Nanoparticles (NP) are organic or inorganic substances, the size of which ranges from 1 to 100 nm, and they possess specific properties which are different from those of the bulk materials in the macroscopic scale. In a recent decade, NP were widely applied in biomedicine as potential probes for imaging, drug-delivery systems and regenerative medicine. However, rapid development of nanotechnologies and their applications in clinical research have raised concerns about the adverse effects of NP on human health and environment. In the present review, special attention is paid to the fetal exposure to NP during the period of pregnancy. The ability to control the beneficial effects of NP and to avoid toxicity during treatment requires comprehensive knowledge about the distribution of NP in maternal body and possible penetration through the maternal-fetal barrier that might impair the embryogenesis. The initial in vivo and ex vivo studies imply that NP are able to cross the placental barrier, but the passage to the fetus depends on the size and the surface coating of NP as well as on the experimental model. The toxicity assays indicate that NP might induce adverse physiological effects and impede embryogenesis. The molecular transport mechanisms which are responsible for the transport of nanomaterials across the placental barrier are still poorly understood, and there is a high need for further studies in order to resolve the NP distribution patterns in the organism and to control the beneficial effects of NP applications during pregnancy without impeding the embryogenesis.
Breast apocrine carcinoma is a rare malignancy characterized histologically by a predominance of acidophilic tumor cells exhibiting apocrine metaplasia. Apocrine tumors represent only about 0.4% of all breast cancers. Many cases are diagnosed at stage I or II; thus, the prognosis is better than that for other types of breast cancer. Here we present a 57-year-old female patient with primary apocrine breast carcinoma that was incidentally discovered by endometrial cytology. The patient had undergone routine uterine cancer screening at the age of 56 with resulting positive endometrial cytology. Subsequent histological examination of an endometrial biopsy revealed suspected metastatic uterine adenocarcinoma. Further evaluation revealed a 3-cm mass in the left breast, which was histopathologically diagnosed as breast cancer. Dual procedures were performed at the departments of gynecology and breast surgery. The patient underwent a modified radical mastectomy of the left breast and left axillary lymph node dissection. Laparotomy revealed multiple adhesions throughout the peritoneal cavity that suggested invasive metastatic cancer, and a right adnexectomy was performed. Histopathological examination of the resected left breast and right ovary tissues revealed apocrine carcinoma. Thus, stage IV breast cancer was diagnosed. The patient finished 6 cycles of paclitaxel and is now under observation on an outpatient basis. In this patient, breast cancer was discovered incidentally through a detailed work-up after a positive result of endometrial cytology. Uterine cancer screening has the potential, although rare, to detect metastatic cancer originating elsewhere. This should be taken into consideration during the work-up due to positive endometrial cytology.
Coronary artery anomalies are rarely encountered in general population. Gender may play a role in the types and incidence of coronary artery anomalies, although the effect of gender is not well established. In the present study, we therefore aimed to investigate the frequency and location of various types of coronary artery anomalies and their correlation with gender. We assessed retrospectively the coronary angiography movies of 7,810 patients (2,214 females and 5,596 males), the method of which is distinct from the earlier studies with angiographic archive records. We defined and classified the coronary artery anomalies according to their origin, course (myocardial bridge), and termination (fistula). The incidence of coronary artery anomalies was 3.35% (262 of 7,810): 130 individuals with anomalous origin (1.66%), 105 individuals with myocardial bridges (1.34%), and 27 with fistulas (0.35%). The frequency of the coronary artery anomalies was significantly higher in the females than the males (p = 0.001). Of the coronary artery origin anomalies, the circumflex and the left anterior descending artery originating from separate ostia in the left aortic sinus were higher in the females compared to the males (P < 0.001). In contrast, the frequency of myocardial bridges was higher in the males (P = 0.01). No gender difference was detected in fistulas. Thus, gender affects the types of coronary artery anomalies, except for fistulas. The determination of the presence of the coronary artery anomalies during the coronary angiography is critical for the planning of the treatment and for the proper clinical follow-up of patients.
Medical education in Japan has undergone significant reforms. Patient perspective and outcome have been highly valued in curricular reforms. Therefore, we evaluated an undergraduate curriculum particularly on communication skills by comparing outpatient satisfaction before and after the reforms implemented at Saga Medical School. Cross-sectional study was conducted at the General Medicine Clinic of Saga University Hospital in 1999 and 2009. A total of 729 newcomer patients evaluated 159 students; namely, 287 patients evaluated sixth-year medical students (n = 82) in 1999, and in 2009, 442 patients evaluated fifth-year medical students (n = 77). Students interviewed newcomer patients prior to a faculty's clinical examination. After a student-patient encounter, the patient was asked to fill in six-item Patient Satisfaction Questionnaire (PSQ) developed by the American Board of Internal Medicine. Mixed model two-way analysis of variance (ANOVA) with covariant of students' gender was conducted. Effect sizes were calculated to evaluate the amplitude of influence. The average score in 2009 was significantly higher than that in 1999 (3.63 ± 0.62 versus 3.36 ± 0.66; p < 0.001). Since the “encouraging and answering questions” and “clear explanations” were lower than those of the other items (3.24 ± 0.98 and 3.46 ± 0.85), these two items showed the most significant improvements (Phi coefficient = 0.31 and 0.24, p < 0.001). Thus, students' performance has improved since 1999, which may represent the success of curricular reforms at Saga Medical School. We propose that “encouraging and answering questions” and “clear explanations” should be emphasized in interview training.
Open heart surgery for infants with low body weight (BW) remains still a challenge. Pulmonary artery banding (PAB) is a useful surgical palliation for small neonates and early infants with excessive pulmonary blood flow who are unable to withstand a heart surgery. This study retrospectively reviewed neonates and infants who underwent PAB to assess the surgical results and the validity of our PAB. We selected 38 acyanotic infants and neonates and divided them into 2 groups: low BW (< 2.5 kg, n = 15, group L) and normal or high BW (≥ 2.5 kg, n = 23, group NH). The average BW at the time of PAB was 2.8 ± 1.1 kg (range, 1.2-5.8 kg), and the average age at the time of PAB was 41.8 ± 44.8 days (range, 2-151 days). Using a 3-mm-wide polyester tape, we tightened the main pulmonary artery to obtain the circumference of (19 mm + 1 mm for each kg of BW). There was no early death but one late death in each group. Postoperative BW continuously increased 1 month after PAB in both groups, although BW was significantly lower in group L than in group NH. Intracardiac repair (ICR) was accomplished in 31 patients (13 in group L and 18 in group NH) at average ages of 1.5 years, while the remaining 5 patients are awaiting ICR. In conclusion, PAB using our formula for the infants even weighing < 2.5 kg has low mortality and is effective as a bridge to ICR.
In vitro gene expression profiling with isolated hepatocytes has been used to assess the hepatotoxicity of certain chemicals because of animal welfare issues. However, whether an in vitro system can completely replace the in vivo system has yet to be elucidated in detail. Using a focused microarray established in our laboratory, we examined gene expression profiles in the mouse liver and primary cultured hepatocytes after treatment with different doses of acetaminophen, a widely used analgesic that frequently causes liver injury. The acute hepatotoxicity of acetaminophen was confirmed by showing the induction of an oxidative stress marker, heme oxygenase-1, elevated levels of serum transaminase, and histopathological findings. In vivo microarray and network analysis showed that acetaminophen treatment provoked alterations in relation to the inflammatory response, and that tumor necrosis factor-α plays a central role in related pathway alterations. By contrast, pathway analyses in in vitro isolated hepatocytes did not find such prominent changes in the inflammation-related networks compared with the in vivo situation. Thus, although in vitro gene expression profiles are useful for evaluating the direct toxicity of chemicals, indirect toxicities including inflammatory responses mediated by cell-cell interactions or secondary toxicity due to pathophysiological changes in the whole body may be overlooked. Our results indicate that the in vitro hepatotoxicity prediction system using isolated hepatocytes does not fully reflect the in vivo cellular response. An in vitro system may be appropriate, therefore, for high throughput screening to detect the direct hepatotoxicity of a test compound.
Citrin deficiency (CD) is an autosomal recessive disorder with SLC25A13 as causative gene that encodes citrin, the liver-type aspartate/glutamate carrier isoform 2 (AGC2). Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), the major CD phenotype at pediatric age, has been previously reported as a self-limiting condition with clinical presentations resolving between 6 months and 1 year of life. We report the prenatal diagnosis of CD in a family with a fatal NICCD proband. The proband was a 10-month-old male presenting cough for 8 days and jaundiced skin 1 day. Physical examination revealed fever, dark jaundiced sclera and skin, hoarse breathing sounds, and hepatosplenomegaly. Laboratory tests uncovered elevated cholestatic indices, increased ammonia, and prolonged activated partial thromboplastin time and prothrombin time, and reduced fibrinogen. Sonography showed the features of liver cirrhosis. Metabolome analysis uncovered large quantity of 4-hydroxyphenyllactate and dicarboxylates in urine and increased citrulline and methionine in blood. The patient passed away due to liver failure at his age of 13.5 months. Mutation analysis revealed him a homozygote of 851del4, a four-base deletion in exon 9 of SLC25A13 gene. On request of the parents who had a second fetus, prenatal diagnosis of CD was performed by PCR-electrophoresis following amniocentesis and amniocyte culture, and demonstrated the fetus a carrier of the same mutation. The fatal proband in the present report has provided clinical evidence challenging the traditional concept on NICCD prognosis. Moreover, as the first trial on CD prenatal diagnosis, this study might open a novel area for clinical management of CD.
Creutzfeldt-Jakob disease (CJD) is a progressive disease that is characterized by the accumulation of abnormal prion-like proteins in the central nervous system. The cerebral cortex is primarily affected in CJD, leading to spongiform changes and dementia. To date, there have been no reported cases of CJD, with local neuroparalysis discovered at an early stage of the disease. Here, we describe a patient who presented unilateral vocal cord and soft palate paralysis before the progression of CJD. After developing forgetfulness 6 months ago, a 76-year-old woman was presented at department of Otorhinolaryngology in a general hospital for recently developed hoarseness and dysphagia. In the oral and laryngeal endoscopic findings, unilateral paralysis of the vocal cord and soft palate was noted. On videofluorography, the larynx failed to elevate straight on swallowing. The right tongue pharyngeal wall was lax, and some contrast agent was retained in the lower right piriform sinus. The paralysis was thought to be due to the glossopharyngeal nerve or vagal nerve damage, which was caused by peripheral nerve injury or infranuclear palsy. Diffusion-weighted magnetic resonance imaging (MRI) revealed high signals in the cerebral cortical area (a signature feature of CJD). The patient died 2.5 years after the onset of illness. The patient was diagnosed as probable sporadic CJD. Since we could not detect any peripheral organic findings that could cause the paralysis, we suspect that CJD is responsible for the paralysis. In treating CJD patients with neurological signs, exclusive investigation is required to obtain a more detailed picture of the disease.
Impaired wound healing in surgical patients with diabetes increases the incidence of infection, prolongs hospitalization, and even increases the rate of mortality. Low-energy extracorporeal shock wave treatment (ESWT) was reported to accelerate chronic wound healing by promoting revascularization and tissue regeneration; however, it is not known if ESWT could also improve healing of acute surgical incisional wounds in diabetes. In this study, using a rat model of diabetes, we investigated the effect of low-energy ESWT on collagen content in wound tissues and its efficacy in incisional wound healing. A single dorsal incisional wound was inflicted in streptozotocin-induced diabetic rats, and they received ESWT at different time post-wounding. Rats were sacrificed on days 7 and 14 post-wounding. Wound breaking strength, hydroxyproline content, histological characteristics and the expression of transforming growth factor beta 1 (TGF-β1) were analyzed. As a result, the wound breaking strength was significantly enhanced and the hydroxyproline content in wound tissues was increased at each time point examined. The number of fibroblasts was signicantly increased, and the new collagen fibers were more abundant at the wound site after ESWT. Furthermore, the expression of TGF-β1 was up-regulated after ESWT on day 7 post-wounding. These results suggest that low-energy ESWT can increase collagen content, enhance wound breaking strength and improve the healing of incisional wound in diabetic rats. The increased collagen content may be attributed, at least in part, to the up-regulation of TGF-β1 expression in wound tissues.
Nursing assistants can work without a professional certification to help registered nurses and licensed practical nurses. Nursing assistants engage in various tasks, e.g., washing laundry, cleaning up, and clerk tasks regarding nursing. Enhancing work motivation among nursing assistants is essential for every hospital, because when nursing assistants do their jobs well, it allows registered nurses and licensed practical nurses to complete their own specialized jobs. We examined the predictors significantly associated with nursing assistants' work motivation. For those predictors, we produced items to examine job satisfaction. Those items are classified into intrinsic and extrinsic facets. The subjects for this study were Japanese nursing assistants working in 26 hospitals with 62-376 beds (4 public and 22 private hospitals). A total of 516 nursing assistants were analyzed, with the average age and standard deviation of 42.7 ± 12.9 years; the age of 456 female subjects was 43.8 ± 12.7 years and that of 60 male subjects was 34.3 ± 11.0 years. Our results show that “work motivation” is significantly associated with “free time to do one's own things,” “nursing assistants as important partners on the job,” “feeling helpful to patients,” “participating in decision making,” and “job-skill improvement.” Free time to do one's own things is an extrinsic item. Hospital administrators must monitor the workload and their quality of life among nursing assistants. All the other significant items are intrinsic. Nursing assistants are not only motivated by money. They highly value the intrinsic nature and experience of their jobs.
Subacute thyroiditis is a painful, inflammatory disease frequently accompanied with fever. It is suspected to be a viral infectious disease, while Graves' disease is an autoimmune disease. Thus, there appears to be no etiological relationship between the two diseases. A total of 25,267 thyroid disease patients made their first visits to our thyroid clinic during a period of 24 years between 1985 and 2008. Among them, subacute thyroiditis and Graves' disease accounted for 918 patients (3.6%) and 4,617 patients (18.2%), respectively. We have encountered 7 patients (one male and six female) with subacute thyroiditis followed by Graves' disease in this period (0.15% of the 4,617 patients with Graves' disease and 0.76% of the 918 patients with subacute thyroiditis). The age ranges were 40~66 years (mean 48.7 years) at the onset of subacute thyroiditis. The intervals between the onsets of subacute thyroiditis and Graves' disease were 1~8 months (mean 4.7 months). Because Graves' disease was preceded by subacute thyroiditis, the signs and symptoms of both diseases were evident together in the intervening period. The diagnosis of Graves' disease in those patients is always difficult because of atypical signs and symptoms and an unclear onset time. The causes of the Graves'disease that followed subacute thyroiditis are still unknown. However, the inflammatory nature of subacute thyroiditis may lead to the activation of the autoimmune response in susceptible subjects, resulting in the onset of Graves' disease. Graves' disease should be suspected when a high blood level of thyroid hormone persists after subacute thyroiditis.
Spermatogenesis is a highly coordinated physiological process that requires the correct expression and functions of thousands of developmentally regulated genes. The regulation of spermatogenesis is not well defined, since majority of the related genes have neither been identified nor fully characterized. Hence, it is meaningful to identify and characterize these genes to reveal the mechanism underlying spermatogenesis. In this study, using digital differential display, we identified a novel human testis-specific gene, testis developmental related gene 1 (TDRG1, GenBank DQ168992), via electronic subtraction of human testis UniGene databases from those of non-reproductive tissues. The transcript of the TDRG1 gene has an open-reading frame that encodes 100 amino acids. We next prepared the anti-TDRG1 monoclonal antibody 10B6 and confirmed that it specifically recognizes an 11-kDa protein in the tissue extracts from an adult human testicular sample (age 31 years) by Western blot analysis. RT-PCR coupled with immunohistochemistry of human tissues demonstrated that TDRG1 is exclusively expressed in the testis but not in any other non-reproductive tissues. TDRG1 is mainly located in spermatogenic cells in seminiferous tubules of adult testis. Furthermore, TDRG1 shows the highest expression level in human post-puberty testis, with the expression levels decreasing afterwards with aging. Importantly, TDRG1 mRNA is undetectable in the fetal testis, as judged by RT-PCR. In conclusion, TDRG1 is a developmentally regulated testicular-specific gene. We suggest that TDRG1, a newly identified testis-specific gene, may play important roles in human spermatogenesis.