeal lateral wall.The influencing factor between Group Ⅲ and Group Ⅰ was the mean thickness of pharyngeal lateral wall.Conclusion:The ratio of minimum anteroposterior/lateral caliber of retropalatal region and the mean thickness of pharyngeal lateral wall are the main factors affecting the source of snoring sound of snoring patients.

[Application of the dizziness handicap inventory in the patients with benign paroxysmal positional vertigo].

Objective:This study was designed to observe the dizziness handicap inventory (DHI) scores in patients with BPPV (benign paroxysmal positional vertigo) before and after maneuver repositioning and aimed to discuss the values of DHI scores in the diagnosing and treatment of BPPV. Method:Charts of 72 patients with BPPV diagnosed by positioning test were reviewed. Four DHI scores were used including the total score (DHIT), the functional score (DHIF), the emotional score (DHIE), and the physical score (DHIP). We compared the pre-repositioning DHI scores and post-repositioning scores of patients, and also compared the DHI scores of patients with and without residual dizziness. Result:All of the 72 patients were underwent maneuver repositioning and recorded the DHI scores. The mean post-repositioning scores were dramatically decreased compared with pre-repositioning scores, and the difference was significant (P<0.01). The differences of the DHIP scores between the residual dizziness group and the non-residual dizziness group was not significant, while the DHIF scores, the DHIE scores and the DHIT scores between the two groups were statistically different. Conclusion:After maneuver repositioning the dizziness handicap of BPPV patients could be significantly improved. The next treatment program for residual dizziness patients after successful repositioning could be aimed at the functional and emotional dizziness.

Elevation of plasma interleukin-18 concentration is associated with insulin levels in patients with systemic lupus erythematosus.

We previously reported that systemic lupus erythematosus (SLE) patients have a higher risk of insulin resistance and abnormal insulin secretion. Recent studies demonstrated that interleukin (IL)-18, a novel pro-inflammatory cytokine, may be involved in triggering the inflammatory processes in SLE and the concentrations of circulating IL-18 in SLE patients were significantly higher than those in healthy subjects. IL-12 has a synergistic effect with IL-18, and both cytokines are inducers of interferon (IFN)-gamma. The objective of this study was to identify the effect of fasting insulin levels on circulating concentrations of IL-18, IL-12 and IFN-gamma in patients with SLE. Plasma levels of proinflammatory Th-1 cytokines were determined by enzyme-linked immunosorbent assay in a total of 70 female SLE patients and 34 age-matched healthy females. Insulin resistance (IR) and secretion were evaluated by homeostasis model assessment (HOMA). All patients were further classified into subgroups based on the quartiles of fasting insulin levels. SLE patients with fasting insulin levels in the top quartile compared with other quartiles had significantly higher plasma levels of IL-18. The presence of insulin auto-antibodies (IAA) in SLE patients had no influence on plasma levels of IL-18. In addition, fasting insulin levels and HOMA IR were positively correlated with IL-18 in all SLE patients, respectively. In conclusion, elevated circulating IL-18 concentrations corresponded with increases in fasting insulin levels and the status of insulin resistance in patients with SLE.

Association of brachial-ankle pulse wave velocity with cardiovascular risk factors in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis. Increasing arterial stiffness is closely associated with atherosclerotic cardiovascular diseases, and pulse wave velocity (PWV) is considered to be an indicator of arterial stiffness. The objective of this study was to identify the relationship between brachial-ankle pulse wave velocity (baPWV) and cardiovascular risk factors in patients with SLE. Age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBS), plasma lipid profile, plasma homocysteine, thiobarbituric acid reactive substances (TBARS), baPWV, ankle-brachial index (ABI), and SLE-related factors were determined in a total of 83 SLE patients (12 males and 71 females). All SLE patients were further classified into two subgroups according to baPWV value (baPWV < 1400 cm/s, n=37 versus baPWV > 1400 cm/s, n=46). The mean baPWV value of studied SLE patients was 1520 +/- 381 cm/s. Age, BMI, SBP, DBP, FBS, TBARS and homocysteine levels were significantly higher in SLE patients with baPWV value > 1400cm/s than in SLE patients with baPWV value < 1400cm/s. In addition, baPWV correlated significantly with age, SBP, DBP, FBS and homocysteine. Moreover, stepwise multiple regression analysis showed that age and SBP were independently associated with baPWV. The results of this study indicate a possible link between vascular stiffness measured by baPWV and cardiovascular risk factors in patients with SLE.

Expression and clinical significance of antinuclear antibody in hepatitis C virus infection.

BACKGROUND: The prevalence of antinuclear antibody (ANA) has been documented in patients with hepatitis C virus (HCV) infection. We attempted to determine the titer and to characterize the patterns and clinical significance of ANA in HCV infection. STUDY: Forty-eight consecutive patients with positive anti-HCV antibody and positive HCV RNA were included in this study. Sera from patients were tested for ANA and anti-smooth muscle antibody by indirect immunofluorescence. Serum aminotransferase, alkaline phosphatase, alpha-fetoprotein, and cryoglobulin levels also were determined. RESULTS: Eleven (23%) of 48 HCV-infected patients were positive for ANA. Antinuclear antibody revealed speckled pattern in 10 (91%) of the 11 ANA-positive HCV-infected patients. Twenty (54%) of 37 ANA-negative HCV-infected patients had detectable pattern with equivocal titer (titer <1.5). The ANA pattern was speckled in all 20 patients. Hepatitis C virus-infected patients with positive ANA were older than the HCV-infected patients with negative ANA (62.90 +/- 11.05 years vs. 56.46 +/- 14.94 years, respectively; p < 0.1). Serum levels of aspartate aminotransferase (39.36 +/- 14.98 IU/L vs. 30.70 +/- 23.15 IU/L, p < 0.05), alkaline phosphatase (189.00 +/- 75.63 IU/L vs. 122.41 +/- 40.88 IU/L, p < 0.01), and alpha-fetoprotein (47.72 +/- 80.47 pg/dL vs. 7.00 +/- 8.28 pg/dL, p < 0.01) were higher in ANA-positive HCV-infected patients than in ANA-negative HCV-infected patients, respectively. There were no significant differences in gender, alanine aminotransferase, anti-smooth muscle antibody, or cryoglobulin between the two groups. CONCLUSIONS: Antinuclear antibody was present in 11 (23%) of 48 patients with HCV infection in our study. Speckled pattern is the major expression pattern of ANA in HCV infection. Antinuclear antibody-positive HCV-infected patients have significantly higher serum aspartate aminotransferase, alkaline phosphatase, and alpha-fetoprotein levels than ANA-negative HCV-infected patients.

Structures of heparin-derived disaccharide bound to cobra cardiotoxins: context-dependent conformational change of heparin upon binding to the rigid core of the three-fingered toxin.

Glycosaminoglycans (GAGs) have been suggested to be a potential target for cobra cardiotoxin (CTX) with high affinity and specificity via a cationic belt at the concave surface of the polypeptide. The interaction of GAGs, such as high-molecular weight heparin, with CTXs not only can induce aggregation of CTX molecules but also can enhance their penetration into membranes. The binding of short chain heparin, such as a heparin-derived disaccharide [DeltaUA2S(1-->4)-alpha-D-GlcNS6S], to CTX A3 from Taiwan cobra (Naja atra), however, will not induce aggregation and was, therefore, investigated by high-resolution (1)H NMR. A novel heparin binding site on the convex side of the CTX, near the rigid disulfide bond-tightened core region of Cys38, was identified due to the observation of intermolecular NOEs between the protein and carbohydrate. The derived carbohydrate conformation using complete relaxation and conformational exchange matrix analysis (CORCEMA) of NOEs indicated that the glycosidic linkage conformation and the ring conformation of the unsaturated uronic acid in the bound state depended significantly on the charge context of CTX molecules near the binding site. Specifically, comparative binding studies of several heparin disaccharide homologues with two CTX homologues (CTX Tgamma from Naja nigricollis and CTX A3) indicated that the electrostatic interaction of N-sulfate of glucosamine with NH(3)(+)zeta of Lys12 and of the 2-O-sulfate of the unsaturated uronic acid with NH(3)(+)zeta of Lys5 played an important role. These results also suggest a model on how the CTX-heparin interaction may regulate heparin-induced aggregation of the toxin via the second heparin binding site.

Heparin reduces the alpha-helical content of cobra basic phospholipase A(2) and promotes its complex formation.

The interaction of phospholipase A(2) (PLA(2)) with glycosaminoglycans (GAGs) has recently attracted attention in view of its implication on inflammation and cell proliferation. By using Fourier Transformed Infrared (FTIR) spectroscopic measurements, we demonstrate here that binding of cobra basic phospholipase A(2) from Naja nigricollis (N-PLA(2)) to heparin may induce a significant conformational change observed in the amide I region of the enzyme's alpha-helical and beta-sheet structure. It is observed that notable conformational change of N-PLA(2) due to heparin binding occurs only when heparin's chain length is at least an octasaccharide as evidenced by circular dichroism and optical density measurements. This correlation may be an important factor in the aggregation of N-PLA(2) and N-PLA(2)-heparin complexes. Heparin induced change in conformation of PLA(2) is suggested to be a notable link in understanding the diversity in PLA(2) activity when rendered to the extracellular matrix of cell membranes that is full of GAG molecules.

[Observation and analyses on voice changes in the normal aged].

OBJECTIVE: To measure the voice samples of the normal aged in order to systemically study the features of the voice changes. METHOD: To collect and analyze 146 voice samples of the normal aged with sonogram. RESULT: The fundamental frequency of the voice of the aged decreases and rises in the male more than 80 years older. The low frequency harmonics are regulation and the intensity is strong in the formant of the aged. The difference reduces in voice between male and female. The harmonics to noise ratio tends downwards and the amplitude perturbation quotient tends upwards along with the growth of age in the aged male. The changes of the above-mentioned parameters are not significant in the aged female. CONCLUSION: The voice changes are normal physiological ones in the normal aged. The changes of the parameters are used to evaluate normal aged voice and abnormal one. The changes show that the function in the aged phonation tends to decline to a certain extent and it must be protected and be trained.

Lipoprotein-induced prostacyclin production in endothelial cells and effects of lipoprotein modification.

Although lipoprotein modification has been implicated in atherogenesis, the effect of modified forms of lipoproteins on vascular cell function has not been fully resolved. We have investigated lipoprotein-induced prostaglandin production by macrovascular endothelial cells. This study delineates early responses of endothelial cells after exposure to native and modified forms of the lipoproteins. Modification of lipoproteins by oxidation or glycation significantly affected the capacity of lipoproteins to induce prostacyclin (PGI2) production by bovine aortic endothelial cells (BAEC). Modified low-density lipoprotein (LDL) increased PGI2 production in the short term (up to 24 h), but oxidized LDL caused an inhibition of PGI2-producing capacity in longer term incubations (48-72 h). Glycated (Glc) high-density lipoprotein 3 (HDL3) caused higher production of PGI2 in the short term (4-24 h) but reached similar levels as HDL3 over time. Glycation of high-density lipoprotein 2 had no effect on the PGI2-producing capacity of the lipoprotein. Thus modification of the lipoproteins affects their potential to induce PGI2 production in endothelial cells, and this may have an influence on vascular function in disease states such as diabetes and atherosclerosis. Although the changes appear to contradict data from long-term in vivo studies, these results from in vitro studies may reflect the situation in very early lesion development. GlcLDL, while causing an increase in endothelial cell PGI2 production, may be involved in compromised endothelial function, since GlcLDL is prone to oxidation.

Fusion of sphingomyelin vesicles induced by proteins from Taiwan cobra (Naja naja atra) venom. Interactions of zwitterionic phospholipids with cardiotoxin analogues.

Egg sphingomyelin vesicles were used to assay aggregation/fusion activities of proteins from Taiwan (Naja naja atra) venom to avoid the problem of phospholipase A2 contamination during protein purification. It led to the identification of a new cardiotoxin (CTX) analogue protein (CTX V) with major aggregation/fusion, but few hemolysis, activities. On the contrary, cardiotoxin (CTX III) induced significant hemolysis of human red blood cells but exhibited few aggregation/fusion activities. To study the structure/activity relationship of these CTX-induced processes, the amino acid sequence of CTX V was determined and its aggregation/fusion activity was compared with that of CTX III by transmission electron microscopy, quasielastic laser light scattering, differential scanning calorimetry, and fluorescence spectroscopy. The results show that the CTX-induced fusion process at temperatures slightly above that of the gel to liquid-crystalline phase transition of sphingomyelin vesicles can ultimately convert small sonicated vesicles into large fused vesicles with sizes of 1-2 microns. The abilities of CTX V to induce the leakage of sphingomyelin vesicles content and to cause the fusion of vesicles are approximately 10-fold higher than those of CTX III. Based on the CTX structures determined in the present and other studies, it is suggested that the amino acid residue X within the well conserved sequence of -Cys-Pro-X-Gly-Lys-Gln-Leu-Cys- plays a role in the interaction of CTX with lipid molecules. The lipid phase transition could further enhance the protein-lipid interaction in the process leading to the fusion of vesicles.