Since there is no infrared fluorescence materials in the living body, infrared fluorescence labeling materials are very useful for making a diagnosis of a micro cancer. We have developed an infrared fluorescence endoscope (IRFE) and indocyanin green (ICG)-derivative as infrared fluorescence labeling materials to evaluate gastrointestinal neoplastic lesions. The study aims were to apply an IRFE and to demonstrate its usefulness in detecting cancerous tissue using an antibody coupled with ICG-derivative.
IRFE consisted of an infrared endoscope equipped with excitation (710-790nm) and barrier (810-920nm) filters and an intensified CCD camera. We have developed ICG N-hydroxy sulfo succinimide ester (ICG-sulfo-OSu) and 3-ICG-acyl-1, 3-thiazolidine-2-thione (ICG-ATT) as an infrared fluorescent-labeling reagent. ICG-derivative-labeled mouse anti-human carcinoembryonic antigen (CEA) antibody and MUC1 antibody were employed in this study. Moreover, we examined the ability of a reinforcement agent, octylglucoside, to intensity fluorescence from the labeled antibody. Biopsy specimens of gastric cancer were stained with anti-CEA antibody by the avidin-biotinylated peroxidase complex method. Among the positive specimens, freshly resected stomach from three cases were used for the infrared (IR) imaging analysis.
The incubation of freshly resected stomach specimens with ICG-anti-CEA antibody-complex resulted in positive staining of the tumor sites by IRFE, and the IR fluorescent images correlated well with the tumor sites. The immunohistochemical studies suggested that the intensity of IR fluorescence of ICG-ATT-MUC1 was stronger than that of ICG-sulfo-OSu. In tumor sections, the reinforcement agent intensified fluorescence, ever at low antibody concentrations.
Therefore, we conclude that an anti-CEA (and/or MUC1) antibody with affinity for cancerous lesions and labeled with ICG-derivative can be imaged with this IRFE.
Specific antibodies tagged with ICG-derivative with the reinforcement agent can label cancer cells and generate a strong enough fluorescent signal to detect small cancers when examined with an IR fluorescence endoscope. J. Med. Invest. 53: 1-8, February, 2006

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Renal cell carcinoma (RCC) is the 10^th most common cancer in United States. It is a heterogeneous disease with various histologic types. Since high-throughput technologies such as microarrays have been introduced, molecular confirmation of previously known findings in RCC has been made and new molecular findings have emerged. We review the accumulating advances in this field and their clinical implications. The published data so far have proved to be significant and promising, and numerous microarray studies with larger number of cases are currently ongoing or being planned. Although various clinical parameters are being refined for diagnosis and prognosis, these data obtained by microarray studies will undoubtedly contribute to both and eventually impacts the treatment of RCC. J. Med. Invest. 53: 9-19, February, 2006

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The proteomics approach was adopted to study the simultaneous expression of serum proteins in patients with nasopharyngeal carcinoma (NPC). We have subjected unfractionated whole sera of ten newly diagnosed Malaysian Chinese patients with WHO type III NPC to two-dimensional gel electrophoresis (2-DE) and image analysis. The results obtained were then compared to that generated from sera of ten normal healthy controls of the same ethnic group and range of age. Our data demonstrated that the serum high abundance 2-DE protein profiles of NPC patients were generally similar to that of the controls, with exception of the ceruloplasmin (CPL) spots (identified by mass spectrometric analysis and MASCOT database search), which showed higher expression. The enhanced expression of CPL in the patients’ sera was confirmed by competitive ELISA. Immunohistochemical analysis of nasopharyngeal lesions of NPC patients demonstrated moderate to strong positive CPL staining in the cytoplasm of cells at the regions of malignancy but only weak cytoplasmic staining at normal epithelial lining areas. When follow-up 2-DE and ELISA studies were performed on five of the NPC patients who responded positively to six months treatment, the difference in CPL expression was no longer significant. J. Med. Invest. 53: 20-28, February, 2006

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The NC/Nga mouse is a model animal for human atopic dermatitis. In this study, we investigated oral tolerance induction in NC/Nga mice. In BALB/c mice, oral administration of ovalbumin (OVA) resulted in suppression of both OVA-specific T and B cell responses induced by OVA immunization. In NC/Nga mice, OVA-induced antigen (Ag) -specific T and B cell responses were significantly less than those in BALB/c mice. Furthermore, oral administration of OVA did not suppress OVA-specific immunoresponses in NC/Nga mice. We further examined antibody (Ab) response against food Ag by feeding mice an experimental diet that contained OVA or casein as a protein source. The level of serum OVA or casein-specific IgG was significantly higher in NC/Nga mice than in BALB/c mice. These results indicate that NC/Nga mice have a defect in the induction of oral tolerance. NC/Nga mice can therefore be used as a model for investigating the mechanism of oral tolerance. J. Med. Invest. 53: 29-33, February, 2006

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Due to high resting energy expenditure (REE) in maintenance hemodialysis patients, an increase in energy intake is usually recommended to improve their nutritional status. However, some patients appear to have poor appetite and low energy intake. In such patients low energy metabolism is expected. We hypothesized that in maintenance hemodialysis patients there are two types of the energy metabolism, high and low. This study was aimed at finding the energy metabolism in maintenance hemodialysis patients, especially in those with poor nutritional status.
Subjects were hemodialysis out-patients (34 males and 20 females, mean age 59.1±10.7y). REE was measured by an indirect calorimeter. Protein intake was obtained from normalized protein catabolic rate (nPCR), and physical activity level (PAL) was obtained by time study. Nutritional status assessed by serum albumin concentration was poor (3.7±0.2g/dL) in spite of the adequate protein intake (1.1±0.3g/kg per day). Only 11% of the subjects had appropriate serum albumin concentration. Mean REE was 24.6kcal/kg per day which was lower than that of healthy Japanese (26.5kcal/kg per day). REE and PAL positively correlated with serum albumin concentration (p<0.01). The results suggest that maintenance hemodialysis patients with poor nutritional status may have low REE. J. Med. Invest. 53: 34-41, February, 2006

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We developed a novel protocol for generation and selective amplification of neural progenitor cells regionally specified to the rostral brain but not the spinal cord from mouse embryonic stem cells (ESCs). The neural progenitors could differentiate in vitro and in vivo into many cholinergic and a few GABAergic neurons but rarely into astrocytes. The transplanted neurospheres could survive in the hippocampus (CA3) of animals with mild traumatic brain injury (TBI). Twelve weeks after transplantation (a week after the behavioral test), we found significant cholinergic differentiation recognized as ChAT immunoreactivity in the eGFP+transplanted cells. Moreover, the grafts contained a few GAD67+cells. However, we barely found GFAP+astrocytes within the grafts. Furthermore, presynaptic formations of graft-derived neurons were recognized by immunohistochemistry of near the grafts around CA3. However, these findings were not observed in severe TBI group. So, we examined NGF, BDNF, and FGF-2 mRNA by RT-PCR in 12 mice including normal, mild TBI and severe TBI group. Increases in the neurotrophic factors’ mRNA were evident in the hippocampus on the ipsilateral side in the mild TBI group. Statistical analysis revealed significant differences between the mild and severe TBI groups. The data also revealed significant differences between the mild TBI and normal groups. The transplanted neurospheres could survive in the mild TBI animals, but not in the severe TBI group. J. Med. Invest. 53: 42-51, February, 2006

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Purpose: In recent years, labeled antibodies have been used for diagnostic imaging in many studies. In this study, we investigated the mode of binding in antibodies labeled with ICG derivatives newly developed for the diagnosis of microcarcinomas, and evaluated the optimal binding molar ratio between the labeling compounds and antibody. Methods: MUC 1 antibody and ICG derivatives (ICG-ATT and ICG-sulfo-OSu) were used. ICG derivatives non-covalently bound to the antibody were removed with ethyl acetate, and the ratio of ICG derivatives covalently bound to the labeled antibody was confirmed. During purification of the labeled antibody, the amount of each labeling compound reacting with 1 molecule of the antibody varied as follows: 4, 8, 16, and 32 molar equivalents. Subsequently, the intensity of fluorescence was evaluated by spectroscopy and infrared fluoroscopy. Results: The ratio of residual ICG derivative labeling the antibody was 67.4% for ICG-ATT and 65.0% for ICG-sulfo-OSu. When fluorescent antibody labeled with ICG-ATT at an F/P ratio of 2.94 or 4.18 was used, specific and clear fluorescent images of the antigen were obtained. When ICG-ATT-labeled antibody at an F/P ratio of 6.50 or 6.75 was used, the fluorescence intensity decreased and the fluorescent images of antigen became unclear. Conclusions: It was found that the ICG-ATT-labeled antibody was a more specific and sensitive marker than ICG-sulfo-OSu-labeled antibody, and that lower binding molar ratios of ICG-ATT were more useful for labeling the antibody. J. Med. Invest. 53: 52-60, February, 2006

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Objective. The goal of this study was to elucidate the effect of neurospheres (NS) on dementia in the mouse model of nucleus basalis of Meynert (NBM) lesion.
Methods. Mouse embryonic stem cell (ES) derived neurospheres were transplanted into the frontal association cortex and barrel field of S1 cortex of C57BL/6 mice 4 weeks after including a lesion of NBM by ibotenic acid, while other healthy mice that received ES cells served as control. Behavioral tests by 8-arm radial maze were conducted 8 weeks after transplantation, and double staining of choline acetyltransferase (ChAT), serotonin, amyloid-β protein (AP) and green fluorescent protein (GFP) 12 weeks after transplantation. We found that the neurospheres transplanted into the mouse cortex survived and produced many ChAT-positive neurons and a few serotonin-positive neurons in and around the grafts. The working memory error decreased significantly in the mice grafted with neurospheres. In contrast, the ES cells developed into teratomas in all of the control mice and expressed no neurons, and the working memory deteriorated remarkably.
Conclusions. Transplantation of neurospheres, but not ES cells, into the prefrontal and parietal cortices, dramatically alleviated the cholinergic deficits and recent memory disruption in the NBM lesioned mice. J. Med. Invest. 53: 61-69, February, 2006

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The Objective of this study was to elucidate if Bisphenol A (BPA) administration modulates T helper (Th) cell component of immune responses in a mouse challenged with ovalbumin (OVA), a major food antigen. BALB/c mice, (6 weeks old, female) were orally given either OVA (OVA-fed) or water (Water-fed), immunized intraperitoneally with OVA and injected with either BPA in corn oil or the vehicle alone. After subsequent 2^nd immunization, serum titers of total IgE, OVA-specific IgE, IgG, IgG1 IgG2a and ability of their splenocytes for production of interferon (IFN) -γ, interleukin (IL) -4 and IL-12 were examined by ELISA. Lymphocyte proliferation assay against concanavalin A (Con A) or OVA was also performed for ³H-Thymidine incorporation. In Water-fed groups, treatment with BPA resulted in lower titers of total IgE (P<0.01) and higher levels IgG2a (P<0.05) followed by a higher IFN-γ (P<0.05) and IL-12 (P<0.05) with an intact IL-4. When OVA-fed groups were examined, the compound did not change production of total and OVA-specific IgE and -IgG2a but resulted in lower production of IFN-γ (P<0.05). Also, BPA resulted in impaired lymphocyte proliferation to Con A in Water-fed groups (P<0.05) but not in tolerated animals. The findings indicate that BPA results in augmentation of Th1 immune responses but no significant effect on an established tolerance to OVA. J. Med. Invest. 53: 70-80, February, 2006

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Repeated injections of D-galactosamine hydrochloride (GalN) increase the survival rate of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson’s disease. The aim of the present study was to investigate the mechanism of GalN for prevention of spontaneous lethal hepatic injury in LEC rats. Male LEC rats were given a single subcutaneous injection of 300 mg/kg of GalN or vehicle (0.9% NaCl) at 14 weeks, and killed at 28 weeks of age. Next, 6-week-old male LEC rats were given weekly subcutaneous injections of 300 mg/kg of GalN or vehicle for 3 or 12 weeks, and their hepatic 8-hydroxydeoxy-2’-guanosine (8-OHdG), glutathione peroxidase (GPX), and catalase activities were measured. None of GalN-treated rats died of hepatic injury (0/12), whereas the mortality rate of control rats given 0.9% NaCl was 17% (2/12). GalN administration for 12 weeks decreased the hepatic 8-OHdG, and GalN administration for either 3 or 12 weeks increased the glutathione peroxidase activity. GalN administration increased the serum level of alanine aminotransferase, and accelerated megalocytic degeneration of the hepatocytes. GalN treatment is effective in preventing lethal hepatitis in LEC rats and decrease of oxidative DNA damage by GalN plays an important role in increase of the survival rate. 53: 81-86, February, 2006

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Background: Plasma adiponectin levels increase after the administration of glimepiride. This unique effects would also be expected to improve other adipocytokines and have anti-atherosclerotic action in patients with metabolic syndrome.
Methods: Thirty-four patients with type 2 diabetes mellitus who were administrated glibenclamide were randomly divided into two groups. In 20 patients glibenclamide was changed to glimepiride (GP group), and the administration of glibenclamide (GB group) was continued in 14 patients. Twelve patients receiving insulin therapy (INS group) were enrolled for comparison. The levels of plasma adiponectin, high sensitive-CRP, TNF-α, interleukin-6, homeostasis model assessment-insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity (baPWV) and augmentation index (AI) were measured before and 28 weeks after the therapy.
Results: HOMA-IR in the GP group was significantly decreased compared to the GB group. Plasma adiponectin levels were significantly increased in the GP group but not in the other groups. TNF-α, interleukin-6 and high sensitive-CRP levels were significantly decreased in the GP group, but not in the other groups. The baPWV and AI levels did not change in either the GB or the INS group, but were significantly decreased in the GP group. Conclusions: Glimepiride appears to improve insulin resistance and atherosclerotic disorders. J. Med. Invest. 53: 87-94, February, 2006

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The degree of ST-segment elevation and amplitude of J waves, which may change in patients with the Brugada-type electrocardiogram (ECG) over time, are influenced by autonomic nervous activity and the administration of antiarrhythmic drugs. In the present study, we evaluated whether the shape of ST-segment elevation in patients with a Brugada-type ECG might alter the parameters of an ¹²³I-MIBG myocardial scintigraphy and body surface signal-averaged ECG (SAECG). The subjects consisted of 12 patients with a Brugada-type ECG and 15 healthy volunteers (N group). The patients with a Brugada-type ECG were classified into the following 2 groups based on the type of ST-segment elevation: 6 patients with the coved type ST-segment elevation (C group), and 6 patients with the saddle-back type ST-segment elevation (S group). Planar and SPECT images were obtained 15 minutes (early images) and 3 hours (delayed images) after the administration of ¹²³I-MIBG, respectively. In addition, the washout rate (% WR) of ¹²³I-MIBG was obtained in a bull’s eye map of the SPECT image. There were no significant differences in the early H/M ratio between the C and S groups. In the C group, however, there were some patients who showed a decreased accumulation or defect of ¹²³I-MIBG in the planar and SPECT images. Furthermore, in contrast to the N and S groups, the C group showed a decreased delayed H/M ratio and increased % WR. SAECG did not show any significant differences between the S and C groups. These results of the present study suggest that the shape of ST-segment elevation may be associated with myocardial autonomic nervous function. In addition, the electric heterogeneity of the action potential in the right ventricular epicardial myocardium, which is frequently influenced by autonomic nervous activity, is closely associated with the development of Brugada syndrome. J. Med. Invest. 53: 95-102, February, 2006

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The human GLB1 gene encodes a lysosomal β-galactosidase (β-Gal) and an elastin-binding protein (EBP). Defect of the EBP as a chaperon for tropoelastin and a component of receptor complex among neuraminidase-1 (NEU1) and protective protein/cathepsin A (PPCA) is suggested responsible for impaired elastogenesis in autosomal recessive β-Gal, PPCA and NEU1 deficiencies. The purpose of this study is to determine effects of GLB1, PPCA and NEU1 gene mutations on elastogenesis in skin fibroblasts. Elastic fiber formation and the EBP mRNA expression were examined by immunofluorescence with an anti-tropoelastin antibody and RT-PCR selective for EBP in skin fibroblasts with these lysosomal enzyme deficiencies. Apparently normal elastogenesis and EBP mRNA expression were observed for fibroblasts from Morquio B disease cases with the GLB1 gene alleles (W273L/W273L, W273L/R482H and W273L/W509C substitutions, respectively), a galactosialidosis case with the PPCA allele (IVS7+3A/IVS7+3A) and a sialidosis case with the NEU1 allele (V217M/G243R) as well as normal subject. In this study, the W273L substitution in the EBP could impossibly cause the proposed defect of elastogenesis, and the typical PPCA splicing mutation and the V217M/G243R substitutions in the NEU1 might hardly have effects on elastic fiber formation in the dermal fibroblasts. J. Med. Invest. 53: 103-112, February, 2006

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Between 1996 and 2002, 22 cases of Hirschsprung’s disease were treated laparoscopically by endorectal pull-through operation. The proximal margin of the resected bowel materials from these 22 patients were examined histologically by frozen sections at surgery and also after surgery using H&E staining, and complete resection of the aganglionic segment was confirmed. Eleven patients, in whom an informed consent was obtained at randomly, underwent suction biopsy from the pulled-though neorectum after surgery. Of these 11 patients, 2 revealed many AchE-positive nerve fibers in the lamina propria, the muscularis mucosa and around the ganglion cells in the submucosal plexuses. These structural changes were similar to intestinal neuronal dysplasia that was characterized by hyperganglionosis and other neuronal abnormalities. The remaining 9 revealed no AchE activity. Unexpectedly, the two patients showing AchE activity in their neorectum continued to have persistent constipation and were treated with laxatives or glycerin enema. It was suggested that their persistent constipation was caused by intestinal neuronal dysplasia showing an abnormal increase of AchE activity in spite of presence of ganglion cells of the neorectum after surgery, but it was uncertain that they were primary condition as a HaIND or secondary reactions after surgery. J. Med. Invest. 53: 113-116, February, 2006

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Heat shock transcription factor on Y (HSFY) is located in one of three candidate regions for azoospermic factor (AZF), AZFb on the Y chromosome. We and others have already revealed that some azoospermic males are missing the regions of the Y chromosome including HSFY. Previously, we showed that murine HSFY-like sequence [mHSFYL (Riken cDNA 4933413G11Rik)], which is the mouse orthologue of HSFY, is exclusively expressed in testis. The sequences encoding the presumed DNA-binding domain in HSFY and mHSFYL were found in other mammals such as dogs, cows and chickens. To elucidate mHSFYL expression in the testes in detail, we carried out in situ hybridization. mHSFYL was predominantly expressed in round spermatids. Furthermore, we clarified the intracellular distribution of mHSFYL in COS1 cells with HA- or GFP-tagged proteins. Both HA-mHSFYL and GFP-mHSFYL were located in the nucleus. Our results suggest that HSFY/mHSFYL may have evolutionarily conserved functions for spermatogenesis. J. Med. Invest. 53: 117-122, February, 2006

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To elucidate the mechanism of antimutagenicity of caraway, we examined the effects of caraway seed extract on N-methyl-N’-nitro-N-nitrosoguanidine (MNNG)-induced mutagenesis in DNA methyltransferase-deficient Salmonella typhimurium strains, O⁶-methylguanine DNA adduct formation, and thiol content in S. typhimurium cells. MNNG was highly mutagenic for ogt^- strains YG7104 (ogt^- ada⁺) and YG7108 (ogt^- ada^-), and it showed slightly higher mutagenicity in strain YG7100 (ogt⁺ ada^-) than in strains TA100 and TA1535. Hot water extract of caraway seeds inhibited MNNG-induced mutation only in the ogt⁺ strains. In the presence of caraway extract, O⁶-methylguanine DNA adducts in strain YG7100 were decreased in proportion to the decrease of MNNG-induced mutagenesis. Although MNNG is known to degrade in the presence of thiols to produce methyl cation which can react with DNA, caraway had no effect on cellular concentrations of acid-soluble thiols. These results indicate that caraway does not directly inactivate MNNG and that Ogt-O⁶-methylguanine-DNA methyltransferase may be involved in the antimutagenic activity of caraway. J. Med. Invest. 53: 123-133, February, 2006

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It has been reported that a relationship exists between obstructive sleep apnea syndrome (OSAS) and cardiovascular and cerebrovascular diseases. To address this issue, we evaluated whether OSAS is associated with adhesion molecules and inflammatory signs, important indicators of atherosclerosis. Levels of high-sensitivity CRP (hs-CRP) and intercellular adhesion molecule-1 (ICAM-1) were measured in 30 patients with ischemic heart disease, confirmed by coronary arteriography (IHD group). Twenty healthy volunteers without sleep apnea were used as controls (Group N). Sleeping respiratory information was collected using a portable sleep polygraph, together on information about oronasal flow, tracheal sound, chest respiration, and percutaneous oxygen saturation (SpO₂) to obtain the apnea-hypopnea index (AHI). In the IHD group, 9 (30%) of the 30 patients showed evidence of OSAS [IHD(AHI≥40) group] and 21 did not [IHD(AHI<40) group]. The levels of hs-CRP and ICAM-1 were significantly higher in the IHD group than in the N group (p<0.01). Moreover, the levels of hs-CRP and ICAM-1 were significantly higher in the IHD(AHI≥40) group than in the IHD(AHI<40) group (p<0.01). However, after the administration of valsartan, angiotensin II receptor antagonists (ARB) to both IHD groups, the levels of hs-CRP and ICAM-1 decreased significantly in both groups. Moreover, a multivariate analysis revealed that the levels of hs-CRP and ICAM-1 were associated with the severity of sleep apnea. These findings suggest that, in OSAS the levels of hs-CRP and ICAM-1 are decreased and that the administration of ARB decreases the risk of atherosclerosis. J. Med. Invest. 53: 134-139, February, 2006

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In order to clarify how we collect saliva for analyzing salivary protein in aged subjects who can not eat well, we compared the effects of suction, spitting and the swab saliva collection method on the yield of protein components in saliva samples from normal volunteers. The saliva collected by suction, spitting and the swab method were designated as, Saliva I, II and III, respectively.
The saliva volume collected by Saliva I was about 2-fold greater than that by of Saliva II and III. This is mainly due to the fact that saliva secretion was stimulated by the suction itself. The content of total protein, S-IgA, trypsin-like activity and human airway trypsin-like protease (HAT) were almost the same in Saliva I and II, and significantly lower in Saliva III than in Saliva I and II. Kallikrein activity was almost the same in Saliva I, II and III. The concentration of each total protein, S-IgA, kallikrein activity, trypsin activity and HAT in Saliva I were significantly positively correlated with that in Saliva II.
These results indicate that we can obtain information of change of salivary protein by analyzing saliva collected by suction method, although this method caused the stimulation of saliva to some extent. J. Med. Invest. 53: 140-146, February, 2006

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Around 10% of males with idiopathic azoospermia or oligozoospermia, which are important causes of male infertility, have partial deletions on the long arm of the Y chromosome. To develop a rapid and accurate detection system for screening major Y deletions found in infertile men, we developed a multiplex PCR system that can simultaneously amplify five loci on the Y chromosome, SRY, AMELY, DBY, RBMY, DAZ and one locus on the X chromosome, AMELX. The size of the PCR products was designed to increase gradually from the distal Yp to the distal Yq. Our system could detect deletions of three major candidate regions for the azoospermic factor, AZFa, AZFb and AZFc on the Y chromosome together with sex. The gradual increase in the size of the PCR products was convenient for imaging the location of deletions on the Y chromosome. Moreover, the multiplex PCR system was combined with microchip-based electrophoresis, and the PCR products derived from each locus were separated within 4min. Our system is useful for screening Y chromosomes bearing the structural anomalies including three major AZF deletions found among azoospermic or oligozoospermic males. J. Med. Invest. 53: 147-152, February, 2006

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Background: The thermic effect of food (TEF) is higher in lean than in obese human subjects.
Objective: Relationships between TEF and insulin resistance during meals, from the point of view of autonomic nervous activity, were evaluated.
Methods: Autonomic nervous activity was evaluated in 20 young adults using the spectral analysis of heart rate variability from one hour before to two hours after a meal. Heart rate data were analyzed based on low frequency components (LF power, 0.04-0.15 Hz), high frequency components (HF power, 0.15-0.40 Hz), and LF/HF ratios. Energy expenditure and the TEF were measured 30 min after a meal. Homeostasis model of insulin resistance index (HOMA-IR) was also measured.
Results: The LF/HF ratio was significantly increased 30 min after a meal (p<0.05). No correlation between LF power and HF power with TEF was found, but the LF/HF ratio was significantly and positively correlated with TEF (r=+0.56, p<0.05). Moreover, a significant negative correlation was found between the HOMA-IR and TEF (r=-0.601, p<0.05).
Conclusions: The findings suggest that a reduction in insulin sensitivity induces a poor response of sympathetic nervous activity in the postprandial phase and a reduction in postprandial energy expenditure. J. Med. Invest. 53: 153-158, February, 2006

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Objective: Obstructive sleep apnea syndrome (OSAS) has been reported to be a new complication of liver cirrhosis with ascites. This fact prompted a study of episodes of sleep apnea as a function of the severity of cirrhosis.
Methods: Forty eight patients with type C liver cirrhosis were divided according to the Child-Pugh score into 3 groups: Group A (16 patients with grade A cirrhosis), Group B (16 patients with grade B cirrhosis), and Group C (16 patients with grade C cirrhosis). Portable sleep polygraphs (Fuji RC, Inc. Tokyo, Japan) were attached to the subjects, and oronasal respiration, tracheal sounds, respiratory movements of the chest, and percutaneous arterial oxygen saturation continuously were recorded. A decrease in the mean airflow to 50% or less was defined as hypopnea, and the number per hour of episodes of apnea and hypopnea per hour lasting 10 seconds or longer (AHI) was counted. A Holter ECG was also recorded, and spectral heart rate variability during sleep was analyzed by measuring low frequency power (0.04-0.15 Hz, LF power), high frequency power (0.15-0.40 Hz, HF power), the ratio of LF power to HF power (LF/HF ratio), and very low frequency power (0.008-0.04 Hz, VLF power). The difference in QT interval between the lead CM5 and the lead CM1 (QTc dispersion) was also examined.
Results: AHI was significantly higher in Group C than in Groups A and B (p<0.05). In Group C, 6 patients with 20 times or more AHI per hour, obstructive sleep apnea, in which respiratory chest movements occur but oronasal respiration decreases or disappears, was observed. Spectral analyses of heart rate variability showed a decrease in HF power without sleep apnea, but increases in HF power and VLF power were observed during sleep apnea. The QTc dispersion increased during episodes of sleep apnea.
Conclusions: As the stage of liver cirrhosis advanced, sleep apnea appeared, and changes in autonomic nervous activities were observed. Furthermore, QTc dispersion was increased during episodes of sleep apnea, presumably increasing the risk of ventricular arrhythmia. J. Med. Invest. 53: 159-166, February, 2006

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Several studies have reported that the use of a distal protection device decreases the incidence of slow-flow and/or no-reflow in patients with myocardial infarctions. In the present study, we investigated the influence of a RESCUE/Thrombuster system and a PercuSurge GuardWire catheter on coronary microcirculation disorders in patients with acute myocardial infarction using the natriuretic polypeptide (ANP), the brain natriuretic peptide (BNP), and ^99mTc-tetrofosmin myocardial scintigraphy (TF). The group consisted of a 77 patients with initial inferior myocardial infarction who had undergone emergency coronary angioplasty. The patients were randomly divided into: Group D (n=28), in which a direct stent alone was inserted, Group R/T (n=25), in which a stent was inserted after RESCUE system or a Thrombuster system was performed, and Group P (n=24), in which a stent was inserted after thrombus suction using a PercuSurge GuardWire catheter. Patients with coronary slow-flow/no-reflow were 3, 2 and 0 cases in Group D, Group R / T and Group P, respectively. In the present study, patients with good-reflow were enrolled in order to investigate the coronary microcirculation disorder in patients with visually similar coronary blood flow obtained in coronary angiography after percutaneous coronary reperfusion therapy. TF myocardial scintigraphy was performed 10±3 days after admission. Bull’s eye images were divided into 8 sections, and each section was evaluated in 4 grades. The grade of each segment was regarded as the defect score. The results were compared with the database prepared based on bull’s eye maps from 50 healthy adults in our hospital, and count areas of -2×SD (standard deviation) or less were calculated as the extent score (%), reflecting the area in which myocardial blood flow was decreased. The extent and severity scores in Groups P and R/T were significantly lower than those in Group D. Coronary angiography at the chronic stage (6 months after surgery) showed the patency of the responsible vascular lesion in all patients. However, the ANP, BNP, cardiac index, and pulmonary capillary wedge pressure (PCWP) were significantly improved in Groups R/T and P, compared to Group D (p<0.01). These results suggest that the use of a RESCUE/Thrombuster system and a PercuSurge GuardWire catheter system in patients with acute inferior wall infarction improves coronary microcirculation disorders and acute- to chronic-phase cardiac function. J. Med. Invest. 53: 167-173, February, 2006

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A 55-year-old man was investigated for right upper abdominal quadrant pain. He had no history of abdominal trauma or surgery. Imaging studies showed a common hepatic artery aneurysm involving the gastroduodenal artery. Following aneurysmectomy, examination with a hand Doppler apparatus yielded clear arterial signals from the liver surface. Therefore, vascular reconstruction was not performed. He had an uneventful postoperative course. J. Med. Invest. 53: 174-176, February, 2006

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In a 58-year-old male, upper digestive endoscopy revealed a protruding lesion in the esophagus on a medical examination. The patient was referred to the Department of Surgery in our hospital to undergo surgery. On the initial consultation, upper digestive endoscopy showed a smooth, soft, black purple, typeII protruding lesion measuring approximately 25 mm at 35 cm apart from the incisor. For diagnotic treatment and patient’s request, endoscopic mucosal resection (EMR) was performed. The resected specimen measured 25 mm × 25 mm. The histological findings suggested cavernous hemangioma. To treat esophageal hemangioma, esohagectomy, tumor enucleation, or sclerotherapy has been performed. However, recently, thorough preoperative examination, such as endoscopic ultrasonography (EUS), has facilitated endoscopic resection, such as EMR. J. Med. Invest. 53: 177-182, February, 2006

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A 63-years-old man was found dead with the body soaking in water lying face up on a riverbank. Autopsy and diatom examination demonstrated that the cause of death was drowning. He had undergone hypophysectomy 20 years earlier. Autopsy, pathological and endocrinological findings demonstrated secondary and chronic hypothyroidism, hypogonadism, and adrenal insufficiency. The cadaver had fallen into the river, and received numerous wounds such as abrasions and subcutaneous hemorrhage. Moreover, it was suspected that he had developed hypothermia before death. Cortisol in the blood and 17- OHCS in urine were within the reference range. We suspect that the adrenocortical hormone was secreted into the blood as a result of various stresses due to wounds and hypothermia. However, it was suspected that sufficient hormone might not be secreted due to chronic adrenal insufficiency. This insufficient cortisol causes the decrease in the stress resistance, and might influence his cause of death. Moreover, as hypothyroidism decreases thermogenesis, he might have fallen into hypothermia easily. In addition, because both adrenocortical insufficiency and hypothyroidism caused the hypoglycemia, he might have fallen into the loss of consciousness. Therefore, it was considered that he had died by drowning, in relation to the adrenocortical insufficiency and panhypopituitarism. J. Med. Invest. 53: 183-187, February, 2006

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