Treatment with low-dose cytosine arabinoside followed by administration of macrophage colony-stimulating factor prolongs the survival of patients with RAEB, RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study

The treatment of patients with aggressive subclasses of myelodysplastic syndrome (MDS) remains a challenge. In an effort to improve the survival of patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-t), or acute myelogenous leukemia transformed from MDS (MDS-AML), we conducted a small trial in which 28 such patients were treated with low-dose cytosine arabinoside (LDAraC) followed by administration of macrophage colony-stimulating factor (M-CSF). The overall rate of response to the treatment was 61%, including 39% with a complete response, which is higher than rates obtained in previous studies in which LDAraC alone was administered to patients with MDS. Median survival was 23.5 months in cases of RAEB, 16.7 months in cases of RAEB-t, and 19.7 months in cases of MDS-AML. The overall survival of the study group appeared to be prolonged in comparison with a historical control group of patients treated with LDAraC alone. It is suggested that M-CSF added to the administration of LDAraC plays an active role in the therapy. No therapy-related death occurred. Some unique actions of M-CSF were suggested in this trial. It is concluded that therapy with LDAraC + M-CSF is a useful treatment option for patients with aggressive subclasses of MDS and MDS-AML to provide better response and survival.     

The efficacy of oral vitamin A supplementation for measles and respiratory syncytial virus (RSV) infection

Recently, the efficacy of oral vitamin A supplementation for measles and respiratory syncytial (RSV) infection has been evaluated in developing countries. However, in developed countries where vitamin A deficiency is little worth consideration, few studies have been conducted on the effect of vitamin A supplementation. The effect of oral vitamin A (100,000 IU) supplementation was evaluated in 105 children with measles (age 5 months to 4 years) and in 96 children with RSV infection (ages a month to 2.5 years) in Fukushima, Japan. Comparisons were made of clinical signs, duration of hospitalization and complications between treated groups and non-treated groups. Treated group (measles n = 47, RSV n = 54) and non-treated groups (measles n = 58, RSV n = 42) had similar baseline characteristics. Patients with measles given a vitamin A supplementation had a shorter duration of cough (7.2 +/- 1.6 vs 9.2 +/- 1.8 days, p < 0.05) and patients with severe RSV infection given a vitamin A supplementation had a shorter duration of retraction (3.6 +/- 1.4 vs 5.3 +/- 0.8 days, p < 0.05) and wheezing (4.4 +/- 1.7 vs 6.3 +/- 1.5 days, p < 0.05). Toxicities, including excess vomiting and bulging fontanel were not observed. Our findings may suggest the efficacy of oral vitamin A supplementation for measles and severe RSV infection, in children who have no malnutrition.     

Immunohistologic study on the expressions of alpha-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma.

Sixty-eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II). In cancerous tissues, the expression rate was significantly higher for PIVKA-II (34 cases [50%]) than AFP (21 cases [31%]) (P <.05), suggesting a higher specificity of PIVKA-II to small HCC. Sixteen of the 68 cases (24%) were positive to both AFP and PIVKA-II, and in 8 of the 16 cases, AFP and PIVKA-II expressing areas within a nodule were clearly divided by a fibrous septum. According to histologic grades, PIVKA-II expression was confirmed in 2 of the 15 well-differentiated HCCs, and in the well-differentiated component of 6 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. AFP expression was not found in well-differentiated HCCs, but found in 16 of the 40 moderately differentiated HCCs (40%) and in the moderately differentiated component of 3 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. The positive rate in the tissues was correlated to the serum levels for both AFP and PIVKA-II. In addition, frequency of tissue-PIVKA-II expression was higher than tissue-AFP expression in the cases whose serum protein level was within the normal range. This indicates that AFP and PIVKA-II have different patterns of tissue expression and of secretion to the blood. In comparison with tissue-AFP-negative cases, tissue-AFP-positive HCCs had a larger tumor size, higher frequencies of portal vein invasion and intrahepatic metastasis, a high Ki-67 labeling index, and a lower rate of recurrence-free survival. Thus, tissue-AFP-positive HCCs are suggested to be biologically more malignant than those HCCs that are AFP-negative and PIVKA-II-positive.     

Genotype,serum level of hepatitis C virus RNA and liver histology as predictors of response to interferon-α 2α therapy in Japanese patients with chronic hepatitis C

Abstract: To determine whether pretreatment HCV-RNA level, hepatitis C virus genotypes, alanine aminotransferase and histology correlate with subsequent response to interferon-α therapy or not, serum HCV-RNA levels and genotype were determined by branched DNA signal amplification assay and genotype-specific polymerase chain reaction in 43 patients with chronic active hepatitis C. Response to recombinant interferon-α 2α (504 million units in total) was defined as complete and sustained CR→SR, n=12), complete response followed by relapse (CR→Rel, n=17), and no response (NR, n=10), excluding dropouts (n=4). Patients who showed CR→SR had a lower HCV-RNA level (0.438 × 10⁶ eq/ml) compared to CR→Rel (2.452 × 10⁶ eq/ml, p=0.008) and NR (4.882 × 10⁶ eq/ml, p=0.009). A higher proportion of patients with CR→SR had type 2a HCV (67%) compared to the CR→Rel (28%) and the NR (0%). There was a trend for type 1b hepatitis C virus infection to have higher serum HCV-RNA levels. There was no correlation between pretreatment HCV-RNA level and alanine aminotransferase. However, no relation between pretreatment HCV-RNA level and liver histology was observed; a high proportion of patients with CAH2a showed CR→SR, compared to those with CAH2b (p=0.001). Moreover, the patients with CAH2b who had low level hepatitis C virus viremia did not show CR→SR. These data indicate that pre-treatment serum HCV-RNA levels, genotype and liver histology are good predictors of subsequent response to interferon-α therapy in Japanese patients with chronic hepatitis C virus infection.     

The physical activity patterns of cardiac rehabilitation program participants

PURPOSE: This investigation aimed to examine the physical activity patterns of cardiac rehabilitation program (CRP) participants. METHODS: The investigation enrolled 53 male and 24 female CRP participants between 46 and 88 years of age. By means of a uniaxial accelerometer (Life-Corder), the amount of physical activity (in kilocalories) and the time spent in physical activity at light (<3 metabolic equivalents [METs]), moderate (3 to 6 METs), and vigorous (>6 METs) intensity were evaluated. In addition to these variables, the MET levels for the CRP and non-CRP periods were calculated. RESULTS: The weekly amount of physical activity energy expenditure averaged 1597 +/- 846 kcal/week, and the time spent in light, moderate, and vigorous physical activity averaged, respectively, 375.5 +/- 124.5 minutes, 125.2 +/- 109.4 minutes, and 5.7 +/- 12.8 minutes per week. These levels were significantly lower on non-CRP days than on CRP days: 177 +/- 113 versus 299 +/- 161 kcal/day and, respectively, 49.3 +/- 19.3 versus 59.7 +/- 19.8 minutes, 10.5 +/- 14.6 versus 26.4 +/- 20.4 minutes, and 0.4 +/- 1.7 versus 1.4 +/- 3.0 minutes per day. CONCLUSIONS: These results indicate that the amount of physical activity was generally adequate on CRP days, but failed to reach target levels on non-CRP days. Thus CRP participants, when it is medically appropriate, should be encouraged to incorporate lifestyle physical activity, additional exercise, or both on non-CRP days to supplement their caloric expenditure from CRP exercise sessions.     

Use of Bacillus brevis for efficient synthesis and secretion of human epidermal growth factor.

Using previously isolated Bacillus brevis strains that secrete large amounts of proteins but little protease into the medium, we have developed a host-vector system for very efficient synthesis and secretion of heterologous proteins. The multiple promoters and the signal-peptide-coding region of the MWP gene, a structural gene for one of the major cell wall proteins of B. brevis strain 47, were used to construct expression-secretion vectors. With this system, a synthetic gene for human epidermal growth factor (hEGF) was expressed efficiently and a large amount (0.24 g per liter of culture) of mature hEGF was secreted into the medium. hEGF purified from the culture supernatant had the same NH2-terminal amino acid sequence, COOH-terminal amino acid, and amino acid composition as natural hEGF, and it was fully active in biological assays. These results, in combination with previous results, showed that mammalian proteins can be produced in active form 10-100 times more efficiently in B. brevis than has been reported in other systems.     

Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states

Plasma levels of activated protein C (APC)-protein C inhibitor (PCI) were significantly increased in patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), acute myocardial infarction (AMI), pulmonary embolism (PE), or deep vein thrombosis (DVT) and in patients undergoing hemodialysis (HD). Plasma levels of APC-alpha(1)-antitrypsin (AT) complex were significantly increased in patients with DIC and in those with TTP. Plasma levels of PCI were significantly decreased in patients with DIC, non-DIC, or TTP and in those undergoing HD. In the pre-DIC stage, the plasma levels of APC-PCI complex were significantly increased but not those of APC-alpha(1)-AT complex. These data suggest that measurements of APC-PCI complex and APC-alpha(1)-AT complex may be useful for the diagnosis of DIC. After treatment of DIC, the plasma levels of APC-PCI complex and APC-alpha(1)-AT complex were significantly decreased, but not those of PCI. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-alpha(2)-plasmin complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were markedly increased in patients with DIC or pre-DIC and were moderately increased in patients with non-DIC, TTP, AMI, PE, or DVT and in those undergoing HD. The receiving operating characteristic (ROC) analysis showed that SFM and the APC-PCT complex are useful markers for diagnosis of DIC. The specificity of plasma TAT and PPIC levels was low. The positive rate of APC-PCI complex was higher than 90% with DIC, TTP, AMI, PE, and it was higher than 60% with DVT and HD. Since the APC-PCI complex was elevated not only in patients with venous thrombosis but also in those with arterial thrombosis, components of the protein C pathway might be useful markers for the diagnosis of arterial thrombosis.