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.     

Histochemical studies on hyaluronic acid in the developing human retina

Changes in the distribution of hyaluronic acid in the developing human retina were investigated histochemically with alcian blue staining and theStreptomyces hyaluronidase digestion method using 56 human embryos and fetuses ranging from 5 to 41 weeks of gestational age. Hyaluronic acid was first detected in the inner layer of the retina at 12 weeks. The site of accumulation extended towards the outer layer by 20 weeks. At the neonatal stage, longitudinal fibers, possibly the processes of Müller cells, were proved to contain hyaluronic acid. These findings suggest that Müller cells produce hyaluronic acid transiently from 12 weeks’ gestation to the neonatal stage.     

Conformationally constrained congeners of 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones active on the cardiovascular system: conformational studies by molecular mechanics calculations and 1H NMR spectroscopy

Unsubstituted phenylpyridazinones 1a and 2a and their tricyclic analogues indenopyridazinone 3a, benzocinnolinone 4a, and benzocycloheptapyridazinone 5a were submitted to conformational analysis with Allinger's MM2(85) program in order to better define the relationship between the cardiovascular properties of some derivatives and their preferred conformations. Structures 1-4, giving rise to highly active compounds, were found to exist in a conformation showing a near-planar arrangement of the phenyl and the pyridazinone ring. On the contrary, 5, whose derivatives were inactive, shows two significantly populated conformations both markedly deviated from planarity. 1H NMR analysis of the tricyclic systems 3-5 was in full agreement with the molecular mechanics calculations.     

Quality of life assessment and HIV infection: A review

In the last few years, survival of patients infected with human immunodeficiency virus (HIV) has been improved because of a decreased incidence of some opportunistic complications attributable to prophylactic treatments and antiretroviral drugs. The impact of these agents should also be reflected in the quality of life (QoL) of patients. We have reviewed this topic with an emphasis on different types of measurements such as Q-TWIST, MOS and the Spitzer score which seem to be most appropriate for this patient population. We do not think that a special type of assessment should be designed for HIV-infected persons. It would be less time-consuming to improve already existing validated scores focusing on HIV infection. QoL in intravenous drug users with HIV should be evaluated more often.     

External beam radiotherapy for retinoblastoma: I. Whole eye technique.

A retrospective analysis has been performed of the results of external beam radiotherapy for retinoblastoma using a whole eye technique. Local tumour control has been assessed in a consecutive series of 175 eyes in 142 children all of whom received external beam radiotherapy as the primary treatment for retinoblastoma. Follow up ranged from 2 to 17 years (median 9 years). Tumour control rates have been analysed with respect to the Reese Ellsworth classification and the series includes eyes in groups I to V. Focal salvage therapy was given for persistent, recurrent, or new tumours after radiotherapy. Following whole eye radiotherapy alone, the overall ocular cure rate was 57%, though with salvage therapy 80% of eyes could be preserved.     

Effect of prostaglandin E1 on graft function of kidneys from living related donors

Prostaglandin E₁ (PGE₁) was used in renal transplant recipients with living related donors. The drug was given intravenously from day 1 to day 7 after transplantation at a dose of 40 µg/kg twice a day. A total of 45 patients were studied divided into two groups: 25 patients were treated with PGE₁ (group B) and the remaining 20 patients did not receive the drug (group A). In group B, 24-h creatinine clearance (Ccr) was 66 ± 12.8 ml/min compared with 40.3 ± 13.4 ml/min in group A on the fifth postoperative day (P < 0.05). Urinary levels of N-acetyl-β-d -glucosaminidase (NAG) and serum levels of platelet factor 4 (PF4) in group B were significantly lower than in group A. On the fourth postoperative day, the urinary excretion of thromboxan B₂ (TxB₂) in group A was higher than in group B, but not significantly (5.1 ± 3.0 ng/day and 2.8 ± 1.1 ng/day, respectively). Acute rejection occurred in four patients in group B and in 10 patients (40%) in group A. The percentage of Leu2a-positive lymphocytes in group B was higher than in group A. We conclude that postoperative administration of PGE₁ improves graft function in kidneys from living related donors.     

Inducible beta-lactamases in clinical isolates of non-aeruginosa Pseudomonas.

The incidence of antimicrobial resistance and expression of imipenem-inducible beta-lactamase were examined in 22 strains of non-aeruginosa Pseudomonas isolated from clinical specimens. The percentage of strains resistant to form one to eight antibiotics was 45. The most active antibiotics against all strains were norfloxacin, ciprofloxacin and imipenem. Eighteen out of the 22 strains were positive for beta-lactamase in a spectrophotometric assay using nitrocefin as substrate. A low inducible beta-lactamase specific activity (0.001-0.999 nmoles nitrocefin hydrolyzed/min/mg protein) was found in twelve strains whereas six strains had a relatively high specific activity (3.5-159.8 nmoles nitrocefin hydrolyzed/min/mg protein). Five strains representing different Pseudomonas spp. and showing high beta-lactamase activity were studied further. Crude enzymes from two species (Pseudomonas mendocina, Pseudomonas acidovorans) hydrolyzed cefazolin at a higher rate than penicillin and ampicillin. All enzymes from the five species were inhibited by cloxacillin and p-chloromercuribenzoate (1 mM), but were insensitive to inhibition by clavulanic acid, ethylenediamine acetic acid (EDTA) at the same concentration. The isoelectric point and molecular weight of the main beta-lactamase band from the 5 species were 6.5-6.8 and 47,000 respectively.     

Destination after discharge from a senile dementia therapy ward before and after the implementation of long-term care insurance in Japan

Background: In Japan a new long‐term care insurance (LTCI) system, the so‐called ‘Kaigo‐Hoken’, was started in April 2000. The present study analyzes the change in the type of destination after discharge from a senile dementia therapy ward before and after the implementation of LTCI at Fukuoka Prefectural Onga Hospital, Japan. Methods: The present study examines data from 199 inpatients discharged from the Fukuoka Prefectural Onga Hospital that had been diagnosed with dementia and met the DSM IV criteria for Alzheimer's type, vascular dementia or other type of dementia. For the purposes of comparison two periods were defined, ‘the first period’ was defined as the period from 1 April 1999 to 31 March 2000, before LTCI was implemented, while ‘the second period’ was defined as the period from 1 April 2000 to 31 March 2001, after LTCI had started. Subject data was analyzed on the basis of where the subject had resided pre‐admission and their destination after discharge using the following classifications: nursing home or geriatric care facility, hospitalization, home and death. Results: While the certification rate of inpatients regarding long‐term care increased slightly in the second period, no significant change was observed based on where the subject had resided pre‐admission and their destination after discharge between the first and second periods. Conclusions: While LTCI is essential for Japan, it is necessary that people with dementia in senile dementia therapy wards are encouraged to return to their homes under the care and support of LTCI.     

Report of a patient of primary Sj?gren syndrome, IgA nephropathy and chronic idiopathic thrombocytopenic purpura]

We describe the case of a 61-year-old woman diagnosed with primary Sj?gren's syndrome (SS) after an 8-year history of IgA nephropathy and a 3-year history of recurrent purpuric rashes. Her two daughters had previously been diagnosed with other autoimmune diseases. One daughter had Graves' disease and the other had Hashimoto's disease and systemic lupus erythematosus. The diagnosis of SS was made based on dryness of mucous membranes, Shirmer test, and parotid sialography. Thrombocytopenia, high platelet-aggregated IgG (PA-IgG) level, and normal megakaryocytes count in bone marrow suggested that her recurrent purpuric rashes were due to idiopathic thrombocytopenic purpura (ITP). Patients with SS may develop other autoimmune diseases. This case aids understanding of the immune pathogenesis and genetic background of SS.