Tissue factor pathway inhibitor can interact with platelets

Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation. However, there is no report on interaction between TFPI and platelets other than that by Tsuji, who found that whole blood anticoagulated with TFPI exhibited remarkable decrease in platelet count. Our study revealed that washed platelets suspended in modified Tyrode's buffer (8 mM CaCl2) containing TFPI exhibit platelet aggregation. However, platelets aggregation was observed without TFPI, but its increase and intensity were slow and weak, compared to that in the presence of TFPI. This aggregation was inhibited by anti-CD41 (anti-GPIIb) antibody. This finding suggested that TFPI promotes platelet aggregation.     

Langerhans cell histiocytosis immunohistochemical expression of fascin,a dendritic cell marker

Langerhans cell histiocytosis (LCH) is a clonal disorder believed to be derivedfrom cells of the dendritic system. Fascin, a 55-kd actin-bundling protein, represents a highly selective marker for dendritic cells of lymphoid tissues and peripheral blood and is involved in the formation of dendritic processes in maturing epidermal Langerhans cells. Since lesional cells of LCH may represent Langerhans cells arrested at an early stage of activation, immunohistochemical expression offascin in epidermal Langerhans cells and in the lesional cells of 34 cases of LCH was evaluated in paraffin sections using an immunoalkaline phosphatase technique. Though epidermal Langerhans cells were nonreactive for fascin, lesional cells in all LCH cases exhibited immunoreactivityforfascin, CD1a, and S-100 protein. Variation in staining intensity was observed in some cases, possibly reflecting differences in cell maturation or activation. Involved tissues included bone, soft tissue, lymph node, thyroid, orbit, and extradural cranial tissue. Immunoreactivity of lesional cells of LCH for fascin supports their derivation from cells of the dendritic system and represents another alteration in the phenotype of Langerhans cells that is associated with maturation, migration, culture, or clonal expansion.     

Tissue-engineered vascular autograft: inferior vena cava replacement in a dog model

Tissue-engineered vascular autografts (TEVAs) were made by seeding 4-6 x 10(6) of mixed cells obtained from femoral veins of mongrel dogs onto tube-shaped biodegradable polymer scaffolds composed of a polyglycolid acid (PGA) nonwoven fabric sheet and a copolymer of L-lactide and caprolactone (n = 4). After 7 days, the inferior vena cavas (IVCs) of the same dogs were replaced with TEVAs. After 3, 4, 5, and 6 months, angiographies were performed, and the dogs were sacrificed. The implanted TEVAs were examined both grossly and immunohistologically. The implanted TEVAs showed no evidence of stenosis or dilatation. No thrombus was found inside the TEVAs, even without any anticoagulation therapy. Remnants of the polymer scaffolds were not observed in all specimens, and the overall gross appearance similar to that of native IVCs. Immunohistological staining revealed the presence of factor VIII positive nucleated cells at the luminal surface of the TEVAs. In addition, lesions were observed where alpha-smooth muscle actin and desmin positive cells existed. Implanted TEVAs contained a sufficient amount of extracellular matrix, and showed neither occlusion nor aneurysmal formation. In addition, endothelial cells were found to line the luminal surface of each TEVA. These results strongly suggest that "ideal" venous grafts with antithrombogenicity can be produced.     

Identification of the products of the equine herpesvirus type 4 gI and gE genes

Summary.  In order to identify the products of the equine herpesvirus type 4 (EHV-4) gI and gE genes, we have constructed recombinant vaccinia viruses containing the putative gI or gE genes. These recombinant viruses synthesized EHV-4 gI and gE with apparent molecular masses of 75 and 80 kDa, respectively. Antibodies raised against both recombinant viruses detected a 75 kDa gI and a 95 kDa gE in EHV-4-infected cells. The results also suggest that the EHV-4 gI and gE would form a complex like in other herpesviruses. Received October 29, 1999 Accepted January 21, 2000     

Epstein-Barr virus-associated post-transplant primary smooth muscle tumor of the liver: Report of an autopsy case

Epstein-Barr (EB) virus-associated primary smooth muscle tumors have been reported in immunosuppressed young patients with acquired immunodeficiency syndrome (AIDS) and young people who have undergone liver transplantation. An autopsy case of EB virus-associated smooth muscle cell tumor in a 21 year old female who received immunosuppres-sive therapy following renal transplantation Is repotted. Multiple tumor nodules were present in the liver, but no primary lesion was found in any other organ. Histologically, the nodules were composed of spindle cells, positive for α-smooth muscle action, which were arranged in fascicles and closely associated with vascular channels, thereby suggesting a vascular smooth muscle cell origin. EB virus infection of the tumor cells was clearly demonstrated by in situ hybridization with an EB virus-encoded RNA 1 (EBER-1) probe. The present case illustrates that EB virus infection may play some role in the development of smooth muscle tumors not only in immunocompromised young patients with liver allo-grafts, but also in those with renal allografts.     

Platelet-activating factor in Japanese cedar pollinosis

Japanese cedar pollinosis is a typical allergic disease and has recently become a big social problem. Many population are suffering from this disease every year from the end of February to the beginning of April. In this study, we planned to examine the role of platelet-activating factor (PAF) in this disease, because PAF has been known to be one of the potent chemical mediators in allergic and inflammatory reactions and many evidences indicate that PAF is deeply involved in the pathogenesis of bronchial asthma, a typical allergic disease. We measured the concentrations of the PAF derivative (lyso-PAF) in serum from patients with cedar pollinosis during the pollen season. The level of lyso-PAF in serum from untreated patients with cedar pollinosis (87.8 +/- 8.7 unit.) was significantly higher than that in healthy control (54.9 +/- 7.7 unit.). We also tested the effect of an anti-allergic drug on the level of serum lyso-PAF of cedar pollinosis. Eighteen pairs of serum samples from patients with cedar pollinosis were employed in this study. Lyso-PAF levels after two weeks' therapy with ketotifen (2 mg/day), an anti-allergic drug, decreased the levels significantly (from 82.6 unit to 41.3 unit). These results suggest that PAF could play some important role in cedar pollinosis and that the clinical effect of anti-allergic drug could be partially due to the anti-PAF action.     

Grading score system: A method for evaluation of the degree of senescence in Senescence Accelerated Mouse (SAM)

For evaluation of the degree of senescence in SAM-P, accelerated senescence prone mouse, formerly called SAM or prone series or P-series, consisting of SAM-P/1, SAM-P/2, SAM-P/3 and SAM-P/4 corresponding to P-1, P-2, P-3 and P-4 series, respectively, in the previous reports, and in SAM-R, accelerated senescence resistant mouse, formerly called resistant series or R-series, consisting of SAM-R/1, SAM-R/2 and SAM-R/3 corresponding to R-1, R-2 and R-3 series, respectively, in the previous reports, the grading score system was adopted. The items to be examined in this system include 11 categories selected from the clinical signs and gross lesions considered to be associated with the aging process. The degree of the senescence in each category was graded from 0 to 4 according to the detailed criteria devised in our laboratory. After 8 months of age each mouse was examined every 4 months, and some of the mice were examined after 2 months of age.In almost all categories, the grading score and incidence began to increase from 4 or 6 months of age and continued to increase with advancing age in both SAM-P and SAM-R. The increase, however, was more marked in SAM-P than in SAM-R. The slow but steady increase in the SAM-R levelled out at 24 months of age and was comparable to that of 12 months of age in SAM-P. In both SAM-P/1 at 8 months of age and SAM-R/2 at 12 months of age, there was a significant reverse correlation between total score of this grading score system and length of residual life after examination.Systematic and extensive studies using the grading score system showed that if the validity of the system is, based on “irreversibility” and “universality” of the changes in     

DNA typing of HLA in the patients with moyamoya disease

Summary Moyamoya disease is a clinical entity demonstrating a chronic occlusion of the cerebrovascular system. Although some possible etiological factors have been postulated, the etiology of this disease is still unknown. So far, some investigations have suggested the association between moyamoya disease and HLA in the serological typing. However, DNA typing of HLA have not been performed yet. Thus, we performed DNA-typing of HLA in the unrelated Japanese patients with definite moyamoya disease, using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) technique. In the total patients,DQB1*0502 had a positive association with the disease. On the other hand,DRB1*0405 andDQB1*0401 showed a negative association. In comparing the early-onset and late-onset groups, two groups did not share the same disease associated alleles at all. Thus, the etiology of moyamoya disease seem to have a genetic background. Furthermore, different genetic factors might also be involved in the difference between the early-onset and late-onset groups.     

Lack of association in Japanese patients between neuroleptic malignant syndrome and a debrisoquine 4-hydroxylase genotype with low enzyme activity

Decreased activity of debrisoquine 4-hydroxylase (CYP2D6), which participates in hepatic metabolism of several frequently used neuroleptics and antidepressants, is inherited as an autosomal recessive trait through polymorphic CYP2D6 gene alleles. In eastern Orientals, a C --> T substitution at nucleotide 188 (Pro34Ser) is primarily responsible for decreased ability to metabolize CYP2D6 substrates. We therefore studied a possible association between neuroleptic malignant syndrome (NMS) and the C188T mutation. We examined the frequency of the C188T mutation by polymerase chain reaction and restriction fragment length polymorphism analysis in 36 Japanese patients previously diagnosed with NMS and 107 neuroleptic-treated schizophrenic patients with no NMS history. The C188T allele frequency was 0.417 in NMS patients and 0.463 in patients without NMS. No significant allele or genotype associations were observed. We cannot conclude that low CYP2D6 activity genotype causes susceptibility to NMS in Japanese patients.