The Keio Journal of Medicine

Publisher: Keiō-Gijuku-Daigaku (Tōkyō). Igakubu

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ISSN 1880-1293
OCLC 162261553
Material type Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aging of the population worldwide has sharply increased the number of post-menopausal osteoporosis patients. Bone fragility caused by osteoporosis often results in fractures; therefore, controlling osteoporosis is crucial to prevent such injuries. To date, various drugs to treat osteoporosis have been developed and launched; however, the molecular mechanisms underlying post-menopausal osteoporosis have not been fully elucidated, and additional factors that could be targeted to treat patients remain to be characterized. Recently, hypoxia inducible factor 1 alpha (HIF1α) was identified as essential for osteoclast activation, an activity that promotes bone loss following menopausal estrogen deficiency. Although osteoclasts, which are located in hypoxic regions of the bone surface, express HIF1α mRNA, in pre-menopausal conditions the presence of estrogen decreases HIF1α protein levels in these cells. In menopausal conditions, however, estrogen deficiency allows HIF1α protein to accumulate in osteoclasts, leading to osteoclast activation and bone loss. Osteoclast-specific conditional HIF1α inactivation protects mice from estrogen deficiency-induced osteoclast activation and bone loss, as does systemic administration of a HIF1α inhibitor. Therefore, HIF1α represents a potential therapeutic target to prevent osteoclast activation and bone loss in post-menopausal patients.
    The Keio Journal of Medicine 08/2015; DOI:10.2302/kjm.2015-0003-RE
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    ABSTRACT: The risk of venous thromboembolism (VTE) in patients with cancer is several-fold higher than that in individuals without cancer. Recent studies demonstrated a high incidence of VTE in patients with hematologic malignancies as well as in patients with solid cancers. The reported incidence of VTE in lymphoma is variable, ranging from less than 5% to 59.5%. The incidence of VTE is higher in non-Hodgkin lymphoma than it is in Hodgkin lymphoma. The incidence of VTE also varies according to the disease grade, the disease stage, the performance status of the patient, and the site of disease. Most VTE cases occur at the diagnosis of cancer or early in the course of cancer treatment. An elevated incidence of VTE is also reported in cases of myeloma. VTE occurs in approximately 5% of myeloma patients treated with conventional chemotherapy, and treatment of myeloma patients with immunomodulatory drugs (IMid)-based therapy increases the risk of VTE. Prophylactic aspirin or anticoagulant is used in myeloma patients treated with IMid-based therapy. Several reports have indicated that the incidence of VTE is relatively low in Asian patients treated with IMid-based therapy, and concomitant use of bortezomib reduces the risk of VTE. The incidence of arterial thrombosis is also increased in patients with myeloma and monoclonal gammopathy of undetermined significance. Further studies are needed to develop a predictive model for identifying patients with lymphoma and myeloma who are at high risk for developing thrombosis.
    The Keio Journal of Medicine 07/2015; DOI:10.2302/kjm.2014-0017-RE
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    ABSTRACT: Neoadjuvant chemoradiation therapy (NACRT) is increasingly used in patients with a potentially or borderline resectable pancreatic ductal adenocarcinoma (PDA) and it has been shown to improve survival and reduce locoregional metastatic disease. It is rare for patients with PDA to have a pathological complete response (pCR) to NACRT, but such patients reportedly have a good prognosis. We report the clinicopathological findings of two cases of pCR to NACRT in PDA. Both patients underwent pancreatectomy after NACRT (5-fluorouracil, mitomycin C, cisplatin, and radiation). Neither had residual invasive carcinoma and both showed extensive fibrotic regions with several ducts regarded as having pancreatic intraepithelial neoplasia 3/carcinoma in situ in their post-therapy specimens. It is noteworthy that both patients had a history of a second primary cancer. They both had comparatively good outcomes: one lived for 9 years after the initial pancreatectomy and the other is still alive without recurrence after 2 years.
    The Keio Journal of Medicine 06/2015; 64(2):26-31. DOI:10.2302/kjm.2014-0014-CR
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    ABSTRACT: Steroid psychosis is a frequent complication of steroid treatment. Although perioperative steroid replacement therapy is generally administered in patients undergoing pituitary surgery, there are no previous reports concerning the development of steroid psychosis after perioperative steroid replacement therapy following pituitary surgery. We herein report a case of steroid psychosis induced by perioperative steroid replacement therapy for pituitary surgery. A 35-year-old man presented with a visual disturbance that had persisted for 1 year. A magnetic resonance imaging scan showed a large pituitary tumor, and a laboratory study revealed slight dysfunction of the hypothalamo-pituitary-adrenal axis. The patient was diagnosed with a non-functioning pituitary tumor and underwent tumor resection via the endoscopic endonasal approach. The initial dose of perioperative steroid replacement therapy was 200 mg of hydrocortisone administered immediately before the operation. The replacement dose was gradually tapered and discontinued over a 7-day period. On postoperative day 4, the patient exhibited an elated mood, grandiose delusions, anxiety, and agitation. We diagnosed these psychiatric symptoms as steroid psychosis induced by steroid replacement and we prescribed risperidone as a treatment. The symptoms gradually improved and did not recur. This case highlights the risk of steroid psychosis following treatment with perioperative steroid replacement therapy for pituitary adenoma and raises questions regarding the appropriateness of perioperative steroid replacement for pituitary adenoma.
    The Keio Journal of Medicine 03/2015; 64(1):11-5. DOI:10.2302/kjm.2014-0007-CR
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    ABSTRACT: Tuberculosis is sometimes perceived as a feared killer of the past but is still a dreadful disease of mankind. Mycobacterium tuberculosis multiplies inside white blood cells known as macrophages. In infected people who don't develop the Tuberculosis, the immune system either the bacteria or impairs bacterial multiplication. The exact mechanisms behind this are not known in detail, hampering the development of effective vaccines and treatments of the disease. Why the disease is manifested in some individual, but not in others, is not completely understood.The recent study shows that a molecule called SOCS3 is required for control of the infection. The discovery was done using an experimental infection of mice genetically modified so that they do not express SOCS3 in different immune cells. These mice were dramatically susceptible to the infection with Mycobacterium tuberculosis. SOCS3 could be a new target for vaccines to improve the protection against Tuberculosis.(Presented at the 1901st Meeting, April 14, 2015).
    The Keio Journal of Medicine 01/2015; 64(2):32. DOI:10.2302/kjm.64-001-ABST
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    ABSTRACT: A 16-year-old Japanese girl with a huge 13-cm-diameter tumor in the pancreas head presented with life-threatening symptoms and findings including severe anemia, obstructive jaundice, duodenal stenosis, and serious portal vein compression. She underwent a pancreatoduodenectomy with combined resection of the portal vein. Reconstruction of the portal vein was successfully performed using an external iliac vein graft and postoperative anticoagulant therapy. Pathological examination revealed a solid pseudopapillary neoplasm of the pancreas. The patient's postoperative course was uneventful, but her menstruation ceased for 14 months. She is now alive with no evidence of recurrence 100 months postoperatively and she suffers no impairments in daily activities of life. As a treatment of solid pseudopapillary neoplasms of the pancreas, pancreatoduodenectomy combined with portal vein resection is rarely performed in adolescent patients, but is reportedly successful, with patients tolerating the operation and surviving without recurrence. An aggressive surgical attitude is recommended when dealing with this tumor type with curative resection, even in adolescent patients.
    The Keio Journal of Medicine 08/2014; 63(3). DOI:10.2302/kjm.2014-0003-CR
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    ABSTRACT: It is sometimes difficult to distinguish late-life schizophrenia from senile dementia because elderly patients with schizophrenia can present in chronic remission and show gradual cognitive decline with aging. We aimed to elucidate the semiological characteristics of late-life chronic schizophrenia. Three patients aged between 60 and 66 years who were admitted to our hospital were included in this study. Detailed history taking and psychiatric interviews were performed and reviewed in the light of psychopathological semiology. Although the three patients with late-life schizophrenia showed significant cognitive decline on the Hasegawa dementia rating scale and their negative symptoms mimicked dementia, the following psychopathological characteristics clearly differentiated them from patients with senile dementia: (1) a shift of temporal organization toward the future with intact memory, (2) hypersensitivity, (3) ambivalent personal relationships, (4) systematic bodily delusions, and (5) an ante festum mindset. Identifying such clinical features of patients with late-life schizophrenia could be important for developing more effective pharmacotherapy and for providing appropriate psychotherapy.
    The Keio Journal of Medicine 06/2014; 63(2). DOI:10.2302/kjm.2012-0009-OA
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    ABSTRACT: Penetrating neck injuries are commonly related to stab wounds and gunshot wounds in the United States. The injuries are classified by penetration site in terms of the three anatomical zones of the neck. Based on this zonal classification system, penetrating injuries to the head and neck have traditionally been evaluated by conventional angiography and/or surgical exploration. In recent years, multidetector-row computed tomography (CT) angiography has significantly improved detectability of vascular injuries and extravascular injuries in the setting of penetrating injuries. CT angiography is a fast and minimally invasive imaging modality to evaluate penetrating injuries of the head and neck for stable patients. The spectrum of penetrating neck injuries includes vascular injury (extravasation, pseudoaneurysm, dissection, occlusion, and arteriovenous fistula), aerodigestive injury (esophageal and tracheal injuries), salivary gland injury, neurologic injury (spinal canal and cerebral injuries), and osseous injury, all of which can be evaluated using CT angiography. Familiarity with the complications and imaging characteristics of penetrating injuries of the head and neck is essential for accurate diagnosis and optimal treatment.
    The Keio Journal of Medicine 06/2014; 63(2). DOI:10.2302/kjm.2013-0009-RE
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    ABSTRACT: A prospective study was conducted to clarify the 1-year changes in lumbar spine and hip bone mineral density (BMD) and bone turnover markers in premenopausal amateur runners and to determine whether jumping and muscle-strengthening exercises have additive effects on the bone parameters in these runners. Thirty-six premenopausal amateur runners were recruited and were divided into the following two groups: a jumping plus muscle-strengthening exercise group (n =21) and a control group (n =15). All participants continued their running practice for 1 year, and the lumbar spine and total hip BMD and bone turnover markers were monitored. For all participants, the lumbar spine and total hip BMD increased modestly after 1 year (1.31% and 1.54%, respectively) in addition to increases in the bone-specific alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase 5b levels (13.2%-27.8%), indicating mild effects of running activity on bone turnover and BMD at clinically relevant skeletal sites. Jumping plus muscle-strengthening exercises did not significantly influence any bone parameters; however, it was difficult to draw definite conclusions because compliance was poor. These results suggest that long-distance running at the recreational level may be useful in maintaining bone health in premenopausal women.
    The Keio Journal of Medicine 06/2014; 63(3). DOI:10.2302/kjm.2013-0010-OA
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    ABSTRACT: Renal afferent arterioles (AFF) regulate glomerular capillary pressure through two main mechanisms: the myogenic response (MYO) and tubuloglomerular feedback (TGF). Because Rho-kinase and nitric oxide synthase (NOS) are established factors that modulate vascular tone, we examined the role of these factors in pressure-induced AFF tone in Wistar-Kyoto rats and in spontaneously hypertensive rats (SHR) using an intravital CCD camera. Elevated renal perfusion pressure elicited marked AFF constriction that was partially inhibited by gadolinium, furosemide and fasudil, which inhibit MYO, TGF and Rho-kinase, respectively; however, this AFF constriction was completely blocked by combined treatment with fasudil+gadolinium or fasudil+furosemide. S-methyl-L-thiocitrulline (SMTC) partially reversed the fasudil-induced inhibition of TGF-mediated, but not that of MYO-mediated, AFF constriction. In SHR, the pressure-induced AFF response was enhanced, and MYO- and TGF-induced constriction were exaggerated. In the presence of gadolinium, SMTC partially mitigated the fasudil-induced inhibition of TGF-mediated AFF constriction. Immunoblot analyses demonstrated that both Rho-kinase activity and neuronal NOS were augmented in SHR kidneys. In conclusion, Rho-kinase contributes to MYO- and TGF-mediated AFF responses, and these responses are enhanced in SHR. Furthermore, neuronal NOS-induced nitric oxide modulates the TGF mechanism. This mechanism constitutes a target for Rho-kinase in TGF-mediated AFF constriction.
    The Keio Journal of Medicine 01/2014; 63(1). DOI:10.2302/kjm.2013-0001-OA
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    ABSTRACT: As technology and communication evolve rapidly in this digital age, scholarly publishing is also undergoing a makeover to match the diverse needs of researchers and clinicians. The BMJ has been at the forefront of innovating the presentation of research to increase its readabillty and usefulness. This article presents some of recent formats used for research communication at the BMJ.
    The Keio Journal of Medicine 01/2014; 63(4):67-8. DOI:10.2302/kjm.2014-0001-RE
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    ABSTRACT: Multiple café-au-lait macules (CALMs) are the hallmark of Von Recklinghausen disease, or neurofibromatosis type 1 (NF1). In 2007 we reported that some individuals with multiple CALMs have a heterozygous mutation in the SPRED1 gene and have NF1-like syndrome, or Legius syndrome. Individuals with Legius syndrome have multiple CALMs with or without freckling, but they do not show the typical NF1-associated tumors such as neurofibromas or optic pathway gliomas. NF1-associated bone abnormalities and Lisch nodules are also not reported in patients with Legius syndrome. Consequently, individuals with Legius syndrome require less intense medical surveillance than those with NF1. The SPRED1 gene was identified in 2001 and codes for a protein that downregulates the RAS-mitogen activated protein kinase (RAS-MAPK) pathway; as does neurofibromin, the protein encoded by the NF1 gene. It is estimated that about 1-4% of individuals with multiple CALMs have a heterozygous SPRED1 mutation. Mutational and clinical data on 209 patients with Legius syndrome are tabulated in an online database ( Mice with homozygous knockout of the Spred1 gene show learning deficits and decreased synaptic plasticity in hippocampal neurons similar to those seen in Nf1 heterozygous mice, underlining the importance of the RAS-MAPK pathway for learning and memory. Recently, specific binding between neurofibromin and SPRED1 was demonstrated. SPRED1 seems to play an important role in recruiting neurofibromin to the plasma membrane.
    The Keio Journal of Medicine 12/2013; 62(4). DOI:10.2302/kjm.2013-0002-RE
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    ABSTRACT: The heart consists of many types of cells, including cardiomyocytes, vascular cells, neural cells, and cardiac fibroblasts. Adult cardiomyocytes are terminally differentiated cells, and loss of cardiomyocytes as a result of heart damage is irreversible. To regenerate damaged hearts and restore cardiac function, understanding the cellular and molecular basis of heart development is of considerable importance. Although it is well known that heart function is tightly regulated by cell-cell interactions, their roles in heart development are not clear. Recent studies, including ours, identified important roles of cell-cell interactions in heart development and function. The balance between neural chemoattractants and chemorepellents secreted from cardiomyocytes determines cardiac nervous development. Nerve growth factor is a potent chemoattractant synthesized by cardiomyocytes, whereas Sema3a is a neural chemorepellent expressed specifically in the subendocardium. Disruption of this molecular balance induces disorganized cardiac innervation and may lead to sudden cardiac death due to lethal arrhythmias. Cardiac fibroblasts, of which there are large populations in the heart, secrete high levels of specific extracellular matrix and growth factors. Embryonic cardiac fibroblast-specific secreted factors collaboratively promote mitotic activity of embryonic cardiomyocytes and expansion of ventricular chambers during cardiogenesis. More recently, utilizing knowledge of the regulatory mechanisms of heart development, we found that cardiac fibroblasts can be directly reprogrammed into cardiomyocyte-like cells in vitro and in vivo by gene transfer of cardiac-specific transcription factors. Understanding the mechanisms of heart development and cardiac reprogramming technology may provide new therapeutic approaches for heart disease in the future.
    The Keio Journal of Medicine 09/2013; 62(4). DOI:10.2302/kjm.2012-0020-RE
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    ABSTRACT: Little information is available on the factors influencing length of stay (LOS) in hospital and medical costs during hospitalization associated with cholecystectomy for acute cholecystitis. We determined the independent factors affecting LOS and medical costs of patients who underwent cholecystectomy for acute cholecystitis based on data from the Diagnosis Procedure Combination (DPC) database. In 2008, a total of 2176 patients with acute cholecystitis were referred for cholecystectomy to 624 hospitals in Japan. We collected patient characteristics and data on treatments for acute cholecystitis using the DPC database and identified independent factors affecting LOS and medical costs during hospitalization using multiple linear regression models. Analysis revealed that early cholecystectomy was significantly associated with a decrease in LOS, whereas longer preoperative antimicrobial therapy was significantly associated with an increase of LOS: the standardized coefficient for early cholecystectomy was -0.372 and that for preoperative antimicrobial therapy was 0.353 (P < 0.001). These procedures were also significant independent factors with regard to medical costs during hospitalization: the standardized coefficient for early cholecystectomy was -0.391 and that for preoperative antimicrobial therapy was 0.335 (P < 0.001). Early cholecystectomy significantly reduces the LOS and medical costs of cholecystectomy for acute cholecystitis, while preoperative antimicrobial therapy increases LOS and medical costs during hospitalization. These results highlight the need for health care implementations such as promotion of early cholecystectomy, appropriate use of antimicrobial drugs, and centralization of patients with cholecystectomy for acute cholecystitis in Japan.
    The Keio Journal of Medicine 08/2013; 62(3). DOI:10.2302/kjm.2012-0015-OA
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    ABSTRACT: In the field of developmental biology, the concept that cells, once terminally differentiated, are fixed in their cell fate was long believed to be true. However, Dr. Gurdon and colleagues challenged this fundamental doctrine and demonstrated that cellular reprogramming and cell fate conversion are possible by somatic nuclear transfer and cell fusion. The Weintraub laboratory discovered in the 1980s that a single transcription factor, MyoD, can convert fibroblasts into skeletal muscle cells, and subsequent studies also demonstrated that several transcription factors are lineage converting factors within the blood cell lineage. In 2006, Takahashi and Yamanaka discovered that transduction of the four stem cell-specific transcription factors Oct4, Sox2, Klf4, and c-Myc can reprogram mouse fibroblast cells into a pluripotent state. In 2007, they demonstrated that the same four factors similarly reprogram human somatic cells into pluripotent stem cells. These discoveries by Dr. Yamanaka and colleagues fundamentally changed research in the fields of disease modeling and regenerative medicine and also inspired the next stage of cellular reprogramming, i.e., the generation of desired cell types without reverting to stem cells by overexpression of lineage-specific transcription factors. Recent studies demonstrated that a diverse range of cell types, such as pancreatic β cells, neurons, neural progenitors, cardiomyocytes, and hepatocytes, can be directly induced from somatic cells by combinations of specific factors. In this article, I review the pioneering works of cellular reprogramming and discuss the recent progress and future perspectives of direct reprogramming technology.
    The Keio Journal of Medicine 06/2013; 62(3). DOI:10.2302/kjm.2012-0017-RE
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    ABSTRACT: Cervical arthroplasty was developed in an attempt to maintain cervical motion and potentially to avoid or minimize adjacent-segment degeneration. If cervical arthroplasty is successful, the long-term results of surgery for cervical disc disease should improve. However, problems associated with cervical arthroplasty have been reported: these include kyphosis, heterotopic ossification-induced motion limitation, no motion preservation even at the index level, and a higher revision rate in a limited number of cases compared with anterior cervical discectomy and fusion (ACDF). In addition, for degenerative cervical disc disorders, the risk of developing adjacent segment degeneration more than 2 years after surgery is reportedly similar for ACDF and cervical arthroplasty. Cervical disc arthroplasty is an emerging motion-sparing technology and is currently undergoing evaluation in many countries as an alternative to arthrodesis for the treatment of cervical radiculopathy and myelopathy. The decision whether to use arthrodesis or arthroplasty is a difficult one. The achievement of good prosthetic performance demands exacting implantation techniques to ensure correct placement. This fact underlines the increasing importance of special instrumentation and surgical skills that involve an understanding of prosthetic lubrication, wear, and biologic effects and familiarity with currently available information regarding kinematics, basic science, testing, and early clinical results. Fortunately, a number of devices are at the late preclinical study stage or at the early clinical trial stage, and results in many cases are promising. In the near future, it is likely that new designs will be produced to replace spinal discs totally or partially in a pathologic entity-specific manner.
    The Keio Journal of Medicine 06/2013; 62(2):47-52. DOI:10.2302/kjm.2012-0014-RE