Ileocolonic lymphomas: a series of 16 cases.

BACKGROUND: Colonoscopic and clinical differences between primary ileocolonic mucosa-associated lymphoid tissue (MALT) lymphoma and mantle cell lymphoma (MCL) have not been defined. METHODS: We reviewed colonoscopic and clinical features in eight patients with primary MALT lymphoma and eight patients with MCL in the terminal ileum and/or colorectum. All cases were examined for CD5 and/or cyclin D1 expression. RESULTS: Endoscopic features of MALT lymphoma were characterized as protrusions that were covered with normal-appearing mucosa with or without ulceration. The gross appearances of MALT lymphomas were categorized as solitary (4 patients), multiple (3 patients), and multiple lymphomatous polyposis (MLP) (1 patient). The gross features of MCL at endoscopy were categorized as multiple protrusions (2 patients), and MLP (6 patients). The clinical stages of patients with MCL were more advanced than in patients with MALT lymphoma. CONCLUSIONS: Solitary or multiple protrusions at an early clinical stage is the most common presentation pattern of patients with MALT lymphoma, but an MLP appearance at an early stage is also possible. On the other hand, MLP appearance with an advanced clinical stage is the main presentation pattern in patients with MCL, although multiple protrusions with an early clinical stage is also possible. Histological and immunohistochemical investigation including that of cyclin D1 and CD5 expression is essential to make the final diagnosis.

Antimicrobial susceptibility of Staphylococcus intermedius isolated from healthy and diseased dogs.

A total of 90 strains of Staphylococcus intermedius isolated from dogs were examined for antimicrobial susceptibility. There were no significant differences in the distribution patterns of MICs between strains from 1982 to 1985 and those from 1999, and between strains from healthy dogs and those from diseased dogs. All of the strains were susceptible to ABPC, DMPPC, CEX, TDM, ERFX, BFLX, and FF at concentrations of 0.05 to 6.25 microg/ml. The MICs of OTC, KM, EM, AIV-TS, and LCM were distributed in a broad range of 0.1 to >100 microg/ml, indicating the existence of resistant as well as susceptible populations of S. intermedius. Thirty-three strains (36.7%) were resistant to one or more anitmicrobial agents such as OTC (n=32), KM (n=9), EM (n=7), AIV-TS (n=7), and LCM (n=7).

Coagulation tests and anti-phospholipid antibodies in patients positive for lupus anticoagulant.

We examined activated partial thromboplastin time, kaolin clotting time, mixing with normal plasma in kaolin clotting time, dilute Russell's viper venom time, dilute Russell's viper venom time at high lipid concentrations, anti-phospholipid antibodies, and anti-cardiolipin-beta2-glycoprotein I complex antibody in 135 patients with prolongation of activated partial thromboplastin time and diagnosed 86 patients positive for lupus anticoagulant. The sensitivity of activated partial thromboplastin time and dilute Russell's viper venom time/dilute Russell's viper venom time-high lipid concentrations ratio for lupus anticoagulant were markedly high, but the specificity of activated partial thromboplastin time for lupus anticoagulant was not markedly high. The specificity, but not the sensitivity, of kaolin clotting time-mixing with normal plasma in kaolin clotting time was markedly high. In summary, dilute Russell's viper venom time to dilute Russell's viper venom time-high lipid concentrations ratio gave high sensitivity as well as specificity, being the only assay to confirm this. Of the patients positive for lupus anticoagulant, 25% were positive for anti-phospholipid antibodies and 17% were positive for anti-cardiolipin-beta2-glycoprotein I complex antibody. Of the lupus anticoagulant-positive patients with thrombosis, 45% were positive for anti-phospholipid antibodies, 35% were positive for anti-cardiolipin-beta2-glycoprotein I complex antibody, 60% were positive for both anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody, and only 17% were negative for anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody. These findings suggest that lupus anticoagulant can be diagnosed by dilute Russell's viper venom time/dilute Russell's viper venom time-high lipid concentrations ratio, and that thrombosis in lupus anticoagulant-positive may be predictable from both anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody. Plasma tissue type plasminogen activator level in lupus anticoagulant patients was significantly increased, and plasma tissue type plasminogen activator and fibrin-D-dimer levels in lupus anticoagulant-positive patients with thrombosis were significantly higher than in those without thrombosis, suggesting that the diagnosis of thrombosis by hemostatic markers might be important in lupus anticoagulant.

Acute promyelocytic leukemia with del(6)(p23).

We report a unique case of de novo acute promyelocytic leukemia (APL) with cryptic 15;17 rearrangements. Cytogenetically, structural rearrangements of the 6p23 region has been reported mainly in secondary leukemia. This patient had a karyotype of 46, XY, del(6)(p23) and no additional chromosomal abnormalities. Molecular analyses revealed the presence of PML-RAR alpha fusion genes. Deletion of the 6p23 region is extremely rare in APL.

Aberrations of the tissue factor pathway in patients positive for lupus anticoagulant.

To evaluate the relationship between the tissue factor (TF) pathway and lupus anticoagulant (LA), in the present study, we measured the plasma levels of TF antigen and TF pathway inhibitor (TFPI) antigen in patients positive for LA. Plasma TF and TFPI levels in LA-positive patients were significantly higher than levels in healthy volunteers (p < 0.01). In LA-positive patients, there were no significant differences in plasma TF and TFPI levels between patients with and without thrombosis. In patients with thrombosis, there was no significant difference in the plasma TF level between LA-positive and LA-negative patients; however, the plasma TFPI level in LA-positive patients was significantly lower than that in LA-negative patients (p < 0.01). We also examined the TF pathway in human umbilical venous endothelial cells (HUVEC) incubated with plasma of LA-positive patients, LA-negative patients, and healthy volunteers. TF activity was significantly higher (p < .05) in HUVECs incubated with the plasma of LA-positive patients than in cells incubated with the plasma of the other two groups (p < .01). However, there was no significant difference in TFPI antigen levels among the media of HUVECs incubated with the plasma of all groups. The viability of HUVEC incubated with the plasma of LA-positive patients with thromboses, LA-positive patients without thromboses, and LA-negative patients with thromboses were significantly lower than that of HUVECs incubated with the plasma of healthy volunteers (p < .01). These findings suggest that abnormalities of the TF pathway plays an important role in the mechanism of hypercoagulability in LA-positive patients. LA may affect vascular endothelial cells causing thrombogenesis.

Increased activated protein C: protein C inhibitor complex and decreased protein C inhibitor levels in patients with chronic renal failure on maintenance hemodialysis.

Hemostatic abnormalities were examined in 55 patients during maintenance hemodialysis (HD). Before HD, plasma protein C and protein S antigens were almost within the normal range, while plasma thrombin-antithrombin III complex (TAT III) and plasmin-plasmin inhibitor complex (PPIC) levels in HD patients were increased slightly, and plasminogen activator inhibitor 1 level was significantly increased, compared to that in normal volunteers. Plasma activated protein C (APC) and protein C inhibitor (PCI) complex and APC alpha 1 antitrypsin (alpha 1AT) complex were not detected in normal volunteers; however, plasma APC-PCI complex was increased in 36 of the patients and plasma APC-alpha 1AT complex was increased in 25 patients. Plasma PCI levels in these patients before HD were significantly decreased. Plasma TAT, PPIC, and tissue type plasminogen activator levels were significantly higher before HD than after 1 hour HD and at the end of HD, while the changes in plasma protein C antigen, protein S antigen, PCI antigen, APC-PCI complex, and APC-alpha 1AT complex were not significant after 1 hour of HD or at the end of HD compared to levels before HD. Plasma PCI levels were correlated with APC-PCI complex, suggesting that decreased PCI levels might be caused by the activation of protein C.

Co-integration, co-expression and co-segregation of an unlinked selectable marker gene and NtFAD3 gene in transgenic rice plants produced by particle bombardment.

Using the scutellar tissue of rice mature embryos as a target tissue, a selectable marker gene, bar, and an unselectable gene, fatty acid desaturase gene from tobacco (NtFAD3), on separate plasmids, were introduced by particle bombardment. Co-integration, co-expression and inheritance of these genes were analyzed as well as seed fertility of the transgenic plants. Twenty-three out of 32 bialaphos-resistant plants integrated the NtFAD3 gene, which was confirmed by Southern-blot analysis of R0 plants, and showed one to more than 20 hybridizing bands of exogenous DNA, indicating a 72% (23/32) co-integration frequency. However, the frequency of the transgenic plants containing the 1.4-kb fragment of NtFAD3 gene was 34% (11/32). Northern-blot analysis revealed that seven out of ten fertile transgenic rice plants which had a 1.4-kb fragment of NtFAD3 cDNA expressed NtFAD3 mRNA. The NtFAD3 gene under the control of CaMV35S promoter stably expressed in the transgenic rice plants and modified the proportions of linoleic acid (18:2) and linolenic acid (18:3) in fatty acids; the content of 18:2 decreased and that of 18:3 increased. Fourteen out of 32 (44%) transgenic plants set seeds and 18 (56%) showed low fertility or sterility. Molecular analysis of the selfed progeny indicated that all copies in almost all R0 plants were inherited as a single dominant hemizygous locus.

Plasma tissue factor and tissue factor pathway inhibitor levels in patients with disseminated intravascular coagulation.

We measured the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. Plasma TF (273 +/- 90 pg/ml) and TFPI (252 +/- 125 ng/ml) levels were significantly increased in patients with DIC compared with non-DIC patients. Plasma TF antigen level was significantly increased in pre-DIC patients (285 +/- 85 pg/ml), while the plasma TFPI level (152 +/- 54 ng/ml) was not markedly increased in such a state. The plasma TF/TFPI ratio was high in the pre-DIC patients (2.10 +/- 0.90), and low in the DIC patients (1.40 +/- 0.87) and healthy volunteers (0.84 +/- 0.26). There was no significant difference between the DIC patients with a good outcome and those with a poor outcome in terms of plasma TF levels, although the plasma TFPI level in the DIC patients with a good outcome (289 +/- 133 ng/ml) was significantly higher than those with a poor outcome (187 +/- 75 ng/ml). During the clinical course of DIC, plasma TF antigen was increased first, and an increase of the plasma TFPI level followed the increase in plasma TF level. These findings suggest that plasma TFPI is released from vascular endothelial cells and it may reflect vascular endothelial cell injury. It is conceivable that TF and TFPI may play an important role in the onset of DIC.

Plasma-activated factor VII level in patients positive for lupus anticoagulant.

We examined plasma levels of activated factor VII (F VIla) in 50 patients positive for lupus anticoagulant (LA), in 83 patients negative for LA, and in 10 healthy volunteers as controls. Plasma F VIIa was present in healthy volunteers; its level was significantly increased, compared to the level in the controls, in patients with thrombosis, collagen diseases, and disseminated intravascular coagulation (DIC), suggesting that it reflected a thrombotic state. Plasma F VIIa was correlated with thrombin-antithrombin complex (TAT) in patients negative for LA but showed no such correlation in those positive for LA. Plasma F VIIa was negatively correlated with activated partial thromboplastin time (APTT) in patients positive for LA, but not in those negative for LA, suggesting that LA could inhibit the F VIIa assay system. Plasma F VIIa level was significantly increased in patients with thrombotic diseases; however, in patients positive for LA, it is possible that increased plasma F VIIa level may not be correlated with thrombogenicity.

Plasma tissue factor and tissue factor pathway inhibitor levels in patients with disseminated intravascular coagulation.

We measured the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. Plasma TF (273 +/- 90 pg/ml) and TFPI (252 +/- 125 ng/ml) levels were significantly increased in patients with DIC compared with non-DIC patients. Plasma TF antigen level was significantly increased in pre-DIC patients (285 +/- 85 pg/ml), while the plasma TFPI level (152 +/- 54 ng/ml) was not markedly increased in such a state. The plasma TF/TFPI ratio was high in the pre-DIC patients (2.10 +/- 0.90), and low in the DIC patients (1.40 +/- 0.87) and healthy volunteers (0.84 +/- 0.26). There was no significant difference between the DIC patients with a good outcome and those with a poor outcome in terms of plasma TF levels, although the plasma TFPI level in the DIC patients with a good outcome (289 +/- 133 ng/ml) was significantly higher than that in those with a poor outcome (187 +/- 75 ng/ml). During the clinical course of DIC, plasma TF antigen was increased first, and an increase of the plasma TFPI level followed the increase in plasma TF level. These findings suggest that plasma TFPI is released from vascular endothelial cells and it may reflect vascular endothelial cell injury. It is conceivable that TF and TFPI may play an important role in the onset of DIC.

Increased plasma-soluble fibrin monomer levels in patients with disseminated intravascular coagulation.

Plasma-soluble fibrin monomer (SFM) level in patients with disseminated intravascular coagulation (DIC) was significantly higher than the level in patients with pre-DIC or in non-DIC patients, and the level in patients with pre-DIC was significantly higher than that in non-DIC patients. There was no significant difference in plasma SFM levels among various diseases underlying DIC. Plasma SFM level in patients with good outcome was significantly decreased after treatment for DIC. The sensitivity of fibrin degradation products and platelet number was high for DIC, but not for pre-DIC. The sensitivity of thrombin-antithrombin III complex, plasmin-plasmin inhibitor complex, and SFM was high for both DIC and pre-DIC. The specificity of these markers was also high. Receiver operating characteristic analysis suggests that plasma SFM level could be the most useful marker for the diagnosis of both DIC and pre-DIC.

Diagnosis of pre-disseminated intravascular coagulation stage with hemostatic molecular markers. The Mie DIC Study Group.

We examined various hemostatic abnormalities in 395 patients with disseminated intravascular coagulation (DIC), in 177 patients in a Pre-DIC stage, and in 99 patients who did not exhibit DIC. Pre-DIC was defined as the condition at least one week before the onset of DIC. The differences in activated partial thromboplastin time (APTT), FDP, prothrombin time (PT) ratio, fibrinogen, and platelet count between DIC and Non-DIC patients were significant, but there were no significant differences in these parameters between Pre-DIC and Non-DIC patients. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (sFM), prothrombin activated peptide F1 + 2 (F1 + 2), thrombomodulin (TM), tissue type plasminogen activator (t-PA), and PA inhibitor (PAI-I) in DIC patients were significantly higher than levels in Non-DIC patients. However, only TAT, sFM and PAI-I values in the Pre-DIC patients were significantly higher than the values in the Non-DIC patients. Almost all the hemostatic molecular markers examined had high sensitivity for DIC, but only TAT and PPIC had high sensitivity for Pre-DIC. Specificity for DIC was also high with TAT, sFM, and F1 + 2. Early diagnosis and early treatment are important in DIC; we believe that it is possible to predict Pre-DIC by assessing values for the combination of hemostatic molecular markers.

[Plasma fibrin monitor level in DIC patients with a hematopoietic malignancy].

The Plasma level of soluble fibrin monomer (sFM) was measured in 218 patients with a hematopoietic malignancy. Of them, 198 were diagnosed with disseminates intravascular coagulation (DIC), 20 with Pre-DIC, and 20 with Non-DIC. Pre-DIC was retrospectively defined as the condition at least 1 week before the onset of DIC. The plasma levels of sFM, thrombin-anti-thrombin III complex (TAT), plasmin alpha 2-antiplasmin inhibitor complex (PIC), and FDP-D-dimer were significantly higher in patients with DIC than in those with Non-DIC. These levels were significantly higher in patients with Pre-DIC than in those with Non-DIC. Among these hemostatic parameters, the plasma sFM showed the highest sensitivity and specificity for DIC or Pre-DIC. These findings suggests that sFM is the most valuable marker hemostatic for the diagnosis of DIC and Pre-DIC.

Plantlet regeneration from mesophyll protoplasts ofBetula platyphylla var.japonica.

InBetula platyphylla var.japonica, colonies were induced efficiently from mesophyll protoplasts cultured in half strength MS (1/2MS) liquid medium containing 0.6 M mannitol, 0.09M sucrose and 1 µM 4-PU and 1 µM NAA at a cell density of 5 × 10(4)/ml. The colonies grew actively and developed into callus after 3 months of culture.Roots differentiated from the protoplast-derived white calluses cultured on the 1 /2MS solid media supplemented with 0.1-1 µM 4-PU and 1 µM NAA, and 10 µM zeatin with no supplementation of NAA. Furthermore, the protoplast-derived green callus differentiated shoots with 1/2MS solid medium containing 1 µM 4-PU or 10 µM zeatin with no supplementation of NAA. When shoots obtained were cultured on the cytokinin-free MS solid medium with 2.5 µM IBA and 0.1 µM NAA, they rooted and developed into plantlets after one month of culture.The phenylurea-type cytokinin, 4-PU, was effective for plantlet regeneration from the mesophyll protoplasts ofB. platyphylla var.japonica. This suggests that there is potential for the use of 4-PU in the culture of protoplasts in many forest tree species.

Hemostatic abnormalities and increased vascular endothelial cell markers in patients with red cell fragmentation syndrome induced by mitomycin C.

We examined red cell fragmentation syndrome (RCFS) induced by mitomycin C (MMC) (13 patients), by thrombotic thrombocytopenic purpura (TTP) (17 patients), and by disseminated intravascular coagulation (DIC) (15 patients). Plasma cytokine levels were increased in the TTP and DIC patients, but not in those whose RCFS was induced by MMC, suggesting that the activation of the immune system plays an important role in the pathogenesis of RCFS due to TTP and DIC but did not in RCFS due to MMC. Plasma thrombomodulin, tissue type plasminogen activator, and plasminogen activator inhibitor-I levels were increased in all RCFS patients, suggesting that RCFS, whether MMC induced, or due to TTP or DIC, might be associated with vascular endothelial cell injury. In TTP, von Willebrand factor (vWF) antigen and high molecular weight vWF multimer levels were reduced, possibly as a result of microthrombus consumption. The hemostatic data in this study showed that the TTP patients were in a hypercoagulable state without hyperfibrinolysis, and that DIC patients were in both a hypercoagulable and a hyperfibrinolytic state, whereas hemostatic abnormalities were slight in patients with MMC induced RCFS. These findings suggest that vascular endothelial cell injuries might be associated with RCFS, and that those injuries in MMC-induced RCFS might not be related to microthrombi or an activated immune system.

Familial macrothrombocytopenia with unusually elongated mitochondria.

We report a familial case of macrothrombocytopenia without inclusion bodies in polymorphonuclear cells or any congenital abnormalities. The results of the hemostatic and platelet function tests were all normal except for the platelet retention rate. The number of megakaryocytes increased slightly and some were relatively small. Electron microscopic studies revealed a unique morphological abnormality of the platelets' mitochondria.

Outcome of disseminated intravascular coagulation in relation to the score when treatment was begun. Mie DIC Study Group.

We examined 395 patients with disseminated intravascular coagulation (DIC) divided into two groups: non-leukemic and leukemic. In 58% of the patients as a whole, treatment of DIC resulted in complete or partial remission, while exacerbation and death occurred in 31%. The efficacy of DIC treatment in the non-leukemic group was less than that in the leukemic group, indicating that the outcome of DIC depended, in part, on the underlying disease. We examined hemostatic indicators in relation to DIC score: prothrombin time (PT) ratio, FDP, platelet count, and fibrinogen levels were found to be important indicators for the diagnosis of DIC, but not for Pre-DIC. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PPIC) were significantly increased in pre-DIC. The efficacy of treatment in relation to the DIC score when the treatment was begun showed that greater efficacy was achieved in pre-DIC than in DIC patients. The outcome was poorer with increasing DIC score, suggesting that early diagnosis and early treatment are important. On examining the relationship between outcome and hemostatic indicators, we found that the PT ratio and the levels of antithrombin, plasminogen, PPIC, the PPIC/TAT ratio, and thrombomodulin were related to outcome, suggesting that very high consumption of blood coagulation factors, liver dysfunction, hypofibrinolysis, or organ failure caused a poor outcome. Although the outcome in DIC patients may not depend substantially on plasma levels of TAT and fibrin-D-dimer, we can use these indicators to treat DIC patients at an early stage.

Tissue factor expression in endothelial cells in health and disease.

Plasma tissue factor (TF) antigen can be detected in healthy volunteers and may be significantly increased in patients with disseminated intravascular coagulation (DIC). Plasma TF antigen level in patients with DIC was significantly reduced after therapy. The TF activity of human umbilical vein endothelial cells (HUVEC) cultured with lipopolysaccharide (LPS), cytokines and the medium of cultured mononuclear cells (MNC) was significantly increased. TF expression was induced in HUVEC and MNC by incubation with lipoproteins, suggesting that hyperlipidaemia is a direct risk factor in thrombotic disease. TF activity in HUVEC was significantly increased in the presence of plasma and this activation was higher in patients with thrombotic thrombocytopenic purpura (TTP) and DIC. Enhanced TF production by endothelial cells may be important in the pathogenesis of thrombotic diseases.

Decreased protein C inhibitor after percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction.

Plasma thrombin-antithrombin III complex (TAT), FDP-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, and tissue type plasminogen activator (t-PA), PA inhibitor-1 (PAI-I) were significantly increased in patients with acute myocardial infarction (AMI) at onset. These patients exhibited a hypercoagulable state and protein C activation at onset. The plasma PCI level at onset of AMI was within the normal range, but was significantly decreased after percutaneous transluminal coronary angioplasty (PTCA). After PTCA, plasma t-PA, FDP-D-dimer, and plasmin-alpha 2-plasmin inhibitor were increased but APC-PCI complex and TAT were not. The decrease in PCI after PTCA may have been caused by the activation of fibrinolysis. PCI may play an important role in the inhibition of fibrinolysis in stimulated or damaged endothelial cells. These findings suggest that the protein C pathway plays an important role in the onset of AMI and after PTCA.

Decreased plasma tissue factor pathway inhibitor levels in patients with thrombotic thrombocytopenic purpura.

We measured plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. TF antigen was detected in the plasma of healthy volunteers, and the levels were significantly increased in the patients with DIC, but decreased slightly in those with TTP. Plasma TFPI levels were significantly decreased in patients with TTP compared with those in healthy volunteers. The concentration of plasma thrombomodulin (TM) antigen was significantly higher in those with TTP than in normal volunteers. One month after treatment, TTP patients showed a significant decrease in plasma TM levels, and a significant increase in plasma TFPI levels, but plasma levels of TF antigen were not significantly increased. As plasma TFPI/TF ratio was significantly increased after treatment, the hypercoagulable state was therefore improved after treatment. There was no significant difference in plasma TF and TFPI levels between those who achieved complete remission (CR) and those who died. However, plasma TM levels were significantly higher in those who died than in those who achieved CR. Plasma TFPI levels might reflect injury of vascular endothelial cells as do plasma TM levels, and decreased plasma TFPI/TF ratio and vascular endothelial cell injuries might play causative roles in TTP.