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Background: Recent studies reveal that metabolically healthy obesity, which is free from the metabolic complications of obesity at present, is a risk of incident diabetes or cardiovascular disease (CVD). It may be because many metabolically healthy obesity individuals transit to metabolically abnormal obesity over time. However, the association between maintain- ing metabolically healthy obesity and incident diabetes or CVD is still unclear. Methods: 2190 participants without diabetes and/or CVD were examined at baseline and at 5-year follow-up, using a retrospective cohort study design. Metabolically abnormal was defined as having ≥ 2 of metabolic abnormalities, hyperten - sion, hypertriglyceridemia, low HDL cholesterol and impaired fasting glucose. Overweight was defined as BMI ≥ 23 kg/ m 2 , which is recommended by WHO for Asian. Adjusted odds ratio (OR) and 95% confidence interval (CI) for incident diabetes or CVD at follow-up were estimated adjusting for potential confounders, compared to maintaining metabolically healthy non-overweight (MHNO). Results: At the follow-up examination, 82 participants developed diabetes. Crude incident proportions of diabetes were 0.6% in maintained MHNO (case/N = 5/859) and 1.3% in maintained metabolically healthy overweight (MHO)(4/314). Adjusted OR for incident diabetes of maintaining MHO was 1.71 (95% CI 0.42-6.57, P = 0.438). At the follow-up examina- tion, 51 participants developed CVD. Crude incident proportions of CVD were 0.8% in maintained MHNO (7/859) and 1.6% in maintained MHO (5/314). Adjusted OR for incident CVD of maintaining MHO was 1.42 (95% CI 0.41-4.56, P = 0.565).

μ-Crystallin is an NADPH-dependent cytosolic T3-binding protein. A knockout study in mice showed that μ-crystallin has a physiological function as a reservoir of T3 in the cytoplasm in vivo. Patients with nonsyndromic deafness were reported to have point mutations in the μ-crystallin gene. The expression of μ-crystallin is regulated by multiple factors. The present study was performed to determine whether thyroid function is related to the expression of μ-crystallin mRNA in peripheral mononuclear cells. We examined 23 normal healthy male and female subjects and 15 patients with Graves' disease. μ-Crystallin protein expression was determined immunohistochemically in peripheral mononuclear cells. The expression of μ-crystallin mRNA was assessed by reverse transcription of total RNA from peripheral mononuclear cells followed by quantitative PCR. μ-Crystallin protein was detected in peripheral mononuclear cells. The mRNA expression was negatively correlated with age in normal female subjects. The values in female subjects were significantly higher than those in males. The values were positively correlated with serum TSH concentration. The values of the thyrotoxic patients with Graves' disease were lower than those in healthy subjects. A transient increase in μ-crystallin expression was observed within 14-42 days after the initial treatment with antithyroid medication. Thyroid hormone inversely relates to the expression of μ-crystallin mRNA in euthyroid mononuclear cells. Abrupt suppression of thyroid function leads to overexpression of μ-crystallin mRNA in thyrotoxic mononuclear cells. Thyroid hormone-regulated μ-crystallin expression may control thyroid hormone action via the intracytoplasmic T? capacity., Article, HORMONE AND METABOLIC RESEARCH. 41(7):548-553 (2009)

Background: Recent studies reveal that metabolically healthy obesity, which is free from the metabolic complications of obesity at present, is a risk of incident diabetes or cardiovascular disease (CVD). It may be because many metabolically healthy obesity individuals transit to metabolically abnormal obesity over time. However, the association between maintaining metabolically healthy obesity and incident diabetes or CVD is still unclear. Methods: 2190 participants without diabetes and/or CVD were examined at baseline and at 5-year follow-up, using a retrospective cohort study design. Metabolically abnormal was defined as having ≥ 2 of metabolic abnormalities, hypertension, hypertriglyceridemia, low HDL cholesterol and impaired fasting glucose. Overweight was defined as BMI ≥ 23 kg/ m2 , which is recommended by WHO for Asian. Adjusted odds ratio (OR) and 95% confidence interval (CI) for incident diabetes or CVD at follow-up were estimated adjusting for potential confounders, compared to maintaining metabolically healthy non-overweight (MHNO). Results: At the follow-up examination, 82 participants developed diabetes. Crude incident proportions of diabetes were 0.6% in maintained MHNO (case/N = 5/859) and 1.3% in maintained metabolically healthy overweight (MHO)(4/314). Adjusted OR for incident diabetes of maintaining MHO was 1.71 (95% CI 0.42-6.57, P = 0.438). At the follow-up examination, 51 participants developed CVD. Crude incident proportions of CVD were 0.8% in maintained MHNO (7/859) and 1.6% in maintained MHO (5/314). Adjusted OR for incident CVD of maintaining MHO was 1.42 (95% CI 0.41-4.56, P = 0.565). Conclusions: Maintaining MHO phenotype was not associated with higher risk of incident diabetes or CVD.

We have attempted to determine whether depressed plasma plasminogen and alpha2 plasmin inhibitor (or alpha2 antiplasmin) activity is, as a result of consumption coagulopathy, a specific finding of disseminated intravascular coagulation (DIC) in septic patients. The hemostatic parameters of 139 septic patients (68 with DIC and 71 without DIC) were analyzed. Among the group as a whole, plasma activities of plasminogen and alpha2 plasmin inhibitor were significantly depressed in septic patients with DIC relative to those without DIC (P < 0.01 and P < 0.05, respectively). Notably, a significant correlation was observed between plasma levels of albumin and plasminogen activity, as well as between plasma levels of albumin and alpha2 plasmin inhibitor activity both in septic patients with DIC and those without DIC. However, no significant correlation was observed between plasma levels of plasmin-alpha2 plasmin inhibitor complex (PIC) and plasminogen activity, nor between PIC and alpha2 plasmin inhibitor activity either in septic patients with DIC or those without DIC. We concluded that depressed activity of plasminogen or alpha2 plasmin inhibitor is not as a result of consumption coagulopathy, but rather a result of low synthetic function of the liver in septic patients with DIC.

The site-specific 1s core-level photoionization of N2O molecules has been studied experimentally and theoretically at a time-dependent density functional level. The photoelectron angular distributions have been measured from the oriented molecules. The effects of site of ionization, of energy dependence and of configurations of molecular axis and polarization vector, have been discussed. The presence of two shape resonances is reflected in the particular behaviours observed in the photoelectron angular distribution, while their nature has been assessed in terms of the calculated photoelectron wavefunction. Comparison with isoelectronic CO2 molecules suggests that symmetry lowering does not play an important role, except for the resonant energy region.

The purpose of this pilot study was to determine the effect of recombinant hirudin (r-hirudin) on coagulopathy and the relationship between concentrations of thrombin-antithrombin III (ATIII) complex (TAT) and thrombin-hirudin complex (THC) in patients with disseminated intravascular coagulation (DIC). Five patients with haematological malignancy associated with DIC were studied. r-Hirudin was administered by continuous intravenous infusion at a dose of 0.005 mg/kg/h for 4-9 days to each patient. Fibrin/fibrinogen degradation products (FDP), D-dimer, TAT and plasmin-alpha 2 antiplasmin complex (PAP) concentrations decreased after treatment with r-hirudin in four patients studied. However, in one patient, serum creatinine increased to 1.7 mg/dl and aPTT was prolonged to 74.4s. Statistical analysis disclosed significant positive correlations between plasma concentrations of hirudin and THC, and between concentrations of THC and TAT. The concentrations of THC were much higher than those of TAT. In conclusion, these findings indicate that r-hirudin more strongly inhibited thrombin than did ATIII without heparin, and that administration of r-hirudin to renal insufficiency required individual adjustment of dosage. The present findings also suggest that r-hirudin can be considered a new agent for the treatment of DIC.

Plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC) and active plasminogen activator inhibitor (PAI) were assayed in 66 cases of disseminated intravascular coagulation (DIC). Significant elevation of both TAT and PIC was observed in all cases of DIC. Most elevated levels of TAT were seen in DIC with acute promyelocytic leukaemia (APL) and sepsis. The highest levels of PIC were seen in DIC with APL but were much lower in sepsis. A significant elevation in active PAI was observed in DIC due to acute leukaemia (apart from APL), chronic myeloid leukaemia and sepsis, but not in APL, non-Hodgkin lymphoma and cancer. Active PAI was higher in patients with multiple organ failure (MOF) than in those without MOF while PIC was lower in patients with this complication. Thus, the balance of coagulation and fibrinolysis varied according to the underlying cause of DIC; APL had more dominant activation of fibrinolysis, while sepsis had greater activation of coagulation. It is suggested that the inhibition of secondary fibrinolytic activation plays an important role in the progression of MOF by the disturbance of the microcirculation.

We report a 74-year-old Japanese woman who had bleeding due to a factor VIII inhibitor in the absence of diseases known to be associated with its development. She abruptly developed a large painful purpura extending from the right hip to the thigh followed by an intramuscular haematoma of her left anterior chest. Examinations revealed a marked depression of factor VIII activity (5%) and the presence of 31 Bethesda units/ml factor VIII inhibiting activity. The phenotypes of these inhibitors were of the IgG-kappa and IgG-lambda types. She was treated with oral prednisolone and double filtration plasmapheresis (DFPP). The inhibitors rapidly disappeared after three sessions of plasmapheresis and her plasma factor VIII activity increased to a normal level. During this treatment, no major adverse effects such as thrombosis and infection were observed and transfusion of fresh frozen plasma (FFP) was not necessary. Heterogeneity of idiopathic factor VIII inhibitors in elderly patients is common and spontaneous disappearance or elimination of such inhibitors by treatment is often difficult to achieve. However, the combination of oral prednisolone and double filtration plasmapheresis is effective and safe for idiopathic factor VIII inhibitors and is a worthwhile approach to treatment.

A new experimental approach for determining the photoionization matrix elements with the use of multi-coincidence velocity-map imaging spectrometry is presented for the case of C1s photoionization of CO2 molecule over the energy region of a shape resonance. Our experimental results provide the complete information on the shape resonance mechanism and clearly demonstrate the inadequacy of presently available theoretical calculations for this system.

With the full use of the experimental data obtained by multi- coincidence velocity- map imaging spectrometry, we have determined the dipole amplitudes and their relative phases that describe the C 1s photoionization dynamics in CS2. It has been found that the sigma shape resonance at about 15 eV above the C 1s ionization threshold appears only in the dipole amplitude d(f sigma). We have also carried out time- dependent density functional theory calculations so as to better understand the photoemission dynamics and shape resonances in the C 1s photoionization of CS2 molecules with heavy atoms ( sulfur) having 3p valence orbitals, which distinguish the present work from well- studied works such as on CO and CO2 molecules.

We have measured the thermal conductivity in the $ab$-plane of La$_{2-x}$Sr$_x$CuO$_4$ ($x =$ 0.10, 0.115, 0.13) in magnetic fields up to 14 T parallel to the c-axis and also parallel to the $ab$-plane. By the application of magnetic fields parallel to the c-axis, the thermal conductivity has been found to be suppressed at low temperatures below the temperature $T_\kappa$ which is located above the superconducting transition temperature and is almost independent of the magnitude of the magnetic field. The suppression is marked in $x =$ 0.10 and 0.13, while it is small in $x =$ 0.115. Furthermore, no suppression is observed in the 1 % Zn-substituted La$_{2-x}$Sr$_x$Cu$_{0.99}$Zn$_{0.01}$O$_4$ with $x =$ 0.115. Taking into account the experimental results that the temperature dependence of the relative reduction of the thermal conductivity is quite similar to the temperature dependence of the intensity of the incommensurate magnetic Bragg peak corresponding to the static stripe order and that the Zn substitution tends to stabilize the static order, it is concluded that the suppression of the thermal conductivity in magnetic fields is attributed to the development of the static stripe order. The present results suggest that the field-induced magnetic order in La$_{2-x}$Sr$_x$CuO$_4$ originates from the pinning of the dynamical stripes of spins and holes by vortex cores., Comment: 8 pages, 5 figures. Fig. 1 has been modified

All-trans retinoic acid (ATRA) has been introduced to the management of acute promyelocytic leukemia (APL) as a differentiation treatment. This drug not only causes complete remission, but also improves disseminated intravascular coagulation (DIC) without adding anticoagulants in APL. We have attempted to determine whether ATRA is effective against DIC in rat models induced by tissue factor (TF) or lipopolysaccharide (LPS), because the anticoagulant effect of ATRA has been considered to induce thrombomodulin upregulation and TF downregulation on endothelial cells as well as on APL cells. In male Wistar rats, DIC was induced by a 4-h infusion of thromboplastin (3.75 U/kg) or lipopolysaccharide (30 mg/kg). The rats were given ATRA orally each day at a dose of 100 mg/kg per day for 1 week before the injection of TF or LPS in ATRA treatment groups, or given low molecular weight heparin (LMWH) 10 min before the injection of TF or LPS (200 U/kg, bolus intravenously) in LMWH treatment groups. No significant changes in hemostatic parameters or markers of organ dysfunction were caused by the ATRA administration, while DIC was significantly improved by LMWH in the TF-induced model. DIC was significantly improved by both ATRA and LMWH in the LPS-induced model. These findings suggested that ATRA was useful for treating DIC only in the LPS-induced model, and that drug efficacy should be carefully assessed because the agents used to induce DIC considerably influenced the outcome.

Tissue factor pathway inhibitor (TFPI) is primarily synthesized by vascular endothelial cells and is found in vivo in association with endothelial cells, lipoproteins, or in free form. Free TFPI is the most potent and important type, because it is released from endothelial cells following an injection of heparin, or as a result of pathological stimuli. In order to study the role of TFPI in disease, the concentration of free form TFPI was measured in the plasma of 114 patients suffering from disseminated intravascular coagulation (DIC), as the result of several underlying diseases. Plasma antigen levels of free TFPI were significantly higher even in those patients not exhibiting DIC than in normal healthy subjects. These levels were even higher among patients exhibiting DIC, especially those with acute promyelocytic leukemia or cancer, receiving continuous heparin drip infusions. A significant correlation was observed between the plasma antigen levels of free form TFPI and those of fibrin/fibrinogen degradation products, and free form TFPI and plasmin inhibitor complex (r = 0.428, P < 0.0001 and r = 0.329, P < 0.0001, respectively) among 114 DIC patients. There were no significant differences between the plasma levels of free TFPI in DIC patients with or without multiple organ failure. It has been suggested that the plasma levels of free TFPI are closely related to the levels of fibrinolysis occurring in DIC patients, although further study is required to clarify the degree to which TFPI is expressed by endothelial cells during DIC.

In order to determine whether prednisolone has a protective effect against the development of disseminated intravascular coagulation (DIC), we measured the effect of prednisolone on changes in hemostatic parameters and plasma levels of inflammatory cytokines in endotoxin-treated rats. Decreases in platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products and levels of thrombin-antithrombin III (TAT) complex following the administration of endotoxin, all of which are associated with DIC, were significantly suppressed by the administration of prednisolone. Heparin administration significantly suppressed changes in all these parameters except for the decrease in platelet count. The combination of prednisolone and heparin was more effective than either treatment alone. In order to determine whether these effects of prednisolone are correlated with the suppression of inflammatory cytokine production, we examined the relationship between changes in plasma levels of cytokine, the hemostatic parameters listed above, and mortality using a number of intervention regimens designed to alter events of the experimentally induced DIC. Changes in hemostatic parameters associated with DIC following 30 mg/kg per 4 h of endotoxin infusion were significantly suppressed by treatment with 1 mg/kg prednisolone 30 min before beginning endotoxin infusion, followed by administration of 250 U/kg heparin 2 h after the start of endotoxin infusion (prednisolone-endotoxin-heparin regimen). The heparin and prednisolone were administrated subcutaneously. The administration of prednisolone and heparin in the reverse order (i.e. heparin first and prednisolone second: heparin-endotoxin-prednisolone regimen) also suppressed changes in hemostatic parameters, albeit to a smaller degree. Cytokine production was also significantly suppressed by the first treatment, but was not affected by the regimen in which heparin was administered first. Administration of prednisolone alone or heparin alone 30 min before endotoxin significantly reduced the number of renal glomeruli with fibrin thrombi. Plasma levels of creatinine and alanine transferase were reduced only by prednisolone. Increased plasma levels of interleukin-1beta, tissue necrosis factor-alpha and interleukin-6 were suppressed by prednisolone but not by heparin, and there were significant correlations between plasma levels of TAT and cytokines. Prednisolone was more effective than heparin in reducing mortality at 24 h after 100 mg/kg over 4 h of endotoxin infusion (four of 20 versus 15 of 20 deaths for prednisolone and heparin, respectively). These findings suggest that prednisolone inhibits the development of endotoxin-induced DIC and reduces mortality by a different mechanism than heparin, possibly through suppressing the production of inflammatory cytokines. Prednisolone may be efficacious in preventing DIC and multiple organ dysfunction caused by endotoxin.

3XT725BRIT J PSYCHOL

There is some clinical evidence that cyclosporine A (CyA) is associated with thrombotic complications of bone marrow and renal transplantation. We investigated plasma concentrations of lipoprotein(a) [Lp(a)], a potentially atherothrombotic lipoprotein, and hemostatic and vascular status in ten patients with aplastic anemia receiving CyA, eleven patients not taking it, and 38 age-matched healthy controls. Patients receiving CyA had significantly higher concentrations of plasma fibrinogen (P < 0.05), prothrombin fragment 1 + 2 (F1 + 2; P < 0.05), plasminogen activator inhibitor-1 (PAI-1; P < 0.05), and von Willebrand factor antigen (P < 0.05) than did patients not taking CyA. Plasma concentrations of Lp(a) were higher in CyA-treated patients than those not receiving it (P < 0.05) or healthy controls (P < 0.05). The difference in the Lp(a) concentration between controls and patients who did not receive CyA-treatment was not significant. Our results suggest that hypercoagulability is likely to occur during CyA therapy. Further, the presence of high concentrations of Lp(a) may accelerate the process of atherosclerosis and increase thrombotic events in patients receiving long-term CyA.

We examined plasma antigen levels of tissue factor (TF) in 95 cases of disseminated intravascular coagulation (DIC), to investigate the role of TF in DIC. A significant elevation of plasma antigen levels of TF was observed in cases of DIC associated with cancer. However, no such significant elevation was observed in cases of DIC associated with acute promyelocytic leukemia (APL), acute leukemia except APL, blastic crisis of chronic myelogenous leukemia, non-Hodgkin lymphoma (NHL), sepsis or fulminant hepatitis. No significant elevation of TF was observed in patients without DIC, except 4 cases of cancer who developed DIC thereafter. Plasma antigen levels of TF were higher in both cases of DIC with renal failure and chronic renal failure without DIC than its levels in those without renal failure. Therefore, plasma antigen levels of TF in DIC patients with renal failure were considered to be carefully estimated. The levels of TF were decreased with the clinical improvement in some cases of DIC but were further increased or remained at high levels in patients who showed no improvement of DIC. Thus, plasma antigen levels of TF is an important marker to predict the development and/or prognosis of DIC, especially in patients with cancer.

To investigate the relationship between changes in plasma concentrations of polymorphonuclear elastase (PMN-E) and haemostatic effects during haemodialysis (HD), changes in the plasma concentrations of elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and fibrinogen (Fbg), cross-linked fibrin degradation products (XDP), thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC) and soluble thrombomodulin (TM) in 49 patients with end-stage chronic glomerulonephritis maintained on chronic HD were measured. Plasma concentrations of TAT, PIC, TM and E-alpha 1 PI significantly increased during a single HD. There was a statistically significant correlation between change in plasma E-alpha 1 PI concentration and changes in plasma concentrations of TAT, PIC and TM during a single HD, as well as between changes in plasma concentrations of TM and TAT during a single HD. These observations suggested that activation of coagulation and fibrinolysis, endothelial cell damage, and activation of polymorphonuclear cells occur during HD. Activation of polymorphonuclear cells may induce activation of coagulation and fibrinolysis, leading to endothelial cell damage, augmented by release of proteases such as elastase.

Octacalcium phosphate (OCP) has been advocated to be a precursor of biomineral s. Tn this report , we aimed at investigating OCP hydrolysis and the interaction of OCP and its hydrolyzates (apatitic products) with bovine serum albumin (BSA). A batch of synthetic OCP was allowed to hydrolyze either (a) in deionized water at 70°C or (b) in Tris buffer (pH 7.4) containing 2 ppm fluoride at 37°C. OCP hydrolysis was completed within reasonable experimental periods: after 48 hours at 70°C and after 10 days at 37°C in the presence of fluoride. The adsorption isotherms of BSA onto the original OCP and its various hydrolyzates were determined at pH 7.4 and 37 °C. The BSA adsorption onto all the adsorbents was described by a Langmurian model. Remarkable findings were that: (1) when the maximum number of BSA adsorption sites was expressed on basis of unit surface area (N , mols/m2), the greatest values of N was obtained for the original OCP; (2) the N values became smaller with the advance of OCP-apatite conversion in both hydrolysis systems; (3) the affinity values (K, ml/µmol) were relatively constant for the OCP anti the non-fluoridated hydrolyzates, while the K values increased markedly after hydrolysis of OCP in the presence of fluoride. The results of the present work support the hypothesis that the process of precursor precipitation and its subsequent hydrolysis taking place in forming hard tissues may be modulated through the matrix protein-crystals interaction. It seems likely that fluoride ions has a dual role, i.e., acceleration of OCP hydrolysis and, once incorporated into the crystals, enhancement of the protein-mineral interaction.

A lipopolysaccharide (BP-LPS) isolated from killed Bordetella pertussis (Tohama strain) was determined to have low toxicity based on the mortality and decrease in body weight of BP-LPS-injected mice. BP-LPS, administered intradermally or intraperitoneally, clearly inhibited the growth of an MM46 murine mammary carcinoma. When compared with a toxic Escherichia coli-derived LPS, BP-LPS displayed excellent anti-tumour activity against MH134 hepatoma and Meth A fibrosarcoma. As part of a combined chemotherapy/immunotherapy regimen, BP-LPS also seemed to prolong the lifespan of mice inoculated with Lewis lung carcinoma. BP-LPS thus appears to have valuable characteristics as an anti-tumour agent.

Disseminated intravascular coagulation (DIC) is a serious clinical condition, but its pathophysiology is very different according to the underlying diseases responsible for DIG, For example, a marked activation of the coagulation and fibrinolytic system is present in most cases of acute promyelocytic leukemia. On the contrary, a little activation of the fibrinolytic system is present in most cases of sepsis with DIC1–4. Therefore, it is important to investigate these pathologic condithions separately according to the underlying disease responsible for DIC.

Changes in thrombin-antithrombin III complex (TAT) over a one week period studied in 42 cases of disseminated intravascular coagulation (DIC); 19 treated with standard (or unfractionated) heparin (UFH) and 23 treated with low-molecular-weight heparin (LMWH). Closer examination of short term changes in TAT (determined 2, 6, 12, 24, 48, and 72 h after starting anticoagulant therapy) was performed in ten cases of DIC; six treated with UFH and four treated with LMWH. In twelve of the 19 cases of DIC treated with UFH and 19 of the 23 cases treated with LMWH, plasma levels of TAT decreased one day after starting anticoagulant therapy, and no exacerbation of DIC was observed for the following week. In the other cases, these levels further increased and most patients had persistently high levels of TAT for the next week. Plasma levels of TAT were significantly lower in patients treated with LMWH than in those treated with UFH, which may suggest that LMWH is more beneficial in DIC. A transient increase in plasma levels of TAT was observed 6 h after the start of anticoagulant therapy in two of the six cases treated with UFH and one of the four cases treated with LMWH. From these results we conclude that fluctuation of TAT was not influenced by the type of heparin (UFH or LMWH), and that the course of DIC for the following week can be predicted by the changes in plasma TAT levels one day after starting anticoagulant therapy.

Following rapid development of chemotherapy to leukemia, reports about tumor-forming-leukemia are on the increase. But ovarian tumor-forming-leukemia is relatively rare, hence not enough is known about it. Recently, the authors experienced a case of young woman with recurrent leukemia which manifested as a giant ovarian tumor. She suffered from acute lymphocytic leukemia (ALL) in February, 1986, and received chemotherapy (predonisolone and cytocine arabinoside) until complete remission in peripheral blood. But she developed a giant abdominal tumor in May, 1988, and admitted to our hospital for close examination and treatment. Preoperative blood examination was within normal range, and peripheral blood smear revealed no leukemic blasts. She had a giant abdominal tumor occupying whole abdominal cavity, and the tumor showed solid pattern in ultra-sonography, CT and NMR-CT. Malignant lower abdominal tumor was suspected, and simple abdominal hysterectomy, bilateral salphingo-oophorectomy and omentumectomy was performed on 27th. May, 1988. A giant abdominal tumor developed from left ovary, infiltrating to the uterus through left Fallopian tube, and metastatic lesion at omentum were present. Postoperative pathological findings in immunochemistry showed that the tumor was recurrence of ALL as tumor-forming-leukemia. After operation, she was treated in the department of internal medicine for postoperative chemotherapy (TCMP-therapy 1 kur) and discharged in December, 1988. She is alive and healthy 10 months after operation, and reveals no signs of recurrence. It was important to recognize lower abdominal tumor in leukemic patients as gynecologic problem, and significance of surgical approach to ovarian tumor-forming-leukemia was indicated.

A study was conducted on twenty-four patients who underwent surgery for retinal detachment as to the clinical effect of acupuncture from the viewpoints of anesthetic dose, intraoperative changes in blood pressure and heart rate, postoperative analgesic state, nausea and vomiting. The patients were divided into two groups: group A, eleven patients receiving neuroleptanesthesia combined with acupuncture analgesia and group N, thirteen patients receiving usual neuroleptanesthesia without acupuncture. A significant difference was found in the dose of fentanyl, used as the narcotic, between group A (0.11 mg) and group N (0.48 mg). No difference was noted in blood pressure between the two groups, but it was high in group N in the postoperative period. There was no difference in heart rate between the two groups. Two patients from group A and five from group N required analgesics in the postoperative period. Nausea and vomiting were encountered in one patient in group A and three in group N. Therefore, it would seem that anesthesia in combination with acupuncture is capable of reducing the required dose of narcotic and offering more comfortable postoperative conditions than usual anesthesia alone.

Despite intensive efforts in the treatment of hepatocellular carcinoma (HCC), its prognosis remains poor, mainly because of intrahepatic metastasis. It is, therefore, important to investigate the invasive and metastatic behavior of HCC. To examine this, murine HCC cells were labeled with the fluorescent carbocyanine dye, DiI and implanted under the capsule of the liver of syngeneic mice. Optimal conditions are described for labeling HCC cells with DiI. Histological analysis using fluorescent and confocal microscopes revealed that HCC cells migrate to and invade the adjacent portal vein, but not the adjacent central vein. Conversely, DiI-labeled hepatocytes were shown not to migrate in the liver. These results suggest that intrahepatic metastasis of HCC occurs by invading the portal venous system. Furthermore, it is indicated that orthotopic implantation of fluorescent dye-labeled tumor cells may be a convenient and useful method to investigate the invasive and metastatic behavior of various types of cancer.

Animal models for various types of cancer are of great help in the study of tumors and antitumor effects. Subcutaneous models have been widely utilized because they can be produced easily by subcutaneously implanting tumor cells into animals. Although subcutaneous models are very convenient for examining tumor development, they are definitely different from clinical manifestations of original tumors. In orthotopic animal models for internal tumors, however, it is difficult to examine tumor development without sacrificing animals. We demonstrate here that the occurrence and growth of liver tumors induced by oral administration of thioacetamide into rats were clearly observable by ultrasonography, and that the sonographic estimation was accurate. It was observed sonographically that the number and volume of liver tumors increased proportionately with TAA treatment periods. These results indicate that sonography is a useful and non-invasive method to investigate liver tumor development in rats.

The regulation of cGMP phosphodiesterase in vertebrate rod photoreceptors is a typical G protein-dependent signal transduction mechanism. The interaction of P gamma, an inhibitory subunit of cGMP phosphodiesterase, with transducin alpha subunit (T alpha) is essential for the activation of cGMP phosphodiesterase. It has been shown that, in a homogenized preparation of frog (Rana catesbeiana) rods, P gamma interacts with GTP.T alpha and remains tightly bound to GDP.T alpha after GTP hydrolysis on T alpha. Association of this complex with beta gamma subunits of transducin (T beta gamma) triggers the release of P gamma from the complex and the subsequent inactivation of cGMP phosphodiesterase. In a system reconstituted with purified components, both GTP- and GDP-bound forms of T alpha were found to interact with P gamma. Under these conditions, P gamma inhibited GTP hydrolysis by transducin in a noncompetitive manner with a Ki of 92 nM. Binding of an hydrolysis-resistant GTP analog to T alpha was also inhibited by P gamma. These inhibitions of transducin function were resulted from the inhibition of both hydrolysis of GTP bound to T alpha and interaction of GDP.T alpha with membrane-bound T beta gamma. However, after GDP.T alpha reassociated with membrane-bound T beta gamma, the inhibitory effect of P gamma on the binding of an hydrolysis-resistant GTP analog to T alpha was greatly diminished, suggesting that the GTP/GDP exchange on T alpha was not inhibited by P gamma. These data indicate that the T alpha function is altered during complexing with P gamma. G protein functions may be modified by interacting with an effector in the G protein-dependent signal transduction.

Because it appears impossible to transfer toxic genes to all the cells of a cancer, the bystander effect is critical to induce effective antitumor effects. In the present study, possible in vitro mechanisms of the bystander effect by the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) were investigated. CD-transduced cancer cells exhibited much higher sensitivity to 5-FC compared to parental cells. CD-transduced cells caused killing of neighboring parental cells in the presence of 5-FC, irrespective of direct cell-to-cell contact. Media conditioned by CD-transduced cells and 5-FC contained considerable amounts of 5-fluorouracil (5-FU) and exhibited profound cytotoxicity on parental cells. Furthermore, this killing ability of conditioned media correlated well with 5-FU levels converted from 5-FC by CD-transduced cells. CD was shown not to be secreted into media from cells. These results indicate that diffusible 5-FU plays the substantially causative role in the in vitro bystander effect caused by the CD/5-FC system.