Great advances in genomic research on the susceptibility to multifactorial genetic diseases and drug sensitivities have broadened the use of genetic information in clinical practice. In the United States, pharmacogenomic information is included in drug package inserts (labels). The United States Food and Drug Administration releases a list of drugs and valid genomic biomarkers for public use. Also in Japan in June 2008 information on the relationship between UGT1A1 variants and the anticancer drug irinotecan was included in the drug label, followed by insurance coverage of genetic testing for UGT1A1 in November of the same year. Such developments signal the start of the age of personalized medicine. Appropriate application of genetic information to personalized medicine in Japan requires different approaches to genetic information, as the current way of handling genetic information regarding single gene disorders in research and clinical practice is based solely on genetic exceptionalism. However, specific issues in introducing pharmacogenomics (PGx) to clinical practices remain unclear. Large differences exist in the implementation of personalized medicine among institutions. The number of genes related to personalized medicine will surely increase in the coming years. The issues that surround personalized medicine will need to be specified and clarified.
Trauma studies, as consolidated in the 1990s from a trans-disciplinary perspective, have come to attach fresh significance to narrative production by trauma sufferers. William Trevor's The Story of Lucy Gault, a novel featuring a girl injured during the Irish War of Independence, describes the difficulties trauma sufferers have to face in constructing their own narrative for recovery and apprises the reader of their long suffering from a medical point of view.
The baculovirus-insect cell system is widely used to express recombinant proteins. Posttranslational modifications of proteins, such as glycosylation and the phosphorylation and incorporation of cofactors, in Escherichia coli are less sufficient than those in mammalian cells. Unfortunately, mammalian cells are not appropriate for large-scale culture. However, insect cells are eukaryotic cells and are suitable for large-scale culture; they can be used to produce recombinant proteins that cannot be expressed in E. coli. We established a baculovirus-insect cell system to express xanthine oxidoreductase and obtained about ∼4mg of purified enzyme from 2 to 4L of culture medium. This amount of enzyme was sufficient for X-ray crystal structureanalysis. Here, we describe of the outline of our methods for culturing insect cells, producing recombinant baculoviruses, and expressing recombinant proteins in large-scale culture.
A 30-year-old Japanese woman had received a diagnosis of Graves' disease 3 years earlier and was treated with thiamazole. However, she discontinued treatment by herself 6 months later. She became aware of emaciation, bilateral leg edema, and dyspnea 4 days before admission. Because of a fever of 39 degrees, she walked to a nearby hospital's emergency room. Physical examination on admission showed a clear consciousness, fever, tachycardia, and enlargement of the thyroid gland. Electrocardiography revealed atrial fibrillation. A chest X-ray film revealed bilateral pleural effusions, pulmonary congestion, and cardiac enlargement. Because thyrotoxic crisis was suspected, she received ventilatory support and was given thiamazole, a potassium iodide preparation, and glucocorticoids. However urinary volume was decreased and serum levels of creatinine, creatinine kinase, and myoglobin were elevated. Acute renal failure due to rhabdomyolysis was suspected. The next day she was transferred to our hospital to undergo hemodialysis. Although her condition improved with intensive care, severe weakness of the proximal limb muscles (manual muscle test 0∼1/5) was shown. The serum potassium level was normal, but electromyography revealed myogenic change suggesting thyrotoxic myopathy. Muscle strength improved through normalization of thyroid function and rehabilitation, and she was discharged on foot. This case suggests that prompt diagnosis and treatment of thyrotoxic crisis are extremely important because the prognosis of thyrotoxic crisis is extremely poor. Moreover, thyrotoxic myopathy should be suspected when limb muscle weakness appears in Graves' disease.
We report two cases of pancreatic cystic endocrine tumors treated by laparoscopic distal pancreatectomy. Case1: A 33-year-old woman was found with computer tomography to have a 4cm cystic tumor and a partially thickened septum in the body of the pancreas. The thickened septum showed enhancement with contrast medium. We suspected an intraductal papillary mucinous neoplasm or a mucinous cystic neoplasm, and performed laparoscopic distal pancreatectomy and splenectomy. Pathological examination of the resected specimen indicated a well differentiated endocrine tumor of uncertain nature. Case 2: A 62-year-old woman was found with computer tomography to have a 4cm cystic tumor and a partially thickened and hypervascular septum in the body of the pancreas. Suspecting a mucinous cystic neoplasm, a solid pseudopapillary tumor, or a cystic endocrine tumor, we performed laparoscopic distal pancreatectomy and splenectomy. Pathological examination of the resected specimen indicated glucagonoma. Neither woman has had recurrence as of this writing. We conclude that pancreatic cystic endocrine tumor is characterized by partial thickening and contrast enchancement of the septum. Laparoscopic surgery is a viable treatment for endocrine tumor of the pancreas.