Hormone replacement therapy (HRT) has become available over the past few decades, but the risk of breast cancer with HRT remains controversial. The Women's Health Initiative Study has recently demonstrated that women receiving estrogen plus progestin (HRT) have an increased risk of invasive breast carcinoma, although women receiving estrogen alone (estrogen replacement therapy) exhibit no increased risk of breast carcinoma. By contrast, the risk of endometrial carcinoma increases with estrogen replacement therapy, while HRT reduces the risk of endometrial carcinoma. These clinical findings suggest that the biological roles of estrogen and progestin in tumorigenesis are certainly different between the endometrium and breast, although both are considered “estrogen-dependent tissues”. In this review, I summarize the recent studies and indicate that the enzymes responsible for intratumoral estrogen metabolism and biosynthesis are markedly different between human breast and endometrial carcinomas. 17β-hydroxysteroid dehydrogenases (17-HSDs) are enzymes estrogen replacement therapyinvolved in the formation of active sex steroids. Estrogens are interconverted by two enzymes, 17-HSD types 1 and 2. Type 1 converts estrone to estradiol, and type 2 catalyzes the reverse reaction. 17-HSD type 5 reduces androstenedione to testosterone. 17-HSD type 1 plays an important role in the regulation of high estradiol levels in breast carcinoma tissues, whereas 17-HSD types 2 and 5 appear to be essential for the maintenance of estradiol concentrations in endometrial carcinoma tissues. In addition, the biological significance of progesterone receptor isoforms differs between endometrial and breast carcinomas. These findings may provide new insights into the biology of “estrogen-dependent tissues”.
The Timed “Up & Go” (TUG) is a representative mobility test for assessing the falling risk of the elderly. Although several tests have been developed, including the TUG, these do not include a “tripping” element, and tripping is a major cause of falling. This study examined the influence of various obstacle heights on test performance in the TUG test and test-retest reliability. Twenty-two healthy elderly women participated in the TUG test and in the TUG test with an obstacle (TUGO). The obstacle is a box (width 120 cm and depth 20 cm), the height of which varies (0, 5 and 17 cm). In the 0-cm height condition, a thin sheet was laid down instead of the box. In the TUGO, subjects stood up from an armchair, walked 5 m, stepped over the box, turned, stepped over the box again, walked back to the chair and sat down. The reliability of the time required for the motion around the obstacle was high and the total time in the TUGO test increased (intra-class correlation coefficient = 0.74-0.99). These parameters were significantly larger for the height order 17, 5, and 0 cm and exhibited significant correlations with time required for the TUG (r = 0.61 - 0.92) and the height of subjects. An obstacle with 5 cm height prolonged the time during standing on one leg just before the obstacle and the time during turning motion after stepping over it. By adding the obstacle to the TUG, the physical mobility of the elderly is assessed more properly.
Panoramic dental radiographs are commonly used in general dentistry and oral and maxillofacial surgery to examine upper and lower teeth, maxilla, mandible and the surroundings simultaneously. Carotid artery calcification, a specific indicator of atherosclerotic change of the carotid arteries, can be seen on the radiographs. Many studies have suggested that cigarette smoking is a risk factor of atherosclerotic change as well as cerebral infarction. We hypothesized that smoking could increase the prevalence of carotid artery calcification, and compared the radiographs of smokers and non-smokers aged 50 years and over: 146 male smokers, 165 male non-smokers, 42 female smokers and 422 female non-smokers. This is the first study to focus on carotid artery calcification seen on panoramic dental radiographs to show the connection between smoking and atherosclerotic change. In male patients, carotid artery calcification was seen in 18 (14.1%) of the smokers, and in 8 (4.8%) of the non-smokers, which clearly shows that male patients aged 50 years old or over are more likely to develop carotid artery calcification if they smoke. However, there is no significant difference between female smokers and female non-smokers in the same age group. Dentists are in a good position to find carotid artery calcification on radiographs. When this is found on a radiograph, the patient should be advised to stop smoking and be referred to a physician for further tests. Clinicians should be aware that this radiographic finding indicates the presence of atherosclerotic change of the carotid arteries.
Size at birth has been proposed to be associated with the risk of type 2 diabetes and cardiovascular disease later in life. It is, however, unclear whether this association is attributed to an unfavorable intrauterine environment or to specific genotypes predisposing both altered fetal growth and common diseases in adult life. The aim of this study was to investigate the associations between the neonatal birth size and the genotypes of polymorphic loci within the insulin gene (INS) region, which is susceptible to diabetes mellitus. We analyzed the genotypes of two polymorphic loci; -23HphI and HUMTH01, in 520 pairs of normal Japanese mothers and their neonates, and compared with the somatoscopic characteristics at birth converted into standard deviation scores (SDS) according to sex, parity and gestational weeks at delivery. It was revealed that neonatal -23HphI T allele and HUMTH01 allele10, which are linked to the INS variable number of tandem repeats (VNTR) class III allele, were associated with increased weight, head circumstance, and length at birth. These associations confirmed that variation within the INS region, most probably at the INS-VNTR, influences fetal growth. Furthermore, the finding that the paternally transmitted -23HphI T allele was exclusively correlated with increased size at birth indicates the involvement of an imprinting mechanism. In conclusion, the INS-VNTR class III allele might accelerate fetal growth in a parent-specific manner.
Heat shock protein 72 (HSP72) and glycoprotein 96 (gp96) are highly expressed in cancer tissues. Recent studies indicate the possible roles of HSP72 and gp96 in the development and progression of gastric carcinomas but detailed information is still ambiguous. In this study, we investigated the correlation between clinicopathology and expression of HSP72 and gp96 in human gastric carcinoma. The expression of HSP72 and gp96 was studied in 60 human gastric carcinomas with or without metastasis as well as in mucous membrane adjacent to cancers by way of immunohistochemistry. HSP72 immunoreactivities were detected in 54 of 60 primary tumors (90.0%) and in 22 of 60 mucous membranes adjacent to cancers (36.7%). Likewise, gp96 immunoreactivities were detected in 49 cases of gastric carcinoma (81.7%) and in 15 samples of mucous membrane adjacent to cancer (25.0%). Both HSP72 and gp96 were stained in cytoplasm. HSP72 and gp96 expression in colonic carcinomas with metastasis was significantly higher than those with non-metastasis (p < 0.05). The results indicate that there exists a significant correlation between the expression of HSP72 and gp96 and the progression of gastric carcinomas. The high-level expression of HSP72 and gp96 may be used as diagnostic or prognostic markers for gastric carcinoma.
There is increasing evidence that nuts have protective effects against coronary artery disease by improving lipid profile and inhibiting lipid oxidation. However, data about pistachio nuts are limited, and to our knowledge, there is no study investigating the effects of pitachio intake on lipid oxidation and serum antioxidant levels. This study, therefore, sought to determine the effects of pistachio intake on serum lipids and determine whether consumption of pistachio would alter serum antioxidant levels. Rats were randomly divided into three groups (n = 12 for each): control group fed basic diet for 10 weeks and treated groups fed basic diet plus pistachio which constituted 20% and 40% of daily caloric intake, respectively. Consumption of pistachio as 20% of daily caloric intake increased high-density lipoprotein (HDL) levels and decreased total cholesterol (TC)/HDL ratio, compared with those not taking pistachio. However, TC, low-density lipoprotein (LDL) cholesterol and triglyceride levels were unaffected by pistachio consumption. Consumption of pistachio as 20% of daily caloric intake increased serum paraoxonase activity by 35% and arylesterase activity by 60%, which are known to inhibit LDL cholesterol oxidation, compared with the control group. However, increased antioxidant activity was blunted when pistachio intake was increased to 40% of daily caloric intake. In conclusion, the present results show that consumption of pistachio as 20% of daily caloric intake leads to significant improvement in HDL and TC/HDL ratio and inhibits LDL cholesterol oxidation. These results suggest that pistachio may be beneficial for both prevention and treatment of coronary artery disease.
Diagnosis of drug-induced pneumonia, which represents pulmonary toxicity caused by certain drugs, is difficult, as a large number of different drugs can elicit various immune-mediated diseases with distinct pathomechanisms. The drug-induced lymphocyte stimulation test (DLST) is widely used for diagnosing drug-induced pneumonia in Japan. Recent reports, however, indicate that DLST is not reliable for diagnosis of drug-induced pneumonia. To diagnose drug-induced pneumonia, a provocation test with the suspected drug is the most reliable method of assessing the relationship between the drug and pneumonia. We examined the correlation between the DLST and the provocation test in 6 cases of suspected drug-induced pneumonia. DLST was performed in all of the patients. The causes of pneumonia in all patients were confirmed by a provocation test. The DLST was positive in 3 of 6 cases of suspected drug-induced pneumonia, but the suspected drugs were ruled out by the provocation test. If we had relied solely on the DLST, these 3 cases would have been labeled as false allergy. The results of the DLST did not coincide with the results of the provocation test in any of the cases. Our results suggest that the DLST is not useful for the diagnosis of drug-induced pneumonia. Following provocation with the causative drug, reappearance of pulmonary infiltration was not observed in any of the cases. These findings indicate that a carefully performed provocation test is the safe and most reliable method.
With the increase of the patients with prostate cancer, the number of radical prostatectomy increased prominently. Meanwhile, surgeons and pathologists have difficulty regarding appropriate surgical dissection of the prostate and the pathological diagnosis. These problems are derived from uncertainty or misunderstanding about the precise anatomy. In fact, many surgeons are not confident of the structures of the prostatic gland, its surrounding capsules, and the sphincter. Here we investigated the surgical anatomy of the normal prostate to provide beneficial information regarding radical prostatectomy and subsequent pathological diagnosis. A 40 year-old cadaver with a history of sudden cardiac arrest was utilized in this study. Whole pelvic organs were extirpated en bloc and fixed in formalin. Whole mount step sections from the membranous urethra to the seminal vesicle were prepared and histologically examined. It has been reported that the prostatic parenchyma is covered with outside layer (lateral pelvic fascia) and inside layer (prostatic fascia, also known as “capsule”). Here, we show that nearly one third of the anterior surface of the apical region of the prostate (apical prostate) lacks this “capsule”. The apical prostate is a mixture of striated muscles, glands, and elastic fibers. Furthermore, the glandular tissue exists within the anterior fibromuscular stroma and some region of the “capsule”. Surgeons often try to preserve neurovascular bundles to maintain erectile function; however, other neural tissue was also observed over the entire surface of the prostate. Surgeons must be aware of these complicated anatomical structures when undertaking radical prostatectomy and subsequently diagnosing extra-prostatic extension.
Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are widespread contaminants in the environment, as well as in wildlife and in humans. The PFOS and PFOA concentrations were determined in historical human serum samples collected in Shenyang, China, in 1987 (n = 15), 1990 (n = 33), 1999 (n = 68) and 2002 (n = 119). The serum donors were students, faculty members and university workers. Since the serum PFOA and PFOS levels did not follow a normal or log-normal distribution, a nonparametric method was applied to analyze the historical trends. For the total male and female subjects, the median level of serum PFOA increased significantly from 0.08 μg/l in 1987 to 4.3 μg/l in 2002 (p < 0.05), while the median level of serum PFOS also increased significantly from 0.03 μg/l in 1987 to 22.4 μg/l in 2002 (p < 0.05). Both the serum PFOA and PFOS levels continued to increase from 1999 to 2002, with remarkable increases observed in females: 6.3-fold increase for PFOA and 13-fold increase for PFOS. In 2002, serum PFOA and PFOS concentrations of female subjects have increased to 4.9 μg/l and 22.4 μg/l in median, respectively, which are comparable to those in U.S.A. and Japan. For male subjects, serum PFOA and PFOS concentrations (1.6 μg/l and 8.3 μg/l in median, respectively) are comparable to those in Italy. The data from this study indicate that females are likely to experience higher exposure to these chemicals.
Although quality of life (QOL) assessment is important in dentistry, it has not been fully investigated in orthodontic patients. We investigated the health-related generic QOL (entire body health) and disease specific QOL (oral health) in adult patients with malocclusions at the first visit. One hundred and twenty-seven orthodontic patients and 66 persons with normal occlusion were recruited for the study. The subjects were divided into the three following groups based on their treatment: 61 patients in need of surgical correction (SURG), 66 patients in need of non-surgical correction (NONS), and 66 control subjects with normal occlusion. Their dentofacial morphology was assessed using a specific Severity Score (SS), which was set up originally based on their cephalometric radiographs and their plaster models of arrangement of their teeth. The subjects also completed a generic QOL assessment questionnaire, the SF-36, and two disease-specific QOL instruments. The patients with malocclusions, especially SURG, had lower disease-specific QOL, although the generic QOL was equal to that of control subjects. Furthermore, in patients with the same severity of dentofacial deformities, especially SS 4 and SS 5, the borderline cases of surgical correction and non-surgical correction, there were differences between SURG and NONS in some items of the QOL. The severity of malocclusion evidently plays an important role in patients' choice of treatment, but also QOL appeared to play a significant role. The QOL assessment may contribute to the selection of the best treatment for improving QOL, especially for borderline cases with moderate degrees of orthodontic abnormality.
The process of glomerular development consists of four developmental stages: vesicle (V) stage, S-shaped body (S) stage, capillary loop (C) stage and maturation (M) stage. However, the development of glomerular endothelial, mesangial and epithelial cells in fetal and infant kidneys remains unclear. In order to determine the characteristics of human glomerular development, we investigated the process of glomerular development by staining fetal and infant kidneys for CD31, CD34 and FB21, markers for endothelial cells, α-smooth muscle actin (α-SMA), a marker for mesangial cells, and nephrin, a marker for podocytes. These series of studies were carried out on kidneys obtained at autopsy from 27 fetuses and 5 infants. The fetuses were divided into the following 5 groups according to gestational age; 13-19, 20-24, 25-29, 30-34 and 35-39 weeks. In each group, glomerular development was classified according to the developmental stage and the staining patterns for CD31, CD34, FB21, α-SMA and nephrin. The proportion of V-stage development in 100 glomeruli examined was highest at 13-19 weeks. After 20 weeks, the V-stage proportion decreased gradually, and the proportion of S stage became highest at 20-24 weeks. The C-stage proportion was highest at 25-29 weeks, while the M-stage proportion was highest in infants aged 1-6 months. The staining patterns for CD31, CD34 and FB21 were similar in endothelial cells after 25 weeks of gestation. Staining of α-SMA and nephrin was first observed in the S stage. In conclusion, maturation of endothelial cells starts at 25 weeks and is completed by 35 weeks of gestation. Epithelial cells and mesangial cells first appear during the S stage.