The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 211, Issue 3
March
Displaying 1-12 of 12 articles from this issue
Invited Review
  • Kazuhisa Takeda, Na-Ho Takahashi, Shigeki Shibahara
    2007 Volume 211 Issue 3 Pages 201-221
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    The skin is armored with “dead cells”, the stratum corneum, and is continuously exposed to external stressful environments, such as atmospheric oxygen, solar radiations, and thermal and chemical insults. Melanocytes of neural crest origin are located in the skin, eye, inner ear, and leptomeninges. Melanin pigment in the skin is produced by melanocytes under the influence of various endogenous factors, derived from neighboring keratinocytes and underlying fibroblasts. The differentiation and functions of melanocytes are regulated at multiple processes, including transcription, RNA editing, melanin synthesis, and the transport of melanosomes to keratinocytes. Impairment at each step causes the pigmentary disorders in humans, with the historical example of oculocutaneous albinism. Moreover, heterozygous mutations in the gene coding for microphthalmia-associated transcription factor, a key regulator for melanocyte development, are associated with Waardenburg syndrome type 2, an auditory-pigmentary disorder. Sun tanning, melasma, aging spots (lentigo senilis), hair graying, and melanoma are well-known melanocyte-related pathologies. Melanocytes therefore have attracted much attention of many ladies, makeup artists and molecular biologists. More recently, we have shown that lipocalin-type prostaglandin D synthase (L-PGDS) is expressed in melanocytes but not in other skin cell types. L-PGDS generates prostaglandin D2 and also functions as an inter-cellular carrier protein for lipophilic ligands, such as bilirubin and thyroid hormones. Thus, melanocytes may exert hitherto unknown functions through L-PGDS and prostaglandin D2. Here we update the neuroendocrine functions of melanocytes and discuss the possible involvement of melanocytes in the control of the central chemosensor that generates respiratory rhythm.
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Regular Contributions
  • Mio Ishibashi, Hideki Tonori, Takeo Miki, Eriko Miyajima, Yasushi Kudo ...
    2007 Volume 211 Issue 3 Pages 223-233
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Sick house syndrome (SHS) is a Japanese concept derived from sick building syndrome (SBS), however SHS includes a broader scope of sickness than does SBS. Symptoms of SHS/SBS disappear after leaving the sick house/building, while symptoms of multiple chemical sensitivity (MCS) are elicited by the chance of chemical exposure after leaving the sick house/building. To establish the concept of SHS, we propose to introduce a new classification for SHS. A total of 214 patients complaining of SHS and/or MCS were independently classified using a new classification by clinical ecologists who are experienced physicians with expert knowledge of clinical ecology and general physicians according to disease pathogenesis from clinical records. The classification is as follows: type 1 (symptoms of chemical intoxication), type 2 (symptoms developed possibly due to chemical exposure), type 3 (symptoms developed not because of chemical exposure but rather because of psychological or mental factors), and type 4 (symptoms developed due to allergies or other diseases). The agreements on the classification made by clinical ecologists and general physicians reached 77.1% (Cohen's kappa = 0.631), suggesting that this new classification was both apt and accurate. Relations between SHS and allergy/MCS were also studied. The cases classified as SHS type 4 more frequently had allergic past histories than did other types. The proportion of possible MCS cases was higher in the chemical induced SHS group (types 1 and 2) than in other types among male patients. For the universal use in clinical practice, it is necessary to prepare helpful diagnostic criteria of this SHS classification based on pathogenesis and carry our study forward all over the country.
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  • Erdal Kalkan, Basar Cander, Mehmet Gul, Sadik Girisgin, Hakan Karabagl ...
    2007 Volume 211 Issue 3 Pages 235-242
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Epidural hematoma (EH) is a serious clinical event observed in 2% of head trauma patients. Studies regarding the effects of epidural hematoma volume (EHV) on prognosis are not sufficient. In this study, we applied the volume fraction approach of the stereological method to estimate the hematoma to brain volume fraction (HBVF), and investigated the relation between the HBVF and prognosis. Fifty-nine EH patients (46 male and 13 female subjects, with average age of 21 years) admitted to the emergency clinic were included. The HBVF was estimated on the printed films of cranial computed tomography scans. For this purpose, common point counting grids were superimposed over the scan frames. According to the clinical results, patients were divided into three groups as complete recovery (43), disability (8) and exitus (8). The HBVF was compared with the clinical results. HBVF was determined as 4.6% in the patients with recovery, 8.1% in disability, and 7.6% in exitus patients. The HBVF values were lowest in recovery patients, and the difference between the recovery and the other two groups was statistically significant (p = 0.007). However, there was no statistically significant difference in HBVF between disability and exitus patients (p > 0.05). In conclusion, the HBVF can be an important tool to determine prognosis, and it can be measured using the volume fraction approach of stereological methods as developed in the present study.
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  • C. Nur Semerci, N. Lale Satiroglu-Tufan, Serap Turan, Abdullah Bereket ...
    2007 Volume 211 Issue 3 Pages 243-249
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    A 45,X karyotype is one of the common chromosomal abnormalities characterized by short stature, lack of development of secondary sexual characteristics, webbed neck and cubitus valgus. This phenotype was described by Turner in 1938 and was called Turner syndrome (TS). About 40-60% of the patients with TS phenotype have a 45,X karyotype, the rest either have a structurally abnormal X or Y chromosome or mosaicism with a second cell line. Determination of Y chromosome derivatives in patients with a 45,X karyotype is important for the management of these patients due to increased risk of gonadoblastoma. Low level mosaicisim of Y chromosome may be missed by cytogenetic methods. The aim of our study is to analyze cryptic Y chromosome derivatives using Y specific sequences in 40 Turkish patients with a pure 45,X karyotype. Fourteen different Y specific sequences along the Y chromosome were selected for the detection of cryptic Y chromosome material by PCR analysis. The present study demonstrated that 2 patients with a 45,X karyotype (5%) have Y specific sequences except sex releated region Y (SRY). One of them had displayed enhanced virilisation whereas other showed no virilisation. In conclusion, it has been found by PCR analysis that 5% of patients with a 45,X karyotype have Y chromosome sequences in the absence of any marker chromosome by cytogenetic analysis. The data also suggest that the patients with a 45,X karyotype should be analyzed for the presence of Y chromosome derivatives by sensitive methods, such as PCR, in order to calculate the future risk of developing gonadoblastoma.
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  • Mitsuhiro Yamashina, Yoshihiro Kaneko, Chihaya Maesawa, Takashi Kajiwa ...
    2007 Volume 211 Issue 3 Pages 251-258
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Little has been known about the role of tumor necrosis factor-α (TNF-α) gene polymorphisms in metabolic syndrome and atherosclerosis in type 2 diabetes, although TNF-α was reported to be involved in these conditions. We examined the association of TNF-α gene promoter polymorphisms, G-238A, G-308A, C-857T, C-863A, and T-1031C, with metabolic syndrome and surrogate markers of atherosclerosis in Japanese patients with type 2 diabetes. DNA was obtained from 162 patients and TNF-α gene promoter polymorphisms determined by direct sequencing. Allelic frequency of -238A, -308A, -857T, -863A, and -1031C was 0.6%, 2.2%, 11.1%, 16.7%, and 15.7%, respectively. Association of the gene polymorphisms with a number of variables, because of their high frequency, was analyzed in the latter 3 polymorphisms. There were no significant differences in components of metabolic syndrome and variables affecting atherosclerosis, except in case of serum low-density-lipoprotein cholesterol (LDL-C) (111 ± 33 vs 125 ± 39 mg/dl, p < 0.05) between -857C/C and -857(C/T + T/T). In contrast, no significant differences were found in these markers between -863C/C and -863(C/A + A/A) and between -1031T/T and -1031(T/C + C/C). Furthermore, 87% of the patients with -857(C/T + T/T) and 64% with -857C/C had carotid plaques (p < 0.05). There was no difference in proportion of patients treated with medications such as statins, fibrates, oral hypoglycemic agents, insulin, or antihypertensive drugs between -857C/C and -857(C/T + T/T). These data imply that TNF-α gene polymorphism (C-857T) is likely associated with higher serum LDL-C levels and carotid plaque formation in Japanese patients with type 2 diabetes.
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  • Isamu Sugawara, Hiroyuki Yamada, Satoru Mizuno
    2007 Volume 211 Issue 3 Pages 259-268
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    In order to examine the relationship between malnutrition and tuberculosis development in vivo, a malnourished guinea pig model fed with a low casein (5%) diet was developed. After being fed with the low casein diet, the guinea pigs were infected with Mycobacterium (M.) tuberculosis Kurono strain by aerosol infection, and seven weeks later were subjected to histopathologic examination, colony-forming unit (CFU) assay, fluorescence-activated cell sorter (FACS) analysis and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-12 and inducible nitric oxide synthase (iNOS) mRNA. Another group of guinea pigs were vaccinated subcutaneously with 106 CFU BCG Tokyo for three weeks and then similarly infected by aerosol. Eighty-eight % (7/8) of the malnourished guinea pigs succumbed to mycobacterial infection within 85 days after infection, while the malnourished guinea pigs vaccinated with BCG Tokyo survived. CFU assay showed that lung and splenic CFUs were higher in the low casein diet-fed groups than in the control diet (20% casein)-fed groups, although both groups had significantly lower CFUs after vaccination with BCG Tokyo (p < 0.01). Examination of lung histopathology revealed that pulmonary granulomas were large and disorganized in the groups fed the low casein diet. The number of visible lesions on the surfaces of the fixed lungs in guinea pigs fed control diet + BCG and low casein diet + BCG was low significantly. Pan T-, CD4-, CD8- and Mac antigen-positive cells were also recognized in the infected lung tissues of low casein-fed guinea pigs and Pan T-, CD4- and Mac antigen-positive cells increased after vaccination with BCG Tokyo. Expression of IFN-γ, TNF-α, IL-12 and iNOS mRNA was also recognized in the infected lung tissues of low casein-fed guinea pigs and IFN-γ and TNF-α mRNA expression was enhanced with BCG vaccination. These results indicate that malnutrition exacerbates mycobacterial infection and that malnourished infected hosts may be protected by BCG vaccination.
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  • Mitsuo Uchida, Hidetoyo Teranishi, Keiko Aoshima, Terutaka Katoh, Mino ...
    2007 Volume 211 Issue 3 Pages 269-274
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Environmental cadmium (Cd) pollution and its effects on human health are still important issues. The most severe and representative manifestation of chronic Cd intoxication is Itai-itai disease, which is a syndrome that includes renal tubular dysfunction, osteomalacia, and generalized pain due to multiple bone fractures. The whole mechanism of how renal dysfunction relates to the development of bone lesions is unresolved. Vitamin D-binding protein (DBP) binds, transports and activates vitamin D, which plays a major role in calcium homeostasis and bone turnover. In this study, we measured urinary DBP levels and investigated their relationship to the markers of renal tubular dysfunction in the inhabitants of a Cd-polluted Jinzu River basin in Toyama Prefecture, Japan (Cd group). We also investigated age-matched subjects from an area known to have lower levels of Cd pollution (reference group). Urinary DBP was measured by a fluorometric enzyme-linked immunosorbent assay (ELISA), which was established in our laboratory. Significantly higher levels of urinary DBP were observed in the Cd group compared to the reference group. We observed significant positive correlations between urinary levels of DBP and renal tubular dysfunction markers in both groups. In the Cd group, urinary levels of DBP had a negative correlation with serum phosphate value. These results indicate that excretion of urinary DBP is increased after long-term Cd exposure and that the loss of DBP in urine may be linked to renal tubular dysfunction and possibly bone lesions in the inhabitants of Cd-polluted areas.
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  • Yuji Kasukawa, Naohisa Miyakoshi, Apurva K. Srivastava, Koji Nozaka, S ...
    2007 Volume 211 Issue 3 Pages 275-283
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Suppression of increased bone resorption is an important issue in treatment of post-menopausal osteoporosis. Celecoxib is a highly selective inhibitor of cyclooxygenase-2 (COX-2), and inhibits osteoclastogenesis in vitro. In the present study, to test whether celecoxib can suppress elevated bone resorption caused by estrogen deficiency in vivo, celecoxib (4 mg/kg) or its vehicle was administered to sham-operated or ovariectomized (OVX) mice (model of post-menopausal osteoporosis). The treatment with celecoxib or vehicle was started immediately after the sham operation or ovariectomy, and lasted for 4 weeks. At 2 and 4 weeks after surgery, OVX mice administered vehicle had significantly higher levels of C-telopeptide, a marker of bone resorption in serum, than sham-operated mice administered vehicle (37% and 60% higher, respectively; p < 0.01). At 2 and 4 weeks after surgery, celecoxib treatment significantly decreased serum C-telopeptide levels in OVX mice, but not in sham-operated mice (45% and 41%, respectively; p < 0.001). In contrast, in both sham-operated and OVX mice, celecoxib did not significantly affect serum osteocalcin levels (a marker of bone formation) or bone mineral density (BMD) of the femur, which was evaluated by peripheral quantitative computed tomography (pQCT). In conclusion, treating OVX mice with celecoxib significantly suppressed the increase in serum levels of the bone resorption marker, but did not affect levels of the bone formation marker. Also, celecoxib did not prevent the decrease of femoral BMD in OVX mice. The present study suggests the possibility that celecoxib may be used to prevent bone loss caused by estrogen deficiency.
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Case Reports
  • Nilgun Araz, Vahap Okan, Mustafa Demirci, Mustafa Araz
    2007 Volume 211 Issue 3 Pages 285-290
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Cholelithiasis rarely occurs in childhood. Ceftriaxone is a widely used antimicrobial agent in pediatrics due to the broad spectrum. Reversible biliary sludge and/or lithiasis, named as pseudolithiasis, have been reported in patients treated with ceftriaxone. We observed ceftriaxone-associated pseudolithiasis in 8 patients with meningitis. The aim of this study was to report the clinical characteristics of these patients and to evaluate the related factors for the development of ceftriaxone-associated pseudolithiasis in children. The study group consisted of 7 boys and 1 girl. All patients received ceftriaxone 100 mg/kg/day for meningitis. The ultrasonographic evaluation was performed on 5th-10th days after the initiation of the therapy. Biliary sludge was detected in one patient, and gallstone was detected in three patients, while biliary sludge with gallstone was detected in four patients. Six of the cases were diagnosed during summer time. Thus, high temperature may cause loss of fluid, leading to easier formation of sludge. Ceftriaxone treatment was discontinued after sonographic demonstration of pseudolithiasis. Gallbladder sonograms were found to be normal in all patients at the follow-up sonographic examinations performed after 30 days of the diagnosis without specific treatment. Clinicians should screen all pediatric patients living in areas with high temperature and receiving ceftriaxone treatment (over 100 mg/kg) by ultrasonography for biliary sludge or gallstone formation even if they are asymptomatic.
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  • Yukihiko Kawasaki, Kazuhide Suyama, Ayumi Matsumoto, Kei Takano, Koich ...
    2007 Volume 211 Issue 3 Pages 291-295
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Henoch-Schoenlein purpura (HSP) is a systemic disorder characterized by a leukocytoplastic vasculitis involving small vessels with the deposition of immunoglobulin A (IgA) immune complexes. Renal involvement is the principal cause of morbidity and mortality in children with HSP. We report here an 11-year-old boy with Henoch-Schoenlein purpura nephritis (HSPN) accompanied by recurrent purpura and persistent nephropathy despite conventional therapy such as prednisolone, methylprednisolone pulse therapy and immunosuppressive agent (Mizoribine). The patient was treated with tonsillectomy plus methylprednisolone pulse therapy. This treatment decreased proteinuria, induced disappearance of microscopic hematuria, and improved renal pathological findings. Tonsillectomy plus methylprednisolone pulse is effective and useful therapy for some children with recurrent purpura and persistent nephropathy.
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  • Isao Uemaetomari, Keiji Tabuchi, Tadamichi Tobita, Shigeki Tsuji, Tets ...
    2007 Volume 211 Issue 3 Pages 297-302
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Polymorphous low-grade adenocarcinoma (PLGA) of the salivary gland is a disease entity that is a recently described form of adenocarcinoma. PLGA most commonly arises in the minor salivary glands. We report two cases of PLGA of the parotid gland. Case 1: A 52-year-old female visited the University of Tsukuba Hospital with a painless mass in the left parotid region. A superficial parotidectomy and postoperative radiotherapy were performed. The patient has been free from disease for 50 months. Case 2: A 55-year-old female initially noticed a painless slowly growing mass in the left parotid region. The tumor was removed with a superficial parotidectomy. The local recurrence was found 6 years after the initial surgery. The recurrent tumor was removed, and radiotherapy was administered thereafter. The patient has been free from the disease for 33 months since the last treatment. The treatment for the primary lesion is crucial for the prognosis since metastasis to the regional lymph node or to distant region is unusual in PLGA. Although surgical extirpation is the recommended modality for treatment of PLGA, wide resection with a safety margin is often difficult in the parotid gland because of the presence of the facial nerve. Our two cases were successfully treated with surgery and postoperative radiotherapy. Although our literature search revealed 32 previously reported cases of PLGA of the parotid gland, only five of the 32 cases were treated postoperative radiotherapy. We highlight the importance of postoperative radiotherapy for PLGA of the parotid gland.
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  • Yosuke Kakisaka, Kazuhiro Haginoya, Noriko Togashi, Taro Kitamiura, Mi ...
    2007 Volume 211 Issue 3 Pages 303-308
    Published: 2007
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Brainstem reticular reflex myoclonus (BRRM) is characterized by sudden, generalized, shock-like movements that can be elicited by sensory stimulation. We present a boy, born after 35 weeks gestation, who was diagnosed with neonatal-onset BRRM. Within 1 hr of birth, the patient showed spasticity and generalized clonic movements of all limbs elicited with tactile stimulation anywhere on the body. Surface electromyography showed co-contraction of agonistic and antagonistic muscles, revealing that his generalized clonic movements were tremulous myoclonus in nature. Brain magnetic resonance imaging (MRI) at 21 hrs after birth disclosed high-intensity lesions in the Rolandic area, thalamus, basal ganglia, and brainstem, including the dorsal pons and medulla, the center of BRRM, in T1-weighted images. Follow-up MRI at 1 month revealed dramatic improvement in the pontine lesion. The patient showed gradual remission of the characteristic movements, which disappeared at 1 year of age, but the patient died unexpectedly at 1 year and 3 months. In conclusion, neonatal BRRM arises as a result of severe brainstem injury, and the associated lesions may only be seen temporarily on MRI taken soon after birth.
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