Effect of Inflammation on Costimulation Blockade-Resistant Allograft Rejection

Previously, we reported that allogeneic skin grafts were rapidly rejected by CD28 and CD40 ligand double deficient mice mediated by CD8⁺ T cells. These results indicated that some elements in addition to CD28- and CD40-mediated costimulation provide stimulatory signals for the activation of donor-specific CD8⁺ T cells. In this report, we investigated the role of inflammation associated with transplantation on costimulation-independent priming of CD8⁺ T cell during graft rejection. B6 RAG1 KO mice were transplanted with BALB/c-skin and adoptively transferred with syngeneic CD8⁺ T cells the same day or 50 days after transplantation. When blockade of CD28- and CD40-mediated costimulation failed to prevent acute rejection of freshly transplanted skin grafts, it efficiently delayed rejection of well-healed skin grafts. These results showed that factors associated with transplantation have essential roles in inducing costimulation blockade-resistant allograft rejection. Costimulation blockade failed to prevent acute graft-infiltration of NK cells and increasing expression of intragraft IL-12 and IL-15. These factors may trigger the graft-infiltration and priming of CD8⁺ T cells to induce costimulation blockade-resistant allograft rejection.     

A case of intraductal papillary mucinous neoplasm with internal pancreatic fistula causing left ureteral obstruction]

A 75-year-old man had been admitted to another hospital because of left abdominal pain, and was given a diagnosis of left hydronephrosis and acute pancreatitis. After a JJ stent insertion and medication, he was transferred to our hospital for further examinations. US and EUS revealed a chronic pancreatitis-like pattern and multicystic lesion in the pancreas head and body. At that time enhanced CT findings showed an extrapancreatic low density area to be inflammatory change, extending from the pancreas body to the left crus of the diaphragm and posteriorly the spreading from the left crus of the diaphragm via the left urinary duct into the left iliopsoas muscle, in which MRI revealed partial high intensity. ERCP and MRCP showed focal irregular narrowing of the pancreatic duct of unknown cause, and we decided that an internal pancreatic fistula due to pancreatitis had induced left ureteral obstruction, caused by a protein plug or alcohol. Follow-up 6 months later showed that extrapancreatic spreading of the low density area had markedly regressed without any change in the ureteral obstruction.     

Use of Glycopeptidolipid Core Antigen for Serodiagnosis of Mycobacterium avium Complex Pulmonary Disease in Immunocompetent Patients

We report the development of a serodiagnostic method for Mycobacterium avium complex (MAC) disease with an enzyme immunoassay (EIA) with the MAC-specific glycopeptidolipid (GPL) core as the antigen. In this study, we confirmed by EIA that the GPL core antibody was in the sera of immunocompetent patients with MAC disease. The EIA for quantifying the GPL core antibody was evaluated as a clinical tool for serodiagnosis of pulmonary MAC disease. A significant increase in GPL core antibodies (immunoglobulins G, A, and M) was detected in sera of patients with MAC pulmonary diseases when they were compared to patients who were colonized with MAC, patients with Mycobacterium kansasii disease or tuberculosis, and healthy subjects. The sensitivities and specificities of the GPL core-based EIA for diagnosis of MAC pulmonary disease were 72.6% and 92.2%, respectively, for IgG, 92.5% and 95.1%, respectively, for IgA, and 78.3% and 91.0%, respectively, for IgM. The best sensitivity and specificity were obtained by measuring immunoglobulin A antibodies against GPL core antigen. The level of GPL core antibodies reflected disease activity, since it decreased in cured MAC patients who had responded to chemotherapy. Measurement of serum antibodies against GPL core is useful for both diagnosis and assessment of disease activity in MAC disease of the lung.     

Significance of the hepatic mitochondrial redox state in the development of posttraumatic jaundice

The effect of the hepatic energy status on the development of posttraumatic jaundice (PTJ) was studied to clarify the mechanism of PTJ. Fifty-four patients with severe torso injury who were expected to develop PTJ on admission with an average Injury Severity Score of 27 were selected for this study. They were retrospectively divided into three groups according to their maximum bilirubin concentration by day 10: group H, 12 patients with marked elevation of serum bilirubin (>8 g/dl); group L, 23 with mild bilirubinemia (2–8 g/dl); and group N, 19 with no bilirubinemia (<2 g/dl). Group H patients, in whom trauma-related shock was severe and prolonged, developed severe hyperbilirubinemia, and their arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state and is closely correlated to its energy production, was significantly lower throughout the first week. In contrast, the AKBR increased to an above normal level, indicating enhanced energy production in groups N and L. The serum direct/total bilirubin was also higher in group H. The abnormal hepatic energy metabolism is considered to have reduced the excretion of conjugated bilirubin from the hepatocytes into the bile canaliculi, which is a process that has to proceed against the bilirubin concentration gradient. The subsequent diffusion of the accumulated water-soluble conjugated bilirubin in hepatocytes into the blood is thus considered to be one of the causes of PTJ.     

Effects of alpha-1-blocking agent in the treatment of detrusor sphincter dyssynergia

Effects of adrenergic alpha-1-blocking agent, prazosin, in the treatment of detrusor external-sphincter dyssynergia (DSD) were evaluated in both experimental and clinical aspects. Experimentally, in the urethral pressure profile in dogs, the maximum urethral closing pressure was depressed after intravenous injection of 1 mg prazosin. When experimental DSD was obtained in dogs by stimulating electrically the unilateral 2nd sacral root, intra-venous injection of 1 mg prazosin inhibited contraction of the external urethral sphincter. Clinically, 74 patients with DSD based on neurogenic bladder from cerebral vascular attack (CVA) (13 cases) and spinal cord injury (61 cases) were retrospectively surveyed in terms of therapeutical effects of prazosin for DSD. Spinal cord injury was subdivided to 4 groups for clinical evaluation; cervical cord injury (C) with complete paralysis, thoracic cord injury (Th) with complete paralysis, lumbar cord injury (L) with complete paralysis and spinal cord injury with incomplete paralysis. Patients with CVA and spinal cord injury with incomplete paralysis showed good response rates in subjective improvement, 69% and 60% respectively. However, those with spinal cord injury with complete paralysis showed a poor response (28% for C, 23% for Th and 14% for L). The amount of residual urine significantly decreased after treatment, in all the groups except that of lumbar cord injury with complete paralysis. In all the groups, however, even after the drug treatment the amount of residual urine ranged from 80 to 170 ml and the rates of needing clean intermittent catheterization unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of solvents on the thermal isomerization of 1 alpha-hydroxyprevitamin D3 diacetate to 1 alpha-hydroxyvitamin D3 diacetate

The thermal conversion of 1 alpha-hydroxyprevitamin D3 (1 alpha-OH-previtamin D3) diacetate to 1 alpha-hydroxyvitamin D3 (1 alpha-OH-vitamin D3) diacetate was investigated in five solvents. The fraction of 1 alpha-OH-vitamin D3 diacetate was calculated from the HPLC peak areas (UV detection) of 1 alpha-OH-previtamin D3 diacetate and 1 alpha-OH-vitamin D3 diacetate. When 1 alpha-OH-previtamin D3 diacetate was dissolved in ethanol, benzene, toluene, isopropyl ether, or n-hexane, and heated at 60 degrees C, the yield of 1 alpha-OH-vitamin D3 diacetate increased during the first 4 h, and reached an equilibrium level after 8.5 h. Differences in the ratio of 1 alpha-OH-previtamin D3 diacetate to 1 alpha-OH-vitamin D3 diacetate at thermal equilibrium, and in the rate of the thermal isomerization were observed among these five solvents. Molecular mechanics (MM) calculations were performed in order to estimate solvent effects on conformation for 1 alpha-OH-previtamin D3 diacetate and 1 alpha-OH-vitamin D3 diacetate. The solvent effect was treated by specifying a dielectric constant representative of each of the three solvents: ethanol (polar), n-hexane (nonpolar), and benzene (aromatic). The dielectric constants used were 24.3 for ethanol, 1.5 for n-hexane, and 2.3 for benzene. It is suggested that the conformation of 1 alpha-OH-vitamin D3 diacetate is stabilized in polar solvent. However, the order of conformational stability when solvent effects are included in the calculations is: ethanol greater than benzene greater than n-hexane. This order does not follow the experimental results. The proton NMR chemical shifts of 1 alpha-OH-vitamin D3 diacetate are different in deuterated n-hexane, ethanol, and benzene. The downfield shift of the C-6 vinyl proton of 1 alpha-OH-vitamin D3 diacetate, when compared to the chemical shift in benzene, is 0.15 and 0.11 ppm relative to the chemical shift in n-hexane and ethanol, respectively, and that of the C-7 proton was 0.30 and 0.33 ppm, respectively. No significant proton shift of 1 alpha-OH-previtamin D3 diacetate is recorded in these three solvents. To account for the increased ratio of 1 alpha-OH-vitamin D3 diacetate to 1 alpha-OH-previtamin D3 diacetate ratio in benzene, we suggest that 1 alpha-OH-vitamin D3 diacetate may be stabilized via specific solute-solvent interactions in benzene.     

Group-transfer alternating copolymerization of 2-phenyl-1,3,2-dioxaphosphorinane with trimethylsilyl 2-(acryloyloxy)ethanesulfonate

This paper describes a new class of reaction, group-transfer alternating copolymerization (GTAC), between 2-phenyl-1,3,2-dioxaphosphorinane ( 1 ) and trimethylsilyl 2-(acryloyloxy)ethanesulfonate ( 2 ). The copolymerization took place without any added catalyst and proceeded via quantitative trimethylsilyl group-transfer process to give a 1:1 alternating copolymer 3a having a ketene silyl acetal group in the main chain. Results of spectroscopy as well as alkaline hydrolysis and bromination of the copolymer confirmed the structure.