Jun dimerization protein 2 is a critical component of the Nrf2/MafK complex regulating the response to ROS homeostasis.

Oxidative stress and reactive oxygen species (ROS) are associated with diseases such as cancer, cardiovascular complications, inflammation and neurodegeneration. Cellular defense systems must work constantly to control ROS levels and to prevent their accumulation. We report here that the Jun dimerization protein 2 (JDP2) has a critical role as a cofactor for transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and small Maf protein family K (MafK) in the regulation of the antioxidant-responsive element (ARE) and production of ROS. Chromatin immunoprecipitation-quantitative PCR (qPCR), electrophoresis mobility shift and ARE-driven reporter assays were carried out to examine the role of JDP2 in ROS production. JDP2 bound directly to the ARE core sequence, associated with Nrf2 and MafK (Nrf2-MafK) via basic leucine zipper domains, and increased DNA-binding activity of the Nrf2-MafK complex to the ARE and the transcription of ARE-dependent genes. In mouse embryonic fibroblasts from Jdp2-knockout (Jdp2 KO) mice, the coordinate transcriptional activation of several ARE-containing genes and the ability of Nrf2 to activate expression of target genes were impaired. Moreover, intracellular accumulation of ROS and increased thickness of the epidermis were detected in Jdp2 KO mice in response to oxidative stress-inducing reagents. These data suggest that JDP2 is required to protect against intracellular oxidation, ROS activation and DNA oxidation. qPCR demonstrated that several Nrf2 target genes such as heme oxygenase-1, glutamate-cysteine ligase catalytic and modifier subunits, the notch receptor ligand jagged 1 and NAD(P)H dehydrogenase quinone 1 are also dependent on JDP2 for full expression. Taken together, these results suggest that JDP2 is an integral component of the Nrf2-MafK complex and that it modulates antioxidant and detoxification programs by acting via the ARE.

Extra-strong graduated compression stocking reduces usage of vasopressor agents during spinal anesthesia for cesarean section.

Because a standard type of graduated compression stocking is not effective for the prevention of spinal anesthesia hypothension during cesarean section, we have used an extra-strong type of graduated compression stocking. This study examined whether the extra-strong stocking reduces usage of vasopressor agents. Forty-eight and 47 full term parturients were fitted with the standard stocking and the extra-strong stocking, respectively. Spinal anesthesia was performed by injecting 2.0 ml 0.3% dibucaine hyperbaric solution. When systolic blood pressure decreased to 90-100 mmHg or to less than 70% of the pre-anesthesia value, ephedrine was injected. There was no significant difference in systolic blood pressure or heart rate during spinal anesthesia between the groups. The mean dose of ephedrine injected during anesthesia was 12.2 and 4.3 mg, and the incidence of ephedrine injected was 85 and 49%, in the standard and extra-strong stocking groups, respectively. The extra-strong stocking group showed significantly lower values. Fitting the extra-strong stocking on both legs for cesarean sections undergoing spinal anesthesia reduced usage of vasopressor agents, suggesting a promising use of this stocking for non-invasive prophylaxis.

Increase of peak expiratory flow by atropine is dependent on circadian rhythm.

PURPOSE: To examine whether the bronchodilatory effect of atropine differs in the evening from the morning. METHODS: Thirteen adult healthy volunteers with no oral medication intake were studied. At 1600, peak expiratory flow (PEF) was measured three times, and the highest value recorded. Subsequently, the volunteer received 0.01 mg(-1) x kg(-1) atropine im, and the PEF was measured every 30 min for 180 min. On a different day, at 0400, the effect of atropine on the PEF was measured again in the same way. RESULTS: The PEF values before atropine at 1600 and 0400 were 485 +/- 92 (350-730) and 458 +/- 76 (340-600) 1 min(-1),(P < 0.05). There was no difference in PEF values between the 1600 and 0400 time courses after atropine. The PEF value was increased only at 90 min at 1600 (P = 0.0012), but at 30, 60, 90 and 120 min at 0400 (P = 0.0001). CONCLUSION: Atropine administration has a weak bronchodilatory effect in the evening, but a stronger effect in the morning. Airways are narrower in the morning than in the evening, and this change is inhibited by atropine such that the PEF values are restored to those observed in the evening.

A phase III randomized trial of cisplatin plus vindesine versus cisplatin plus vindesine plus mitomycin C versus cisplatin plus vindesine plus ifosfamide for advanced non-small-cell lung cancer.

A randomized trial of chemotherapy in 105 patients with advanced and metastatic non-small-cell lung cancer (NCSLC) was conducted in order to compare the effect of the additional drug mitomycin C (PVM) or ifosfamide (PVI), to the combination of cisplatin plus vindesine (PV). An objective response rate was observed in 42.8% of the patients treated with PVM, 42.4% with PVI and 28.6% with PV and these response rates were not statistically significant (P > 0.20). No patient achieved the complete response with either of the three regimens. Comparison of the median response durations among the three regimens showed an advantage of PVI over PVM (P < 0.02) and PV (P < 0.05). The median survival times (MST) were similar for all three regimens (PVM, 33.5; PVI, 40.0 and PV, 36.5 weeks); moreover, the difference in survival time between the three regimens of responders was not statistically significant. The univariate analysis showed that significant predictors of survival were performance status (PS) zero (P = 0.0002), limited disease (P = 0.004), no previous weight loss (P = 0.01) and normal serum albumin (P = 0.016), and in multivariate analysis by a stepwise Cox proportional hazard model, these were PS zero (a hazard ratio of 2.3, P = 0.0001) and limited disease (a hazard ratio of 1.9, P = 0.048). Toxicity did not differ among the three treatment regimens.

[Clinical evaluation of fiberoptic bronchoscopy for the diagnosis of solitary pulmonary nodules 2 cm or less in diameter of chest roentgenogram].

The value of fiberoptic bronchoscopy in the diagnosis of solitary pulmonary nodules was studied. The subjects were 59 patients with chest-roentgenographic evidence of a solitary pulmonary nodule 2 cm or less in diameter. Definitive diagnoses were made in 34 patients (57.6%). Primary lung care was diagnosed 21 of 32 patients (65.6%), pulmonary tuberculosis in 7 of 12 (58.3%), metastatic lung cancer in 3 of 5 (60%), old lesions in 3 of 5 (60%), and pulmonary filariasis in 0 of 1 (0%). The diagnostic sensitivity of transbronchial biopsy was superior to that of curettage, and combining the two techniques further improved the diagnostic yield. Bronchial lavage was not effective for diagnosis of lung cancer, but was effective for diagnosis of pulmonary tuberculosis. Diagnostic yield was less for nodules in upper lobes than for those in other lobes, and most malignant tumors that were not diagnosed from the results of fiberoptic bronchoscopy were in upper lobes. We conclude that combining various fiberoptic bronchoscopic procedures can improve the diagnostic yield in patients with small pulmonary nodules. CT-guided needle biopsy and video-assisted thoracoscopic biopsy are two such procedures. Early diagnosis of small pulmonary nodules requires a skilled bronchoscopist who can choose the most appropriate method for biopsy.

[The variation of Japanese urinary excretion of iodine in different decades of age].

In order to evaluate whether or not iodine intake in Japanese is variable among different aged subjects and also whether this variation is concordant with the age distribution in patients with chronic thyroiditis, we tried to examine the urinary iodine excretion of euthyroid people in various decades of age. One hundred and twenty outpatients without thyroid disorders, aged 22 to 77 y.o., were selected at random and were divided into 6 groups according to age. Mean total urinary iodine excretion (UIT) and concentration (UIC) were 336.1 micrograms/day and 31.4 micrograms/dl/cr, respectively, and they were in good correlation (r = +0.82, p < 0.001). A straight line on log normal probability was recognized between the ratio of cumulative frequency and values of UIT. UIT and UIC were significantly correlated with serum nonhormonal iodine, respectively (r = +0.21, p < 0.01; r = +0.28, p < 0.01). These indicators in the 3rd decade were lower than those in the 6th decade (p < 0.01, p < 0.05). UIT increased with age up to the 6th decade and then decreased gradually to the 8th decade. Therefore, UIT in all the subjects formed a bell-shaped distribution with a significant peak in the 6th decade (H = 12.1, p < 0.05). Rates of renal iodine clearance (UIC/SNI) in the 6th decade increased significantly more than those in the 4th decade (p < 0.01), and the distribution of those rates in the 6 groups were similar to that of UIT.(ABSTRACT TRUNCATED AT 250 WORDS)

[The prevalence of antithyroid antibodies and long term follow-up in patients with lipiodol iodine-induced goiter].

We have carried out a follow-up study on iodine-induced goiter to clarify whether or not iodine could be a factor in the progression as well as the promotion of thyroid autoimmunity. We selected 143 women of child-bearing age without any previous thyroid disorders who had received hysterosalpingography (H.S.G.). 45 Sex and age-matched healthy subjects were chosen as controls. Serum nonhormonal iodine (S.N.I.) levels, frequency of goiter and antimicrosomal antibody (MCHA) in all the Lipiodol-cases were significantly higher than those in the controls (p < 0.001, < 0.01 and < 0.01), respectively. When the subjects were divided into 9 groups according to the duration of each 5 months after H.S.G., serum TSH and S.N.I. levels, incidence of goiter and MCHA in the initial group were significantly higher than those in the other groups (p < 0.05). The S.N.I. levels became normalized in 30 months after H.S.G. and the goiters disappeared in almost the same duration, while the incidence of higher MCHA titers declined gradually but significantly around 40 months after H.S.G. compared with that in the first 5 months after H.S.G. (p < 0.05). The frequency of goiter and MCHA in 44 cases after a 6-39 month follow-up decreased significantly compared to that in the initial group (p < 0.05). Therefore, we tried an individual longitudinal follow-up study on MCHA titer in 12 cases for 35-103 months, resulting in a significant reduction or negativeness of the titer in 6 cases. Likewise, MCHA titers in all cases decreased significantly (p < 0.05) on later evaluation. The present data suggest that iodine in Lipiodol administered via the vagina will act not only as the promoting factor, but as an aggravating agent for thyroid autoimmunity.

[A case of giant bulla which ruptured and disappeared on chest roentgenogram].

We experienced a case of progressive giant bulla which ruptured and disappeared on chest roentgenogram. The patient was a 60-year-old male who had been treated with home oxygen therapy for chronic pulmonary emphysema. One year after initiating home oxygen, emphysematous bulla occurred and expanded to become giant bulla which occupied 3/4 of the right hemithorax. Although we attempted to persuade him to undergo surgery for bullectomy, he refused. While being followed as an outpatient, sudden right anterior chest pain occurred, and dyspnea was markedly alleviated at the same time. Chest roentgenogram revealed right pneumothorax and pleural effusion, and the giant bulla subsequently receded. The patient has been stable for the approximately one year period since, without evidence of recurrence. It is rare for giant bullae to cause a pneumothorax. In addition, there are no previous reports in the literature with a clinical course such as that experienced by our patient.

[A case of piperacillin-induced pneumonitis].

A 43-year-old woman was treated with piperacillin (PIPC) for spiking fever. Although she was afebrile, fever recurred on the 18th day of PIPC administration with progressive dyspnea and diffuse ground glass shadows on the chest X-ray. Bronchoalveolar lavage fluid (BALF) showed marked increase of total cell number and percentage of lymphocytes and a reduction of the ratio of CD4/CD8. Transbronchial lung biopsy (TBLB) specimen revealed interstitial infiltration of lymphocytes and histiocytes with granulomatous lesions. The drug lymphocyte stimulation test (DLST) was positive for PIPC. Based on these findings, the diagnosis of PIPC-induced pneumonitis was made. Recently, the incidence of drug-induced pneumonitis has increased, but to our knowledge this is a rare case report of PIPC-induced pneumonitis.

[A case of chronic thyroiditis with transient painful thyroiditis occurring after the administration of lipiodol].

We reported a female case of painful thyroiditis occurring after hysterosalpingography and investigated whether the destructive thyroiditis was iodine-induced. The patient, aged 28, had TBG deficiency and the previous episode of thyrotoxicosis caused by Graves' disease. Lipiodol (containing 4.8g of iodide in 10ml solution) was administered via vagina for hysterosalpingography. One month after the radiography, serum inorganic iodide and Tg were elevated abnormally, but she was asymptomatic. After the subsequent 3 months she developed a painful and 3rd grade-sized goiter with concomitant marked elevation of thyroid hormones and inorganic iodide and also high titer of MCHA (320(2)X). A dramatic response was obtained with steroid. Thereafter she was treated with acupuncture on the thyroid gland, resulting in a sudden reappearance of tender goiter. This traumatic thyroiditis disappeared successfully in 2 weeks with steroid treatment. The painful thyroiditis subsided in 5 months throughout the course and she remained euthyroid for the ensuing 2 years. Aspiration biopsy was performed twice and revealed lymphocytic thyroiditis. Values of serum Tg varied in good correlation with those of serum inorganic iodide or rT3 throughout the course, respectively (P < 0.01, P < 0.05). Significant correlations between FT4 and FT3, and also T4 and T3 were observed, respectively (P < 0.01, P < 0.05). Serum inorganic iodide was elevated to 316 micrograms/dl at the symptomatic stage of the thyroiditis and decreased to 170 micrograms/dl at the resolving phase 2 months after the inflammation. Iodide disappearance curve showed a diphasic slope. The BHL was calculated as 60.3 days during the symptomatic stage and 6.9 months in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)

[Supplemental studies on self-curing resins. 2. On polymerizing temperature of reline materials].

The objective of this study was to find the best way to keep down the peak temperature of self-curing reline materials. The experiments were done by using three kinds of self-curing reline materials (Rebaron, REBASE and KOOLiner) and three kinds of the reline materials of different thickness (1.5mm, 2mm and 3mm) under three different intraoral conditions. When these reline materials cured under rinsing the mouth with cold water (18 degrees C), the data analysis of these reline materials showed a considerable reduction in the peak curing temperatures clinical acceptance. The results obtained were as follows: 1. Both extraoral and interoral curing tests showed that the thicker the material is the higher the peak temperature becomes. 2. Highly significant differences in time to the peak temperature were found among the three kinds of reline materials. 3. Dangerously high temperature was found in polymerizing of the thickest material, 3mm.

[Influence of the anti-T4 autoantibody cross-reacting with T3 on serum T3 level determined by RIA].

We encountered a patient who showed remarkably high binding capacities of both 125I-T4 and 125I-T3, which suggests the presence of antithyroid hormone autoantibody. However, the serum level of T3 in the patient was not abnormal. Study of the specificity of anti-thyroid autoantibody revealed that the antibody present in the patient was the anti T4 antibody, which cross-reacted with T3. In addition, the binding capacity of the T4 autoantibody with T3 was inhibited by T4. Endogenous T4 is always present when T3 is determined by radioimmunoassay. Our findings indicate that the normal T3 level in the patient was because endogenous T4 inhibited the autoantibody binding with T3.