Remodeling of chromatin structure through the modification of histone acetylation is critical in the regulation of transcription. A variety of hematological malignancies have genetic aberrations associated with mechanisms involved in the regulation of acetylation. For cases in which aberrant acetylation contributes to the development of malignant phenotypes, the restoration of the physiological acetylation pattern is expected to lead to the normal phenotype. This form of differentiation therapy is exemplified by the successful treatment of acute promyelocytic leukemia (APL) with all-transretinoic acid. This review summarizes hematological malignancies resulting from genetic abnormalities leading to abnormal acetylation patterns and discusses the underlying role of these mechanisms in oncogenesis. Modification of aberrant acetylation patterns may specifically direct malignant cells along differentiation pathways thereby restoring the normal phenotype. This form of treatment is disease-oriented and, because it is designed to repair abnormalities at the molecular level, can be regarded as“molecular target”therapy.

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Anterior lumbar interbody fusion (ALIF), under laparoscope or retroperitoneoscope is a well accepted procedure for treatment of degenerative spinal abnormalities. Interbody fusion cages have been shown to promote good initial fixation in a variety of animal models, however few studies have examined the effects of the type of cage or direction of insertion on initial fixation strength. The present study biomechanically measured the initial fixation strength of ALIF using a threaded interbody fusion cage on fresh porcine spine. We performed two studies; Study 1 compared the effects of the number and the direction of insertion of cylindrical cages at the L4/5, 5/6 level on stiffness, and Study 2 investigated the effects of the type of cage and number using two types of cages (cylindrical and conical cages) at the L6/S1 level. In Study 1, there was significantly more stiffness with flexion in the single anterior group, the double anterior group, and the single anterolateral group compared to the control group (no cage insertion) . In addition, stiffness was significantly better in the single anterolateral group than in the single anterior group. There was no differentces between any of the groups in any loading mode. In Study 2, for extension, there was significantly better stiffness in the groups that received cylindrical or conical cages compared to no-insertion controls. In lateral bending, the two cylindrical cage groups had significantly better stiffness than controls. There were no differences in flexion and axial torsion between any of the groups. Again, there were no significant differences between any of the groups in any loading mode.

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A comparative study on coagulopathy and platelet dysfunction in patients undergoing cardiovascular surgery with normo- and hypothermic cardiopulmonary bypass (CPB) was performed using Sonoclot signature determinations. Forty-six patients were divided into two groups : 19 had normothermic CPB (group A) ; and 27 had hypothermic CPB and circulatory arrest (group B) . Sonoclot signatures were recorded before the start of CPB and after heparin neutralization after weaning from CPB. Son ACT (active clotting time) and clot rate were analyzed as parameters for coagulopathy, and time-to-peak and peak angle for platelet dysfunction. Significant prolongation of Son ACT and a lower clot rate after CPB were found in group B, though the protamine dose for heparin neutralization was identical to that of group A. Time-to-peak was also significantly prolonged, and platelet loss was greater in group B. Blood loss during surgery was significantly greater in group B, however significant differences could not be detected in postoperative blood loss when the abnormal Sonoclot signatures were corrected to baseline levels by supplemental use of fresh frozen plasma or platelet concentrate. More profound coagulopathy and platelet loss and dysfunction develop in hypothermic CPB and circulatory arrest than in normothermic CPB. Sonoclot^® measurement quickly gives reliable information regarding abnormal coagulability and platelet dysfunction after CPB. Excessive blood loss might be prevented postoperatively by correcting abnormal Sonoclot signatures to a baseline level by appropriate choice of hemostatic therapy.

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and proliferation of synovial membrane tissue. A number of studies have reported the etiologic role of stress proteins in RA. However, the role of the well-characterized stress protein, heme oxygenase-1 (HO-1), in relation to RA, remains to be elucidated. In this investigation, we employed double immunohistochemical staining techniques to identify HO-1-expressing cells in the synovial tissue of a mouse model of RA. The RA model used was that of human T cell leukemia virus type-I (HTLV-I) transgenic (Tg) mouse. The physical characteristics of synovial tissue in limb joints were additionally analyzed. Morphological data revealed a marked increase in the thickness of synovial membrane layers in two- to three month-old Tg mice. HO-1-like immunopositive cells were identified in synovial tissue from both wild-type and HTLV-I Tg mice. Notably, cell numbers in Tg mice were dramatically increased. A double immunofluorescence study revealed the presence of HO-1-immunopositive cells in T cells, fibroblasts and macrophages. The percentage of T cells expressing HO-1 was relatively higher than that of fibroblasts and macrophages. These results suggest that HO-1 levels increase in synovial tissue during RA. Moreover, the protein participates in the regulation of RA pathogenesis.

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Several genetic alterations have been associated with the malignant transformation from endometriosis to ovarian cancer. However, the role of each genetic alteration in this multi-step process of tumorigenesis has not been clarified. Regions of endometriosis, atypical endometriosis, and ovarian endometrioid carcinoma were separated by laser microdissection, and examined for the presence of K-ras mutation and microsatellite instability. K-ras mutation and microsatellite instability were detected in endometrioid carcinoma tissue, but not in endometriosis and atypical endometriosis bordering the cancerous region. K-ras mutation and microsatellite instability may be associated with the malignant transformation from atypical endometriosis to ovarian endometrioid carcinoma, but not from endometriosis to atypical endometriosis.

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A database which allows bi-directional communication between an emergency room (ER) and a department of pharmacy services was developed to facilitate the rapid treatment of patients with life-threatening exposure to toxic substances. Accurate information regarding the substances involved is essential for effective treatment. These substances may be prescription drugs or may be of domestic origin such as washing detergents or herbicides. Microsoft^® Access 2000 was employed as the database software to store patient records from 1995 to 2001. For cases involving intoxication or poisoning, the data fields were as follows : the date and time, the estimated period of exposure, ingestion mode, the suspected toxic materials, classification of drugs, and electrocardiogram. To maximize ease of use, information could be entered via a dialog screen. Live access was always maintained for both facilities, ieonce data had been entered in the database, it could be immediately accessed from either the pharmacy division or the ER. To protect patient confidentiality, only the patient's identification number was entered. The database itself was protected by password access. Major advantages of this system are that it can be online 24 hours per day and it will reduce the time involved in transferring information from the pharmacy services to ER.

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Histamine induces a variety of responses including contraction of airway smooth muscle, vasodilation, plasma exudation and mucus production in acute allergic reactions and is an important proinflammatory mediator in bronchial asthma. It also reduces tracheal tone centrally, through the sympathetic pathway. This study examined whether central histamine can attenuate airway responsiveness to methacholine (MCh) in asthma. C57BL/ 6 male mice were sensitized and challenged with ovalbumin (OVA) or saline. The enhanced pause (Penh) was determined as an index of airway obstruction 24 h after the last challenge using a barometric whole body plethysmograph. MCh inhalation increased Penh in a dose-dependent manner and was higher in OVA-sensitized and challenged mice (OVA mice) than in control mice. This suggests that OVA mice have airway hyperresponsiveness (AHR) . Eosinophils accumulated around bronchioles and serum total IgE was increased in OVA mice. Therefore, our system can be regarded as a model of asthma in mice. Histamine administered into the lateral ventricle (i.c.v.) of asthmatic mice lowered AHR when compared to control animals given artificial cerebrospinal fluid i.c.v. Down-regulation of AHR in response to histamine i.c.v. was not seen in asthmatic mice after injection of the β 2-adrenoceptor antagonist butoxamine. These results suggest that central histamine attenuates AHR in asthmatic model (AM) mice via β2-adrenaline receptors, and possibly via the sympathetic nervous system.

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To retrospectively examine PMMA intraocular lenses with glistenings for the grade of glistenings, the time from implantation to development of glistenings, and effect on visual function. Approximately, 14, 000 PMMA lenses were implanted in our hospital from January 1979 to December 1992. This study examined 163 eyes in 127 of the patients who had received an implanted lens over the period from May 2001 to March 2002. In 15 eyes that showed glistenings (13 patients), we studied various factors related to glistenings. Contrast sensitivity was measured using CSV-1000E (Vector Vision), with and without glare, in 7 eyes of 6 patients with PMMA lenses implanted in the posterior chamber who were able to visit our hospital. Glistenings developed in PMMA lenses, whether manufactured by lathe cutting or by injection molding, some of which contained a UV absorber. Glistenings developed later on average (5.9 years after implantation in the earliest case) in more PMMA lenses than in acrylic lenses. The glistenings were graded as follows : glistenings with 50 bright spots per 1 mm³ were graded as G1; those with 100 spots per 1 mm³ as G2, and those with 200 per 1 mm³ as G3. Among the 7 eyes evaluated there were 5, 1 and 1 lens with G 1, G2 and G3 glistenings, respectively. All eyes examined showed reduced contrast sensitivity under conditions of glare. Glistenings developed in PMMA lenses 6 or more years after they were implanted. There was no statistical difference in the appearance of the glistenings between lenses manufactured by injection molding compared with those manufactured by lathe cutting (P=0.413, 2×2 Chi square test), nor were the manufacturing methods related to the grade of glistenings (P=0.407, Mann-Whitney U-test) . Glistenings in PMMA lenses do not affect visual acuity or contrast sensitivity, but may reduce contrast sensitivity at low, middle and high frequency ranges when exposed to glare.

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From July 1987, when the retroperitoneal approach was first employed for the treatment of abdominal aortic aneurysm (AAA), to April 2003, elective AAA surgery was performed on a total of 209 patients in our department. Transabdominal incision (TAI) was performed in 61 patients ; paramedian retroperitoneal incision (PRI) in 27 patients ; Williams retroperitoneal incision (WRI) incision in 60 patients ; and midline retroperitoneal incision (MRI) in 61 patients. While there were no significant differences in age, gender ratio, or incidence of concomitant iliac vessel aneurysm among the four groups, the mean aneurysm diameter was larger in the TAI group than in the three retroperitoneal groups. Operative time was significantly shorter in the MRI group than in the TAI·group (288 ± 82 and 331 ± 88 minutes respectively, p<0.01) . No significant difference was apparent in the duration from start of skin incision to aortic clamp between the TAI group (105 ± 43 minutes) and the WRI or MRI groups (PRl group : 132± 128 minutes, WRI group : 108 ± 36 minutes, and MRI group : 119 ± 46 minutes) . Blood loss was significantly less in the MRI group than in the TAI group (p<0.01) (TAl group : 605 ± 355 g, and MRI : 447 ± 274 g) . Time to oral intake was reduced in the three retroperitoneal groups, with resumption of at least 75% oral intake being achieved in 9.3 ± 6.2 days for the TAI group, 5.9 ± 2.5 days for the PRI group, 5.3 ± 3.1 days for the WRI group and 5.5 ± 4.0 days for the MRI group (p<0.01) . When compared to the TAI group, postoperative hospital stay was shorter in the WRI and MRI groups. Postoperative course for the three retroperitoneal groups was therefore more favorable than for the TAI group, and in particular, MRI was shown to be useful in terms of recovery in intestinal function, additional skin incision and late abdominal bulge.

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The role of hepatic stem cells in liver regeneration following severe liver damage was studied by immunohistochemistry. Hepatobiopsy specimens were obtained from 16 patients with a serious liver disorder and c-kit ⁺CD34⁺ cells were counted following immunostaining with antibodies against c-kit and CD34. The liver was spatially divided into affected and non-affected areas ; the affected area was further segmented into central and border areas. The temporal and spatial appearance of the c-kit ⁺ CD34⁺ cells in the liver was assessed, as well as the relationship of these cells with CK 19-positive bile ducts. The c-kit⁺CD34⁺cells appeared soon after onset of the liver disorder, and independently of the underlying disease in all patients. Regardless of time after onset of the liver disorder, the number of c-kit⁺CD34⁺cells was high in the affected areas. The appearance rate tended to be high in the central affected areas in the early stages of damage, and high in the border affected areas at the later stages of the disorder. The absolute number of c-kit⁺CD34⁺ cells appeared to be smaller in the affected areas and with respect to the number of regenerated bile ducts. We suggest that following serious liver disorder, c-kit⁺CD34⁺cells are supplied early from the extrahepatic tissues for liver regeneration. These cells move to the regeneration site together with hepatic stem cells, and over time, play a role as hepatic tissue stem cells. It is probable that c-kit ⁺ CD34 ⁺ cells have the capacity to not only directly transdifferentiate into hepatocytes and biliary cells, but also to induce the growth and differentiation of hepatocytes.

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A 71-year-old Japanese male with liver cirrhosis due to hepatitis C virus infection showed a markedly elevated serum α -fetoprotein (AFP) concentration. Computed tomography (CT) revealed a hypervascular tumor compatible with hepatocellular carcinoma (HCC) in Couinaud's segment 4 (S4) in the liver. One month later, the tumor was enlarged and five months later, the serum AFP level began to decrease without any therapy. The tumor in S4 subsequently regressed over two months. Tumor stains were not observed in the S4 area on digital subtraction angiography (DSA) and the serum AFP level had decreased to within normal range. On admission, another hypervascular tumor was visualized in S5 by CT and the lesion was treated with transarterial chemoembolization (TAE) . After TAE treatment, there was no finding of HCC recurrence on CT for at least twenty months. This report describes a case of spontaneous regression of HCC with a second enlarged tumor, which was satisfactorily treated with TAE.

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