Post-transplant consolidation therapy using thalidomide alone for the patients with multiple myeloma: a feasibility study in Japanese population

In order to test for improved survival following autologous transplantation (ASCT), we conducted a prospective clinical trial of post-ASCT thalidomide therapy in Japanese patients with multiple myeloma (MM). Twenty-five newly diagnosed patients received double or single ASCT with high-dose melphalan (200?mg/m²). Two months after stem cell infusion, if the patients failed to achieve a near-complete response, thalidomide was administered at 200?mg/day until disease progression or occurrence of intolerable adverse events. Seventeen patients were in partial response or minimal response after ASCT and received thalidomide alone. Their median progression-free survival (PFS) from ASCT was 17.4?months, and the median overall survival (OS) was 42.9?months. Some patients with normal karyotype experienced durable disease stabilization for over 5?years. Five patients who exhibited high-risk chromosomal changes such as t(4;14) or deletion of chromosome 13 or 17 showed very short PFS and OS compared with those who did not. Observed grade 3 or 4 toxicities included infection in three patients, hematological toxicities in three, and gastrointestinal toxicities in two, but there was no grade 3 or higher peripheral neuropathy, probably due to appropriate dose modifications. This long-term prospective study is the first to demonstrate the feasibility of post-ASCT thalidomide therapy in Japanese patients with MM.     

Tibial tubercle malposition in patellar joint instability: A computed tomography study in full extension and at 30° flexion

We evaluated the tibial tubercle position in knees with patellar instability. CT in full extension and at 30° flexion was used in 18 knees with instability and 18 control knees. Scans were taken at the level of the femoral epicondyles, tibial tubercle and distal tibia. We found that in full extension, the tibial tubercle was in a more lateral position in the unstable than in the control knees. At 30° flexion, the tibial tubercle in the unstable knees rotated internally, but it was never within the normal range. CT scans taken in full extension and at 30° flexion seem to be of value for ascertaining the degree of tibial tubercle malposition during knee flexion in patellar instability.     

Successful repair of intimal dissection following coronary angioplasty with a 48-hour inflation of spiral inflation coil and local delivery of heparin

We report on an unusual patient with a threatened occlusive dissection, in whom prolonged (48-hr) inflation of a balloon catheter with localized heparin infusion proved successful. This intracoronary infusion catheter maintained distal coronary flow on a unique spiral coil design, and may provide an alternative or a bridge to emergency operation or stent implantation. © 1996 Wiley-Liss, Inc.     

Hyperdynamic circulation in the left gastric venous area in patients with portal hypertension: Angiological assessment

The time of appearance of the left gastric vein on serial celiac arteriograms in patients with portal hypertension and esophageal varices was compared with that of the portal vein to assess regional hemodynamics in the left venous portion of the stomach, an area located in close proximity to the varices. In two thirds of all the patients with cirrhosis or non-cirrhotic idiopathic portal hypertension (IPH), the left gastric vein was visualized earlier or simultaneously than or with the portal vein, while in all but one patient with prehepatic portal obstruction, there was a delayed opacification of the left gastric vein. These results suggest the presence of a hyperdynamic circulatory state which promotes venous hypertension in the left gastric venous area of the stomach of a considerable number of patients with cirrhosis or IPH. In such a hemodynamic state, selective decompression of varices can be achieved by a left gastric venous caval shunt.     

Control of expression of Agrobacterium vir genes by synergistic actions of phenolic signal molecules and monosaccharides

Most virulence (vir) genes of Agrobacterium tumefaciens that are required for the formation of crown gall tumors are expressed in response to such plant signal molecules as acetosyringone and lignin precursors. The phenolic signals are transduced through a receptor VirA protein in the inner membrane of the bacterial cell. The expression of these genes triggers the transfer of a specific DNA segment, called transferred DNA (T-DNA), from the Ti plasmid to plant cells, and its integration into their nuclear DNA. We show here that a group of aldoses (L-arabinose, D-xylose, D-lyxose, D-glucose, D-mannose, D-idose, D-galactose, and D-talose) can markedly enhance acetosyringone-dependent expression of vir genes when the concentration of acetosyringone is limited (10 microM) but does not enhance the expression of noninducible genes. Likewise, a 2-deoxy-D-glucose, a nonmetabolized sugar, is also effective. When a deletion was introduced into the virA gene in the region encoding the periplasmic portion of the VirA protein, enhancement by glucose disappeared, but vir expression was induced by acetosyringone in this mutant. These results suggest that these sugars directly enhance a signaling process initiated by phenolic inducers that results in an increase in expression of the vir genes.     

Reliability of the skin blotting method when used on the elderly

The aim of this study was to compare protein secretion on intact skin of extremities and verify the relationship between the marker proteins on abdominal skin and systemic factors using skin blotting. A cross‐sectional study was conducted among elderly patients aged 65 years and older (N = 73) at a long‐term medical facility in Japan. Skin blotting was performed on the right and left forearms, right and left lower legs, and abdomen. Pearson's correlations and Bland–Altman plots were utilised for comparing the protein secretion from the skin between the right or left forearms or lower legs. Multiple regression analysis was applied to determine the relationship between intensity levels of 3 proteins on the abdominal skin and the systemic factors. Bland–Altman plots demonstrated that there was no significant difference between right and left secretion levels on the forearms and lower legs among 3 proteins. Multiple regression analysis showed that age and antiplatelet use was positively associated with decreased collagen type IV and increased matrix metalloproteinase 2 levels, respectively. Our findings suggested that collecting samples from either the right or the left skin would be sufficient if skin properties between arms and legs are evaluated using skin blotting.     

Quantitative analysis of hepatitis B virus precore mutant in hepatitis type B.

Active liver disease has been detected in chronic hepatitis B after seroconversion from positive HBe antigen to positive anti-HBe antibody. Active replication of HB virus (HBV) containing a precore stop-codon mutation has been implicated in this condition. The usual methods, such as direct sequencing, to characterize the responsible mutant of HBV are not suitable for routine clinical use. Here we employed the competitive mutation site specific assay (CMSSA) to detect precore mutant HBV-DNA in patients with positive HB surface antigen. In patients with HBe antigen, precore mutant HBV-DNA was significantly higher than in patients with HBe antibody. The level of precore mutant HBV-DNA in patients with elevated serum ALT was significantly higher than in patients with normal serum ALT. Sex, age and the level of serum HBV-associated DNA polymerase levels were not correlated with levels of precore mutant HBV-DNA. Ten of 11 negative patients for the precore mutant by polymerase chain reaction followed by restriction fragment length polymorphism assay (PCRRFLP) were positive for the precore mutant by CMSSA. These results suggest that the precore mutant has already emerged in the HBeAg-positive phase as determined by CMSSA, which is more sensitive than PCR-RFLP and is useful for evaluating the clinical course of patients with chronic hepatitis B.     

The influence of physical activity in the progression of experimental lung cancer in mice

Lung cancer is one of the most incident neoplasms in the world, representing the main cause of mortality for cancer. Many epidemiologic studies have suggested that physical activity may reduce the risk of lung cancer, other works evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. The aim of this study was to evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Lung tumors were induced with a dose of 3mg of urethane/kg, in 67 male Balb - C type mice, divided in three groups: group 1_24 mice treated with urethane and without physical activity; group 2_25 mice with urethane and subjected to aerobic swimming free exercise; group 3_18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5-20% of body weight. All the animals were sacrificed after 20 weeks, and lung lesions were analyzed. The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5-3 (p=0.052). When comparing only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 as compared with group 1 (p=0.03) but not in relation to group 2. There were no metastases or other changes in other organs. The anaerobic physical activity, but not aerobic, diminishes the incidence of experimental lung tumors.     

Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study

Matsukuma S, Takeo H, Kono T, Nagata Y & Sato K
(2012) Histopathology  61, 857–862 Aberrant cytokeratin 7 expression of centrilobular hepatocytes: a clinicopathological study Aims: This study has attempted to elucidate the clinicopathological features of aberrant cytokeratin 7 (CK7) expression by centrilobular hepatocytes. Methods and results: A total of 113 liver biopsy specimens from patients with common non‐neoplastic liver diseases, including hepatitis B or C, non‐alcoholic steatohepatitis, alcoholic liver disease and other diseases were examined. In 56 specimens (49.6%), CK7‐positive centrilobular hepatocytes (CK7 + CHs) were identified and sometimes showed binuclear features. CK7 + CHs were associated with patients’ older age (P = 0.004), higher serum levels of aspartate aminotransferase (P = 0.016) and γ‐glutamyltransferase (P = 0.006), centrilobular fibrosis (P < 0.001), prominent thickening of hepatocytic plates (P < 0.001) and higher scores of total and periportal CK7‐positive hepatocytes (both P < 0.001), but were not correlated with gender, steatosis, serum levels of total bilirubin or alanine aminotransferase. In 55 cases of hepatitis B and hepatitis C only, CK7 + CHs were related to a higher stage of fibrosis (P = 0.006). Conclusion: CK7 + CHs occur relatively frequently in non‐neoplastic liver disease, associated with centrilobular scarring and the presence of CK7‐positive periportal hepatocytes, and appear to be a non‐specific phenomenon with respect aetiology of underlying disease. CK7 + CHs may represent age‐dependent activation of hepatic progenitor cells or a regenerative phenomenon of hepatocytes themselves, both of which might contribute to liver regeneration.