Differences in pain thresholds elicited by intraoral electrical stimuli between individuals with and without diabetes mellitus.

There is little evidence of sensation in individuals with diabetes mellitus (DM) in the dental research field. We investigated whether pain thresholds (PTs) differ between individuals with and without DM (non-DM; NDM). To this end, we assessed whether PTs obtained from the oral cavity, hands, and feet differed from each other and across groups, and whether PTs differed for the three current frequencies used for testing (2000 Hz, 250 Hz, and 5 Hz). Pain threshold measurements were obtained from the oral mucosa and the tips of the fingers and toes of 56 volunteers, including 21 individuals with DM (12 men and 9 women, average age: 72.1 ± 4.7 years) and 35 NDM individuals (17 males and 18 females, average age: 51.2 ± 23.9 years) using the Neurometer CPT/C® device to deliver electrical stimulation. A single operator obtained PT measurements from around the left greater palatine foramen and from the tip of the left first finger and of the left great toe. Individuals with DM had significantly lower PT values than those without DM. The PT values for the oral cavity, hands, and feet differed significantly from each other (foot > hand, foot > oral cavity, hand > oral cavity). Moreover, there was a significant difference in the PT values for 5 Hz and 2000 Hz, as well as for 250 Hz and 2000 Hz. This study concluded that PT values derived from DM participants are lower than those from NDM participants, although PT measurements varied across regions and with current frequency.

Potential for acceleration of bone formation after implant surgery by using a dietary supplement: an animal study.

Dental implant treatment is an effective modality to restore lost aesthetic and masticatory functions. However, healing after implant surgery takes at least 3-6 months. This prolonged healing period poses several difficulties for individuals with a large edentulous area and decreases their quality of life. Consequently, shortening the healing period and accelerating final prosthesis placement after surgery is very clinically important. Peri-implant bone formation may be enhanced by systemic approaches, such as the use of osteoporosis supplements, to promote bone metabolism. To confirm whether intake of a supplement developed for osteoporosis, synthetic bone mineral (SBM), was effective in accelerating peri-implant bone formation as part of the healing process after implantation. Twenty-four 5-week-old female Wistar rats were randomly assigned to receive a standardised diet without (control group, n = 12) or with SBM (n = 12). The rats had implant surgery at 8 weeks of age under general anaesthesia. The main outcome measures were bone mineral density (BMD) and pull-out strength in the implant and femur, which were compared between the groups at 2 and 4 weeks after implantation using the Mann-Whitney U test. BMD was significantly greater in the SBM group at 2 and 4 weeks after implantation compared to the control group. Pull-out strength was significantly greater in the SBM groups at 2 and 4 weeks after implantation compared to the control group. This study demonstrated that SBM could be effective in accelerating peri-implant bone formation during the healing period after implantation.

Reliability of pain tolerance threshold testing by applying an electrical current stimulus to the alveolar ridge.

The purpose of this study was to assess the reliability of testing pain tolerance threshold (PTT) by applying an electrical current stimulus to the alveolar ridge. Twenty volunteers studying or working at the Nihon University School of Dentistry at Matsudo participated in this study. Participants were seated comfortably on a dental chair in a quiet room during testing. A single operator obtained mucosal PTT measurements around the right greater palatine foramen using a Neurometer CPT/C(®) device (Neurotron Inc., Baltimore, MD, USA) to deliver electrical stimulation at frequencies of 5, 250 and 2000 Hz. The participant released a button to automatically discontinue the stimulus when it could no longer be tolerated. Two types of factors were confirmed: the consistency of repeated measurements and a potential carry-over effect on PTTs. The consistency and carry-over effects of pain with regard to PTT measurements were analysed via Cronbach's coefficient α. The Cronbach's coefficient α of PTTs calculated more than 6 days of PTT testing at 5, 250 and 2000 Hz was 0.97, 0.95 and 0.97, respectively, suggesting that the consistency of the measurements was excellent. The Cronbach's coefficient α calculated when the three frequencies of 5, 250 and 2000 Hz were applied in different orders was 0.91, 0.87 and 0.90, respectively, suggesting no carry-over effect. In conclusion, the measurement of PTTs at the alveolar ridge as assessed by applying an electrical current stimulus with an electro-diagnostic device exhibited excellent reliability, and thus, it constitutes a widely available option for PTT measurement in the clinical setting.

Effect of dentist's clinical experience on treatment satisfaction of a complete denture.

The relationship between the prosthodontic experience of dentists and satisfaction of complete denture wearers remains unknown. To investigate whether a prosthodontist's clinical experience affects treatment satisfaction of a complete denture wearer. From April 2004 to July 2006, we conducted a randomised controlled trial at two centres, including 74 edentulous patients; of these, 32 and 30 were randomly allocated to the ED or ID group, respectively. All the patients rated their satisfaction with dentures, including general satisfaction and satisfaction of chewing ability, speaking, cleaning, stability, retention, comfort and aesthetics. These satisfaction ratings were measured by a 100-mm visual analog scale (VAS). Perceived chewing ability to foods, divided into five grades, was measured using a questionnaire. The mastication index (MI) was calculated for each grade. General satisfaction and satisfaction of speaking, stability and retention were significantly higher in the ED than in the ID group (P = 0·049, 0·003, 0·019 and 0·041, respectively). No significant difference existed between the MI of the ED (71·3 ± 18·4) and ID group (64·1 ± 16·53). However, the perceived chewing ability of grade 5 food, whose texture was the hardest among all the grades, was significantly higher in the ED group than in the ID group. Within its limitations, this study showed that a clinician's prosthodontic experience affects a complete denture wearer's satisfaction ratings.

Subjective Evaluation of Denture Adhesives: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Many reports show that denture adhesives improve the retention and stability of dentures. However, few randomized controlled trials have examined the effects of denture adhesives. OBJECTIVE: This 10-center randomized controlled trial with parallel groups involving 200 edentulous patients wearing complete dentures aimed to evaluate the effects of short-term use of cream and powder denture adhesives. METHODS: Patients were allocated into 2 cream- and powder-type adhesive groups and 1 control group. Intervention groups were treated with the 2 adhesives (1 each), and the control group received saline solution. Adhesive or control was applied to the denture-mucosal surface for 4 d, and data at baseline and after day 4 of intervention (i.e., 8 meals) were obtained. Patient satisfaction was evaluated with a 100-mm visual analog scale. Oral health-related quality of life was measured with the Japanese version of the Oral Health Impact Profile for Edentulous Patients. Perceived chewing ability was evaluated by a questionnaire regarding ease of chewing and swallowing food. Between-group comparisons were performed with Kruskal-Wallis tests with the Mann-Whitney U test adjusted by Bonferroni correction. Within-group comparisons of pre- and postintervention measurements were performed with the Wilcoxon signed-rank test. Intention-to-treat analysis was also performed. RESULTS: Between-group comparisons showed no significant differences for general satisfaction or Oral Health Impact Profile for Edentulous Patients. However, significant differences in satisfaction with various denture functions with cream- and powder-type adhesives were seen in pre- and postintervention comparisons (P < 0.05). Significant differences were also observed for perceived chewing ability of hard foods (P < 0.05). CONCLUSION: These results suggest that although denture adhesives do not invariably improve denture function, they do affect subjective evaluations and possibly chewing of hard foods. Therefore, the effects of denture adhesive use are insufficient to resolve any fundamental dissatisfaction with dentures ( ClinicalTrials.gov NCT01712802 ). KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that denture adhesives should be applied under certain conditions; however, an appropriate diagnosis is important before application. These practice-based data provide information to establish evidence-based guidelines for applying denture adhesives.

Asymptomatic hypoesthesia of the maxillary alveolar ridge in complete denture wearers.

This study was carried out to investigate the effect of compression induced by complete dentures on the function of the nerves underlying the dentures. The influence of compression induced by complete dentures on nerve function was analysed using current perception threshold (CPT) in 33 complete denture wearers aged 50-80 at Nihon University School of Dentistry (Matsudo, Japan). Based on the age range of the complete denture group, dentate subjects were selected as a control. Because the group characteristics (such as subject age, gender, body mass index) and oral mucosal thickness were not matched, a multiple regression analysis was used to adjust for the influence of heterogeneous characteristics on the CPT. Statistically significant differences were found between subject groups for the nasopalatine and the greater palatine nerve. The results of the study were that complete denture wearers experience asymptomatic hypoesthesia mainly affecting the nasopalatine and greater palatine nerves, but not the infraorbital nerve.

Regulation of striatal dopamine responsiveness by Notch/RBP-J signaling.

Dopamine signaling is essential for reward learning and fear-related learning, and thought to be involved in neuropsychiatric diseases. However, the molecular mechanisms underlying the regulation of dopamine responsiveness is unclear. Here we show the critical roles of Notch/RBP-J signaling in the regulation of dopamine responsiveness in the striatum. Notch/RBP-J signaling regulates various neural cell fate specification, and neuronal functions in the adult central nervous system. Conditional deletion of RBP-J specifically in neuronal cells causes enhanced response to apomorphine, a non-selective dopamine agonist, and SKF38393, a D1 agonist, and impaired dopamine-dependent instrumental avoidance learning, which is corrected by SCH23390, a D1 antagonist. RBP-J deficiency drastically reduced dopamine release in the striatum and caused a subtle decrease in the number of dopaminergic neurons. Lentivirus-mediated gene transfer experiments showed that RBP-J deficiency in the striatum was sufficient for these deficits. These findings demonstrated that Notch/RBP-J signaling regulates dopamine responsiveness in the striatum, which may explain the mechanism whereby Notch/RBP-J signaling affects an individual's susceptibility to neuropsychiatric disease.

Maternal Separation Induces Orofacial Mechanical Allodynia in Adulthood.

It is well known that exposure to maternal separation (MS) in early life causes plastic changes in the nervous system in adulthood, occasionally resulting in ubiquitous chronic pain. However, the pathogenic mechanisms of pain hypersensitivity remain unclear. Here, the authors examined the involvement of corticosterone in orofacial mechanical hypersensitivity induced by MS. To establish a rat model of MS, pups were placed in isolated cages 180 min/d and kept in a temperature-controlled environment at 22 ± 2 °C for 14 d. Mechanical allodynia in the whisker pad skin in adulthood was induced by MS and was significantly suppressed by successive postnatal subcutaneous administration of the glucocorticoid receptor antagonist mifepristone. Corticosterone levels were increased in the serum of MS rats, and successive postnatal administration of subcutaneous corticosterone to naive rats induced mechanical allodynia in the whisker pad skin. The number of P2X3 receptor-immunoreactive (P2X3R-IR) trigeminal ganglion (TG) neurons innervating the whisker pad skin was significantly increased in MS rats and decreased following subcutaneous administration of mifepristone. The number of P2X3R-IR TG neurons innervating the whisker pad skin was also significantly increased following successive postnatal administration of subcutaneous corticosterone in naive rats. Moreover, the mechanical allodynia was suppressed 30 min after administration of the P2X3R antagonist A317491 to the whisker pad skin in MS rats. These findings suggest that the increase in P2X3R-IR TG neurons innervating the whisker pad skin via enhanced neonatal corticosterone signaling by MS plays an important role in orofacial mechanical allodynia in adulthood.

The effect of glucocorticoid on the synthesis of biglycan and decorin in human osteoblasts and bone marrow stromal cells.

We have previously demonstrated that glucocorticoids induce differentiation of human bone marrow stromal cells (BMSC) into cells expressing mature osteoblast phenotype. As glucocorticoids have marked effects on extracellular matrix protein synthesis in bone, and because proteoglycans are important components of bone matrix and may condition the differentiation and biological activities of osteoblasts, we studied the effects of dexamethasone (Dex) on the synthesis of small proteoglycans [decorin (DCN) and biglycan (BGN)] in adult human BMSC and human osteoblasts (HOB). First passaged HOB and BMSC were treated with either ethanol or 10(-7) M Dex for 7 days. After treatment, the cells were metabolically labeled with either [35S]SO4 alone or [35S]SO4 and [3H]leucine together for 24 h. Conditioned media were collected, and cell layers were extracted with 4 M guanidine HCl. The extracts and conditioned media were subjected to gel filtration and ion exchange chromatography. Fractions containing radiolabeled proteoglycans were analyzed either directly or after immunoprecipitation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Dex treatment resulted in a dramatic increase in DCN and an associated decrease in BGN in both the conditioned medium and the cell layer of HOB cultures. In Dex-treated BMSC cultures, BGN was decreased in both the conditioned medium and cell layer, whereas DCN was stimulated in the majority of cultures. Northern blot analysis indicated that steady state messenger RNA (mRNA) concentration of DCN was increased by Dex in all of the HOB cultures and in seven of eight BMSC cultures analyzed. The steady state mRNA level of BGN was decreased by Dex in both HOB and BMSC cultures. The regulation of DCN and BGN mRNA by Dex in both HOB and BMSC (when responsive) was dose dependent. Time-course analysis indicated that as little as 1 day of treatment with Dex was sufficient to decrease BGN mRNA and increase DCN mRNA (when observed) levels in BMSC; the regulation spanned a 4-week interval, during which the extracellular matrix of BMSC was mineralized. The effect of Dex on the steady state mRNA levels of DCN and BGN in HOB was also apparent after 1 day of treatment. These accumulated results suggest that Dex modulates the synthesis of small proteoglycans in both human bone marrow stromal osteoprogenitor cells and mature osteoblasts.

Plasma endothelin levels in hypertension and chronic renal failure.

Endothelin-1 is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-1, plasma levels of immunoreactive endothelin-1 were measured in 32 research subjects with normal renal function (21 normal subjects and 11 patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-1 levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-1 levels than normal subjects (2.29 +/- 1.09 vs. 1.41 +/- 0.50 pg/ml, p less than 0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n = 17) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 7) (3.08 +/- 3.43 vs. 0.73 +/- 0.34 pg/ml, p less than 0.05), and the hemodialyzed hypertensive group (n = 18) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 33) (2.66 +/- 1.92 vs. 1.35 +/- 0.73 pg/ml, p less than 0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-1 levels. These data suggest that circulating endothelin-1 may be partly involved in the development or maintenance of hypertension in humans.

Induction of manganese superoxide dismutase by thyroid stimulating hormone in rat thyroid cells.

Alterations in the superoxide dismutase (SOD) content of thyroid tissues occurring in association with thyroid dysfunction have been reported. In this study, the Mn-SOD content was found to increase in thyroid tissues of rats administered thyroid stimulating hormone (TSH) and in thyrocytes cultured in medium supplemented with TSH. Furthermore, in the thyroid glands of rats whose serum TSH level was elevated by inhibiting the synthesis of T3 and T4 by 6-methyl-2-thiouracil, the Mn-SOD increased as the TSH concentration increased. In the cultured thyrocytes, the increase in Mn-SOD induced by TSH was inhibited by the C-kinase inhibitor H7. These findings suggest the induction of Mn-SOD by TSH in thyroid cells and point to a role of C-kinase in this process, thereby indicating that a close relationship exists between the serum TSH level and the change in Mn-SOD content in thyrocytes with thyroid dysfunction.

Synthesis and antiarrhythmic activity of new 1-[1-[2-[3-(alkylamino)-2-hydroxypropoxy]phenyl]vinyl]-1 H-imidazoles and related compounds.

Various 1-[1-[2-[3-(alkylamino)-2-hydroxypropoxy]phenyl]vinyl]-1 H-azoles were synthesized and investigated for beta-adrenoceptor-blocking and antiarrhythmic activities. Although no compounds showed more potent beta-blocking effects than propranolol in the isolated guinea pig right atria, many compounds exhibited significant antiarrhythmic effects against aconitine or ischemic arrhythmia in mice or dogs. 1-[2,5-Dichloro-6-[1-(1H-imidazol-1-yl)-ethenyl] phenoxy]-3-[(1-methylethyl)amino]-2-propanol hydrochloride (48) (711389-S) was selected as a candidate for clinical evaluation in man, since its antiarrhythmic effects were superior to those of quinidine, disopyramide, or propranolol. Asymmetric synthesis of (R)-(+)- and (S)-(-)-48 is described, and it is proven that there is no stereospecificity in the antiarrhythmic effect of 48.

Pharmacologic stimulation of adenosine A2 receptor supplants ischemic preconditioning in providing ischemic tolerance in rat livers.

BACKGROUND: Ischemic preconditioning (IPC) is a promising strategy for conferring ischemic tolerance. We confirmed the acquisition of ischemic tolerance in the liver immediately after IPC and the role of adenosine kinetics in this process. METHODS: Male Lewis rats were used. IPC was administered with a 10-minute ischemia followed by a 10-minute reperfusion. Ischemic tolerance was tested with a 45-minute ischemia. Changes in the adenosine concentrations in liver tissue were evaluated, and the effects of adenosine A1 or A2 receptor agonists or antagonists were examined either in place of or against IPC. RESULTS: The 7-day animal survival was significantly better in the IPC group than in the control group (87% vs 53%; n = 15, P < .05). The release of liver-related enzymes during reperfusion was suppressed better in the IPC group (P < .01). Recovery of adenosine triphosphate levels was faster in the IPC group (P < .01). After IPC, adenosine concentrations in liver tissue immediately increased to 1555 +/- 299 pmol/g wet tissue and were maintained at that level during a subsequent 45-minute ischemia. The ischemic tolerance generated by IPC was mimicked by the administration of adenosine A2 receptor agonist and opposed by adenosine A2 receptor antagonist. CONCLUSIONS: The ischemic tolerance of the liver immediately after IPC can be supplanted by selective pharmacologic stimulation of adenosine A2 receptors.

Distortion behavior of heat-activated acrylic denture-base resin in conventional and long, low-temperature processing methods.

There have been many reports on fatal distortion of heat-activated acrylic denture-base resin which is still widely used in the field of removable prosthodontics. However, these reports have failed to report quantitatively on polymerization and thermal shrinkage factors. In the present study, we attempted to verify that the shrinkage of heat-activated acrylic denture-base resin was caused mainly by thermal contraction after processing. Furthermore, we examined the degree of distortion resulting from long, low-temperature processing, and compared the results with that of the conventional method. The strain gauge and thermo-couple were embedded in a specimen at the time of resin packing. The measurement started from the beginning of processing and continued until the specimen was bench-cooled and immediately before and after it was de-flasked, as well as during seven-day immersion in water at 37 degrees C. The resin expanded when processed by the conventional method. Meanwhile, mild shrinkage, possibly polymerization shrinkage, was observed when the resin was processed by the low-temperature method. This suggested that polymerization shrinkage was compensated for by thermal expansion during processing by the conventional method. Moreover, the shrinkage strains in the period from the completion of processing to immediately after de-flasking, in both the conventional and low-temperature methods, were identical to the theoretical value of thermal shrinkage which we obtained by multiplying the linear coefficients of thermal expansion by temperature differences. The shrinkage strain in the specimen processed by the low-temperature method, measured from the end of processing to immediately after de-flasking, averaged 64% of that in the specimen processed by the conventional method. The results revealed quantitatively that the shrinkage of heat-activated acrylic denture-base resin was mainly thermal shrinkage, and demonstrated the advantage of the low-temperature method in reducing thermal shrinkage.

Sarcoidosis with membranous nephropathy and granulomatous interstitial nephritis.

A 49-year-old woman, who had been diagnosed as sarcoidosis based on bilateral hilar lymphadenopathy and lung biopsy, presented increased serum creatinine and calcium concentrations. Renal biopsy showed the presence of interstitial nephritis with non-caseating epithelioid granuloma and focal membranous transformation. Therapy with prednisolone was effective in normalizing serum creatinine, serum calcium, serum angiotensin converting enzyme, and urine beta2 microglobulin, but these abnormalities reappeared after rapid withdrawal of prednisolone. This is a rare case of sarcoidosis manifested by both membranous nephropathy and granulomatous interstitial nephritis, and indicates the necessity of long-term treatment of corticosteroid.

Studies of an aspect of renal function with the aid of dynamic CT and renogram.

Dynamic CT scans were conducted on 94 persons who had been randomly selected among the patients and the volunteers. The test results were used to obtain the time-density curve. A part of the subjects (20 cases) underwent the renogram examination for the comparative studies. The cortico-aortic (CA) ratio derived from the time-density curve demonstrated good correlation between the dynamic CT and the renal function (r = 0.68). When the dynamic CT studies and the renogram were compared, the vascular phase of the renogram showed strong correlation with CA ratio. Consequently the dynamic CT study the CA ratio was believed to demonstrate the renal function.

Quantitative measurement of portal blood flow by magnetic resonance phase contrast: comparative study of flow phantom and Doppler ultrasound in vivo.

A non-invasive method for measuring portal blood flow by magnetic resonance (MR) phase contrast was evaluated in a flow phantom and 20 healthy volunteers. In a flow phantom study, the flow volumes and mean flow velocities measured by MR phase contrast showed close correlations with those measured by electromagnetic flowmetry. In 20 healthy volunteers, the cross-sectional areas, flow volumes and mean flow velocities measured by MR phase contrast correlated well with those measured by the Doppler ultrasound method. Portal blood flow averaged during the imaging time could be measured under natural breathing conditions by using a large number of acquisitions without the limitations imposed on the Doppler ultrasound method. MR phase contrast is considered to be useful for the non-invasive measurement of portal blood flow.

A comparative study of dynamic CT and ultrasonic pulsed Doppler method for estimation of the portal blood flow.

A new dynamic CT method for evaluating the portal blood flow is described. Thirty healthy volunteers were injected with non-ionic hypo-osmotic iodine contrast medium to estimate the portal blood flow. Time density curves (TD-curves) for the abdominal aorta and the main trunk of the portal vein were determined on the basis of data obtained by dynamic CT. From the TD-curves, portal blood flow coefficient and circulation time to flow into the portal vein (P-P time) were calculated. More detailed data of the TD-curves could be obtained by the new dynamic CT than by the previous methods. Subjects were simultaneously studied by an ultrasonic pulsed Doppler method which has been clinically accepted. There was a significant correlation between our dynamic CT method (portal blood flow coefficient) and the ultrasonic pulsed Doppler method concerning the measurement of portal blood flow. Therefore, it may be concluded that this CT method is reliable and clinically acceptable.

Comparative effects of vitamin K2 and estradiol on experimental arteriosclerosis with diabetes mellitus.

In order to further investigate the radical scavenging and anti-arteriosclerotic activities of vitamin K2 and estradiol, the comparative effects of vitamin K2 and estradiol on aortic calcium (Ca) and inorganic phosphorus (P) levels in the aorta and the elastin fraction (fr.) were investigated in male rats after experimental arteriosclerosis with diabetes mellitus was induced by vitamin D2 and radical producing substance, streptozotocin (STZ). Pharmacological dose of vitamin K2 (100 mg/kg b.w.) and medical dose of estradiol (83 micrograms/kg b.w.) suppressed the increased serum glucose, and vitamin K2 and estradiol increased the decrease in serum insulin. Moreover, vitamin K2 and estradiol inhibited the increase of Ca and P in the aorta and the elastin fr. Vitamin K2 and estradiol decreased the increase in serum lipid peroxide (LPO). It is suggested that both the pharmacological dose of vitamin K2 and medical dose of estradiol suppressed the development of arteriosclerosis associated with diabetes mellitus, owing to radical scavenging activity of vitamin K2 and estradiol.

Study on cathepsin B activity in human thyroid tumors.

Cathepsin B activity was measured in human thyroid tissue obtained surgically from 2 patients with Grave's disease, 3 with follicular adenoma, 4 with papillary carcinoma, and 4 with follicular carcinoma. Three normal thyroid tissues were also studied. Comparisons were made between cathepsin B activity and clinical findings, including histopathological diagnosis and the presence or absence of extra-capsular invasion and metastasis. The abilities of original tumors to degrade type I and type IV collagen were also measured. Mean cathepsin B activities of both specimens with benign and those with malignant disease were significantly higher than those of normal thyroid. On cases of thyroid carcinoma, those with extra-capsular invasions and metastasis had the highest cathepsin B activities. Cases with high cathepsin B activities also tended to show high type I and IV collagen degrading abilities. These findings suggest that cathepsin B plays a role in the development of extra-capsular invasion and lymph node metastasis in human thyroid tumors.