Phenotypic and Genotypic Lineage Switch of a Lymphoma with Shared Chromosome Translocation and T-Cell Receptor γ Gene Rearrangement

A case of non-Hodgkin's lymphoma showed a phenotypic and genotypic cell lineage switch twice during nine years of his clinical history; first, T-cell type, pleomorphic small cell lymphoma developed, followed by B-cell type, diffuse centroblastic/centrocytic lymphoma, and finally T-zone lymphoma without follicles again developed, from which AST-1 cultured cell line was established. Karyotype analysis demonstrated a shared abnormal chromosome, der(1)t(1;?)(p36;?), among the first relapsed B-cell tumor, the second relapsed T-cell tumor and AST-1 cell line. Furthermore, T-cell receptor (TCR) γ gene rearrangement bands of the same size were observed in the first relapsed B-cell tumor and the second relapsed T-cell tumor as well as AST-1 cell line. These results suggested that both relapsed tumors of different cell lineages are derived from a common malignant clone, presumably a committed lymphoid stem cell. A unique translocation, t(2;14)(q37;q11.2), which may involve TCR δ/α gene complex, was observed in the second relapsed tumor and AST-1 cells. To attempt to isolate the breakpoint of this translocation, the configuration of TCR δ/α gene complex was studied. The result showed that two rearrangements of TCR α gene detected with J_α probes were the products of the normal TCR rearrangement process, and were not involved in the translocation at this region. This patient, together with the AST-1 cell line, provided us a unique opportunity to study the development and clonal evolution of malignant lymphoma.     

ABC proteins: key molecules for lipid homeostasis

Forty-nine ABC protein genes exist on human chromosomes. Eukaryotic ABC proteins were originally recognized as drug efflux pumps involved in the multidrug resistance of cancer cells. However, it is now realized that one of their major physiological roles is cellular lipid transport and homeostasis, and their dysfunction is often associated with human diseases. ABCA1 and ABCA7 mediate the apolipoprotein-dependent formation of a high-density lipoprotein–cholesterol complex. ABCA3 is indispensable for pulmonary surfactant secretion. ABCG5 and ABCG8 are involved in the secretion of plant sterols and cholesterol into bile. However, the primary substrates and mechanism of action of these ABC proteins have not been precisely defined. In this review article, we first describe the general structure and functions of eukaryotic ABC proteins. The current model of ABCA1 functionality is then explained based on studies on a topological model, subcellular localization, apoA-I dependence of HDL formation, functional defects of Tangier disease mutants, and ATP hydrolysis of purified ABCA1. ABCA1 is supposed to function as a transporter of lipids as well as a receptor for apoA-I. ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures.     

A second group of hepatitis C viruses

cDNA clone 11–7 was isolated by immunoscreening a cDNA library that was prepared from a pooled plasma of non-A non-B hepatitis (NANBH) patients using expression vector gt 11. This cDNA corresponds to known nucleotide positions 3983–4745 of the genome of hepatitis C virus (HCV). This clone was used as a probe for screening the HCV-related cDNAs in a cDNA library similarly prepared by using gt 10. As a result, six more cDNA clones were isolated and analyzed for their nucleotide sequences. The results strongly suggested that there are at least two groups of HCV, group I and group II. According to our classification, the prototype HCV and clone 11–7 belong to group I HCV, and their nucleotide and deduced amino acid sequences were diverged from those of group II HCV. Genetic variation observed in the nucleotide and the amino acid sequences between the two groups resembles that in the NS3 region of the genome between Japanese encephalitis virus and West Nile fever virus. Polypeptides produced inEscherichia coli carrying a clone 11–7 or a group II cDNA clone E reacted with antibodies in the blood of 12 or 4 out of 14 individual chronic NANBH patients, respectively. Our data clearly indicate the existence of a second group of HCV.     

Metastatic seeding of bile duct carcinoma in the transhepatic catheter tract: Report of a case

We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutaneous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile, duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.     

金钱草抗炎利胆有效部位研究

目的:寻找金钱草抗炎利胆有效部位。方法:采用二甲苯致小鼠耳廓肿胀实验和醋酸致小鼠腹腔毛细血管通透性增高实验对金钱草各提取部位进行了抗炎活性筛选,用小鼠及大鼠胆汁分泌实验进行利胆活性筛选。结果:金钱草醇提物和乙酸乙酯提取物能显著抑制二甲苯所致的小鼠耳廓肿胀和醋酸所致的小鼠腹腔毛细血管通透性亢进,明显促进小鼠和大鼠胆汁的分泌。结论:乙酸乙酯提取部分可能是金钱草抗炎利胆的有效部位。     

Increased plasma ghrelin level in lung cancer cachexia.

PURPOSE: Ghrelin, a novel growth hormone-releasing peptide,has been shown to cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in cachexia associated with lung cancer. EXPERIMENTAL DESIGN: Plasma ghrelin level was measured in 43 patients with lung cancer and 21 control subjects. Patients with lung cancer were divided into two groups: patients with cachexia (n = 21) and those without cachexia (n = 22). RESULTS: Plasma ghrelin level did not significantly differ between all patients with lung cancer and controls (157 +/- 10 versus 132 +/- 8 fmol/ml, P = 0.1). However, plasma ghrelin level was significantly higher in patients with cachexia than in those without cachexia (180 +/- 17 versus 135 +/- 10 fmol/ml, P = 0.011). Furthermore, plasma ghrelin level increased significantly in patients with decreased food intake after chemotherapy (from 136 +/- 11 fmol/ml to 170 +/- 16 fmol/ml on day 8, 179 +/- 20 fmol/ml on day 21 after start of chemotherapy), although plasma ghrelin level did not significantly change in those without decreased food intake. CONCLUSIONS: Baseline plasma ghrelin level was elevated in cachectic patients with lung cancer, and follow-up plasma ghrelin level increased in patients with anorexia after chemotherapy. Considering the positive energy effects induced by ghrelin, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with lung cancer.     

Associations of alcohol, height, and reproductive factors with serum hormone concentrations in postmenopausal Japanese women

We measured serum levels of estradiol (E₂), sex hormone-binding globulin (SHBG), progesterone, and dehydroepiandrosterone sulfate (DHEAS) in 61 postmenopausal women drawn from female residents in a community in Japan to evaluate the relationships between these hormone levels and potential breast cancer risk factors. The information on reproductive history, body size, alcohol use, and physical activity was obtained by means of a self-administered questionnaire. There was a significant trend in increasing E₂ level with increasing height after taking account of age and body mass index (BMI) (p for trend = 0.04). BMI was inversely associated with SHBG level after controlling for age (p for trend = 0.01). Decreasing progesterone with increasing BMI was observed after controlling age and history of hysterectomy (P=0.05). Alcohol consumption was positively associated with E₂ level and there was a strong linear trend after controlling for age, height, and BMI (p for trend=0.001). Trend for increasing DHEAS with alcohol consumption was also statistically significant after controlling for age and history of hysterectomy (p for trend=0.01). Reproductive factors as well as physical activity were not related to any of the hormone levels.     

The biphasic effect of extracellular glucose concentration on carbachol‐induced fluid secretion from mouse submandibular glands

Cholinergic agonists evoke elevations of the cytoplasmic free‐calcium concentration ([Ca²⁺]_i) to stimulate fluid secretion in salivary glands. Salivary flow rates are significantly reduced in diabetic patients. However, it remains elusive how salivary secretion is impaired in diabetes. Here, we used an ex vivo submandibular gland perfusion technique to characterize the dependency of salivary flow rates on extracellular glucose concentration and activities of glucose transporters expressed in the glands. The cholinergic agonist carbachol (CCh) induced sustained fluid secretion, the rates of which were modulated by the extracellular glucose concentration in a biphasic manner. Both lowering the extracellular glucose concentration to less than 2.5 mM and elevating it to higher than 5 mM resulted in decreased CCh‐induced fluid secretion. The CCh‐induced salivary flow was suppressed by phlorizin, an inhibitor of the sodium–glucose cotransporter 1 (SGLT1) located basolaterally in submandibular acinar cells, which is altered at the protein expression level in diabetic animal models. Our data suggest that SGLT1‐mediated glucose uptake in acinar cells is required to maintain the fluid secretion by sustaining Cl^? secretion in real‐time. High extracellular glucose levels may suppress the CCh‐induced secretion of salivary fluid by altering the activities of ion channels and transporters downstream of [Ca²⁺]_i signals.     

Complementarity determining region-III is a useful molecular marker for the evaluation of minimal residual disease in mantle cell lymphoma

Bone marrow (BM) and peripheral blood (PB) involvement in 10 patients with mantle cell lymphoma (MCL) was analysed by a polymerase chain reaction (PCR)-mediated RNase protection assay. The complementarity determining regions (CDR)-III of all 10 MCLs examined was amplified efficiently with consensus V_H and J_H primers by PCR, and BM and/or PB involvement was evaluated by RNase protection assay in all 10 patients examined. Our assay showed BM and/or PB of the entire group to have neoplastic cells at presentation, despite the fact that eight patients were found to have BM and/or PB involvement on the basis of morphological examination and/or surface marker analysis. We also examined minimal residual disease (MRD) after conventional chemotherapy, and detected MRD in a patient in complete remission (CR). Although previous studies have shown that t(11;14) breakpoint amplification by PCR was only applicable to about 30–40% of cases, the present study indicates that CDR-III is a useful molecular marker and the PCR-mediated RNase protection assay is a good tool for the evaluation of MRD in MCL. It is suggested that BM and PB of MCL patients are quite frequently involved at presentation and even after conventional chemotherapy at the molecular level.