Ex vivo purging of leukemia cells using tumor-necrosis-factor-related apoptosis-inducing ligand in hematopoietic stem cell transplantation.

The aim of this study was to evaluate the potential of tumor-necrosis-factor-related apoptosis-inducing ligand TRAIL to eradicate leukemia cell lines, while sparing normal hematopoietic stem cells. Human Jurkat and Molt-4 cell lines were used to optimize the purging process in umbilical cord blood (UCB) mononuclear cells. The Jurkat cell line was TRAIL sensitive and TRAIL-resistant Molt-4 cell line became sensitive after being treated with TRAIL and a low dose of doxorubicin (0.1 micro M), but UCB mononuclear cells remained resistant. DR4 expression was increased when Jurkat cells were treated with TRAIL, and DR5 expression increased after exposing Molt-4 cells to TRAIL plus a low dose of doxorubicin for 24 h. The expression of DR4 and DR5 in UCB mononuclear cells was unchanged after treatment with TRAIL, a low-dose doxorubicin, or TRAIL plus a low dose of doxorubicin. In TRAIL-sensitive Jurkat cells, caspases 8, 9, 3, and 7 were activated by TRAIL treatment and activation of caspases was augmented by TRAIL plus a low dose of doxorubicin than TRAIL or a low dose of doxorubicin alone in Molt-4 cells. Experiments involving mixture of UCB mononuclear cells and Jurkat or Molt-4 cells showed a marked eradication of leukemia cells and the limiting dilution assay demonstrated an eradication rate of more than 4 logs after 24 h incubation with 100 ng/ml of TRAIL in Jurkat cells. In the case of Molt-4 cells, the eradication rate was about 3 logs when TRAIL was used in combination with a low dose of doxorubicin. No significant decrease in the number of granulocyte-macrophage colony-forming unit) (CFU-GM) colonies was detected when UCB mononuclear cells were treated with TRAIL in combination with a low dose of doxorubicin. These results suggest that TRAIL offers the possibility of being used as an ex vivo purging agent for autologous transplantation in hematologic malignancies.

A case of malignant proliferating trichilemmoma of the scalp with multiple metastases.

We report a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. The patient demonstrated a round mass in the right occipital area for 12 months and the lesion grew rapidly to assume 8 x 6.5 x 4 cm in diameter, with areas of superficial erosion and crusting within the recent 3 months. The entire lesion was removed with a wide surgical excision. It recurred on the neck area 4 months after excision and the lesion was removed with surgical resection again. There was evidence of multiple metastases on CNS and mediastinal lymph nodes after 6 months. The patient was treated with cisplatin and etoposide combination chemotherapy and a partial response was achieved.

Thrombopoietin is synergistic with other cytokines for expansion of cord blood progenitor cells.

We investigated the effects of recombinant human thrombopoietin (TPO) in combination with various cytokines including erythropoietin (EPO), interleukin-3 (IL-3), interleukin-6 (IL-6), and stem cell factor (SCF) on megakaryopoiesis, and the expansion of CD34+CD41a+ cells from human cord blood CD34+ cells with these cytokines under serum-free conditions. Human cord blood CD34+ cells were cultured in Megacult (Stem Cell Technologies Inc. Vancouver, Canada) in the presence of recombinant growth factors. Colony-forming unit-megakaryocyte (CFU-M) colonies were counted on day 14. CD34+CD41a+ and CD34-CD41a+ cell expansion was analyzed using a serum-free liquid culture system for 7 days with recombinant growth factors. TPO alone had a concentration-dependent effect on megakaryocyte colony growth. At concentrations above 1 ng/ml, TPO supported significant CFU-Meg colony formation in a concentration-dependent manner. The combination of TPO plus other cytokines, including EPO, IL-3, and SCF, resulted in a synergistic enhancement of the number of CFU-Meg colonies, but IL-6 failed to enhance the effect of TPO. The number of CD41a+ cells increased after 7 days in liquid culture of human cord blood CD34+ cells with various cytokines (EPO, IL-3, IL-6, SCF) combined with TPO, but SCF plus TPO only resulted in a significant synergistic increment of CD34+CD41a+ cells compared with TPO alone. The results of the present study indicate that EPO, IL-3, and SCF can be synergistic with TPO to stimulate proliferation of CFU-Meg and suggest that SCF plus TPO can expand CD34+CD41a+ cells to effect the rapid recovery of platelets in patients following stem cell transplantation.

A case of CMV disease of the jejunum in a patient with non-Hodgkin's lymphoma.

CMV infection may occur anywhere in the gastrointestinal tract. Among the small intestine, ileum is the most common site of CMV disease and infection of jejunum is a rare one in patients with CMV gastroenteritis. Although rare, the reason why the recognition of this diagnosis is important is that it cause the lethal hemorrhage and perforation of gastrointestinal tract when its diagnosis and treatment was delayed. Rapid diagnosis are able to using the immunohistochemical stain in shell vial culture of infected specimen or peripheral neutrophils preparation in viremic patients within 8 to 36 hours. The treatment of choice is antiviral agent or surgical resection. We experienced a case of CMV disease of jejunum in patient with non-Hodgkin's lymphoma who showed severe ulceration in jejunum and massive intestinal hemorrhage, and he survived after successful treatment with segmental resection of jejunum and intravenous ganciclovir.

A case of coagulation factor V deficiency complicated with intracranial hemorrhage.

Factor V deficiency is a relatively uncommon disorder, inherited as an autosomal recessive trait that manifests clinically only in individuals who inherit the defective gene from both parents. The hemorrhage of nasal and oral cavity and ecchymosis are common but intracranial hemorrhage is very rare. We experienced a 53 year old male patient with intracranial hemorrhage due to factor V deficiency. The laboratory tests showed prolongation of APTT and PT, normal bleeding time and normal thrombin time. The levels of the coagulation profiles on the patient revealed a significant decrease factor V, below 1% of normal range (60-140%). Other coagulation factors were normal. He was treated with fresh frozen plasma and completely recovered 3 weeks after treatment.

A case of lymphomatoid papulosis occurred simultaneously with Ki-1-positive anaplastic large cell lymphoma.

Lymphomatoid papulosis (LyP) is a chronic self-healing skin eruption that is clinically benign but histologically mimics a malignant lymphoma. However, lymphomatoid papulosis with anaplastic large cell lymphoma responds poorly to medical treatments, including chemotherapies. We experienced a 60-year-old male patient with lymphomatoid papulosis occurred simultaneously with relapsed Ki-1-positive anaplastic large cell lymphoma who was treated with salvage chemotherapy but, unfortunately, failed to be rescued. We report it with a review of the literature.

A case of granulocytic sarcoma of the brain in a patient with myelodysplastic syndrome.

Granulocytic sarcoma is rare extramedullary tumor composed of myeloblasts and other granulocytic precursors. The majority of cases have been reported in association with acute myeloid leukemia (AML) or myeloproliferative disorders. Granulocytic sarcoma may occur in patients with myelodysplastic syndromes. Reports are very rare, especially in the brain. We report an unusual case of granulocytic sarcoma of the parenchyma of the brain, occurring in a patient with myelodysplastic syndrome, diagnosed by cerebro-spinal fluid cytology and magnetic resonance imaging brain scan.

Plasma t-PA and PAI-1 antigen concentrations in non-insulin dependent diabetic patients: implication for diabetic retinopathy.

Parameters of fibrinolysis, including basal plasma tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen levels were studied in 49 non-insulin dependent diabetic patients (23 men, 26 women: ages 51.3 +/- 14.9 years) and 16 age matched non-diabetic subjects (9 men, 7 women ages 49.8 +/- 12.2 years) as a control group. Compared to a control group, the diabetic patients had a significantly higher mean plasma t-PA antigen (4.94 +/- 2.68 vs 3.20 +/- 2.30 ng/ml) and PAI-1 antigen (34.86 +/- 16.71 vs. 17.60 +/- 15.36 ng/ml) levels (P < 0.05). Significant univariate correlations were observed between t-PA and body mass index (BMI) (P = 0.0009, r = 0.7217), and PAI-1 were positively correlated with BMI and FBS (fasting blood sugar) in the total diabetic patients (P = 0.0003, r = 0.7217; P = 0.0477, r = 0.2858, respectively). In diabetic patients with proliferative diabetic retinopathy, both PAI-1 and t-PA antigen levels were significantly lower than those of diabetic patients with negative or background retinopathy (P = < 0.05). There were no significant differences of the plasma t-PA and PAI-1 levels between diabetic patients with micro- and macroproteinuria. This study conducted on non-insulin dependent diabetic patients suggests that they have significantly higher t-PA and PAI-1 antigen levels than do control subjects, and these findings appear to correlate negatively with proliferative retinopathy observed among the patients studied.

Plasma t-PA and PAl-1 antigen concentrations in non-insulin dependent diabetic patients: effects of treatment modality on fibrinolysis.

Basal plasma tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAl-1) antigen levels were studied in 49 non-insulin dependent diabetic patients (23 men, 26 women: ages 51.3 +/- 14.9 years) and 16 age matched non-diabetic subjects (9 men, 7 women: ages 49.8 +/- 12.2 years) as a control group. Compared to a control group, the diabetic patients had a significantly higher mean t-PA antigen (5.15 +/- 3.02 vs 3.20 +/- 2.30 ng/ml) and PAl-1 antigen (35.89 +/- 18.59 vs 17.60 +/- 15.36 ng/ml) levels (p < 0.05). Plasma t-PA antigen level was not influenced by each treatment modality. There was a significant decrease of plasma PAl-1 antigen level after Metformin administration compared to that of before Metformin administration (39.74 +/- 19.39 vs 25.14 +/- 16.18 ng/ml) (p < 0.05), and the insulin-treated group showed a tendency for a decrease of plasma PAl-1 antigen levels after insulin administration but this did not reach statistical significance (29.93 +/- 15.37 vs 17.32 +/- 10.60 ng/ml). Sulfonylurea did not change both plasma t-PA and PAl-1 antigen levels. In conclusion, diabetic patients have high t-PA and PAl-1 antigen levels. Biguanide reduced plasma PAl-1 antigen levels, which might play some helpful role in the improvement of chronic complications in NIDDM.

Peritoneal solute clearances after four years of continuous ambulatory peritoneal dialysis (CAPD).

In order to evaluate peritoneal membrane function and responsiveness of peritoneal microcirculation to vasoactive agents in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, we studied peritoneal clearances of urea (Curea) and creatinine (Ccr), protein concentrations in drained dialysate (DPC), peritoneal glucose absorption (% GA), and drained dialysate volume (VD) before and after nitroprusside (NP) addition to dialysis solution in 17 long-term CAPD patients (mean duration of CAPD: 52 months) and the results were compared to those of 18 patients who were just trained for CAPD (mean duration: 0.6 month). There were no differences in the control (without NP) Curea, Ccr, DPC, %GA, and VD between the new and long-term CAPD patients. Curea, Ccr, and DPC increased significantly with NP in both new and long-term patients. Curea and Ccr with NP were not different between the new and long-term patients but DPC with NP was significantly lower in the long-term CAPD patients. The results of this study suggest that peritoneal solute clearances and the responsiveness of peritoneal microcirculation to NP remain unchanged after four years of CAPD, despite recurrent episodes of peritonitis.