Juntendo Medical Journal
Online ISSN : 2188-2126
Print ISSN : 2187-9737
ISSN-L : 2187-9737
Volume 60, Issue 1
Displaying 1-20 of 20 articles from this issue
Contents
Health Topics for Tokyoites: The Bowels and Health
  • YOSHIKAZU OHTSUKA
    2014 Volume 60 Issue 1 Pages 2-7
    Published: 2014
    Released on J-STAGE: July 31, 2014
    JOURNAL FREE ACCESS
    The physiological need for nutrient absorption requires the gut to have a large surface area, lined by a single layer of columnar epithelium. This means that the immune system of the gut is constantly bombarded by foreign proteins (food), while at the same time, the immune system is specifically designed to react to the foreign proteins of pathogens. To get around this problem, the gut immune system has acquired mechanisms to avoid excessive reactions to food, yet at the same time retain the ability to react to infectious agents. This system works efficiently in most individuals, but for an as-yet undefined reason, some people react to food antigens as though they were pathogens, and since food antigens are needed for nutrition, disease persists until the offending antigen is identified and eliminated from the diet. The clinical features of inappropriate immunological responses to food, including eczema, urticaria, vomiting, diarrhea, bloody stool, and failure to thrive, are defined as food allergies.
    Ingested food is normally digested into peptides and amino acids by digestive enzymes before being absorbed by gut epithelial cells. Amino acids do not induce immunological reactions because they are too small to be recognized by antigen-presenting cells (APC). However, some proteins are poorly digested in the intestinal lumen and so intact macromolecules can be detected by immune cells and recognized as antigens.
    In infants, non-specific defenses in the gut may be compromised. First, both intracellular and paracellular transport of macromolecules through the epithelium is increased. Second, insufficient secretion of digestive enzymes causes reduced digestion and increases the amount of undigested proteins in the intestinal lumen. Furthermore, frequent infections activate mucosal immune cells and induce further reactions.
    Meanwhile, there is a function called “induction of tolerance”. TGF-β is an important cytokine that mediates active suppression against orally administered antigens, allowing the induction of non-responsiveness against transmitted antigens in breast milk. Lack of co-stimulatory and/or adhesion molecules on the surface of lymphocytes may partially explain the unresponsiveness of T cells to food, especially during infancy.
    Identification and elimination of the proteins that cause these adverse reactions improves the condition of these patients. Elimination of the offending food from the diet should prevent further allergic reactions. Moreover, oral tolerance can be introduced only by continuing to eat a small amount of antigenic food after determining the amount and the way to eat such food after challenge tests, which we call Specific Oral Tolerance Induction (SOTI). Since challenge tests and SOTI can be dangerous and may introduce shock, these procedures should be performed under intensive surveillance by experienced doctors.
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  • AKIHITO NAGAHARA, MARIKO HOJO, DAISUKE ASAOKA, KENSHI MATSUMOTO, YUJI ...
    2014 Volume 60 Issue 1 Pages 8-15
    Published: 2014
    Released on J-STAGE: July 31, 2014
    JOURNAL FREE ACCESS
    The spread of H. pylori started from the African continent 58,000 years ago, with changes in its virulence during the great spread of ancient humans throughout the world. Unfortunately, carcinogenic risk is high in association with the East Asia strain, which is the main strain isolated in Japan. After the Japanese government health insurance approved eradication therapy in 2000, the incidence of peptic ulcers clearly decreased. Moreover, the incidence of gastric cancer is expected to decrease about one-third by eradication, and its effect is profound among the young whose atrophic change in the gastric mucosa is mild. In other words, the risk of gastric cancer does not reach zero, but still persists. Therefore, periodic upper GI endoscopy should be performed every 1 to 2 years to diagnose gastric cancer, which could develop after eradication.
    The term “chronic gastritis” was originally defined as “morphological gastritis” such as mucosal inflammation. However, conventionally, patients suffering from epigastralgia and/or dysmotility have been diagnosed with “chronic gastritis” in the Japanese language. That is, two different conditions of “morphological gastritis” and “symptomatic gastritis” are expressed using the same term of “chronic gastritis”. Patients with “chronic gastritis” expect to be treated for certain symptoms, so the meaning of “chronic gastritis” here is “symptomatic gastritis”. Patients have less concern about treatment when suffering from “morphological gastritis”, so only doctors are concerned with this “morphological gastritis” in the case of treatment of “chronic gastritis”. In this way, both doctors and patients have been confused about the term “chronic gastritis” in clinical practice in Japan. Finally, “symptomatic gastritis” is independent of these and clearly defined as functional dyspepsia (FD) in Japanese clinical practice in 2013.
    FD is known as a multifactorial disease. Many kinds of treatment strategy for it have been studied. H. pylori has a few but clear effects on the pathogenesis of FD. Indeed, for every 13 patients in which it is eradicated, only 1 patient can be cured. However, many physicians feel that the symptoms of many more FD patients are relieved by eradication therapy in clinical practice. To explain this phenomenon, the placebo effect has an important role. From the results of a systematic review, placebo eradication therapy provided a high placebo effect of more than 50%. Therefore, many patients who undertook eradication therapy might improve symptoms via the placebo effect. We should keep this in mind when dealing with FD.
    There are 3 reasons for the significance of eradication therapy for FD patients. First, H. pylori is the cause of a certain percentage of cases; second, eradication results in the prevention of gastric cancer, which is the most significant effect of eradication therapy; and third, adverse effects by eradication therapy are generally mild and acceptable. From these points of view, eradication should be the first option in patients with H. pylori-positive FD.
    Since the prevalence of H. pylori-negative gastric cancer (which means not post-eradication, but never infected) is reported to be very low, at less than 1% among gastric cancer cases, infection control should be the most important factor to eradicate gastric cancer from Japan. H. pylori infection occurs from infancy to childhood, so infection control during these periods should be important. When parents are infected, their children would be infected by them. Regrettably, parents become infectious sources for their own children. Therefore, ideally, eradication of H.
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  • MASAHIKO URAO
    2014 Volume 60 Issue 1 Pages 16-24
    Published: 2014
    Released on J-STAGE: July 31, 2014
    JOURNAL FREE ACCESS
    Constipation is a combination of symptoms, such as fewer than three bowel movements per week, hard stool and a sense of incomplete evacuation. Most patients with constipation treat themselves. However, this does not always produce good management and may induce another illness. It is known that patients with constipation show reduced labor productivity and various increased risks, such as for anal diseases and colon cancer.
    There are many causes of constipation. The classifications of chronic constipation are as follows: 1) functional constipation including irritable bowel syndrome, 2) secondary constipation due to systemic diseases, 3) drug-induced constipation, 4) organic constipation due to digestive tract obstruction and 5) uncertain pathogenesis.
    It is important to be systemic to make a differential diagnosis. By taking the patient’s history and performing a physical examination, secondary constipation can be diagnosed. If one of the following is found, extensive examination may be required and it may be necessary to consult with a medical specialist: 1) anal bleeding at defecation, 2) more than 50 years old, 3) a family history of colorectal cancer and 4) rapid weight reduction. If constipation improves after stopping medication, it is diagnosed as drug-induced constipation. Most cases of chronic constipation are functional constipation, which can be controlled by improvement of lifestyle in many cases. Namely, an appropriate life rhythm includes good sleep, exposure to sunlight, eating breakfast and regular light exercise. Moreover, in order to improve the intestinal environment, consuming yogurt and dietary fiber, as well as 2 liters of water per day, is favorable. In additional, abdominal massage, adjustment of the defecation posture and producing a relaxed environment promote smooth defecation.
    There are several kinds of laxative, such as bulk-forming, stimulant and osmotic. 5-HT4 receptor agonist and tegaserod are also effective for slow-transit constipation.
    Although the main approach is always to start with changes in lifestyle and diet before commencing treatment with a laxative, functional constipation should be treated adequately with medicine since it may develop into severer constipation, which may require a surgical operation. However, aimless continuation of medication with stimulant laxatives is not recommended.
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  • CLOSELY RELATED TO HEALTH AND DISEASE OF THE HOST
    YUICHIRO YAMASHIRO
    2014 Volume 60 Issue 1 Pages 25-34
    Published: 2014
    Released on J-STAGE: July 31, 2014
    JOURNAL FREE ACCESS
    Culture-independent methods to study microbial communities have advanced our knowledge of the human gut microbiota. The gut microbiota in humans includes various kinds of microorganism inhabiting the length and width of the gastrointestinal tract. The composition of the microbiota is host-specific, evolving throughout an individual’s lifetime and susceptible to both exogenous and endogenous modifications. It is estimated that the human gut microbiota contains as many as 1014 bacterial cells and 500 to 1,000 species. The process of initial colonization of gut microbiota begins at the time of delivery, when the fetus leaves the germ-free intra-uterine environment and enters the extra-uterine setting. It is now well accepted that the colonization of bacteria, including Bifidobacteria and Lactobacilli, is necessary for the normal development of intestinal innate and adaptive defenses. Most preterm infants are delivered by cesarean (C) section for various reasons, so the transfer of bacteria from mother to infant is completely absent during the delivery; thus, infants delivered by C section are colonized with anaerobic bacteria later than vaginally delivered infants, leading to an unbalanced composition of the intestinal microbiota, namely, dysbiosis. Diet is known to modulate the composition of the gut microbiota in humans over the long term. The alteration of gut microbiota composition, dysbiosis, may contribute to the risk and pathogenesis of both undernutrition and overnutrition through effects on nutrient metabolism and immune function.
    The nexus between nutrient metabolism and the immune system occurs at many levels, ranging from endocrine signaling to direct sensing of nutrients by immune cells. The ability to use macronutrients is essential for the generation and maintenance of a protective effector immune response. Short-chain fatty acids (SCFAs) provide one of the clearest examples of how nutrient processing by the microbiota and host diet combine to shape immune responses. SCFAs are end products of the microbial fermentation of macronutrients, the most notable being plant polysaccharides that cannot be digested by humans.
    Changes in lifestyle and an increase in the availability of energy-rich food are important contributors to the worldwide obesity epidemic. The microbial inhabitants of the gut can also have an influence on metabolic processes, such as energy extraction from food, and should be considered as an environmental factor that contributes to obesity and its comorbidities, such as insulin resistance, type 2 diabetes, cardiovascular disease and also cancer.
    Accumulating evidence indicates that gut microbiota may be a target for preventing and treating obesity; this will require probiotics that are selected for specific clinical manifestations of metabolic syndrome.
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Original Articles
  • TOMOYUKI FUJITA, SHIORI KAWASAKI, SATOSHI MATSUSHITA, HIROTAKA INABA, ...
    2014 Volume 60 Issue 1 Pages 35-42
    Published: 2014
    Released on J-STAGE: July 31, 2014
    JOURNAL FREE ACCESS
    Pleural effusions after the Fontan procedure contribute to morbidity, prolonged hospital stay, increased risk of infection, and may necessitate a pleurodesis procedure. Although the exact pathophysiological pathways are not fully understood, diuretics are generally used for the treatment of pleural effusions. On the other hand, postoperative elevation in antidiuretic hormone and decrease in atrial natriuretic peptide have been proven, indicating an effect of resistance to diuretic therapy. This paper reports on the efficacy of a high-dose diuretics regimen to prevent pleural effusions in the early postoperative period after the Fontan procedure.
    From June 1997 to November 2012, 36 cases underwent the Fontan procedure. From August 2008, a new regimen using high-dose diuretics has been adopted and applied to 15 patients. Four out of 15 patients were excluded from this study due to early death or serious complications, so 11 patients were defined as the high-dose group. Before August 2008, 3 out of 21 patients were excluded for a similar reason, with 18 patients being defined as the control group. The high-dose group received a high-dose diuretic regimen that consisted of 20 mg of furosemide and 20 mg of spironolactone, three times a day after every meal. Perioperative data and postoperative course were compared between the two groups retrospectively.
    Patient characteristics were not significantly different between the two groups. However, preoperative body weight was lower in the high-dose group(10.3±1.12 vs. 11.8±2.34kg, p<0.05). The average amount of urine from postoperative day 1 to day 3 was significantly higher in the high-dose group(49.2±10.7 vs. 40.0±14.6ml /kg/day, p<0.05). The amount of chest drainage was significantly lower in the high-dose group(486±182 vs. 870±635ml , p<0.05). No patients received drip infusions of albumin preparation in the high-dose group, while 6 out of 18 patients received it in the control group. Further pleural drainage after the removal of chest tubes was performed on eight patients in the control group, but it was performed only twice on one patient in the high-dose group(p<0.05). No patient showed serious complications, such as renal failure, thrombus formation, arrhythmias, reintubation, the need for increasing inotropic support, or the need for pleural sclerosis.
    The high-dose diuretics regimen using furosemide and spironolactone after the Fontan procedure increased urine in the early postoperative period, reduced overall pleural effusions, and minimized the need for additional treatment.
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  • Relationships Between CBT/Graduation Examination and OSCE/Advanced OSCE
    YUICHI TOMIKI, TAKASHI DAMBARA, TAKAO OKADA, MASAKO NISHIZUKA, KAZUO K ...
    2014 Volume 60 Issue 1 Pages 43-48
    Published: 2014
    Released on J-STAGE: July 31, 2014
    JOURNAL FREE ACCESS
    Objective: The present study examined whether Objective Structured Clinical Examination (OSCE) scores are related to Computer-Based Test (CBT) and graduation examination scores, and considered the OSCE’s application to undergraduate medical education.
    Study design: The subjects were 282 students who underwent a common achievement examination and a graduation examination at Juntendo University. The subjects were divided into four (A to D) groups according to their ranking on academic-year-specific CBT and graduation examination scores. Correct answer rates and global rating scores were compared among the four ranks.
    Results: The correct answer rate on the OSCE was 89.06±3.86, and the global rating score was 4.67±0.36. The correct answer rate on the Advanced OSCE was 80.13±9.85, and the global rating score was 4.50±0.74. The top-ranked group also scored highest on the OSCE and Advanced OSCE. The correct answer rates and global rating scores of both OSCE and Advanced OSCE decreased as rank decreased from Rank A to Rank D.
    Conclusions: The correct answer rates for the OSCE and Advanced OSCE in students who received low CBT and graduation examination scores were lower than those of the high-score group. It is necessary to encourage students to develop and improve their skills based on knowledge that will facilitate smooth postgraduate clinical training.
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  • YOSHIKO HOSOE-NAGAI
    2014 Volume 60 Issue 1 Pages 49-55
    Published: 2014
    Released on J-STAGE: July 31, 2014
    JOURNAL FREE ACCESS
    Objective: Sall1 is a zinc finger containing transcription factor that is highly expressed during mammalian embryogenesis and known as the initial key step for matenephros development. Sall1-deficient animals die at birth due to kidney deficits. However, its function in mature podocytes and/or injured podocytes has not been characterized. The present study indicated the role of Sall1 in mature podocytes as well as in injured podocytes.
    Materials and Methods: To clarify the role of Sall1 in mature podocytes, we generated podocyte-specific Sall1 KO (pSall1 KO) mice. To clarify the role of Sall1 in injured podocytes, we used Lipopolysaccharide (LPS) -injected mice as a minimal-change disease (MCD) model and ADR-injected mice as a nephrosis and glomerulosclerosis model.
    Results: We observed that the pSall1 KO mice showed no obvious phenotype under physiological conditions. There was no significant difference in the level of urinary protein among WT mice and pSall1 KO mice groups 48 hours after the injection of LPS. The level of urinary protein was significantly increased in pSall1 KO mice on day 28 after ADR injection. Sall1 affected the localization of the slit diaphragm protein nephrin in ADR-injected pSall1 KO mice.
    Conclusions: Sall1 may have a crucial renoprotective role in the mechanism of recovery from severe podocyte injury.
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Lecture Note
  • AKIRA ORIMO
    2014 Volume 60 Issue 1 Pages 56-62
    Published: 2014
    Released on J-STAGE: July 31, 2014
    JOURNAL FREE ACCESS
    Metastasis is a life-threatening disease that accounts for as much as 90% of cancer-related mortality. Carcinoma cells have often spread to distant organs at the time patients present with cancer. Routine clinical examinations have produced significant progress in detecting metastasis but existing methods for screening cancer patients are incapable of detecting micrometastasis and disseminated tumour cells (DTCs) in distant organs. Adjuvant chemotherapy and adjuvant radiotherapy are anticipated to prevent relapse and death. However, over periods of time ranging from years to decades, these metastatic cells residing in distant organs often relapse, corrupt the local microenvironment and acquire the ability to develop into macrometastases. Metastatic nodules are known to be formed by carcinoma cells harboring increased numbers of epi/genetic alterations conferring aggressive and drug-resistant propensities. In addition, more recently emerging evidence supports the notion that the tumour-associated stroma, consisting of endothelial cells, leukocytes, macrophages, myofibroblasts, bone marrow-derived progenitors and abundant extracellular matrix (ECM), significantly facilitates tumour metastasis. The molecular signalling underlying the complexity of heterogeneous stromal-tumour interactions that is relevant to tumour metastasis is the subject of intensive research. The tumour-associated stroma, in addition to tumour cell-autonomous alterations plays significant roles to instigate and support progression of the multi-step processes of tumour metastasis.
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  • TADASHI BABA
    2014 Volume 60 Issue 1 Pages 63-65
    Published: 2014
    Released on J-STAGE: July 31, 2014
    JOURNAL FREE ACCESS
    A bacterial genome is characteristic to its circular chromosomal DNA most of which consist of coding sequences, showing clear contrast to eukaryotic cells carrying multiple numbers of linear chromosomes with lower ratio of the coding sequences than bacteria. The genes involved in a common biochemical pathway often form a polycistronic unit called operon, which is not seen in the eukaryotic cells. By knowing such unique characters of a bacterial genome, we can infer physiological features of a bacterium from its genome sequence, and the work is probably much simpler than that for eukaryotic cells.
    The department of Bacteriology of the Juntendo Univ. determined the whole genome sequence of Staphylococcal aureus, a causative microorganism of nosocomial infections, for the first time in the world in collaboration with other domestic groups. By employing the obtained genome information, we performed comparative analyses with genomes of other S. aureus strains as well as those of related species of staphylococci. We thereby found that (i) a S. aureus genome carries its unique domains designated genomic islands that has been presumably acquired horizontally and are often accompanied with virulence or drug-resistant genes, in addition, (ii) the genomic islands show polymorphism among S. aureus strains, leading to carriage of different sets of the virulence determinants, indicating the toxicity of a S. aureus strain upon infection differs form the others.
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