A neck-preserving short stem better reconstructs the centre of rotation than straight stems: a computed tomography-based cadaver study.

INTRODUCTION: Short femoral hip stems with a metaphyseal anchoring concept have been designed to treat younger patients with good bone quality. The aim of this study was to reconstruct the centre of rotation and soft tissue balancing and preserve bone in the long-term perspective. MATERIALS AND METHODS: Eighteen human femurs were randomised into three groups: (1) metaphyseal anchoring short stem, (2) shortened straight stem, (3) straight stem). Prior to the implantation of the hip stems, a computed tomography (CT) of the bones was performed and the femoral ante-torsion and ante-tilt was measured and compared to the results of the post-implantation CT. This could be calculated based on the 3D coordinates taken from the pre- and post-op CT scans, which were transformed into the same coordinate systems. RESULTS: The mean preoperative caput-collum-diaphyseal (CCD) angle for the three groups was 126.87° ± 3.50° (Group 3: 129.64° ± 3.53°, Group 1: 123.76° ± 5.56°, Group 2: 127.53° ± 1.42°) and was consistent with published reports. The postoperative CCD angles with 126.85° ± 3.43° were within a very good reconstruction range for all three groups. The anterior offset comparison among these three groups showed significant difference in reconstruction. The smallest difference between the anatomical (preoperative) and postoperative condition was seen in Group 1 (1.47° ± 0.60°), followed by Group 2 (3.60° ± 0.23°) and Group 3 (8.00° ± 0.70°) groups. The horizontal offset showed no significant difference among the groups and was within the window of ± 5 mm. CONCLUSION: In this cadaver study, we found that the metaphyseal anchoring, partially neck-preserving short hip stem best reconstructs the ante-torsion and the ante-tilt of the femoral neck. Therefore, it can be a useful stem in younger or active middle-aged patients.

Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants.

OBJECTIVE: Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants. METHODS: We investigated clinicopathological features of PLC (n = 11) compared with those of other variants of invasive lobular carcinoma (ILC, non-PLC) (n = 32). Histological variants of the non-PLC group consisted of classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n = 4). A review of cytological reports and fine needle aspiration (FNA) smear samples was performed for the PLC (n = 9) and non-PLC (n = 27) groups. RESULTS: Patients with PLC were older, and had a higher nuclear grade and a higher incidence of axillary lymph node metastasis and triple negative phenotype than non-PLC patients (P = 0.007, P < 0.001, P = 0.02 and P < 0.001, respectively). Cytological findings in PLC included medium- to large-sized nuclei, prominent nucleoli, a moderate-to-severe degree of pleomorphism, apocrine change and background necrosis, none of which were evident in the smears of the non-PLC group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, and P = 0.03, respectively). Despite these differences, patients with PLC and non-PLC showed similar clinical outcomes in our follow-up period. CONCLUSIONS: Based on our results, a cytological diagnosis of PLC should be proposed if there are moderate- to large-sized nuclei, prominent nucleoli, a moderate-to severe degree of nuclear pleomorphism, apocrine change and necrosis in the background in FNA biopsy samples.

Mucinous carcinoma of the breast: a comparative study on cytohistological findings associated with neuroendocrine differentiation.

OBJECTIVE: Mucinous carcinoma (MCA) may show neuroendocrine differentiation (ND), but the cytological features characteristic of ND remains elusive. We compared fine needle aspiration (FNA) findings of MCA between cases with high and low degrees of ND. METHODS: Histological sections of 37 MCA cases were immunohistochemically evaluated for expression of chromogranin A and synaptophysin, and were graded as 0 to 3+ degrees of ND. They were divided into low ND (grade 0 and 1+) and high ND (grade 2+ and 3+) groups. Pre-operative FNA samples of each group were assessed for cytological features. RESULTS: The mean age of the high ND group (n = 18) was higher than the low ND group (n = 19, P = 0.01). In FNA samples of the high ND group, 17 cases showed moderate to severe degrees of discohesiveness, but low ND cases mainly showed no or only mild discohesiveness (P < 0.001). Nine of the low ND cases displayed overlapped, cohesive cell clusters, whereas, in the high ND cases, the cells were arranged in a loose, flat and monolayered pattern (P = 0.045). Fourteen of the high ND cases had round nuclei, but oval nuclei were predominant in the low ND cases (P = 0.027). The nuclei were eccentrically located in 12 of the high ND cases but were centrally located in 14 of the low ND cases (P = 0.01). CONCLUSIONS: Mucinous carcinoma with high ND may be diagnosed by the presence of discohesiveness, a flat, monolayered pattern, and round or eccentrically located nuclei. Features of ND in carcinomas in other organs, such as intracytoplasmic granules and coarse chromatin, may not be reliable cytological features of ND in MCA.

Extracorporeal shock wave therapy induces therapeutic lymphangiogenesis in a rat model of secondary lymphoedema.

OBJECTIVE: Lymphoedema is a common complication after cancer treatment. We have reported that low-energy extracorporeal shock wave (SW) therapy up-regulates vascular endothelial growth factor (VEGF) in ischaemic myocardium. As VEGF plays an important role in lymphangiogenesis, we investigated whether our low-energy SW therapy enhances lymphangiogenesis in rats. METHODS: We created a tail model of lymphoedema in rats. The tail was treated with or without low-energy SW therapy (0.25 mJ mm(-2), 500 impulses) four times (days 3, 5, 7, and 9). The tail volume and the fluorescence intensity of indocyanine green (ICG) were measured. The expression of VEGF-C and basic fibroblast growth factor (bFGF) were evaluated by RT-PCR, and the lymphatic vessel density was assessed histochemically. RESULTS: The tail volume increased significantly in the control group and was significantly improved in the SW group. The lymphatic system function (evaluated with fluorescence intensity of ICG), the lymphatic vessel density, and the expression of VEGF-C and bFGF were all enhanced by the SW therapy (all P < 0.05). CONCLUSIONS: The low-energy SW therapy induces therapeutic lymphangiogenesis by up-regulating VEGF-C and bFGF, and improves lymphoedema in a rat-tail model, suggesting that low-energy SW therapy could be a non-invasive and effective strategy for lymphoedema in humans.

Suppressive effects of 1,4-dihydroxy-2-naphthoic acid administration on bone resorption.

SUMMARY: The main component of the metabolic by-products of fermentation by Propionibacterium freudenreichii ET-3 is 1,4-dihydroxy-2-naphthoic acid (DHNA), which has a naphthoquinone skeleton, as in vitamin K2. This study showed that DHNA improved bone mass reduction with osteoporosis model mice caused by FK506. INTRODUCTION: Growth of the intestinal bacterium Lactobacillus bifidus is specifically facilitated by DHNA. The present study used osteoporosis model mice to investigate the effects of DHNA on bone remodeling. METHODS: FK506, an immunosuppressant, was used to prepare osteoporosis model mice. Thirty mice were divided into three groups: FK group, FK+DHNA group, and control group. In the FK group, FK506 was administered to induce bone mass reduction. In the FK-DHNA group, FK506 and DHNA were administered concurrently to observe improvements in bone mass reduction. To ascertain systemic and local effects of DHNA, we investigated systemic pathological changes in colon, kidney function and cytokine dynamics, and morphological and organic changes in bone and osteoclast dynamics as assessed by culture experiments. RESULTS: Compared to the FK group without DHNA, colon damage and kidney dysfunction were milder for FK+DHNA group, and production of inflammatory cytokines (interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha) was more suppressed. Furthermore, compared to the group without DHNA, histological analyses and radiography showed that bone resorption was suppressed for the DHNA group. Culture experiments using osteoclasts from murine bone marrow showed osteoclast suppression for the DHNA group compared to the group without DHNA. CONCLUSION: These results show that DHNA has some effects for improving bone mass reduction caused by FK506.

First case of bacteremia due to chromosome-encoded CfxA3-beta-lactamase-producing Capnocytophaga sputigena in a pediatric patient with acute erythroblastic leukemia.

Bacteremia due to Capnocytophaga sputigena occurred in a 4-year and 9-month-old Japanese girl patient with acute erythroblastic leukemia in Shinshu University Hospital, Japan. On her admission to the hospital, she had a temperature of 38.2 degrees C with canker sore. Prior to the commencement of chemotherapy, peripheral blood culture was carried out with the BacT/Alert 3D System ver. 4.00D (bioMerieux Japan Ltd., Tokyo, Japan) using both the PF and the SN bottles. At 48 hrs of incubation, the System showed the positive sign only in the anaerobic SN bottle for bacterial growth. The strain isolated from the SN bottle was morphologically, biochemically, and genetically characterized, and finally identified as Capnocytophaga sputigena. The causative Capnocytophaga sputigena isolate was found to be a beta-lactamase-producer demonstrating to possess cfxA3 gene. The gene responsible for the production of CfxA3-beta-lactamase was proved to be chromosome-encoded, by means of southern hybridization analysis. This was the first case of bacteremia caused by chromosome-encoded CfxA3-beta-lactamase-producing Capnocytophaga sputigena.

A new evaluation of masticatory ability in patients with dysphagia: The Saku-Saku Test.

OBJECTIVE: In the elderly and patients with dysphagia, masticatory problems often cause aspiration or choking. Although simple methods to predict aspiration and silent aspiration exist, methods for evaluating the masticatory function of patients with dysphagia are lacking. Accordingly, we developed a simple test to assess the chewing and swallowing ability of patients with dysphagia. METHODS: One hundred and five patients with dysphagia were included. We used the Saku-Saku Test (SST), in which patients were asked to eat a rice cracker, and evaluated the quality of mandibular rotation during mastication. We studied the participants' ability to grind, aggregate, and swallow using videoendoscopic evaluation (VE) and investigated its association with mandibular rotation. RESULTS: The SST showed good reliability between two examiners, with a kappa coefficient of 0.80. 92.4% of the patients ate the rice cracker without aspiration. The SST showed a high sensitivity of 73.3% and specificity of 93.3% for the degree of grinding. The degree of food bolus aggregation had a sensitivity of 45.0% and specificity of 90.6%, and aspiration had a sensitivity of 25.0% and specificity of 84.5%, both of which showed high specificity. CONCLUSIONS: The results of this study suggested that the SST might be simple and useful for identifying patients with dysphagia who are able to masticate, even if they do not eat foods that need chewing and could be used before starting these patients on foods that need chewing.

Molecular alterations of newly formed mandibular bone caused by zoledronate.

Bone quality is defined by structural and material characteristics. Most studies on the mandible have focused on the analysis of structural characteristics, with insufficient investigation of material characteristics. This study tested whether zoledronate affects the material characteristics of newly formed mandibular bone. Thirty-six female Wistar rats were assigned to three groups: sham-ovariectomized rats (SHAM, n=12), ovariectomized rats (OVX, n=12), and ovariectomized rats treated with zoledronate (ZOL, n=12). The left side of the mandibular ramus of all rats was drilled bicortically. Twenty-eight days after surgery, all surviving rats were euthanized and all mandibles were removed. Raman microspectroscopy was performed, and five spectra per specimen of newly formed mandibular bone were analysed. Compared with OVX rats, the mineral/matrix ratio in ZOL rats was significantly increased (5.43±1.88 vs. 7.86±2.05), while crystallinity (0.055±0.002 vs. 0.050±0.002), relative proteoglycan content (0.43±0.10 vs. 0.31±0.05), and collagen structural integrity (1.16±0.21 vs. 0.72±0.06) were significantly decreased. These changes in material characteristics may explain why rats that received zoledronate exhibited peculiar biological phenomena such as bisphosphonate-related osteonecrosis of the jaw.

Remodeling of neutrophil phospholipids with 15(S)-hydroxyeicosatetraenoic acid inhibits leukotriene B4-induced neutrophil migration across endothelium.

5-Lipoxygenase products, such as leukotrienes, are important stimuli for leukocyte-mediated tissue injury in acute inflammation. 15-Hydroxyeicosatetraenoic acid (15-HETE) is an eicosanoid generated by a variety of cell types via the actions of 15-lipoxygenases and, in addition, cyclooxygenases and epoxygenases. 15-HETE levels are frequently elevated at sites of inflammation, and extracellular 15(S)-HETE is esterified rapidly into neutrophil (PMN) phospholipids in vitro to levels that are comparable with arachidonic acid. We present evidence that remodeling of PMN phospholipids with 15(S)-HETE stereoselectively inhibits PMN migration across endothelium in response to leukotriene B4 (LTB4) and other chemoattractants. Esterified 15(S)-HETE causes a striking reduction in the affinity of LTB4 cell-surface receptors for their ligand and inhibition of LTB4-triggered stimulus-response coupling. As a result of these actions, esterified 15(S)-HETE attenuates the cytoskeletal rearrangements and CD11/CD18-mediated adhesive events that subserve directed locomotion of PMN across endothelium. These observations indicate that products of the 5-lipoxygenase and 15-lipoxygenase pathways can exert counterbalancing influences on PMN trafficking across endothelium. They suggest that 15(S)-HETE may be a potent endogenous inhibitor of PMN-endothelial interactions in vivo and serve to limit or reverse acute inflammation.

Cementless total hip replacement after previous intertrochanteric valgus osteotomy for advanced osteoarthritis.

We present a series of 30 uncemented total hip replacements performed between June 1985 and January 2002 with a mean follow-up of seven years (5 to 20) in 27 patients who had previously undergone a valgus intertrochanteric osteotomy. No further osteotomy was undertaken to enable hip replacement. We used a number of uncemented modular or monoblock femoral components, acetabular components and bearings. The patients were followed up clinically and radiologically. We report 100% survival of the femoral component. One acetabular component was revised at five years post-implantation for aseptic loosening. We noted cortical hypertrophy around the tip of the monoblock stems in six patients. We believe that modular femoral components should be used when undertaking total hip replacement in patients who have previously undergone valgus femoral osteotomy.

A case of gain-of-function mutation in calcium-sensing receptor: supplemental hydration is required for renal protection.

AIMS: The calcium-sensing receptor (CaSR) regulates the extracellular calcium level, mainly by controlling parathyroid hormon secretion and renal calcium reabsorption. In gain-of-function CaSR mutations, the genetic abnormalities increase CaSR activity leading to the development of such clinical manifestations as hypercalciuric hypocalcemia and hypoparathyroidism. We report a Japanese case of CaSR gain-of-function mutation and represent a therapeutic intervention based on the functional characteristics of CaSR in renal tubule. METHODS AND RESULTS (CASE): DNA sequence analysis revealed a heterozygous G to T mutation identified in a 12-year-old Japanese girl presenting with sporadic onset of hypercalciuric hypocalcemia and hypoparathyroidism. The mutation is located in the N-terminal extracellular domain of the CaSR gene, one of the most important parts for the three-dimensional construction of the receptor, resulting in the substitution of phenylalanine for cysteine at amino acid 131 (C131F) in exon 3. Based on the diagnosis of the gain-of-function mutation in the CaSR, oral hydrochlorothiazide administration and supplemental hydration were started in addition to calcium supplementation. The combination therapy of thiazide and supplemental hydration markedly reduced both renal calcium excretion and urinary calcium concentration from 0.4-0.7 to less than 0.1 mg/mg (urinary calcium/creatinine ratio) and from 10-15 to 3-5 mg/dl (urinary calcium concentration), respectively. This therapy stopped the progression of renal calcification during the follow-up period. CONCLUSION: Supplemental hydration should be considered essential for the following reasons: (1) calcium supplementation activates the CaSR in the kidney and suppresses renal urinary concentrating ability, (2) the thiazide has a diuretic effect, (3) as calcium supplementation increases renal calcium excretion, the supplemental hydration decreases urinary calcium concentration by increasing urinary volume, thereby diminishing the risk of intratubular crystallization of calcium ion.

Modeling the pressure inactivation dynamics of Escherichia coli.

Escherichia coli, as a model microorganism, was treated in phosphate-buffered saline under high hydrostatic pressure between 100 and 300 MPa, and the inactivation dynamics was investigated from the viewpoint of predictive microbiology. Inactivation data were curve fitted by typical predictive models: logistic, Gompertz and Weibull functions. Weibull function described the inactivation curve the best. Two parameters of Weibull function were calculated for each holding pressure and their dependence on holding pressure was obtained by interpolation. With the interpolated parameters, inactivation curves were simulated and compared with the experimental data sets.

Prognosis of isolated systolic and isolated diastolic hypertension as assessed by self-measurement of blood pressure at home: the Ohasama study.

BACKGROUND: Although the clinical significance of systolic-diastolic hypertension and isolated systolic hypertension has been established, the significance of isolated diastolic hypertension has not been fully investigated. OBJECTIVE: To clarify the prognostic significance of isolated systolic and isolated diastolic hypertension as assessed by self-measurement of blood pressure (BP) at home (home BP measurements), which has a better reproducibility and prognostic value than casual BP measurements in the general population. SUBJECTS AND METHODS: We obtained home BP measurements for 1913 subjects aged 40 years or older, then followed up their survival status (mean, 8.6 years). We classified the subjects into the following 4 groups according to their home BP levels: systolic-diastolic hypertension, isolated systolic hypertension, isolated diastolic hypertension, and normotension. The prognostic significance of each type of hypertension for the risk of cardiovascular mortality risk was investigated using a Cox proportional hazards regression model adjusted for possible confounding factors. RESULTS: The risk for isolated systolic hypertension and systolic-diastolic hypertension were significantly higher than the relative hazard for normotension, while isolated diastolic hypertension was associated with no significant increase in risk. Home pulse pressure measurement was also independently associated with an increase in the risk of cardiovascular mortality. CONCLUSIONS: Isolated diastolic hypertension, as assessed by home BP measurements, carried a low risk of cardiovascular mortality, similar to that found in subjects with normotension, suggesting that the prognosis of hypertension would be improved by treatment focused on systolic rather than on diastolic home BP measurements. To our knowledge, this study is the first to demonstrate the clinical significance of pulse pressure as assessed by home BP measurement. Arch Intern Med. 2000;160:3301-3306.

Retinoic acids and thyroid hormone act synergistically with dexamethasone to increase growth hormone-releasing hormone receptor messenger ribonucleic acid expression.

The effects of all-trans-retinoic acid (RA), 9-cis-retinoic acid (9cRA), and thyroid hormone (T3) on GH-releasing hormone receptor (GHRH-R) messenger RNA (mRNA) expression were studied using ribonuclease protection assay in the fetal rat pituitary gland and in MtT/S cells, a clonal GH cell line derived from an estrogen-induced somatotropic tumor in the rat. Although RA (1 microM), 9cRA (1 microM), or T3 (1 nM) alone showed little effect on GHRH-R mRNA expression in the MtT/S cells, each of these substances was found to act synergistically with dexamethasone (DEX; 500 nM) to increase GHRH-R mRNA expression. The effects of RAs and T3 were dose dependent, with maximum effects observed at 1 microM and 1 nM, respectively. The maximum effect of RAs or T3 was not further augmented by the addition of T3 or RAs, respectively. No apparent differences were observed in this study between the actions of RA and 9cRA. The Northern analyses showed that MtT/S cells express retinoic acid receptor alpha2 mRNA and thyroid hormone receptor beta2 mRNA, and DEX did not affect the levels of these mRNAs. This suggests that the role of DEX in enabling RAs or T3 to up-regulate GHRH-R mRNA levels is not an induction of the expression of each specific receptor for RAs and T3. The similar enhancement of DEX induction of GHRH-R mRNA by RAs or T3 was also observed in the fetal rat pituitary gland in culture, suggesting that RA and/or T3 is involved in the mechanisms responsible for the developmentally regulated expression of GHRH-R mRNA.

Effect of dexamethasone on growth hormone (GH) response to growth hormone releasing hormone in acromegaly.

The effect of dexamethasone on the GH response to GH-releasing hormone (GHRH) was studied in vivo in six patients with acromegaly as well as in vitro in monolayer cultures of GH-secreting pituitary tumor cells obtained from three of these patients. Oral administration of 9 mg/day dexamethasone for 2 days decreased plasma GH responses to iv injection of 100 micrograms GHRH-(1-44 amide) in all six patients. Blood glucose levels were significantly increased, while plasma somatomedin-C levels were significantly decreased by this regimen of dexamethasone treatment. On the other hand, 2-day pretreatment with 50 nM dexamethasone of monolayer cultures of pituitary adenoma cells potentiated GH release basally and/or in response to 100 pM to 1 nM GHRH in vitro. These results indicate that the potentiating action of 2-day treatment of dexamethasone in vitro is overwhelmed in vivo by some extra-pituitary action, probably on the central nervous system, of glucocorticoids in patients with acromegaly.

The SixA phospho-histidine phosphatase modulates the ArcB phosphorelay signal transduction in Escherichia coli.

The Escherichia coli SixA protein is the first discovered prokaryotic phospho-histidine phosphatase, which was implicated in a His-to-Asp phosphorelay. The sixA gene was originally identified as the one that interferes with, at its multi-copy state, the cross-phosphorelay between the histidine-containing phosphotransmitter (HPt) domain of the ArcB anaerobic sensor and its non-cognate OmpR response regulator. Nevertheless, no evidence has been provided that the SixA phosphatase is indeed involved in a signaling circuitry of the authentic ArcB-to-ArcA phosphorelay in a physiologically meaningful manner. In this study, a SixA-deficient mutant was characterized with special reference to the ArcB signaling, which allows E. coli cells to respond to not only external oxygen, but also certain anaerobic respiratory conditions. Here evidence is provided for the first time that the SixA phosphatase is a crucial regulatory factor that is involved in the ArcB signaling, particularly, under certain anaerobic respiratory growth conditions. We propose a novel mechanism, involving an HPt domain and a phospho-histidine phosphatase, by which a given multi-step His-to-Asp signaling can be modulated.

MARCKS, a major protein kinase C substrate, assumes non-helical conformations both in solution and in complex with Ca2+-calmodulin.

MARCKS, a major cellular substrate for protein kinase C, plays important roles in various cellular functions and its functions are regulated by calmodulin. We have studied the conformational properties of recombinant human MARCKS in solution and in complex with calmodulin. Circular dichroism (CD) spectra showed a high content of random coil in physiological solution. When MARCKS or MARCKS-derived calmodulin-binding peptide was complexed with Ca2+-calmodulin, little change was observed in the CD spectra, suggesting that MARCKS binds with calmodulin in a non-helical conformation, which is unique among the calmodulin-binding proteins.

Achievement of renaturation of subtilisin BPN' by a novel procedure using organic salts and a digestible mutant of Streptomyces subtilisin inhibitor.

The pro-sequences of proteases have been considered to be required for the refolding of denatured proteases. However, here we report achievement of almost complete restoration of enzymatic activity of subtilisin BPN' in the absence of its pro-sequence. The presence of 2 M potassium acetate in the folding medium enhanced the refolding efficiency of guanidine hydrochloride (GdnHCl)-denatured subtilisin BPN' by up to 28%, and other organic salts were also found to be useful, suggesting that general contribution of the bulky hydrophobic moieties of the salts to the formation of a favorable environment required for folding. This finding will provide new insights into the folding mechanisms not only of proteases but also of various other proteins. Almost complete restoration of enzymatic activity of denatured subtilisin in the organic salt solution was accomplished by further addition of mutated Streptomyces subtilisin inhibitor (SSI), which had been converted to a digestible temporary inhibitor by removal of the disulfide bridge near the reactive site.

Renaturation of the mature subtilisin BPN' immobilized on agarose beads.

We report here another example of renaturation of subtilisin BPN'(Sbtl) by using an immobilized preparation instead of applying a digestible mutant of Streptomyces subtilisin inhibitor (SSI), a proteinaceous inhibitor of Sbtl [M. Matsubara et al. (1994) FEBS Letters 342, 193-196]. The mature Sbtl was immobilized on agarose beads employing the amino group of the protein. After thorough washing, the immobilized Sbtl was subjected to denaturation in 6 M guanidine hydrochloride (GdnHCl) at pH 2.4 for 4 h, followed by renaturation in 2 M potassium acetate at pH 6.5 for 24 h. This denaturation/renaturation cycle was repeated five times. The recovered activity of the renatured immobilized Sbtl settled at a constant level after the third denaturation/renaturation cycle, demonstrating that almost 100% renaturation was attained by use of the immobilized Sbtl. This immobilized Sbtl preparation could well be utilized for the mechanistic study of protein folding. We then found that 2 M potassium acetate was superior to 2 M potassium chloride as a refolding medium and that the ability of SSI to induce the correct shape of the mature Sbtl was lacking in several refolding media in both thermodynamic and kinetic criteria. Thus the main cause for the increase of refolding yield of Sbtl by coexistence of SSI was prevention of the autolysis of Sbtl.