Allogeneic Bone Marrow Transplantation for the Treatment of Acute Leukemia: The Kanazawa Experience

Twelve patients with acute leukemia (7 with nonlymphoblasticleukemia and 5 with lymphoblastic leukemia) were treated withhigh-dose cyclophosphamide and 1,000 rad total body irradiationfollowed by allogeneic bone marrow transplantation from theirHLA-identical sibling donors. Of eight patients given transplantsat relapse, only one patient has become a long-term survivor;he is alive in disease-free complete remission (CR) 4 yr afterthe transplantation. A cure is probable in this patient. Offour patients given transplants during remission, two have survivedin unmaintained CR for almost 1 yr or more. Recurrent leukemiawas observed in two patients whose disease was resistant toconventional therapy at the time of transplantation. Major causesof treatment failure were interstitial pneumonia, hepatic failuredue to veno-occlusive disease, severe infection and relapse.Transplantation-related complications were more frequent andserious in patients who received transplants at relapse thanin those receiving them during remission. The incidence of graft-versus-hostdisease was relatively high but the disease was neither primarynor leading cause of death. These preliminary but relativelyencouraging data suggest that transplantation during remissionmay reduce posttransplant morbidity and mortality. This approachwill contribute to producing long-term survival or cure in patientswith adult acute leukemia if a suitable donor is available.     

Loss of heterozygosity and analysis of mutation of p53 in hepatocellular carcinoma

Abstract Thirty-six hepatocellular carcinoma (HCC) tissues obtained from 34 patients were classified according to histological diagnosis into six well-differentiated HCC, 20 moderately differentiated HCC and 10 poorly differentiated HCC. High molecular weight DNA was prepared from each tumour and the corresponding non-tumour tissue. Loss of heterozygosity (LOH) on chromosomes 4q, 5q, 10q, 11p, 16q, 17p, mutation of the p53 gene and polymorphism of intron 25 of the retinoblastoma (RB) gene were simultaneously analysed. The patients were composed of three cases of small HCC (the diameter of which was < 3 cm) and 31 cases of advanced HCC. Twenty-nine of 34 (85.3%) patients analysed had been exposed to hepatitis B virus and/or hepatitis C virus. The frequencies of LOH on seven chromosomes were 57.9% in 17p13.3, 45.1% in 17p, 45.1% in 11p, 41.9% in 5q, 41.9% in 16q24, 29.0% in 4q, 25.8% in 10q in advanced HCC (four of well differentiated, 18 of moderately differentiated and nine of poorly differentiated carcinoma). In contrast, LOH was observed on 4q, 5q, 16q and 17p in 33% (1/3) of the small HCC (two of well differentiated and one of moderately differentiated carcinoma). The mutation of the p53 genes and polymorphism of the RB gene were present in 25.8% (8/31) and 12.9% (4/31) of the advanced tumours, respectively, but the mutation was not found in small HCC. LOH on every chromosome and the p53 mutation were observed more frequently in more advanced tumours, and the genetic changes accumulated with the increase of the histopathological grade. These findings suggest that the accumulation of genetic changes in multiple tumour suppressor genes is involved in the progression of HCC.     

Type C chronic hepatitis associated with thrombocytopenia in two patients

Abstract Portal hypertension in the presence of chronic hepatitis is generally thought to develop during the progression of the chronic hepatitis to cirrhosis. Before the establishment of assays for diagnosing hepatitis C virus infection, such a case of portal hypertension without liver cirrhosis could be misdiagnosed as idiopathic portal hypertension. It had not fully determined whether portal hypertension might precede the onset of cirrhosis in type C chronic hepatitis. This report presents two cases of women with chronic hepatitis C who developed severe thrombocytopenia; each showed splenomegaly and hypersplenism due to portal hypertension. Angiographic study and histological analysis were conducted to determine the cause of the portal hypertension. Histological evaluation showed an intrahepatic presinusoidal block pattern and fibrotic changes in the periportal area, but no evidence of liver cirrhosis or of other incidental complications such as idiopathic portal hypertension. Both of these patients exhibited normal platelet counts after splenectomy. Thus, type C chronic hepatitis can lead to portal hypertension, as demonstrated in these two patients.     

A Case of Concomitant Association of Early Esophageal Carcinoma, Early Gastric Carcinoma and Malignant Lymphoma of the Stomach

A case of concomitant association of early esophageal carcinoma,cancer of the early gastric carcinoma and malignant lymphomaof the stomach was reported. The intrathoracic esophagus wasresected with the whole stomach, and the esophagus was reconstructedwith the right side colon. There were two separate early carcinomasin the upper and lower esophagus. The upper lesion was intraepithelialsquamous cell carcinoma, and the extension of lower lesion alsolimited in the intraepithelial layer. He had also signet ringcell carcinoma of the stomach which was limited only in themucosal layer. In addition, there was malignant lymphoma invadedinto the mucosa and sub-mucosa at the antral rigion of the stomach.There was no lymph node metastasis. The patient is living wellnow. The association of early esophageal carcinoma with earlystomach carcinoma is rare. Only five such cases have been reportedin the Japanese literature.     

Idiopathic Ventricular Arrhythmias Originating from the Papillary Muscles in the Left Ventricle: Prevalence, Electrocardiographic and Electrophysiological Characteristics, and Results of the Radiofrequency Catheter Ablation

Idiopathic VAs Originating from the LV Papillary Muscles.   Introduction: Idiopathic ventricular arrhythmias (VAs) can originate from the left ventricular (LV) papillary muscles (PAMs). This study investigated the prevalence, electrocardiographic and electrophysiological characteristics, and results of catheter ablation of these VAs, and compared them with other LV VAs.
Methods and Results: We studied 71 patients with VAs originating from the LV anterolateral and posteroseptal regions among 159 patients undergoing successful catheter ablation of idiopathic LV VAs. PAM VAs were uncommon, rare in a sustained form, and more common from the posterior papillary muscle (PPM) than anterior papillary muscle (APM). A younger age was a good predictor for differentiating left posterior fascicular VAs from PPM VAs. There were several electrocardiographic features that accurately differentiated PAM and LV fascicular VAs from mitral annular VAs. However, an R/S ratio ≤1 in lead V6 in the LV anterolateral region and a QRS duration >160 ms in the LV posteroseptal region were the only reliable predictors for differentiating PAM VAs from LV fascicular VAs. A sharp ventricular prepotential was recorded at the successful ablation site during 42% of the PAM VAs. Radiofrequency current with an irrigated or conventional 8-mm tip ablation catheter was required to achieve a lasting ablation of the PAM VA origins whereas that with a nonirrigated 4-mm tip ablation catheter produced excellent results in LV fascicular and mitral annular VAs.
Conclusions: There are differences in the electrocardiographic and electrophysiological features among VAs originating from these regions that are helpful for their diagnosis and effective catheter ablation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 62–69, January 2010)     

Atypical Epstein-Barr virus infection during and after intermittent FK506 therapy

Atypical Epstein-Barr virus (EBV) infection developed in a patient under intermittent administration of FK506 (one dose in 10 days) after living-related liver transplantation. The clinical course was similar to severe chronic active EBV infection syndrome (SCAEBV), which is characterized by extremely high titers of antibody to EBV antigens. The clinical symptoms improved without graft rejection even after the cessation of FK506; however, the titers of antibody to EBV antigens remained at high levels. It was considered that: (i) even intermittent use of FK506 could influence the immune response, which then induced atypical EBV infection similar to SCAEBV; and (ii) the impaired immune response, especially to EBV antigens, remained after complete cessation of FK506.     

Direct Production of the Fab Fragment Derived From the Sperm Immobilizing Antibody Using Polymerase Chain Reaction and cDNA Expression Vectors

PROBLEM : Sperm immobilizing antibodies cause infertility mainly through complement dependent sperm immobilization. To analyze any effect of sperm immobilizing antibody on fertilization, we had already established cell lines that secrete IgM monoclonal antibody (MAb H6-3C4) and IgG monoclonal antibody (MAb EnBCMGS). The latter was a class-switched recombinant IgG antibody that shares the same variable region as MAb H6-3C4. The biological effects of the IgG antibody were also reported previously to eliminate sperm immobilizing or sperm agglutinating activities. However, the method of chemical digestion of IgG had some disadvantage to prepare the purified Fab fragment stably and in large quantities. This time we report a unique method to obtain the recombinant Fab fragments (Fab EnBCMGS) using polymerase chain reaction (PCR) and cDNA expression vectors. METHOD : Two kinds of PCR primers were designed to make a truncated heavy chain (Fd) gene of MAb EnBCMGS. The amplified Fd gene and light chain gene were ligated into cDNA expression vectors and then transfected into mammalian cells. RESULTS : Expression of the Fd gene and light chain gene were confirmed by Northern blotting. Secretion of the recombinant Fab fragment from mammalian cells was also confirmed by Western blotting. The Fab fragment showed biological activity as is expected by FACS analysis. CONCLUSION : This method enables the stable production of genuine Fab fragments of IgG in mammalian cells without any chemical treatment that may be time consuming and affect the quality of the Fab fragments.