Adenylate kinase (hereinafter referred to as AK) catalyzes a reversible high-energy phosphoryl transfer reaction between adenine nucleotides. The enzyme contributes to the homeostasis of cellular adenine nucleotide composition in addition to the nucleotide biosynthesis. So far, six AK isozymes, AK1, AK2, AK3, AK4, AK5, and AK6, were identified. AK1 is localized in neuronal processes, sperm tail and on the cytoskeleton in cardiac cells at high concentrations, suggesting its regulatory function as a high-energy β-phosphoryl transfer chain from ATP-synthesizing sites to the ATP-utilizing sites in the cell. AK2, AK3 and AK4 are mitochondrial proteins. AK2 is expressed in the intermembrane space, while AK3 and AK4 are localized in the mitochondrial matrix. AK3 is expressed in all tissues except for red blood cells indicating that AK3 gene is a housekeeping-type gene. On the other hand, AK4 is tissue-specifically expressed mainly in kidney, brain, heart, and liver although its enzymatic activity is not yet detected. AK5 is solely expressed in a limited area of brain. AK6 is recently identified in nucleus, suggesting its role in nuclear nucleotide metabolism. All data, so far reported, indicated the function of AK is associated with the mechanism of efficient transfer of high-energy phosphate in micro-compartment within the cell. J. Med. Invest. 52: 127-136, August, 2005

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Stress is the coordinated physiological processes to maintain a dynamic equilibrium under stressful conditions. The equilibrium is threatened by certain physiological and psychological stressors. Stressors trigger physiological, behavioural, and metabolic responses that are aimed at reinstating homeostasis. The hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system play an essential role in the stress response. Excessive, prolonged, or inadequate response that is termed as “allostasis” or “allostatic load” leads to pathological outcomes. Dysregulation of the HPA axis activity is involved in the pathogenesis of stress-related disorders including major depression. The complex brain-immune-endocrine network regulates the HPA axis, and hereditary predisposition as well as environmental factors such as traumatic experiences in early life also modifies the capacity of an individual to cope. Therefore, it is difficult to correctly assess the complex stress response. We have developed a microarray carrying 1,467 cDNAs that were selected to specifically measure stress response in peripheral blood leukocytes. Using this tool, we have succeeded to objectively assess individual response to acute psychological stress and to detect unique expression profiles in patients with depression. Gene expression profile in peripheral blood leukocytes may be a potentially useful for the detection of disease-associated, abnormal stress responses. J. Med. Invest. 52: 137-144, August, 2005

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The hot water extract of the herbal tea, Gynostemma pentaphyllum Makino, was not found to be mutagenic in Salmonella mutation assay with or without metabolic activation. However, the extract had both DT-diaphorase inducing activity in the murine hepatoma (Hepa1c1c7) cell line and antimutagenic properties towards chemical-induced mutation in Salmonella typhimurium strains TA98 and TA100. Mutagenicity of aflatoxin B1 (AFB₁), 2-amino-6-methyldipyrido [1, 2-a: 3’, 2’, 3-d] imidazole (Glu-P-1), 2-aminodipyrido [1, 2-a: 3’, 2’, 3-d] imidazole (Glu-P-2), 2-amino-1, 4-dimethyl-5H-pyrido [4, 3-b] indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido [4, 3-b] indole (Trp-P-2), 2-amino-3-methylimidazo [4, 5-f] quinoline (IQ) and Benzo [a] pyrene (B[a]P) was inhibited by the extract of Gynostemma pentaphyllum Makino in a dose-dependent manner, but no effect was found on the mutagenic activity of 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide (AF-2). However, the extract enhanced the mutagenicity induced by 2-aminoanthracene (2AA), and N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). J. Med. Invest. 52: 145-150, August, 2005

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Object: Matrix metalloproteinase (MMP) 2 and 9 are important for tissue breakdown in the process of tumor invasion. The aim of this study is to evaluate the relationship between the expression of MMP-2, MMP-9, MIB-1 LI and cavernous sinus invasion in pituitary adenomas.
Methods: Tissue samples from 54 patients with pituitary adenomas were studied. Expression of MMP-2, MMP-9, and MIB-1 labeling index (LI) were evaluated by immunohistochemical method. In sixteen cases, the expression of MMP-2 and MMP-9 mRNA was also examined by RT-PCR assay.
Results: Thirty-four patients were women and 20 were men, with a mean age of 49.9 years old (range 18-76 years). There were 12 cases with cavernous sinus invasion, and 42 were noninvasive cases. MMP-2 and MMP-9 score of invasive case (3.9±0.5, 4.1±0.4) were significantly higher than those (2.3±0.2; p<0.01; 2.6±0.2; p<0.01) without invasion. The MIB-1 LI of this study presented no significantly difference between the invasive and noninvasive pituitary adenomas. The percentage of MMP-2 mRNA/β-actin mRNA and MMP-9 mRNA/β-actin mRNA were also observed significantly higher in invasive pituitary adenomas (68.2±15.3%; 59.7±12.5%) than noninvasive pituitary adenomas (21.8±8.2%, p<0.05; 33.3±5.4%, p<0.05).
Conclusions: Our study suggests that the expression of MMP-2 and MMP-9 may have a value to assess the invasive pituitary adenomas, and proliferation and invasion of pituitary adenomas may present a different mechanism. J. Med. Invest. 52: 151-158, August, 2005

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Effects of pre-germinated brown rice (PGBR) on postprandial blood glucose and insulin concentrations were compared with brown rice (BR) and white rice (WR) in two studies. In the first study, we investigated the time course of postprandial blood glucose and insulin concentrations after ingesting 25% (W/V) glucose solution, PGBR, BR or WR in 19 healthy young subjects. In the second study, dose-dependent effect of PGBR on the time course of postprandial blood glucose concentrations was compared among 4 different mixtures of PGBR and WR in 13 healthy young subjects. They were solely PGBR, 2/3 PGBR (PGBR: WR=2: 1), 1/3 PGBR (PGBR: WR=1: 2) and solely WR. Each sample was studied on a different day. The samples were selected randomly by the subjects. All the rice samples contained 50g of available carbohydrates. The previous day the subjects ate the assigned dinner by 9:00 pm and then were allowed only water until the examination. The next morning, they ingested each test rice sample with 150ml of water in 5-10 min. Blood was collected into capillary tubes from finger at 0, 30, 60, 90 and 120 min after the ingestion. The incremental areas under the curve (IAUC) of blood glucose concentrations (IAUC-Glc) for 120 min after the administration of PGBR and BR were lower than those after WR. In contrast the IAUC-Glc of BR and PGBR were not different (Study 1). The higher the ratio of PGBR/WR, the lower the glycemic index became (Study 2). These results suggest that intake of PGBR instead of WR is effective for the control of postprandial blood glucose concentration without increasing the insulin secretion. J. Med. Invest. 52: 159-164, August, 2005

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Urinary incontinence and falls are serious problem among elderly people, because of restriction of the Activities of Daily Living (ADL) and Quality of Life. Previous studies have examined the association between urinary incontinence and falls. However, results have been inconsistent. In Japan, with the rapid aging of the society, the number of elderly women who have urinary incontinence and are at risk of falling is increasing. We investigated the relationship between type of urinary incontinence and risk of falls among elderly users of day-care services in a long-term care system. Our study population comprised 118 ambulatory women. At baseline, we evaluated incontinent status, lower extremity muscle strength, balance ability, ADL, and Instrumental ADL. We asked subjects about number of falls every 4 months during a year. In univariate analysis, lower extremity muscle strength (p=0.001) and mixed incontinence (p=0.050) differed significantly according to the fall status. Stress and urge incontinence were not significantly associated with falls. In logistic regression analysis, subjects who had mixed incontinence were 3.05 (95% confidence interval 1.01-10.2) times more likely to fall than those without. These results suggest that mixed incontinence have independent associations with falls. Incontinent status should be considered to prevent falls among elderly persons who are partially dependent and need support. J. Med. Invest. 52: 165-171, August, 2005

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To determine the effect of anti-immunoglobulin antibodies on the measurement of the humoral immune response in hepatitis C virus (HCV) infected patients. Anti-immunoglobulin antibodies were defined using sheep immunoglobulins as a target to characterize distinct changes in patterns of immunoglobulin levels. Serum immunoglobulin A, G and M concentrations were measured by ELISA in 45 patients with recent-onset HCV infection and 45 matched normal individuals. It was found that normal individuals had mean IgA, IgG and IgM levels of 2.67 mg/ml, 9.39 mg/ml and 1.77 mg/ml, respectively while HCV infected patients had mean levels of 3.19 mg/ml, 10.76 mg/ml and 1.94 mg/ml. These represented significant increases in immunoglobulin levels in the sera of HCV patients compared to normal individuals (p<0.0001, p<0.00004 and p<0.0004). Anti-immunoglobulin antibodies lead to an overestimation of serum immunoglobulin levels in HCV patients. Interestingly, the mean levels of immunoglobulins A, G and M in HCV infected sera, determined after purification from anti-sheep immunoglobulins, was 2.73 mg/ml, 9.55 mg/ml and 1.79 mg/ml. Therefore, there was no significant difference in HCV patients compared to normal individuals (p<0.42, p<0.36 and p<0.44). The presence of circulating immune complex in serum during the early phase of infection may contribute to immunopathological effects in the infected host and provide some new insights into antibody response to HCV. J. Med. Invest. 52: 172-177, August, 2005

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Purpose. We studied the relationship between minute distance calculated from pulmonary venous flow (PVF) velocity tracing and cardiac output (CO) measured with thermodilution method in patients undergoing cardiovascular surgery.
Methods. In 32 patients undergoing cardiovascular surgery, simultaneous measurements of hemodynamics including CO and transesophageal pulsed Doppler signals of PVF velocity were performed before and after surgical repair. Minute distance was calculated as the product of the heart rate and the sum of time-velocity integrals of PVF.
Results. The minute distance after surgical intervention increased from 1121 ± 347 cm·sec^-1 to 1764 ± 538 cm·sec^-1 (p<0.001; mean ± SD), while CO increased after surgical intervention from 3.5 ± 0.9 L·min^-1 to 5.3 ± 1.1 L·min^-1. Simple linear regression analysis showed that minute distance was related with CO before and after surgical intervention (r=0.81 and r=0.76, respectively). The changes in minute distance were also related with those in CO (r=0.80).
Conclusion. The present study demonstrated that minute distance obtained from the pulsed Doppler tracings of PVF velocity was related with CO during cardiovascular surgery in adults. These results suggest that the changes in CO could be estimated from minute distance in pulmonary vein. J. Med. Invest. 52: 178-185, August, 2005

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Objective: There has been reports on the usefulness of diffusion tensor imaging (DTI) about age-or disease-related degradation. DTI is generally evaluated by the region of interest (ROI) methodology. In this study, we applied a statistical way using Statistical Parametric Mapping (SPM) to assess normal aging by DTI and compared results of these two methods.
Methods: Ten young and ten senior normal volunteers were examined. On SPM, tensor images were changed into normalized tensor images. They were compared between the two groups by t-test.
Results: In the senior group, fractional anisotropy (FA) values were higher on the basal ganglia, cingulated gyrus and other cortical gray matter, lower in the corona radiata, internal capsule, centrum semiovale and corpus callosum by using SPM. In the ROI method, the results were almost compatible except in the brain periphery.
Conclusions: Aging changes on water diffusion anisotropy was clearly shown by SPM method which would be useful to evaluate change of water diffusion anisotropy without operator bias even in clinical setting instead of ROI measurement. J. Med. Invest. 52: 186-190, August, 2005

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Composite neuroendocrine-exocrine carcinomas (NEECs) with two distinct components of adenocarcinoma and neuroendocrine (NE) carcinoma within the same tumor are rare but may have a clue for clarifying the pathogenesis of NE tumors arising from non-endocrine organs. This study was done to characterize histological and immunohistochemical features of NEECs of the stomach comparing with pure NE tumors of the gastrointestinal (GI) tract. Microscopically, adenocarcinoma components in 6 of 8 NEECs were well differentiated and located superficially, whereas NE components were poorly differentiated and located deeply. In the remaining two cases, smaller NE components were intermingled within adenocarcinoma components. Immunohistochemically, neural cell adhesion molecule (NCAM) was positive in 5 NE components, of which 3 cases were homogeneously positive, and 2 adenocarcinoma components of 8 NEECs, while 19 of 21 pure NE tumors of GI tract were homogeneously positive for NCAM. Ghrelin-immunoreactivity was found in 4 NE components and 2 adenocarcinoma components of NEECs, although 20 pure NE tumors were positive for ghrelin. Smad4 was positive in both components of 7 NEECs. These findings suggest that composite NEECs and pure NE tumors of GI tract may have different NE properties and that most NE components of composite NEECs of the stomach may originate from an adenocarcinoma precursor cell and occasional tumors from a pluripotent cell. J. Med. Invest. 52: 191-202, August, 2005

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A 51-year-old Japanese male with chief complaints of slightly high fever and epigastralgia was hospitalized at our facility. The inflammatory response was enhanced, and liver dysfunction was observed. Abdominal ultrasonography demonstrated a hyperechoic lesion occupying the left portal vein, and abdominal plain CT indicated a low density of the lesion with a clear boundary, measuring about 3 cm × 2 cm, between the porta hepatis and segment IV of the liver. Contrast CT showed no enhancement in the arterial and portal phases, but a reduction in the density inside the tumor in the equilibration phase was noted. MRI showed hypointensity by T1-weighted imaging and hyperintensity by T2-weighted imaging. Angiography demonstrated an obstruction of the left portal vein and superior mesenteric vein, and endoscopic retrograde cholangiography revealed a constriction in the left intrahepatic bile duct. Since the possibility of intrahepatic cholangiocarcinoma could not be excluded, extended left hepatectomy combined with caudate lobectomy was performed. The tumor, measuring 31 mm × 21 mm × 20 mm, was pathohistologically diagnosed as an extrahepatic portal obstruction. Extrahepatic portal obstruction is an important disease that is sometimes difficult to rule out oncologic origin. J. Med. Invest. 52: 203-207, August, 2005

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A 75-year-old man was referred to our hospital because of the emphysema and tumor of the right intermediate bronchus. Thoracic CT scan and bronchoscopic examination demonstrated a spherical tumor of the right intermediate bronchus covering a normal mucosa. The biopsy specimen obtained from this tumor was histologically diagnosed as “glandular type of adenocarcinoma in the bronchus”. Surgical treatment was not feasible because of poor pulmonary function. Therefore, the patient underwent Photodynamic therapy (PDT) using porfimer sodium (Photofrin) and an excimer dye laser. After 4 months, the tumor disappeared and there has been no recurrence for 3 years 3 months. PDT can affect a submucosal tumor of the central airway, and is safe for patients with poor pulmonary function. Our report recommends that PDT should be applied not only to early lung cancer but also submucosal tumor of the central bronchus. J. Med. Invest. 52: 208-211, August, 2005

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We report a patient with duodenal varices oozing blood who had undergone low anterior resection of the rectum and resection of the liver tumor because of multiple liver metastasis from rectal cancer 80 months previously. Although endoscopic variceal ligation (EVL) was carried out for the ruptured duodenal varices, their bleeding persisted and hepatic encephalopathy also appeared. Finally, balloon occluded retrograde transvenous obliteration (BRTO) with percutaneous transhepatic obliteration (PTO) was carried out for the duodenal varices. Percutaneous transhepatic portography revealed detailed hemodynamics. Following PTO, the duodenal varices were stagnated by BRTO, and no complications were recognized. No re-bleeding episode has been observed since the treatment. In addition, the hepatic encephalopathy was also improved. J. Med. Invest. 52: 212-217, August, 2005

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Angiomyolipoma (AML) is a rare benign tumor that occurs most commonly in the kidney. Lesions in the liver are usually solitary and multiple AMLs of the liver are extremely rare. Furthermore, extra renal or hepatic AML are rarely found. We report an unusual case of a 34-year-old man with a solitary omental AML and multiple hepatic AMLs. At the age of 23, the patient underwent right nephrectomy and enucleation of a left renal tumor because of bilateral AMLs. At the age of 34, more than 6 lesions in the liver and an enlarged solitary omental AML were discovered. The omental tumor, 50×40mm, 49g, was extirpated; it was well-defined and encapsulated a soft elastic mass. Histologically it was an epithelioid AML and positive for the melanogenesis-related marker HMB-45, the same as the earlier right renal tumor. We describe the first case of a solitary omental AML, which had metastasized, and with more than 6 hepatic AMLs. J. Med. Invest. 52: 218-222, August, 2005

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