Granular lymphocyte proliferative disorder after autologous peripheral blood stem cell transplantation for multiple myeloma

A 57-yr-old woman with multiple myeloma underwent tandem autologous peripheral blood stem cell transplantation (APBSCT). Fever, anemia, and thrombocytopenia, followed by the proliferation of granular lymphocytes in the peripheral blood occurred, after a second APBSCT. Clonal rearrangement of the T-cell receptor was detected using Southern blot analysis of peripheral blood samples. Granular lymphocyte proliferative disorders (GLPD) were diagnosed. After steroid therapy, the symptoms resolved. Lymphocytosis did not recur after the discontinuation of steroids. There have been a few reports of GLPD after solid organ and allogeneic hematopoietic stem cell transplantations. We report a first case of GLPD after APBSCT.     

Strategy for treating elderly Japanese with hypercholesterolemia*

Background: It has been widely accepted that control of serum cholesterol levels is effective for prevention of cardiovascular events. Recent data have suggested that this is also the case in the elderly. Methods: A research group (chaired by T. Kita) was organized as part of the Comprehensive Research on Aging and Health conducted by the Japanese Ministry for Health, Labour, and Welfare in 1999–2002 to determine the best strategy for control of cholesterol levels in elderly Japanese with hypercholesterolemia. In order to do this a review of the literature was conducted. Conclusion: The research group concluded: (i) Japanese patients aged 65–74 years with hypercholesterolemia should be treated by following the Guideline for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases by the Japan Atherosclerosis Society (2002), as cholesterol‐lowering therapy would bring a similar, or even larger, preventive effect to the elderly, whose absolute risk of cardiovascular events is higher than that in the younger population; (ii) target cholesterol levels in elderly Japanese aged ≥ 75 years with hypercholesterolemia should be determined individually according to their physical activities. It is noted that the elderly are more susceptible to drug‐related adverse effects than the younger since renal and liver functions, required for metabolizing drugs, in the elderly are relatively weaker.     

Enhanced botrocetin-induced type IIB von Willebrand factor binding to platelet glycoprotein Ib initiates hyperagglutination of normal platelets

Botrocetin, a protein isolated from the venom of the snake Bothrops jararaca, induces platelet aggregation/agglutination by von Willebrand factor (vWF) binding to the membrane glycoprotein (GP) Ib, an action resembling that of ristocetin. However, some differences in the interaction between vWF and platelet GPIb induced by these two substances have been reported. We have recently shown that the GPIb binding domain on the vWF molecule, in both instances, resides in the tryptic 52/48 kDa fragment extending from amino acid residue 449 to 728 of the constituent subunit. In the present report, we demonstrate that botrocetin does not induce agglutination of formalin-fixed platelets from a patient with Bernard-Soulier syndrome congenitally lacking GPIb and GPIX as well as GPV, a finding similar to that shown with ristocetin. A monoclonal antibody against GPIb (AP-1) inhibits either ristocetin- or botrocetin-dependent vWF binding to formalin-fixed platelets from normal individuals. Therefore, botrocetin-induced vWF binding to formalin-fixed platelets may reflect the interaction between vWF and platelet GPIb. To strengthen this concept, we have now found that heightened botrocetin-induced type IIB vWF binding to platelet GPIb causes hyperagglutination of normal platelets.     

Enhanced DNA synthesis of cultured vascular smooth muscle cells from spontaneously hypertensive rats. Difference of response to growth factor, intracellular free calcium concentration and DNA synthesizing cell cycle

It is widely reported that cultured vascular smooth muscle cells (CVSMCs) from spontaneously hypertensive rats (SHR) show enhanced proliferation compared with cells from Wistar-Kyoto rats (WKY). The present studies were designed to find out whether this exaggerated proliferation in SHR is determined genetically and, if so, to evaluate the mechanism on the cell cycle. (1) Incorporation of [3H]thymidine into DNA was enhanced in CVSMCs from 3- and 12-week-old SHR compared with WKY but not in CVSMCs from DOCA-salt hypertensive rats compared with the cells from sham-operated rats. (2) DNA synthesis in SHR cells was enhanced further by addition of insulin (which is considered to be a progression factor) but not by arginine-vasopressin (AVP; considered to be a competence factor) or by angiotensin II (AII). On the other hand, insulin, AVP and AII significantly augmented DNA synthesis in WKY cells. (3) Intracellular free calcium concentration was slightly, but significantly, higher in SHR cells. (4) An increase in the population of DNA-synthesizing S-phase cells and decrease in (G2 + M)-phase cells in SHR were observed by flowcytometry. These data suggest (1) that enhanced DNA synthesis in CVSMCs from SHR is determined genetically, (2) that enhanced DNA synthesis in CVSMCs from SHR is largely dependent on an increased proportion of S-phase cells and (3) that this increase in S-phase cells in CVSMCs from SHR could be due to enhanced competence gene expression in SHR cells. (4) The increased intracellular free calcium concentration is compatible with an activation of the inositol-trisphosphate pathway.     

Diffuse intrahepatic recurrence after resection of hepatocellular carcinoma

BACKGROUND/AIMS: An early diffuse type in the pattern of the postoperative intrahepatic recurrence of hepatocellular carcinoma has been recognized. The purpose of this study was to elucidate risk factors for diffuse recurrence of hepatocellular carcinoma. METHODOLOGY: The subjects involved in the present study were 114 patients with hepatocellular carcinomas resected in Tenri Hospital during the past 12 years. Univariate analysis was used for retrospective determination of the factors related to diffuse recurrences after surgery in 10 cases among 114 patients. RESULTS: The risk factors linked to diffuse recurrence were microscopical portal infiltration (P < 0.01), elevated alpha-fetoprotein (more than 1000 ng/mL) (P < 0.05), the absence of preoperative transcatheter arterial embolization (P < 0.01), and two or more segmentectomies of the liver (P < 0.01). Six of 10 patients with microscopical portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL) had diffuse recurrence (P < 0.01). Six of 8 patients with two or more segmentectomies without preoperative TAE had diffuse recurrence (P < 0.01). CONCLUSIONS: When patients with the diagnosis of operable hepatocellular carcinoma have portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL), two or more segmentectomies of the liver without preoperative transcatheter arterial embolization should be avoided.     

Scrobiculosides A and B from the deep-sea sponge Pachastrella scrobiculosa

Journal of Natural Medicines - Two new steroidal saponins, scrobiculosides A and B, were isolated from the deep-sea sponge Pachastrella scrobiculosa, collected at a depth of 200&nbsp;m off...     

Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia

Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5–16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41–69%) and 97% (95%CI: 87–99%), respectively. Median telomere length in responders was −0.4 standard deviation (SD) (−2.7 to +3.0 SD) and −1.5 SD (−4.0 to +1.6 (SD)) in non-responders (P<0.001). Multivariate analysis showed that telomere length shorter than −1.0 SD (hazard ratio (HR): 22.0; 95%CI: 4.19–115; P<0.001), platelet count at diagnosis less than 25×10⁹/L (HR: 13.9; 95%CI: 2.00–96.1; P=0.008), and interval from diagnosis to immunosuppressive therapy longer than 25 days (HR: 4.81; 95%CI: 1.15–20.1; P=0.031) were the significant variables for poor response to immunosuppressive therapy. Conversely to what has been found in adult patients, measurement of the telomere length of lymphocytes at diagnosis is a promising assay in predicting the response to immunosuppressive therapy in children with aplastic anemia.