The Keio Journal of Medicine

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

Description

  • Impact factor
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  • 5-year impact
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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: 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;
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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;
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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;
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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;
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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;
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    ABSTRACT: Two percent of scapular fractures occur as a result of indirect trauma caused by traction of the muscles and ligaments attached to the scapula. We present two cases involving adults with incomplete avulsion fractures of the scapular spine caused by violent voluntary contraction of the deltoid muscle. These cases are the first reported avulsion fractures confined to the scapular spine medial to the spinoglenoid notch. Although the fractures were incomplete, one patient had a typical symptom of scapular fracture - pseudo-rupture of the rotator cuff characterized by clinical signs of a complete rupture of the musculotendinous cuff. Although this symptom is generally thought to be caused by massive hemorrhaging under the rotator-cuff muscle bellies, it may develop from modest bleeding through the formation of an intramuscular hematoma and a resultant elevation in intramuscular pressure. Confirming the presence of tenderness on the scapular spine and performing appropriate imaging investigation constitute a clinically effective method for preventing misdiagnosis.
    The Keio Journal of Medicine 12/2013;
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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 (http://www.lovd.nl/SPRED1). 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;
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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;
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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;
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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;
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    ABSTRACT: We report the case of a 29-year-old woman who attempted suicide by oral ingestion of potentially fatal doses of multiple drugs including quetiapine. Intravenous lipid emulsion (ILE) was administered at a dose higher than that used in the standard management of toxicity. Rapid improvement was observed in the patient's status, and no additional treatment was required during the period of observation. No adverse effect of lipid administration was observed. ILE treatment seems to have great potential in the management of lipophilic drug toxicity in the future.
    The Keio Journal of Medicine 05/2013;
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    ABSTRACT: Many membrane-bound molecules are cleaved at the cell surface, thereby releasing their extracellular domains. This process, often referred to as ectodomain shedding, has emerged as a critical post-translational mechanism for various membrane-bound ligands, receptors, and adhesion molecules. Tumor necrosis factor α (TNFα)-converting enzyme (TACE/ADAM17) was originally identified as an enzyme responsible for releasing the membrane-bound TNFα precursor. However, subsequent studies found an exceptionally large number of target molecules of TACE, including the ligands for epidermal growth factor receptor, L-selectin, CD44, and vascular growth factor receptor 2. Furthermore, in vivo studies using TACE-conditional knockout mice demonstrated the crucial roles of TACE and ectodomain shedding under both physiological and pathological conditions. However, the potential clinical application of the manipulation of TACE activity remains to be investigated.
    The Keio Journal of Medicine 01/2013; 62(1):29-36.
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    ABSTRACT: The proteasome is a sophisticated, 2.5-MDa, multisubunit complex that contains a catalytic core particle (CP) and two terminal regulatory particles (RPs); the RPs associate with the termini of the central CP at opposite orientations. The CP consists of four axially stacked heptameric rings (two outer α-rings and two inner β-rings), which are made up of seven structurally related, but not identical, α and β subunits. The CP contains catalytic threonine residues (in β1, β2, and β5 with caspase-like, trypsin-like, and chymotrypsin-like activities, respectively) on the surface of the chamber formed by two abutting β-rings. The RP recognizes polyubiquitylated substrate proteins and unfolds and translocates these proteins to the interior of the CP for degradation. The RP comprises 19 different subunits, which are thought to form two subcomplexes called the lid and the base. One longstanding question is how the complex structure of the proteasome is organized with high fidelity. Recently, we proposed a novel assembly mechanism that is assisted by multiple proteasome-dedicated chaperones. In addition, we discovered two immuno-type proteasomes, the immunoproteasome and the thymoproteasome, whose catalytic subunits are replaced by homologous counterparts. These two isoforms perform specialized functions that help discriminate self from non-self in cell-mediated immunity (i.e., they function as enzymes that process intracellular antigens for cytotoxic T lymphocyte responses and thymic positive selection). Moreover, emerging evidence suggests that the proteasome is crucially involved in the pathophysiology of various intractable diseases that are increasing in today's aging society.
    The Keio Journal of Medicine 01/2013; 62(1):1-12.
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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 01/2013; 62(2):47-52.
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    ABSTRACT: Even in the adult brain, new neurons are continuously generated from endogenous neural stem cells that reside in two restricted regions: the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus of the hippocampus. These new neurons are integrated into the mature neuronal circuitry and become involved in various functions, thereby contributing to structural and functional plasticity in the adult brain. In this review, we summarize our recent findings on the regulatory mechanisms of SVZ neurogenesis under physiological and pathological conditions in various animal models. Some of these findings were presented in the Kitazato Prize Lecture at Keio University School of Medicine in 2011.
    The Keio Journal of Medicine 01/2013; 62(1):13-28.
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    ABSTRACT: Until a certain developmental stage, cutaneous wounds in mammalian fetuses heal rapidly without scars with complete regeneration of the skin. In the process of fetal wound healing, inflammatory responses, granulation proliferation, and scar formation that are observed in adults are not seen. Numerous studies have reported the causes of fetal scarless cutaneous regeneration, including reduced expression of TGF-β1 and higher levels of hyaluronan in the extracellular matrix, from the viewpoints of molecular biology and cellular biology, but the mechanisms are not completely understood. Although a variety of substances that inhibit scar formation have been investigated, currently it is almost impossible for adult cutaneous wounds to heal completely without scars. Except for a few animal species, perfect regeneration after wounding can occur only during the gestation period. By strictly comparing the stages before and after the transition from the regeneration of skin to scarring, it will be possible to investigate the mechanisms of cutaneous regeneration.
    The Keio Journal of Medicine 12/2012; 61(4):101-8.
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    ABSTRACT: Thirty years have passed since Warren and Marshall's discovery of Helicobacter pylori (H.pylori). Since then, not only peptic ulcer diseases and chronic gastritis but also non-cardia gastric cancers have been recognized as diseases originating from H. pylori infection. Several combination therapies consisting of multiple antibiotics have been developed as first- or second-line regimens to eradicate H. pylori infection. Our extensive experience in the field of anti-H. pylori medicine suggests that clinicians should consider a possible role for unidentified, invisible pathogens to elucidate the pathogenesis and improve the treatment of refractory diseases of unknown etiology.
    The Keio Journal of Medicine 12/2012; 61(4):109-19.
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    ABSTRACT: Evidence of the causal relationship between hypercholesterolemia and coronary artery disease (CAD) has been established worldwide. However, little attention has been paid to the relationship between hypercholesterolemia and stroke, despite stroke being the most common cardiovascular disease in Japan. We therefore reviewed cohort studies that investigated this relationship in the Japanese population over the past 20 years, and compared their findings with clinical trials and cohort studies in Western countries. Fourteen cohort studies were carried out in Japan during this period. The number of subjects in the studies ranged from 1621 to 91,219 and the mean follow-up period ranged from 7.6 to 32 years. The majority of studies showed no association between hypercholesterolemia and total stroke. However, one report showed a positive association between low-density lipoprotein cholesterol and atherothrombotic cerebral infarction. The relationship between hypercholesterolemia and cerebral infarction may be modified by the proportion of atherothrombotic infarctions in the population surveyed. Randomized controlled trials on statins have shown a substantial reduction in cerebral infarction, and so the discrepancy between cohort studies and clinical trials requires further study. However, some studies have reported that subjects with low blood cholesterol are more susceptible to intracerebral hemorrhage. Two hypotheses have been proposed to explain this association between low cholesterol and intracerebral hemorrhage. First, low blood cholesterol may induce angionecrosis, possibly in combination with hypertension, and second, low blood cholesterol may reflect a poor nutritional status. Either way, further continuous research in various fields of medical science is required to clarify the overall effect of blood cholesterol on stroke in humans.
    The Keio Journal of Medicine 09/2012; 61(3):79-88.

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