Gene testing of hereditary cancer on comprehensive gene medical examination support system

It has been estimated that genetic factors or a combination of genetic and environmental factors play a role in the development of 10-15% of all cancers. A genetic cause of hereditary cancer has been identified in more than 40 diseases till now. For preventing this cancer, gene testing is essential because it has no definite clinical marker as in hereditary non-polyposis colorectal cancer: HNPCC. Much more experience must be accumulated in this testing at the clinical base in order to increase specificity and sensitivity while safeguarding ethical, legal and social issues (ELSI). Recently, the Personal Information Protection Law was enforced. Gene inspection involving hereditary cancer should be carried out under a comprehensive gene medical examination organization. It is important for the family doctor, medical specialist, and gene inspection person in charge to cooperate closely with one another, and this will be a subject of future study.     

Effect of particle shape of active pharmaceutical ingredients prepared by fluidized-bed jet-milling on cohesiveness

Milling is a common procedure to improve bioavailability of many active pharmaceutical ingredients (APIs), which typically have low solubility in water. But such micronization can yield an increase in the cohesiveness of particles. Although particle cohesiveness is desirable for tablet strength in the subsequent formulation process, increased particle cohesiveness can lead to operational difficulties in a milling equipment due to compaction of particles inside. In this article, the impact of milling via a fluidized-bed jet-mill on the cohesive strength and interparticle force was studied using Ethenzamide as a pharmaceutical model compound. As a result, the particle shape was found to affect both the tensile strength of powder bed and the interparticle cohesive force. A powder bed, having relatively high void fraction by direct tensile test, shows a positive correlation between the cohesive force and the particle sphericity, while powders with low void fraction by diametral compression test show a positive correlation between the cohesive force and the angularity of the particle.     

A rice diet is associated with less fat synthesis/accumulation than a bread diet before exercise therapy

For effective exercise therapy after waking up, we focused on the staple food in diet therapy, and compared rice and bread diets. The subjects were 10 healthy college male students. After fasting for 12 h or more from the previous day, the subjects had breakfast consisting of rice (protein, 6.3 g; fat, 0.9 g: CHO, 79.3 g; energy, 368 kcal) or bread (protein, 15.7 g; fat, 5.8 g; CHO, 79.2 g; and energy, 450 kcal) containing the same amount of carbohydrates and the same side dishes (protein, 7.0 g; fat, 9.5 g; CHO, 21.3 g; energy, 199 kcal) in the morning 30 min before the initiation of exercise on a bicycle ergometer at an intensity of about 50% VO2max for 60 min. Measurements of the heart rate and expired gas were initiated 15 min before the start of exercise and continued until 10 min after exercise. Blood was collected before the meal, immediately before and 15, 30, and 45 min after the initiation of exercise, and immediately, 15, and 30 min after its termination. After breakfast containing carbohydrates, decreases were observed in the levels of free fatty acid and noradrenalin. Blood insulin (mealxtime, p<0.05 ANOVA) and triglyceride (meal x time, p<0.01, ANOVA) changed at higher levels in the bread diet than in the rice diet. Blood triglyceride is a resource of fat synthesis/accumulation, and insulin promotes its action. Therefore, the bread diet may promote fat synthesis/accumulation compared with the rice diet.     

Divergent effects of unilateral and subtotal nephrectomy on insulin sensitivity in rats

OBJECTIVES: Insulin resistance is associated with chronic renal failure, which may amplify its cardiovascular pathologic manifestations. We previously showed the presence of insulin resistance in mild renal insufficiency due to chronic glomerulonephritis. These observations may be explained by a decrease in insulin sensitivity due to renal dysfunction. The aim of the present study was to evaluate the effects of unilateral and subtotal nephrectomy on insulin sensitivity. METHODS: Unilateral heminephrectomy and five-sixths nephrectomy (5/6Nx) were performed in male Sprague-Dawley rats, measuring steady-state plasma glucose (SSPG) during the insulin suppression test. RESULTS: The glomerular filtration rate (GFR) decreased significantly from sham-operated rats, to unilateral heminephrectomy group, to 5/6Nx rats. SSPG was unexpectedly lower in the unilateral heminephrectomy group than in controls, suggesting that unilateral heminephrectomy increased the sensitivity to insulin despite a mild decrease in renal function. However, when the analysis was limited to the 5/6Nx group, SSPG was inversely correlated with GFR (r = -0.65, p < 0.05). When renal failure caused by 5/6Nx had reached end stage, the rats became insulin resistant, despite a profound reduction in renal mass. CONCLUSION: It is suggested that unilateral heminephrectomy reduced GFR and increased the sensitivity to insulin. When rats became uremic, insulin sensitivity decreased, even, in 5/6Nx.     

Clinicopathologic Features and Outcome After Liver Resection for Hepatocellular Carcinoma in Patients with Concurrent Versus Previous Chronic Hepatitis B

Purpose We compared the clinicopathologic features affecting outcome after surgery for hepatocellular carcinoma (HCC) between patients with concurrent and previous chronic hepatitis B.Methods Group A consisted of 58 patients with concurrent chronic hepatitis B, defined by seropositivity for the hepatitis B surface antigen (HBsAg), and group B consisted of 18 patients whose HCC was detected after disappearance of the HBsAg. We assessed the influence of various characteristics on outcome.Results The mean age and percentage of patients suffering from alcohol abuse or diabetes mellitus were significantly greater in group B than in group A, whereas histologic hepatitis activity, hepatic fibrosis, and alanine aminotransferase activity were significantly lower in group B than in group A. The tumor-free survival rates were similar between the two groups, but the risk factors of recurrence differed. In group A, relative youth, high aspartate aminotransferase activity, low platelet count, multiple tumors, large tumor size, portal invasion, cirrhosis, nonanatomic resection, and positive surgical margin were risk factors. In group B, large tumor size and poor differentiation were risk factors.Conclusion Hepatitis B status, tumor factors, and the type of operation affected cancer recurrence after surgery for HCC in patients with concurrent chronic HBV, as opposed to only tumor factors in patients with previous chronic hepatitis B.     

Brain magnetic resonance imaging and single photon emission computerized tomography findings in a case of relapsing polychondritis showing cognitive impairment and personality changes

A 57-year-old female with relapsing polychondritis (RP) showing CNS complications is described with reference to the MRI and SPECT findings. At the age of 56, the patient was diagnosed with RP based on her symptoms, which included bilateral auricular chondritis, nonerosive seronegative inflammatory polyarthritis, and ocular inflammation, as well as vestibular dysfunction. During the course of the disease, she suffered from aseptic meningitis accompanied by delirium, which was resolved by treatment with cyclophosphamide, in addition to prednisolone concurrent with the improvement of her physical condition. After the meningitis improved, she developed a number of cognitive impairments, including time disorientation, agraphia, acalculia, constitutional apraxia, and personality changes. Simultaneously, we observed, via SPECT, a decrease in cerebral blood flow (CBF) in several regions, including the bilateral frontal, lateral temporal, and parietal regions. This is the first study to report on the CNS manifestations of RP with reference to MRI and SPECT findings.     

Premature ovarian failure in a female with proximal symphalangism and Noggin mutation

OBJECTIVE: To report a case of premature ovarian failure (POF) and a mutation of the gene for Noggin (NOG). DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 33-year-old Japanese female with POF and proximal symphalangism. INTERVENTION(S): Direct sequence analysis of the NOG gene. MAIN OUTCOME MEASURE(S): Occurrence of POF. RESULT(S): A novel heterozygous G to A transition was identified at the nucleotide position 142 (142 G>A), which is predicted to cause an amino acid substitution of glutamic acid by lysine (E48K). CONCLUSION(S): Because NOG is expressed in the ovary and interacts with bone morphogenetic proteins, which play an important role in the ovarian function, a NOG mutation may constitute one of the multiple susceptibility genes for the development of POF.     

Prefrontal cortical activation associated with working memory in adults and preschool children: an event-related optical topography study

It is well known that lateral areas of the prefrontal cortex (LPFC) play a central role in working memory (a critical basis of various cognitive functions), but it remains unknown whether the LPFC of children of preschool age is responsible for working memory. To address this issue, we adopted a recently developed non-invasive imaging technique, optical topography (OT), which can potentially be applied to functional mapping in childhood. We firstly examined changes of activity in the LPFC using OT while adult subjects performed an item-recognition task, which requires working memory, under different memory-load conditions. We observed activation in the bilateral LPFC during performance of this task, the magnitude of which differed depending on memory-load. Then, we applied the same technique on 5- and 6-year-old children and observed the activation associated with working memory in the LPFC. Areas and properties of such activity were similar in adults and preschool children. Thus, for the first time, we demonstrate that the LPFC of preschoolers is active during working memory processes, indicating that in 5- and 6-year-old children, the LPFC has already developed processing of this important cognitive function.