Regional brain cerebral glucose metabolism and temperament: a positron emission tomography study

Personality, and in particular temperament, is thought to have a biological basis. In the present study, the relationships between regional brain glucose metabolism and temperament have been investigated. Regional brain glucose metabolism was measured using [18F] fluorodeoxyglucose positron emission tomography in 31 healthy subjects. Temperament was assessed using the Temperament and Character Inventory. Temperament dimensions were observed to be significantly correlated with specific brain regions. In particular, novelty seeking was significantly correlated with the superior temporal gyrus, inferior parietal lobule, and the precuneus, which have been reported to be related with impulsiveness, while reward dependence was significantly correlated with the caudate head, which has been shown to be associated with reward processing. The various aspects of temperament may have biological bases in the specific brain regions. The accumulation of results from studies of this kind should provide further evidence connecting personality traits with their biological bases.     

Osteosarcoma in a patient with neurofibromatosis type 1: a case report and review of the literature

Neurofibromatosis type 1 (NF1) or von Recklinghausen's disease is a genetic disease generally characterized by café-au-lait spots and neurofibromas. Malignant tumors of the nervous system, such as malignant schwannomas, gliomas, or astrocytomas, have been well known to coexist with neurofibromatosis. However, occurrence of malignant tumors unrelated to the nervous system is rare. We report an unusual case of a 29-year-old NF1 female suffering from malignant peripheral nerve sheath tumor (MPNST) that eventually developed osteosarcoma in the proximal femur. Osteosarcoma is the most common high-grade malignant bone tumor in which the neoplastic cells produce osteoid. At 23 and 24 years old, she underwent excision of MPNST in the left posterior thigh. No osteosarcomatous portion was identified in these specimens. The patient underwent postoperative chemotherapy. At 29, left proximal thigh pain and swelling appeared. Computed tomography demonstrated cortical bone destruction in the left proximal femur where MPNST occurred. Magnetic resonance imaging revealed extraskeletal growth of the tumor. Bone scintigraphy demonstrated increased uptake in the left proximal femur. Hip disarticulation was performed. The removed tumor was composed of highly anaplastic cells. Lace-like irregular osteoid formation was observed among the tumor cells. MPNST component was totally absent. The tumor was diagnosed as osteoblastic type osteosarcoma. Two months after disarticulation the patient died of bilateral pulmonary metastasis. The correlation between the histogenesis of osteosarcoma and the genetic abnormality in NF1 patients has not been elucidated, but the finding of osteosarcomatous transformation in this case suggests the divergent cellular differentiation to mesenchymal malignant tumors of neuroectodermal tissue in NF1 patients.     

Dosing time-dependent effect of temocapril on the mortality of stroke-prone spontaneously hypertensive rats

This study was undertaken to evaluate a dosing time-dependent effect of temocapril, an angiotensin-converting enzyme (ACE) inhibitor, on the mortality of stroke-prone spontaneously hypertensive rats (SHRSP). Temocapril (1 mg/kg/day) prolonged the survival rate of these animals, with a maximum effect after dosing at the early resting period and a minimum effect after dosing at the early active period. The pharmacokinetics of temocaprilat, an active metabolite of temocapril, did not differ significantly between the two dosing times. However, the inhibition of ACE activity in serum and organs (brain and aorta) and the reduction of blood pressure were significantly greater after dosing at the early resting period than at the early active period. These data suggest that the effect of temocapril on the mortality of SHRSP depends on the time of dosing, with a maximum effect seen after dosing at the early resting period. Dosing time-dependent differences in the pharmacodynamics of temocapril might be involved in explaining this phenomenon.     

Implications of transcriptional factor, OCT-4, in human bladder malignancy and tumor recurrence

OCT-4, which is also known as POU5f1, is a key regulator of self-renewal in embryonic stem cells. The new cancer stem cell concept proposes that the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of the cancer behavior, such as recurrence or metastasis. This study investigated the association between OCT-4 expression in cancer tissues obtained by transurethral surgery and the clinical data to clarify the involvement of OCT-4 in human bladder malignancy. Immunohistochemical analysis demonstrated that a positive rate of OCT-4 expression was significantly associated with the higher-grade cancer (G2 and G3) in comparison with that of the lower grade (G1). In addition, positive OCT-4 expression was significantly associated with the intra-bladder tumor recurrence after the operation. The staining intensity of OCT-4 expression was also correlated with tumor recurrence. These data indicate that positive OCT-4 expression may be involved in the development of high-grade bladder cancer and with the bladder cancer recurrence. This is the first study showing a correlation between the expression of OCT-4 and bladder cancer recurrence. OCT-4 may be a valuable clinical marker for the progression of bladder cancer and may be an attractive therapeutic target for the development of new medicines for the treatment of malignancy.     

Simple and rapid analysis of sennoside A and sennoside B contained in crude drugs and crude drug products by solid-phase extraction and high-performance liquid chromatography

The sennoside A (SA) and sennoside B (SB) contents of various samples of crude drugs were determined using solid-phase extraction (SPE) and HPLC. The samples examined were crude drugs (senna leaf, senna pods, and rhubarb), conventional crude drug products, and Kampo formulations. The sample solution was purified using an Oasis MAX cartridge, which has strong anion-exchange and reversed-phase properties. The samples containing SA and SB were dissolved in a solution of methanol–0.2% sodium bicarbonate (7:3, v/v) and applied to the Oasis MAX cartridge. The cartridge was washed with a solution of methanol containing 1% acetic acid. SA and SB were eluted with methanol–water–formic acid (70:30:2, v/v), and the eluate was used as the sample solution for HPLC analysis. SA and SB were analyzed using a conventional octadecylsilyl (ODS) column at a detection wavelength of 380 nm; water–acetonitrile–phosphoric acid (800:200:1, v/v) was used as the mobile phase. The SA and SB components in most samples were completely separated from other interfering constituents within 10 min. In particular, several interfering peaks adjacent to the SB peak were eliminated by SPE using the Oasis MAX cartridge. On subjecting the Kampo extracts to an additional recovery experiment, high recovery rates of SA and SB were obtained. The method employed in this study proved to be a simple and rapid method for the quantification of SA and SB.     

Human gastric cancer development with TNF-α-inducing protein secreted from Helicobacter pylori

TNF-α-inducing protein (Tipα) is a unique carcinogenic factor of Helicobacter pylori, which is secreted into culture broth. The biological activities of Tipα and deletion mutant were studied. Tipα protein specifically binds to cell-surface nucleolin and then enters the gastric cancer cells, where TNF-α and chemokine gene expressions are induced by NF-κB activation. Nucleolin localizes on the surface of gastric cancer cells, and interaction between Tipα and cell-surface nucleolin causes a cancer-oriented microenvironment that increases the risk of gastric cancer. This paper discusses a new mechanism of gastric cancer development with H. pylori and provides a new preventive strategy.     

Clinical Evaluation of Severe Asthma Attacks Requiring Tracheal Intubation and Mechanical Ventilation

BackgroundAlthough the number of patients requiring hospitalization due to asthma attacks has decreased over the years, there are many who still require hospitalization for tracheal intubation and mechanical ventilation following a severe asthma attack. Therefore, we evaluated the characteristics of patients with asthma who required tracheal intubation and mechanical ventilation in our hospital.MethodsWe evaluated 20 patients who had severely exacerbated asthma, requiring tracheal intubation and mechanical ventilation. An evaluation was made based on their smoking history, the number of days from the onset of the asthma attack to admission, the level of asthma control, treatments before presenting to our hospital, the frequency of hospital visits, the reason for tracheal intubation and mechanical ventilation, and outcome. Results: Of the 20 patients with asthma 13 were men and 7 women, with a mean age of 48.7 years. The characteristics of patients who required tracheal intubation and mechanical ventilation were as follows: ? smokers, ? not taking or irregularly taking medication, ? using inhaled short-acting 02agonist (SABA) alone as needed, and ? not using inhaled corticosteroids (ICS).ConclusionsOur findings suggest that treatment mainly using ICS, in addition to increased awareness of the dangers of asthma among the patients themselves, are important in preventing severe asthma attacks requiring tracheal intubation and mechanical ventilation.     

Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia

Pediatric de novo acute myeloid leukemia (AML) is an aggressive malignancy with current therapy resulting in cure rates of only 60%. To better understand the cause of the marked heterogeneity in therapeutic response and to identify new prognostic markers and therapeutic targets a comprehensive list of the genetic mutations that underlie the pathogenesis of AML is needed. To approach this goal, we examined diagnostic leukemic samples from a cohort of 111 children with de novo AML using single-nucleotide-polymorphism microarrays and candidate gene resequencing. Our data demonstrate that, in contrast to pediatric acute lymphoblastic leukemia (ALL), de novo AML is characterized by a very low burden of genomic alterations, with a mean of only 2.38 somatic copy-number alterations per leukemia, and less than 1 nonsynonymous point mutation per leukemia in the 25 genes analyzed. Even more surprising was the observation that 34% of the leukemias lacked any identifiable copy-number alterations, and 28% of the leukemias with recurrent translocations lacked any identifiable sequence or numerical abnormalities. The only exception to the presence of few mutations was acute megakaryocytic leukemias, with the majority of these leukemias being characterized by a high number of copy-number alterations but rare point mutations. Despite the low overall number of lesions across the patient cohort, novel recurring regions of genetic alteration were identified that harbor known, and potential new cancer genes. These data reflect a remarkably low burden of genomic alterations within pediatric de novo AML, which is in stark contrast to most other human malignancies.