Control of protein function through oxidation and reduction of persulfidated states.

Irreversible oxidation of Cys residues to sulfinic/sulfonic forms typically impairs protein function. We found that persulfidation (CysSSH) protects Cys from irreversible oxidative loss of function by the formation of CysSSO1-3H derivatives that can subsequently be reduced back to native thiols. Reductive reactivation of oxidized persulfides by the thioredoxin system was demonstrated in albumin, Prx2, and PTP1B. In cells, this mechanism protects and regulates key proteins of signaling pathways, including Prx2, PTEN, PTP1B, HSP90, and KEAP1. Using quantitative mass spectrometry, we show that (i) CysSSH and CysSSO3H species are abundant in mouse liver and enzymatically regulated by the glutathione and thioredoxin systems and (ii) deletion of the thioredoxin-related protein TRP14 in mice altered CysSSH levels on a subset of proteins, predicting a role for TRP14 in persulfide signaling. Furthermore, selenium supplementation, polysulfide treatment, or knockdown of TRP14 mediated cellular responses to EGF, suggesting a role for TrxR1/TRP14-regulated oxidative persulfidation in growth factor responsiveness.

Acceleration of tendon-bone healing in anterior cruciate ligament reconstruction using an enamel matrix derivative in a rat model.

We examined whether enamel matrix derivative (EMD) could improve healing of the tendon-bone interface following reconstruction of the anterior cruciate ligament (ACL) using a hamstring tendon in a rat model. ACL reconstruction was performed in both knees of 30 Sprague-Dawley rats using the flexor digitorum tendon. The effect of commercially available EMD (EMDOGAIN), a preparation of matrix proteins from developing porcine teeth, was evaluated. In the left knee joint the space around the tendon-bone interface was filled with 40 µl of EMD mixed with propylene glycol alginate (PGA). In the right knee joint PGA alone was used. The ligament reconstructions were evaluated histologically and biomechanically at four, eight and 12 weeks (n = 5 at each time point). At eight weeks, EMD had induced a significant increase in collagen fibres connecting to bone at the tendon-bone interface (p = 0.047), whereas the control group had few fibres and the tendon-bone interface was composed of cellular and vascular fibrous tissues. At both eight and 12 weeks, the mean load to failure in the treated specimens was higher than in the controls (p = 0.009). EMD improved histological tendon-bone healing at eight weeks and biomechanical healing at both eight and 12 weeks. EMD might therefore have a human application to enhance tendon-bone repair in ACL reconstruction.

Peripheral ameloblastoma: biological profile based on 160 cases from the literature.

The present profile of the peripheral ameloblastoma (PA) is based on a literature survey of 160 published tumour cases. The PA is an exophytic growth localized to the soft tissues overlying the tooth-bearing areas of the jaws, the initial diagnosis often being fibrous epulis. In most cases there is no radiological evidence of bone involvement, but a superficial bone erosion--known as cupping or saucerization--may be detected at operation. The PA accounts for 2-10% of all ameloblastomas. The overall average age is 52.1 years, slightly higher for males (52.9 years) than for females (50.6 years). Thus, the PA occurs at a significantly higher age than the intraosseous ameloblastoma (IA; 37.4 years). The male/female ratio amounts to 1.9:1, as opposed to 1.2:1 for the IA. The male/female ratio for the Japanese cases included in this survey is 2.5:1 as opposed to that of non-Japanese cases 1.4:1. As to the location of PA, the maxilla/mandible ratio is 1:2.6. The mandibular premolar region accounts for 32.6% of all sites. Five extra-gingival lesions have been reported under the term PA. As these cases most likely represent salivary gland tumours, they are not accepted under the diagnosis of PA. The odontogenic gingival epithelial hamartoma shows clinical, histological and behavioural features almost identical to the PA, and it is discussed whether this lesion and the PA should be considered one and the same entity. Pathogenetically, two major sources are discussed: remnants of the dental lamina and the oral surface epithelium. Histologically, the PA consists of proliferating odontogenic epithelium exhibiting the same histomorphological cell types and patterns as seen in the IA. The stroma is that of a mature, fibrous connective tissue. The indolent biological behaviour dictates a conservative therapeutical approach. It is discussed whether PA is a true neoplastic counterpart of the IA or rather an odontogenic hamartomatous lesion. Six cases of malignant PA have been reported.

Employee stress status during the past decade (1982-1992) based on a nation-wide survey conducted by the Ministry of Labour in Japan.

In this paper we will report the results of nation-wide surveys on employee health conducted and published by the Ministry of Labour in 1982, 1987, and 1992. The subjects were approximately 20,000 employees in 1982, approximately 15,000 in 1987, and approximately 16,000 in 1992, from throughout Japan. Using the results of the surveys, we will show trends in the status of employee work-related stress, as well as trends in means of relaxation over the past decade. The percentage of employees with work-related stress among all subjects gradually increased as follows: 50.6% in 1982, 55.0% in 1987, and 57.3% in 1992. The percentage of employees with work-related stress increased remarkably from 1982 through 1992 among the following groups: the 50-59 age group in males; employees in the electricity, gas, heat and water-supply industries; those in the real estate industry; administrative and managerial workers; employees of large establishments with more than 5,000 employees; and employees performing shift work involving no night duty. The problem of "human relationships in the workplace" was associated with the increasing stress levels among 50-59-year-old males, 40-49-year-old females, employees of large establishments with more than 5,000 employees, those in the real estate industry, and service workers. In terms of means of relaxing to relieve fatigue and stress, employees tended to engage in active pursuits such as "eating out and shopping" and "driving and traveling" over the past decade. In 1992, on the other hand, 22.0% of males and 5.9% of females selected "smoking" as a means of relaxation. This shows the need for stress management in the workplace in order to prevent health problems related to smoking.

[TV-assisted thoracoscopic surgery with a lung forceps combined with thoracoscope under local anesthesia for spontaneous pneumothorax with a persistent air leak--a single access port approach].

TV-assisted thoracoscopic surgery was performed under local anesthesia by through a single access port to control a continuing air leak in spontaneous pneumotorax. A 75-year-old man was admitted with severe dyspnea and right-sided chest pain. The chest X-ray film showed right lung collapse. A right spontaneous pneumothorax was diagnosed and was treated by chest tube drainage. However, the lung did not re-expand because of a continuing air leak and subcutaneous emphysema developed. TV-assisted thoracoscopic surgery was performed under local anesthesia to treat the persistent air leak on day 12. By endoscopy, the ruptured bulla was double-ligated with an Endoloop through a single access port using lung forceps combined with endoscope. The air leak subsequently ceased and the lung re-expanded. This method is minimally invasive and is very suitable for controlling a continuing air-leak causing spontaneous pneumothorax in a patient.

Specific inhibitory effect of dietary eicosapentaenoic acid on N-nitroso-N-methylurea-induced mammary carcinogenesis in female Sprague-Dawley rats.

We have investigated the effects of two qualitatively different types of unsaturated fatty acids on N-nitroso-N-methylurea (NMU)-induced mammary carcinogenesis in female Sprague-Dawley rats. Semipurified diets containing 4.7% eicosapentaenoic acid (EPA) plus 0.3% linoleic acid or 5% linoleic acid were prepared. Animals maintained on these diets were given an i.v. injection of NMU (50 mg/kg body wt) at 50 days of age and killed 20 weeks later. Both tumor incidence and tumor number per rat were significantly lower in the EPA diet group (60.0% and 2.3 +/- 2.5 versus 93.3% and 5.1 +/- 4.5 respectively) for the 5% linoleic acid diet. Furthermore, the average weight of tumor material (total) per rat was significantly lower in the EPA as compared to linoleic acid diet group (2.9 +/- 4.2 g and 11.4 +/- 12.2 g respectively). Analysis of phospholipid fatty acids in the mammary tumors in the EPA diet group showed a higher proportion of C16:0, C18:2, omega-3 fatty acids C20:5 and C22:6 and a lower proportion of C20:4. Furthermore, mammary tumors in rats fed the EPA diet demonstrated significant reduction in prostaglandins. The results thus suggest that inhibition by EPA of NMU-induced mammary carcinogenesis may be mediated via the modulation of lipid metabolism and associated reduction in prostaglandin synthesis.

Correlation between clinical and histological evaluations of the peri-implant gingiva around the single-crystal sapphire endosseous implant.

The correlation between clinical periodontal parameters and histological structure of the gingiva around a single-crystal sapphire implant has been evaluated in two volunteer subjects. The implants had functioned after 6 years as the distal abutment of implant bridges in the Kennedy class II mandible. First, clinical evaluation was performed (gingival bleeding index, crevicular fluid volume, plaque index and probing depth) of the gingiva around the implant and natural teeth abutments and then a small piece of peri-implant gingiva was excised from the lingual site of the implant of each subject for histological evaluation. The clinical evaluation using the periodontal parameter indices corresponded with the histological evaluation of the peri-implant gingiva. The result suggests that it is possible for such parameters to be used in practice for judging the success of an implant.

Effect of dietary eicosapentaenoic acid on azoxymethane-induced colon carcinogenesis in rats.

The effects of eicosapentaenoic acid (EPA, n-3 polyunsaturated fatty acid) and linoleic acid (n-6 polyunsaturated fatty acid) on azoxymethane-induced colon carcinogenesis in rats were studied. Male Donryu rats were given two types of semipurified diet containing 4.7% EPA plus 0.3% linoleic acid and 5% linoleic acid. The rats were given s.c. injection of azoxymethane (7.4 mg/kg body weight once a week for 11 weeks) and sacrificed 15 weeks after the last injection of azoxymethane. The tumor incidence and tumor yields (tumors per rat) of the colon were significantly lower in rats on the EPA diet compared to those on the linoleic acid diet; i.e., 33%, 0.41 +/- 0.61 and 69%, 1.66 +/- 1.69, respectively. In the analysis of phospholipid fatty acid composition, the colon tumor showed higher levels of arachidonic acid and lower levels of linoleic acid than those in the normal colon mucosa in both diet groups. Despite the increase of arachidonic acid in colon tumor, the EPA diet suppressed the excessive production of prostaglandin E2, which may be accompanied with neoplastic formation, whereas linoleic acid diet caused a marked increase in the tumor content of prostaglandin E2 compared to normal colon mucosa. These results suggest that EPA exerts its inhibitory effect on colon carcinogenesis by modulating lipid metabolism and inhibiting prostaglandin E2 synthesis in tumor cells.

Initial bone-implant interfaces of submergible and supramergible endosseous single-crystal sapphire implants.

Three types of bone-single-crystal sapphire implant interfaces were histologically determined in submergible and supramergible implant: direct bone apposition (type I), thin connective tissue with poor collagen fibers (type II), and dense fibrous connective tissue (type III). Type I interface was predominant and type III interface was sparsely seen in submergible implants. In contrast to these findings, type III interfaces frequently appeared in supramergible implants, primarily at the apical region. These differences were considered to occur by the biomechanical variable of postoperative healing.