The amount of soy products consumed in Japan is much greater than that in Western countries. Recent evidence indicates that soy isoflavones play a beneficial role in obesity, cancer, osteoporosis, and cardiovascular disease. The soybean isoflavone genistein is present at high levels in soy products. Genistein is structurally similar to 17β-estradiol (E2), and genistein has been suggested to be act as E2 or an antagonist against E2. Genistein suppresses antigen-specific immune response in vivo and lymphocyte proliferation response in vitro. However, genistein enhances the cytotoxic response mediated by NK and cytotoxic T cells and the cytokine production from T cells. Thus, the effect of genistein on immunity is immune cell-dependent. Due to its unique effect on immune function, genistein has been used for the treatment of the diseases in animal models and it has been found that genistein inhibits allergic inflammatory responses. In this review, we summarize current studies related to the effect of isoflavone genistein on the immune system. J. Med. Invest. 55: 167-173, August, 2008

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The ABO blood group was discovered in 1900 by Austrian scientist, Karl Landsteiner. At present, the International Society of Blood Transfusion (ISBT) approves as 29 human blood group systems. The ABO blood group system consists of four antigens (A, B, O and AB). These antigens are known as oligosaccharide antigens, and widely expressed on the membranes of red cell and tissue cells as well as, in the saliva and body fluid.
The ABO blood group antigens are one of the most important issues in transfusion medicine to evaluate the adaptability of donor blood cells with bone marrow transplantations, and lifespan of the hemocytes.
This article reviews the serology, biochemistry and genetic characteristics, and clinical application of ABO antigens. J. Med. Invest. 55: 174-182, August, 2008

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We showed previously that 8-wk consumption of a diet containing palatinose (P, a slowly-absorbed sucrose analogue) and oleic acid (O) ameliorates but a diet containing sucrose (S) and linoleic acid (L) aggravates metabolic abnormalities in Zucker fatty (fa/fa) rats. In this study, we aimed to identify early changes in metabolism in rats induced by certain combinations of carbohydrates and fatty acids. Specifically, male Zucker fatty rats were fed an isocaloric diet containing various combinations of carbohydrates (P; S) and fatty acids (O; L). After 4 wk, no significant differences in body weight, visceral fat mass, plasma parameters (glucose, insulin, lipids, and adipokines), hepatic adiposity and gene expression, and adipose inflammation were observed between dietary groups. In contrast, pancreatic islets of palatinose-fed (PO and PL) rats were smaller and less fibrotic than sucrose-fed (SO and SL) rats. The abnormal α-cell distribution and sporadic staining of active caspase-3 common to islets of linoleic-acid-fed rats were not observed in oleic-acid-fed (PO and SO) rats. Accordingly, progressive β-cell loss was seen in SL rats, but not in PO rats. These findings suggest that pancreatic islets may be initial sites that translate the effects of different combinations of dietary carbohydrates and fats into metabolic changes. J. Med. Invest. 55: 183-195, August, 2008

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We investigated macronutrient intake after intraventricular injection of galanin (GAL, 3 nmol/5 µl/rat) and/or serotonin (5-HT, 50 nmol/5 µl/rat) in self-selecting fasted rats with preferences for either carbohydrates or fats. GAL injection significantly increased carbohydrate and total intake in all rats irrespective of macronutrient preference, whereas 5-HT alone did not affect macronutrient intake. The GAL-induced increase in total intake decreased to the level of saline controls when GAL was coinjected with 5-HT. The ratio of kilocalories of carbohydrates, fats and proteins (macronutrient energy ratio) after injections of GAL and/or 5-HT was similar to the saline control. In carbohydrate-preferring rats, GAL increased carbohydrate, protein and fat intake as well as total intake. Coinjection of GAL and 5-HT tended to decrease carbohydrate intake, but increase protein and fat intake. The macronutrient energy ratio after injection of GAL did not change, but the carbohydrate energy ratio decreased after 5-HT was injected, with or without GAL. In contrast, in fat-preferring rats, GAL significantly increased carbohydrate intake. Injection of 5-HT with or without GAL did not change total macronutrient intake. The macronutrient energy ratio did not change after GAL injection with or without 5-HT. These differences suggest that macronutrient preferences should be considered in any macronutrient intake study, and that serotonergic neurons play a part in the regulation of GAL-induced macronutrient intake. J. Med. Invest. 55: 196-203, August, 2008

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Ultraviolet B (UVB) is a serious irritant for the skin and increases a risk for skin cancer. To identify UVB-sensitive genes in peripheral blood, 11 healthy male volunteers were exposed to 0.3 J/cm² of narrow-band (NB)-UVB, about half of minimal erythema dose (MED) in Japanese, and gene expression in blood was analyzed at 4 h, 24 h, 4 d and 7 d after the irradiation using microarray carrying oligonucleotide probes for 2,000 stress-responsive genes. RNA prepared before the irradiation was used as a reference control. Microarray analysis identified 21 genes as UVB-responsive genes with a peak at 24 h in 6 subjects, and real-time PCR validated the significant down-regulation of 9 (ABCB10, ATF1, ABCD3, TANK, FAS, SLC30A9, CHUK, CASP1, and ABCE1) out of the 21 genes in 11 subjects. Considering sensitive and characteristic features of 9 marker genes, they may be useful indicators for monitoring systemic response to UVB irradiation.
J. Med. Invest. 55: 204-210, August, 2008

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Purpose: To evaluate outcomes of submacular surgery to remove massive submacular hard exudates with diabetic macular edema. Design: Retrospective, non-comparative, interventional consecutive case series. Participants: Fifty-six eyes of 40 patients with massive submacular hard exudates with diabetic macular edema. Intervention: Submacular surgery was performed to remove massive submacular hard exudates. Main Outcome Measures: Preoperative and postoperative visual acuities and clinical findings. All patients were followed for more than 1 year postoperatively. Results: The macular hard exudates underlying the fovea almost disappeared, and macular edema remarkably reduced following surgery. Visual acuities ranged from 0.01 to 0.3 before surgery, and from 0.04 to 1.0 after surgery. Visual acuity improved by two lines or more in 45 eyes (80.4%), remained unchanged in 8 eyes (14.3%) and worsened in 3 eyes (5.3%). Visual acuity improved to 0.3 or more in 24 eyes (42.9%). Better postoperative visual acuity (0.3 or better) was related to hemoglobin A1C (HbA1C) and the size of hard exudates. Conclusions: Results showed the efficacy of submacular surgery to remove massive hard exudates with diabetic macular edema, and outcomes were satisfactory. J. Med. Invest. 55: 211-215, August, 2008

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Tooth development is regulated by epithelial-mesenchymal interactions and their reciprocal molecular signaling. Bone morphogenetic protein 2 (BMP2) is known as one of the inducers for tooth development. To analyze the molecular mechanisms of BMP2 on ameloblast differentiation (amelogenesis), we performed microarray analyses using rat dental epithelial cell line, HAT-7. After confirming that BMP2 could activate the canonical BMP-Smads signaling in HAT-7 cells, we analyzed the effects of BMP2 on 14,815 gene expressions and profiled them. Seventy-three genes were up-regulated and 28 genes were down-regulated by BMP2 treatment for 24 hours in HAT-7 cells. Functional classification revealed that 18% of up-regulated genes were ECM/adhesion molecules present in the enamel organ. Furthermore, we examined the expression of several differentiation markers in dental epithelial four cell-lineages including inner enamel epithelium (ameloblasts), stratum intermedium, stratum reticulum, and outer enamel epithelium. The results indicated that BMP2 might induce at least two different cell-lineage markers including a BMP antagonist expressed in HAT-7 cells, suggesting that BMP2 could accelerate amelogenesis via BMP signaling. J. Med. Invest. 55: 216-226, August, 2008

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To evaluate the level of stress induced by clinical training, ambulatory electrocardiograms from 12 healthy female medical technology students were recorded and the spectral components of heart rate variability (HRV) were analyzed as an index of autonomic nervous function. The HF power reflecting parasympathetic tone was significantly decreased at awakening, compared with that before clinical training (p<0.01). The LF/HF ratio reflecting sympathetic activity also significantly increased during, compared with before clinical training (p<0.01). The slope of the spectral density also changed before and during the clinical training from -1.20±0.04 to -1.09±0.03 (p<0.05). The 1/f fluctuation of HRV appeared comfortable, and tension was apparently adequate while undergoing clinical training. None of these HRV indices statistically changed while asleep. Thus, the students perceived the stress as a comfortable level of tension and analyzing spectral components and 1/f fluctuation of HRV might be a useful method for evaluating study stress. J. Med. Invest. 55: 227-230, August, 2008

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Purpose: To investigate cases with massive subretinal hemorrhage after photodynamic therapy (PDT).
Subjects and Methods: We studied four cases (3 men and 1 woman, mean 80.5 yeas old) with massive subretinal hemorrhage after PDT about type of disease, spot size, period to the onset of hemorrhage, visual acuity (VA) before and after PDT.
Results: Four cases consisted of one with age-related macula degeneration (AMD) and 3 with polypoidal choroidal vasculopathy (PCV). The average spot size of PDT was 5525µm. Two patients underwent the second PDT about 3 months after the initial PDT. Four periods to the onset of hemorrhage were 22, 27, 137, and 208 days respectively. The latter 2 cases underwent PDT twice, and the periods were the days from the initial PDT. Two patients among four underwent vitrectomy. Average VA before PDT was 0.20, and the final one was 0.02 after PDT.
Conclusions: PDT has a risk to cause massive subretinal hemorrhage leading to grave visual disturbance. Especially PDT for PCV seems to have more risk. Therefore we need to inform patients about the risk before PDT, since treating patients with massive subretinal hemorrhage is very difficult J. Med. Invest. 55: 231-235, August, 2008

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To obtain monkey-tropic (mt) HIV-1 derivatives with distinct biological characteristics and to improve the viral growth property, we have generated several variants from a prototype mt HIV-1 designated NL-DT5R (X4-tropic). The prototype HIV-1 contains a portion of gag and entire vif genes from SIVmac in its genome. The two derivatives carrying 3’ half-genomic region of the SF162 (R5-tropic) or 89.6 (dual-tropic) isolate displayed very retarded or no viral growth, respectively, in a simian cell line HSC-F. In contrast, the three clones containing a part of env gene (encoding the V1-V4 region) from SF162, YU-2 (R5-tropic) or 89.6 showed different growth kinetics in HSC-F cells, although they grew somewhat more poorly than the NL-DT5R. Comparison of various viral proteins potentially involved in the different biological properties has revealed that, while amino acid sequences of Tat, Rev, Vpr, Vpu and Nef are quite conserved among the clones, those in the surface (SU) region of Env are relatively heterologous. Our data described here have shown that the 3’ half of viral genome other than gag and vif genes greatly affects the growth property of mt HIV-1 in simian cells. J. Med. Invest. 55: 236-240, August, 2008

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In this study, we investigated methamphetamine (METH)- induced peroxidative DNA damage in various regions of the rat brain. We injected METH to rats following 2 protocols. For the single administration experiment (group I), 50 mg/kg (i. p. ) of METH was administered to observe the acute influence of METH. For the repeated administration experiment (group II), 10 mg/kg/day (i. p. ) of METH was injected for 5 days. Immunohistochemically, peroxidative damage DNA, 8-hydroxy-2’- deoxyguanosine (8-OH-dG) was observed, and in situ apoptosis was also observed. In group I, immunoreactivity of 8-OH-dG was only enhanced in neurons of the nucleus accumben of METH-treated rats. On in situ apoptosis detection, positive findings were also enhanced in all examined parts compared to those in the control, though there were no significant increases in 8-OH-dG-immunopositive neurons except in the nucleus accumben. In group II, the nucleus accumben also showed enhanced 8-OH-dG immunopositivity compared to that in the control. There was no significant difference in apoptosis between the control and METH groups. Based on our observations, it is considered that METH induces oxidative DNA damage in the brain, especially in the nucleus accumben. However, those DNA damage might be caused differently between acute and chronic administration.
J. Med. Invest. 55: 241-245, August, 2008

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After establishing a linear relationship between the amount of penicillin-binding protein (PBP) 2a and membrane proteins of methicillin-resistant Staphylococcus aureus (MRSA) COL by dot-blot analysis using an antibody against PBP 2a, we determined the PBP 2a quantities in membrane fractions prepared from 14 different MRSA cells. Methicillin-sensitive S. aureus ATCC 6538P was used as a quality control strain. The amounts of PBP 2a diverged among the strains, and no relationship to β-lactam MIC values were observed in the corresponding strains. J. Med. Invest. 55: 246-253, August, 2008

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In recent years, the problem of interpersonal relationships has been reported to be associated with various adolescent psychiatric problems. Egocentrism is one factor related to the problem of interpersonal relationships. The Adolescent Egocentrism-Sociocentrism (AES) scale is used to assess egocentrism in Western countries, but no such scale has been developed in Japan.
The purpose of our current study was to develop the Japanese version of the AES scale and investigate the relationship between the egocentrism assessed by the AES scale and the self-consciousness assessed by the Japanese version of the self-consciousness scale. The original version of the AES scale was first translated into Japanese using the forward-backward method and examined for factorial reliability and validity. The results demonstrated that the Japanese version of the AES scale shows adequate factorial reliability and validity, but different from the original version the “egocentrism personal fable” subscale which measures the feeling that oneself is special and unique was not extracted in the Japanese version. We found a moderate correlation between the non-social focuses of the AES scale and the public self-consciousness subscale of the self-consciousness scale. This correlation suggests that a strong attention of others’ view on oneself results in the avoidance of others.
The Japanese version of the AES scale can examine egocentrism adequately together with sociocentrism and non-social focuses. As this scale is self-reporting and easy to complete, it may have practical utility in a clinical setting. J. Med. Invest. 55: 254-259, August, 2008

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Background: Gemcitabine plus UFT combination chemotherapy are highly effective and less toxic in the first line setting in patients with non-small cell lung cancer (NSCLC). The purpose of the study is to confirm the feasibility of this regimen as second- or third-line therapy in NSCLC. Methods: Fifteen patients with performance status of 0-1 were enrolled. UFT (tegafur 250 mg/m²/day) was administered orally twice a day from days 1-14, and gemcitabine of 900 mg/m² was administered intravenously on days 8 and 15 every three weeks on an outpatient setting. The treatment was repeated for at least 3 cycles and continued unless the disease progressed. Results: The response rate and the disease control rate were 6.7% and 66.7%, respectively. Grade 3-4 toxicities included neutropenia in one patient and elevation of transaminases in one patient. The mean relative dose intensity of gemcitabine and UFT were 0.93 and 0.97, respectively. Conclusion: High disease control rate and less toxicity suggested the potential of gemcitabine and UFT combination chemotherapy as second- or third-line therapy in NSCLC. J. Med. Invest. 55: 260-266, August, 2008

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The effect of exposure to extremely low frequency-electromagnetic field (ELF-EMF: 3 mT, 60 Hz) on differentiation of mouse osteoblast-like MC3T3-E1 cells was examined together with addition of insulin-like growth factor I (IGF-I). As a marker of the differentiation, the cellular collagen content was determined by the absorbance of Sirius red-stained cells measured at the wavelength of 510-520 nm with an imaging microspectroscopy.
Exposure to ELF-EMF increased significantly the collagen in the cells. Treatment with PD98059, an inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2) activation, reduced the collagen in all of the cells examined on control, IGF-I addition and ELF-EMF exposure, however, PD98059 did not prevent the increase in the collagen caused by ELF-EMF exposure, and IGF-I also increased the collagen in the presence of the inhibitor. When phosphatidylinositol 3-kinase (PI3K) pathway was inhibited by LY294002, the increase in collagen induced by ELF-EMF exposure was accelerated, however, the increase in collagen observed by IGF-I addition was suppressed. Treatment with SB203580, an inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), suppressed the increase in the collagen induced by ELF-EMF exposure, whereas IGF-I addition increased the collagen in the presence of the inhibitor.
These results suggested that collagen synthesis stimulated by ELF-EMF exposure was carried out by the participation of p38 MAPK pathway, and that PI3K pathway may have the role to suppress the collagen synthesis induced by ELF-EMF exposure, and that the suppression of the PI3K pathway may allow the acceleration of the collagen synthesis. J. Med. Invest. 55: 267-278, August, 2008

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Purpose: To determine whether or not a sub-Tenon’s capsule injection of triamcinolone acetonide(TA) is an effective treatment for refractory diabetic macular edema after vitrectomy. Methods: Thirty-nine eyes of 26 patients with diabetic macular edema were injected with 20 mg TA into the sub-Tenon’s capsule. The central macular thickness (CMT) measured by an optical coherence tomography (OCT) and visual acuities were compared between pre-treatment and 1, 3 months post-treatment. Results: The decrease in the mean CMT between the baseline (435 µm) and 1 month (326 µm) or 3months (303 µm) time points was statistically significant. Seven eyes (70%) at 1 month and 3 months post-treatment in the vitrectomized eyes or PPV(pars plana vitrectomy)(+) group, 15 eyes(52%) at 1 month, and 19 eyes (66%) at 3 months in the non-vitrectomized eyes or PPV(-)group maintained 20% reduction in CMT from pre-treatment with a single injection of TA. The recurrence of macular edema was observed in 1 eye (14%) in the PPV(+)group, and 3 eyes (16%) in the PPV(-)group. Conclusion: The sub-Tenon’s capsule injection of TA was effective for refractory diabetic macular edema after vitrectomy. In addition, it was suggested that the treatment of vitrectomized eyes was more effective than that of non-vitrectomized eyes. J. Med. Invest. 55: 279-282, August, 2008

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Purpose: To evaluate the long-term outcome and safety of vitrectomy for the treatment of an idiopathic macular hole using indocyanine green (ICG) to peel the internal limiting membrane(ILM). Subjects and Methods: By means of a retrospective study, we evaluated the outcomes of 56 eyes in 56 patients with an idiopathic macular hole who all underwent a primary vitrectomy with successful closure of macular hole. We compared the outcomes of 35 eyes in 35 patients who underwent a vitrectomy with ICG-assisted ILM peeling to those of 21 eyes in 21 patients who underwent the same procedure without ILM peeling. The main outcomes were compared between preoperative and postoperative visual acuities. Results: The periods to achieve the postoperative best visual acuity were 11.1 months in the ILM peeling group and 8.9 months in the non-ILM peeling group. However, there were no significant differences between the two groups regarding the postoperative best visual acuity and the final visual acuity. Complications related to ILM peeling with ICG were not found. Conclusion: These results support the safety of ILM peeling with ICG. J. Med. Invest. 55: 283-286, August, 2008

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Purpose: To evaluate effects and safety of primary phacoemulsification plus intraocular lens implantation for controlled chronic angle-closure glaucoma (CACG) or primary angle-closure (PAC). Design: Prospective, non-randomized comparative trial. Methods: Two treatment groups were used. The IOL group included the use of phacoemulsification plus intraocular lens (IOL) implantation in 27 eyes. The LI group included treatment by laser iridotomy (LI) in 23 eyes. Intraocular pressure (IOP), numbers of anti-glaucoma medications, complications, and corneal endothelial cell counts were examined in each group. Results: In the IOL group, IOP was significantly reduced from a preoperative mean of 14.8 ± 4.2 mmHg to a 6-month-postoperative mean of 10.8 ± 1.6 mmHg (P < .05). However, in the LI group, mean preoperative IOP was 15.5 ± 4.1 mmHg, and the 6-month-postoperative IOP was 14.7 ± 4.7 mmHg (P = .76). In the IOL group, no patient used anti-glaucoma medications 6-month postoperatively, whereas in the LI group, mean number of anti-glaucoma medications was 0.2 ± 0.4 (P < .05). There were no significant differences in preoperative and postoperative corneal endothelial cell counts between IOL and LI groups (P = .39). Conclusions: Primary phacoemulsification plus intraocular lens implantation for controlled CACG or PAC seems to be a safe and effective method in reducing IOP. This procedure might become the first treatment of choice for controlled CACG or PAC with cataract. J. Med. Invest. 55: 287-291, August, 2008

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We examined the efficacy of liposomal amphotericin B (L-AMB) for intractable cryptococcal meningoencephalitis in a patient with acquired immunodeficiency syndrome (AIDS) and the presence of immune reconstitution syndrome (IRS) caused by the treatment. A 34-year-old patient presented with meningitis. Cryptococcal organisms were detected microscopically in the cerebrospinal fluid (CSF) with Indian ink staining, and were then cultured from the CSF. Initial treatment with amphotericin B and flucytosine (5-FC) or voriconazole and/or fluconazole failed to eradicate cryptococcal organisms from the CSF. Secondary treatment with L-AMB and 5-FC following seven months of antiretroviral therapy was successful. Simultaneously, treatment with L-AMB caused severe brain edema likely due to IRS. There were large differences in immune function improvement and liposomalization of the fungicide between the initial and secondary treatments. In conclusion, differences in immune status should be considered when administering L-AMB, in order to prevent IRS-related complications. J. Med. Invest. 55: 292-296, August, 2008

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We studied the therapeutic effects of one-year alendronate treatment in three cases (two males and one female) of osteoporosis with parietal thinning of skull. Plain radiography and three dimensional computed tomography revealed asymmetric external thinning of the posteromedial part of the bilateral parietal bones. Technetium-99m methylenediphosphate bone scintigraphy did not show any changes in these three cases. Pretreatment levels of urinary type I collagen cross-linked N-telopeptides (NTX) in all three cases were high compared to the normal range. Pretreatment levels of serum bone-specific alkaline phosphatase (BAP) in the two male patients were high in contrast to the normal values in the female patient. Pretreatment mean bone mineral density (BMD) values of the 2nd to 4th lumbar vertebrae (L2-4BMD), head BMD, femoral neck BMD, and whole body BMD of all three patients were low compared with the respective normal ranges.
One-year alendronate treatment decreased both urinary NTX and serum BAP in all three cases to normal values. Treatment also increased the whole body BMD in all three cases, the L2-4BMD of the female patient, the femoral neck BMD of the female patient and one male patient, and the head BMD of the female patient when compared to pretreatment levels. J. Med. Invest. 55: 297-302, August, 2008

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