Phase transformation behaviour and bending properties of hybrid nickel-titanium rotary endodontic instruments.

AIM: To investigate the bending properties of hybrid rotary nickel-titanium endodontic instruments in relation to their transformation behaviour. METHODOLOGY: Four types of nickel-titanium rotary endodontic instruments with different cross-sectional shapes (triangular-based and rectangular-based) and different heat treatment conditions (super-elastic type and hybrid type with shape memory effect) were selected to investigate bending properties and phase transformation behaviour. Bending load of the instruments was measured in a cantilever-bending test at 37 degrees C with the maximum deflection of 3.0 mm. A commercial rotary instrument, ProFile (PF; Dentsply Maillefer, Ballaigues, Switzerland) was used as a reference for the bending test. Phase transformation temperatures were calculated from the diagrams obtained from differential scanning calorimetry. Data were analysed by anova and Scheffe's test. RESULTS: The bending load values of the hybrid type that had undergone additional heat treatment at the tip were significantly lower (P < 0.05) than those of the super-elastic type with no additional heat treatment. The bending load values of rectangular-based cross-sectional shaped instruments were significantly lower (P < 0.05) than those of triangular-based cross-sectional shaped instruments. Phase transformation temperatures (M(s) and A(f) points) of the hybrid type were significantly higher (P < 0.05) than the super-elastic type. The M(f) and A(s) points of the tip part were significantly higher (P < 0.05) than those of the whole part of the hybrid instrument. CONCLUSIONS: Additional heat treatment of hybrid nickel-titanium instruments may be effective in increasing the flexibility of nickel-titanium rotary instruments.

Symptomatic colonic spirochaetosis in an immunocompetent patient.

Spirochaetes are organisms that can infect the colon of people with normal or compromised immune systems. Infected patients can present with a variety of gastrointestinal symptoms, including diarrhoea and rectal bleeding. However, some report a lack of association between specific symptoms and the presence of spirochaetes. It is therefore unclear whether the spirochaetes colonising the colon are true pathogens. Diagnosis is typically made by histological examination, with the biopsy specimen showing a band-like growth of spirochaetes adherent to the colonic luminal surface, giving an accentuated brush-border appearance. A course of metronidazole can eliminate the spirochaetes, but treatment might not lead to improvement of symptoms. Owing to the lack of a definite association between symptoms and the presence of spirochaetes, observation without specific antibiotic treatment can be pursued in most patients.

Birt-Hogg-Dubé gene mutations in human endometrial carcinomas with microsatellite instability.

Birt-Hogg-Dubé (BHD) syndrome is a rare form of autosomal dominantly inherited genodermatosis characterized by benign hamartomatous skin lesions named fibrofolliculomas, and an increased risk for developing pulmonary cyst/pneumothorax and various forms of renal cell carcinoma. Many of the patients harbour insertion/deletion mutations in the hypermutable poly(C)8 tract in exon 11 of the BHD gene. This mutational hot spot is also reported to be a target of mutation in microsatellite instability (MSI) sporadic colorectal cancer. To test the hypothesis that the BHD gene is also a mutational target in sporadic endometrial carcinoma with microsatellite instability, 139 cases of sporadic endometrial carcinoma were screened for MSI status, and mutations of the poly(C)8 tract in exon 11 as well as other coding exons of the BHD gene. The poly(G)8 tract of the BAX gene, the poly(C)8 tract of MSH6, and methylation status of hMLH1 were also assessed. Thirty-nine of 139 cases (28%) showed MSI. Mutations in the poly(C)8 tract of BHD were detected in five of the 39 MSI cases (12.8%). Of these, one showed additional mutation in exon 4, possibly satisfying the two-hit hypothesis of tumour suppressor genes. BAX gene mutation was detected in ten of the 39 MSI cases (25.6%). Four tumours showed both BAX and BHD mutations, and a significant positive association was found between mutations of the two genes. No association was found between BHD status and MSH6 mutation or hMLH1 methylation. When multiple foci were microdissected and individually screened for mutation, BHD mutations were shown to have been acquired during tumour progression, after mutation of the BAX gene, in three of five cases. Taken together, these findings show that the BHD gene is a target gene in MSI endometrial carcinoma. However, its mutational frequency is lower than that of BAX, and BHD mutation tends to occur during neoplastic progression after the acquisition of mutations in another MSI target gene, BAX.

Influence of phase transformation on the torsional and bending properties of nickel-titanium rotary endodontic instruments.

AIM: To investigate the relationship between the functional properties and the phase transformation of nickel-titanium endodontic instruments. METHODOLOGY: Five types of rotary nickel-titanium endodontic instruments with a 0.30 mm diameter tip (EndoWave, HERO 642, K3, ProFile.06, and ProTaper) were selected to investigate torsional and bending properties, and phase transformation behaviour. A torsional test was performed according to ISO publication 3630-1, and maximum torque and angular deflection at fracture were measured. Bending load of the instruments was measured in a cantilever-bending test at 37 degrees C with the maximum deflection of 4.0 mm. A stainless steel K-file was used for reference. Phase transformation behaviour was measured by differential scanning calorimetry (DSC). From the DSC curve, transformation temperatures were calculated. Data were analysed by anova and the Tukey-Kramer's test. RESULTS: The maximum torsional torque values of HERO, K3 and ProTaper were significantly higher (P < 0.05) than those of EndoWave, ProFile and K-file. The K-files had the lowest torque value. Angular deflection at fracture was significantly higher (P < 0.05) for K-files than that for any nickel-titanium instrument. The bending load values of HERO and K3 were significantly higher (P < 0.05) than those of EndoWave, ProFile, ProTaper and K-file. The K-files had the lowest load value, although residual deflection remained. The transformation temperatures of HERO and K3 were significantly lower (P < 0.05) than those of EndoWave, ProFile and ProTaper. CONCLUSIONS: The functional properties of nickel-titanium endodontic instruments, especially their flexible bending load level, were closely related to the transformation behaviour of the alloys.

Prolonged recovery of ultraviolet B-irradiated skin in neuropsin (KLK8)-deficient mice.

BACKGROUND: Neuropsin (KLK8), a serine protease of the kallikrein family, is thought to be involved in the function of keratinocytes, i.e. migration, differentiation and desquamation. However, how neuropsin participates is still unknown. OBJECTIVE: To observe the epidermal function of serine protease in neuropsin-deficient mice. METHODS: We irradiated the skin of neuropsin-deficient mice with ultraviolet light to induce acute inflammation and compared the morphology with that of wild-type mice. RESULTS: We observed a phenotypic change in the epidermis. An acute inflammatory dose of ultraviolet light induced a marked increase in neuropsin mRNA expression in the skin. The signal intensity of the mRNA expression was highest on day 2-3 after irradiation, when keratinocytes were aligned irregularly in the recovery period. Morphological comparison between neuropsin -/- and +/+ mice revealed that an irregular alignment of cells in the thickened epidermis was obvious on day 2 after irradiation in the wild-type mice, whereas it was prolonged for at least 2 days in the neuropsin-deficient mice. The stratum corneum of neuropsin-deficient mice was remarkably thicker than that of the wild-type mice at 5, 14 and 21 days after irradiation. The increase, as a response to this stimulus, in involucrin immunoreactivity, a marker for cell envelope assembly, was delayed in the mutant mice. CONCLUSIONS: Thus, neuropsin might be involved early in the process of differentiation, such as in the assembly of the cell envelope, but not in migration and desquamation.

Optimizing filler content in an adhesive system containing pre-reacted glass-ionomer fillers.

OBJECTIVES: (1) To evaluate the optimal concentration of the calcium type pre-reacted glass-ionomer (PRG-Ca) fillers in experimental light-activated adhesives for bonding to tooth substrates and fluoride release; (2) to evaluate the polymerization reactivity of these experimental filled adhesives; and (3) to examine the ultrastructure of the resin-dentin interface bonded with the commercial version of this self-etching adhesive (Imperva Fluoro Bond, Shofu Inc., Kyoto, Japan). MATERIALS AND METHODS: PRG-Ca fillers were prepared from the acid-base reaction of calcium type fluoroaluminosilicate glass with poly(acrylic acid) in water. Different experimental light-cured adhesives were prepared, with 0-57wt% PRG-Ca fillers and 3wt% aerosil silica incorporated in a resin matrix. Twenty-four hours shear bond strengths to bovine enamel and dentin were assessed using the adhesive with/or without accelerated aging. The cumulative amount of fluoride released from the cured adhesives and differential scanning calorimetry (DSC) measurements were also conducted. 180-grit SiC paper polished human dentin disks were treated with Imperva Fluoro Bond that contains 17wt% PRG-Ca fillers and prepared for TEM examination. RESULTS: Increase in PRG-Ca filler content of experimental adhesives was highly correlated with the decrease in bond strengths to dentin (r=-0.96 to -0.99), the increase in cumulative fluoride release, (r=0.97) and the decrease in polymerization energy (cal/g) of the adhesives (r=-0.99) (p<0.001). A PRG-Ca content of 17wt% provided optimal bond strength to enamel and dentin after accelerated aging and fluoride release. TEM showed that salt-like matrices were present around the hydrogels and remnant glass cores of the PRG-Ca fillers. The commercial self-etching primer completely dissolved the smear layer and formed 2 micrometer thick hybrid layers in intact dentin. SIGNIFICANCE: The use of silanized PRG-Ca fillers provides good adhesion and a source of fluoride release in a commercially available self-etching adhesive system.

Epidermal expression of serine protease, neuropsin (KLK8) in normal and pathological skin samples.

AIMS: The expression of human neuropsin (KLK8) mRNA in normal and pathological skin samples was analysed and the results compared with those for tissue plasminogen activator (tPA) mRNA. METHODS: Northern blot and in situ hybridisation analyses of KLK8 mRNA in normal and lesional skin of patients with cutaneous diseases were performed. RESULTS: A weak signal for KLK8 mRNA and no signal for tPA mRNA was seen in normal skin on northern blot analysis. Weak signals for KLK8 were localised to the superficial cells beneath the cornified layer in normal skin on in situ hybridisation. Psoriasis vulgaris, seborrheic keratosis, lichen planus, and squamous cell carcinoma skin samples, which show severe hyperkeratosis, displayed a high density of KLK8 mRNA on northern and in situ hybridisation analyses. The signals were localised in granular and spinous layers of lesional skin in all hyperkeratic samples, including the area surrounding the horn pearls of squamous cell carcinoma. To examine the relation between mRNA expression and terminal differentiation, the expression of KLK8 mRNA was analysed in cell cultures. When keratinisation proceeded in high calcium medium, a correlative increase in the expression of KLK8 mRNA was observed. CONCLUSION: The results are consistent with a role for this protease in the terminal differentiation of keratinocytes.

Reinforcement effect of short glass fibers with CaO- P(2)O(5) -SiO(2) -Al(2)O(3) glass on strength of glass-ionomer cement.

OBJECTIVES: A high strength glass-ionomer (not resin-modified) cement was developed using short fibers of CaO--P(2)O(5)--SiO(2)--Al(2)O(3) (CPSA) glass. The purpose of this study was to clarify the effect of the CPSA short fibers contained in the flexural strength of the glass-ionomer cement. METHOD: The 40 mass% short fibers of CPSA glass were added to the powder of commercial glass-ionomer cement. Beam specimens of set cement (25 x 2 x 2 mm) were prepared for measuring the flexural strength (FS). The specimens of set commercial glass-ionomer cement (GI) were used for comparison with glass ionomer cement with CPSA (FRGI). Half of all specimens were thermocycled in water for 60s of dwell time at 4 and 60 degrees C for 2500, 5000, and 10,000 cycles. The other specimens were stored in water at 37 degrees C as a control. The measurements were statistically analyzed using ANOVA. RESULTS: The initial FS of FRGI was 18.1 and that of GI was 7.7 MPa. After thermocycling, the mean FS ranged from 19.3 to 26.3 MPa and 9.8 to 11.1 MPa for FRGI and GI, respectively. After storage in water, the mean FS of FRGI and GI ranged from 20.4 to 25.9 MPa and 9.4 to 10.1 MPa, respectively. CONCLUSION: These findings suggested that glass-ionomer cement reinforced with CPSA short fibers maintains a higher strength than the conventional cement after aging.

Intramural duodenal hematoma presenting as a complication of peptic ulcer disease.

We report the first case in the English literature of an intramural duodenal hematoma presenting as a complication of Helicobacter pylori-induced peptic ulcer disease. Intramural duodenal hematomas have been previously described in patients-usually in the setting of blunt trauma, postendoscopic biopsy, gastrostomy placement, and hemostatic therapy and in patients with a coagulopathy or bleeding diathesis-but not as a presentation of peptic ulcer disease. It is important to recognize this complication, as surgical management may benefit patients with a duodenal hematoma.

Abnormalities of synapses and neurons in the hippocampus of neuropsin-deficient mice.

In the present study, we produced null-mutant mice of neuropsin, an extracellular matrix serine protease, to examine the neural functions of this protein particularly in the hippocampus. Golgi-Cox impregnation and Nissl-staining revealed morphological change of cell soma in the mutant mice compared to wild-type mice. However, Golgi-Cox impregnation revealed no apparent change in the dendritic arborization and spine density. Quantitative electronmicroscopic analysis revealed that number of asymmetrical synapses were significantly decreased in the stratum radiatum, the major terminal field of Schaffer-collaterals, whereas free boutons still holding synaptic vesicles but with no synaptic specialization were increased in number in the same microscopic fields. An increased number of parvalbumin-immunoreactive cells (known as fast spiking cells) in mutant was also observed. These results strongly suggest that neuropsin is involved in connectivity of a group of CA1 synapses and consequently in the hippocampal networking.

[5'-DFUR chemoprophylaxis in superficial bladder cancer. Kanagawa Urology 5'-DFUR Study Group].

5'-Deoxy-5-fluorouridine (5'-DFUR), an oral fluorinated pyrimidine carbamate, is widely used in patients with gastrointestinal and breast cancers because of its effectiveness. However, in bladder cancer, response rates have only been reported in Phase II clinical trials. Therefore, we conducted a prospective randomized trial to investigate chemoprophylactic effect of 5'-DFUR against recurrence of superficial bladder cancer after transurethral bladder tumor resection (TUR-Bt). The subjects were grouped as follows: 1) 5'-DFUR group (n = 31), received 600 mg/day of 5'-DFUR starting 2-3 weeks after TUR-Bt for 2 years; and 2) control group (n = 31) received no 5'-DFUR. Although there was no significant difference between groups, the cumulative recurrence rates was more favorable in the 5'-DFUR group (p = 0.256) than in the controls. Results according to cancer factors showed that, in patients with G2 based on grading, those in the 5'-DFUR group tended to have a lower recurrence rate than the control group (p = 0.070). There was a 40% incidence of adverse drug reactions (12/30 patients), primarily slight gastrointestinal symptoms which disappeared or improved with drug discontinuation. The results of the present study suggest that 5'-DFUR might be the choice of treatment to prevent recurrence of superficial bladder cancer.

Strengthening of glass-ionomer cement by compounding short fibres with CaO-P2O5-SiO2-Al2O3 glass.

The purpose of this study was to determine if short fibres of CaO-P2O5-SiO2-Al2O3 (CPSA) glass possessing a particular aspect ratio (length/diameter) could be used as a reinforcing agent for glass-ionomer cement. The powder of a commercial glass-ionomer cement (not resin modified) was mixed with variously sized CPSA glass short fibres before mixing with the liquid of the glass-ionomer cement. The mixed powders containing 60 mass% CPSA glass short fibres (diameter, 9.7 +/- 2.1 microm, aspect ratio, 5.0 +/- 0.9) obtained maximum values of 18 and 35 MPa for the diametral tensile strength (DTS) and flexural strength (FS) of set cements, respectively, after 24 h. These DTS and FS values were 1.8 and 4.5 times larger, respectively, than those of the set glass-ionomer cement not containing short fibres. Moreover, it was found that the addition of CPSA glass short fibres was remarkably more effective in the strengthening than electric glass (a typical glass fibre) short fibres. The results suggested that the CPSA glass short fibres acted as a reinforcing agent for strengthening the glass-ionomer cement, because of the shape of short fibres and reactivity between the mixing liquid and short fibres.

Evolutionary molecular engineering by random elongation mutagenesis.

We describe a new method of random mutagenesis that employs the addition of peptide tails with random sequences to the C-terminal of enzyme molecules. A mutant population of catalase I from Bacillus stearothermophilus prepared by this method has a diversity in thermostability and enzyme activity equal to that obtained after random point mutagenesis. When a triple mutant of catalase I (I108T/D130N/1222T)-the thermostability of which is much lower than that of the wild type-was subjected to random elongation mutagenesis, we generated a mutant population containing only mutants with higher thermostability than the triple mutant. Some had an even higher stability than the wild-type enzyme, whose thermostability is considered to be optimized. These results indicate that peptide addition expands the protein sequence space resulting in a new fitness landscape. The enzyme can then move along the routes of the new landscape until it reaches a new optimum. The combination of random elongation mutagenesis with random point mutagenesis should be a useful approach to the in vitro evolution of proteins with new properties.

Genetic basis of congenital hypothyroidism: abnormalities in the TSHbeta gene, the PIT1 gene, and the NIS gene.

We have elucidated the molecular pathology of three types of congenital hypothyroidism. Thyrotropin (TSH) is the major regulator of thyroid function. In cases of isolated congenital TSH deficiency, we found that they are caused by a missense mutation in the conserved CAGYC region of the TSHbeta gene. Pit-1/GHF-1 is a pituitary specific POU-domain DNA binding factor, which transactivates the growth hormone (GH), prolactin (PRL), TSHbeta genes, and the PIT1 gene itself. In cases of combined deficiency of GH, PRL, and TSH, we found that they are caused by abnormalities in the PIT1 gene, either recessively or dominantly. Sodium dependent iodide symporter (NIS) actively transports iodide into the thyroid cells to produce thyroid hormones. In cases of iodide transport defect, we elucidated that a missense mutation in the transmembrane region of the NIS gene caused them.

[Long-term administration study of propiverine hydrochloride (BUP-4 tablets) in pollakiuria and urinary incontinence].

The safety and efficacy of one-year administration of propiverine hydrochloride (BUP-4 tablets) were assessed in facilities affiliated with the Department of Urology of Yokohama City University School of Medicine. Changes in subjective symptoms showed significant improvement in mean frequency of urination in the daytime from 10.3 +/- 4.0 times before administration to 7.1 +/- 2.9 times 1 year after the start of administration, in mean frequency of voiding at night from 4.2 +/- 1.7 times to 2.1 +/- 1.1 times and in mean incidence of urinary incontinence from 2.9 +/- 2.1 times to 0.7 +/- 1.0 times. The final degree of overall improvement rate was 82.0% (41/50 cases). Adverse effects were observed 26 times in 22 patients, the incidence being 15.6% (22/141 cases). They consisted of digestive symptoms in 9.9% (6 events of dry mouth, 4 of constipation, 2 of abdominal discomfort, 2 of diarrhea and 1 of gastritis), urinary tract symptoms in 3.5% (4 of dysuria and 1 of residual urine), abnormal laboratory findings in 1.4% (increase in glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase or lactate dehydrogenase levels) and others (1.4%). These results provide further evidence of the safety and efficacy of propiverine hydrochloride (BUP-4 tablets) even when administered for a long-term in the treatment of patients with pollakiuria and urinary incontinence.

Clinical significance of interruption of therapy with allylestrenol in patients with benign prostatic hypertrophy.

BACKGROUND: A multicenter, clinical trial investigated the effects of an interruption of antiandrogen therapy on subjective and objective clinical parameters in patients with benign prostatic hypertrophy (BPH). METHODS: Patients were given antiandrogen therapy with allylestrenol (50 mg/day) for 16 weeks. The medication was then withheld and the patients were carefully monitored for an additional 16 weeks. There were 34 BPH patients ranging in age from 55 to 82 years (mean, 66.1 years). The efficacy of allylestrenol was evaluated by its effects on prostate volume, maximum urinary flow rate (MFR), and symptom scores at the end of 16 weeks of treatment and then again at 32 weeks (16 weeks after cessation of therapy). RESULTS: Allylestrenol was effective in the treatment of BPH, and was still effective 16 weeks after the cessation of medication. The prostate volume did not change after treatment cessation nor did the total symptom score, but the MFR reversed to the pretreatment level. Serum testosterone (1.95 ng/mL), dihydrotestosterone, and gonadotropin levels decreased on therapy, but were completely reversed by the end of this study. A prostate needle biopsy revealed that after 16 weeks without therapy, some glands showed regressive glandular changes, while some glands showed slight hyperplastic changes of the secretory epithelium. Eight per cent of patients complained of loss of libido during this study. CONCLUSIONS: Allylestrenol is an effective and safe medical treatment for patients with symptomatic BPH. Hormonal and histopathologic findings suggest that the prostate gland may regrow after discontinuation of medication.

[Prognosis in the cases with renal cell carcinoma according to clinical parameters].

BACKGROUND: The objects of this study is to evaluate the clinical prognostic factors in renal cell carcinoma. MATERIALS AND METHODS: During a 30-year period from January 1965 to December 1994, 1301 cases with renal cell carcinoma were treated at the Yokohama City University Hospital and its affiliated hospitals. In these cases, cause specific 679 cases from January 1965 to December 1990 were analyzed in a study undertaken to investigate long-term treatment results and clinical prognostic factors. RESULTS: 1. The cause specific 5-, 10-, 15-, and 20-year survival rates were 48.7%, 41.1%, 32.3%, and 26.5% respectively, indicating thus that a great number of cases had an ominous prognosis even 5 years or moreafter surgical treatment. 2. Among patients under 40 years of age (n = 29) none died more than 2 years after receiving operation, the prognosis for this particular group of cases being relatively good. 3. Female, incidentally detected cancer, small tumor size (< or = 4.0 cm), slow growing type and low stage were proven to be favourable prognostic factors in renal cell carcinoma. 4. The cause specific 5-year survival rate for the patients (n = 239) from 1965 to 1981 was 33.8%, while the rate for the patients (n = 440) from 1982 to 1990 was 56.5%. This improvement of survival rate was brought by the increase of the incidentally detected renal cell carcinoma. 5. In the incidentally detected renal cell carcinoma, the incidence of slow growing cases and the cases of less than 4.0 cm tumor size were higher than in the symptomatic renal cell carcinoma. 6. Multivariate analysis using Cox's proportional hazard model showed that stage was the most important prognostic factor. CONCLUSIONS: These results suggested that sex, age, symptom, tumor size, growing type, and stage were important prognostic factors in renal cell carcinoma.

Effect of site directed mutagenesis in the CMGCC region of the alpha-subunit on immunoreactive human thyrotropin.

The cDNA of the common alpha-subunit of human glycoprotein hormone was mutated by site directed mutagenesis in the CMGCC region composed of cysteine-methionine-glycine-cysteine-cysteine (position 28-32). The cDNA of wild-type human thyrotropin (hTSH) beta-subunit and that of wild-type or mutant common alpha-subunits were co-transfected into COS-I cells. The concentration of hTSH determined by two immunoradiometric assay systems was detectable in culture media of COS-I cells transfected with wild-type (CMGCC) and a mutant (CRGCC) alpha-subunits but not four other mutants (YMGCC) (CMRCC) (CMACC) (CMDCC). The present data with the other studies on wild-type or mutant glycoprotein hormones support our hypothesis that an amino acid motif of "C-X-G-X-C" in the common alpha-(CMGCC in human) and beta-(CAGYC in human) subunits play an important role in biosynthesis of glycoprotein hormones in all species.

[Nonoperative management of major blunt renal lacerations with urinary extravasation: report of two cases].

Two cases of major blunt renal trauma with urinary extravasation managed by conservative treatment are presented herein. The first case: A 13-year-old girl fell from a bicycle. A computed tomographic (CT) scan showed right renal laceration with retroperitoneal hematoma. Renal arteriography showed evidence of fresh arterial bleeding without visualization of the lower pole. She was treated conservatively with superselective arterial embolization of the lower pole. She developed no urinoma with normal renal function. Renal renin and blood pressures stayed within the normal range in follow up studies. The second case: A 12-year-old boy fell from a tree and hit his right flank. A CT scan showed fragmentation of right renal cortex with retroperitoneal hematoma. He was treated conservatively as his vital signs remained stable, no active arterial bleeding was found no renal arteriography and both renal pelvis and ureters were well visualized by intra venous pyelography. Retroperitoneal hematoma was absorbed without formation of urinoma. Renal function remained within normal limits in follow up studies.