2,3,7,8-tetrachlorodibenzo-p-dioxin augments the modulation of gene expression mediated by the thyroid hormone receptor

Previously, we reported on genes whose expression was highly modulated by T3 in the HeLaTR cells that stably expressed the thyroid hormone receptor (TR). In this study, we examined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on TR-mediated gene expression. In the HeLaTR cells, T3 induced the expression of the reporter gene in a thyroid hormone responsible element (TRE)-dependent manner. When the cells were cultured in the presence of T3, the addition of TCDD but not 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl (PCB-OH), bisphenol A (BPA), or di(2-ethylhexyl)phthalate (DEHP) to the culture media further enhanced the T3-induced expression of the reporter gene. RT-PCR revealed that mRNA levels of 4-1BB, fmfc, PSCA, PSG7, RANTES, and TRAF1, which were highly increased by T3, were further elevated in cells exposed to T3 and TCDD. Also, the mRNA level of BMP6, which was decreased by T3, further declined in the cells exposed to both T3 and TCDD. In contrast to the effect of TCDD, PCB-OH suppressed the modulation of these gene expressions by T3. Neither TCDD nor PCB-OH alone affected the expression of 4-1BB, fmfc, PSCA, PSG7, RANTES, TRAF1, or BMP6. These results indicate that TCDD augments the cellular responses to T3 by hyperactivating TR-mediated gene expression, whereas PCB-OH suppresses cellular responses to T3 by negatively regulating it. Based on these findings, enzyme-linked immunosorbent assay (ELISA) for the PSCA protein in the HeLaTR cells was established. Such assays will be useful to monitor the effects of endocrine disrupting chemicals (EDCs) on TR-mediated gene expression.     

Small lung tumors with the size of 1cm or less in diameter: clinical, radiological, and histopathological characteristics

BACKGROUND: The detection rate of small nodules in the peripheral lung area is increasing due to the widespread use of CT scanning. However, the radiological and pathological characteristics of very small tumors have not been fully investigated. METHODS: We evaluated 44 lung tumors with the size of 1cm or less in diameter resected from 38 patients (19 men and 19 women, with an average of 62 years) from 1997 through 2001. The clinical records, the findings of high-resolution CT (HRCT) and histopathological features of resected specimens were analyzed. Adenocarcinoma was histologically further subclassified into types A to F according to the Noguchi's classification. RESULTS: Lobectomy was performed in 20 patients, wedge resection in 15 and segmentectomy in 3, respectively. Thirty-two tumors were adenocarcinomas, 4 were squamous cell carcinomas, and eight were atypical adenomatous hyperplasia (AAH), respectively. All carcinoma cases were proved to be stage IA. In adenocarcinoma, type A was detected in 12 tumors, type B in 13, type C in 1, type D in 2, type E in 1, and type F in 3, respectively. Most of AAH and type A showed pure ground-glass attenuation on HRCT scan, whereas types B to F as well as squamous cell carcinoma frequently had malignant CT signs such as lobulation and convergence of peripheral vessels. Lymphatic or vascular invasion was observed in two adenocarcinomas (types D and F) and two squamous cell carcinomas, and HRCT scan of these four tumors showed soft-tissue attenuation occupying more than two-thirds of each nodule. All patients are currently alive without signs of recurrence after a mean follow-up period of 35.5 months. CONCLUSION: Types A and B of adenocarcinoma were the most common histologic types among lung tumors with the size of 1cm or less in diameter. Limited lung resection appears to be an adequate for such small lung tumors in which soft-tissue attenuation consists of less than two-thirds of the nodule on HRCT.     

Effectiveness of measuring bone mineral density in preventing osteoporosis

A self-administrated questionnaire was performed to clarify the actual circumstances of community-based screening for osteoporosis. The results revealed that only 25 percent of communities performed follow-up of high-risk participants, representing a disappointing result for assessing evidence of the benefits of measuring bone mineral density in preventing osteoporosis. Secondly, a review of the literature was performed to clarify the benefits of measuring bone mineral density in preventing osteoporosis. The review revealed that increased measurements could predict fractures among elderly and peri- and postmenopausal women, and elderly men.     

Bilateral coronary ostial stenosis after aortic valve replacement with freestyle stentless bioprosthesis: a case report

An 80-year-old woman underwent aortic valve replacement with Freestyle stentless prosthetic valve for the stenosis. Four months later, she was admitted with myocardial ischemia. Coronary angiography revealed severe stenosis in the ostium of both right and left coronary arteries. Coronary artery bypass grafting was performed. One year later, percutaneous coronary intervention was carried out for the bilateral coronary arteries because of unstable angina. Intravascular ultrasonography demonstrated localized, membranous, homogeneous, and severe stenoses in the ostium of the right and left coronary arteries. Histological examination of a specimen taken by directional coronary atherectomy showed intimal hypertrophy, mucinous degeneration, and hyaline degeneration without reactive change. There were no findings of atherosclerosis. These clinical, angiographical histological and intravascular ultrasonography findings suggest that the immunological reaction to the heterograft was the mechanism of the bilateral ostial coronary arteries stenoses in the present case. The possibility of immunological reaction after aortic valve replacement with heterograft should be considered. There have been no report on intravascular echocardiographic and histological findings.     

Coexistence of spindle cell lipoma and ordinary lipoma

We report a patient with a spindle cell lipoma on the nape and three ordinary lipomas on the abdomen and extremities. The coexistence of spindle cell lipoma and ordinary lipoma in a single patient is rare. Abundant CD34-positive spindle cells and mast cells were found in the spindle cell lipoma, but in the ordinary lipomas, only a small number of CD34-positive spindle cells were found in the interstitial connective tissue and no mast cells were seen. Because mast cells are known to stimulate mesenchymal cell proliferation and collagen production, mast cell infiltration may be a trigger for the proliferation of CD34-positive spindle cells, leading to the conversion of ordinary lipoma into spindle cell lipoma.     

Expression profile of mRNAs from rat hippocampus and its application to microarray

Stress refers to physiological or psychological stimuli that disrupt homeostasis and induce pathophysiological conditions due to maladaptive response, sometimes resulting in mental disorders including depression and post-traumatic stress disorder. Severe stress has been shown to induce neuronal atrophy and apoptosis, especially in the hippocampus, which is thought to be a region of the brain important in stress-related disorders. We have analyzed gene expression in rat hippocampus comprehensively to clarify the molecular mechanism of stress-related disorders. In the present study, we identified and catalogued 13,660 partial complementary DNA sequences (expressed sequence tags (ESTs)) of randomly selected clones from a cDNA library of rat hippocampus. Sequence analysis showed that these clones cluster into 7173 non-redundant sequences comprising 1794 clusters and 5379 singletons. As a result of nucleotide and peptide database search, 2594 were found to represent known rat sequences. Of the remaining 4579 genes, 599 non-redundant ESTs represent rat homologs of genes identified in other species or new members of structurally related families. In addition, we illustrate the use of these clone sets by constructing a cDNA microarray focused on genes categorized into "cell/organism defense". These ESTs and our own microarray thus provide an improved genomic source for molecular studies of animal models of stress-related disorders.     

Efficacy of the herbal medicine Unkei-to as an adjunctive treatment to hormone replacement therapy for postmenopausal women with depressive symptoms

OBJECTIVE: Although hormone replacement therapy (HRT) improves menopausal depressive symptoms, women unresponsive to HRT need an antidepressant drug as an effective adjunctive therapy. The aim of this study was to assess whether the herbal medicine Unkei-to has an impact on HRT-resistant menopausal depressive symptoms as an effective adjunctive therapy combined with HRT. METHODS: Twenty-four HRT-resistant menopausal depressive women were randomly assigned to group 1 (n = 12) or group 2 (n = 12). Subjects in group 1 were accessioned into 6 months of open treatment with Unkei-to as an adjunctive therapy and changed to Toki-shakuyaku-san for 6 months following a 1-month washout period. Group 2 started with Toki-shakuyaku-san for 6 months and then changed to Unkei-to for 6 months following a 1-month washout period. RESULTS: Three months' treatment with Unkei-to as an adjunctive therapy significantly improved Zung's Self-Rating Depression Scale (ZSDS) scores, State-Anxiety (STAI-1) scores, and Trait-Anxiety (STAI-2) scores noted before treatment, and this effect continued at 6 months. Treatment with Unkei-to was also significantly effective in reduction of ZSDS scores, STAI-1 scores, and STAI-2 scores at 3 months compared with Toki-shakuyaku-san treatment, and this effect continued at 6 months. CONCLUSIONS: Unkei-to is another option as an adjunctive herbal therapy in HRT-resistant menopausal depressive women.     

Inhalant use, abuse, and dependence among adolescent patients: commonly comorbid problems

OBJECTIVE: Little is known about adolescents with DSM-IV-defined inhalant abuse and dependence. The aim of this study was to compare comorbidity among (1) adolescents with inhalant use disorders, (2) adolescents who reported using inhalants without inhalant use disorder, and (3) other adolescent patients drawn from an adolescent drug and alcohol treatment program. METHOD: The authors examined 847 admissions of patients who had completed structured diagnostic assessments. The three groups were compared for noninhalant substance use disorders, posttraumatic stress disorder, conduct disorder, major depression, previous suicide attempts, and physical/sexual abuse and neglect. RESULTS: Adolescents with inhalant abuse or dependence (group 1; n = 28) were significantly more likely to meet lifetime criteria for abuse or dependence on alcohol, hallucinogens, nicotine, cocaine, and amphetamines, to have had major depression, and to have attempted suicide compared with other adolescent patients who reported never using inhalants (group 3); adolescents with inhalant use disorders also reported significantly more abuse and neglect. Adolescents with inhalant abuse or dependence (group 1) did not differ significantly on any measure compared with adolescents who reported using inhalants without an inhalant use disorder (group 2). CONCLUSIONS: Adolescent patients with a history of inhalant use, abuse, or dependence entering treatment should be carefully screened for noninhalant substance use disorders, major depression, suicidality, and abuse and neglect.     

Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease

Neprilysin (NEP), also known as neutral endopeptidase, enkephalinase, CD 10, and common acute lymphoblastic leukemia antigen, is a 97-kD protein. NEP can degrade amyloid beta peptides, and its mRNA and protein levels are known to be reduced in the brains of patients with Alzheimer's disease (AD), making the NEP gene a substantial candidate for an AD risk factor. We examined the genetic association of three NEP polymorphisms, a GT-repeat polymorphism and two single nucleotide polymorphisms (SNPs, -1075A>G and -1284G>C) in its promoter region, with AD in a Japanese case-control sample (240 patients and 163 controls). The GT-repeat polymorphism, but not the SNPs, was significantly associated with late-onset AD (p = 0.0007). Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.