Quality of life in adult patients after stem cell transplantation.

Many articles pertaining to quality of life (QOL) following stem cell transplantation have been published in the US and western Europe. However, since the actions of health insurance systems and overall cultural aspects are strongly associated with QOL, investigations into QOL should be carried out within all countries. Therefore, we have investigated the QOL of adult patients following stem cell transplantation at 31 hospitals in Japan. The survivors, who were surveyed by mail questionnaire, were 20 years or older at the time of this study. The underlying diseases were acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, myelodysplastic syndrome, and multiple myeloma. Median age at the time of the study was 36 years, and median interval after transplantation was 35.3 months. Of 383 patients surveyed, 282 (73.6%) responded to the questionnaire. One hundred and ninety-two patients were treated with an allogeneic-related transplantation, 52 with allogeneic-unrelated, and 38 with an autologous transplantation. Our data revealed that the length of time since transplantation and the diagnosis of chronic GVHD were associated with QOL. When unrelated and related transplantation recipients were compared, ratings on relief from pain, stability in weight, and confidence in dealing with daily life were lower among unrelated transplantation patients.

Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). The Lymphoma Study Group of the Japan Clinical Oncology Group.

BACKGROUND: The main form of cytotoxic treatment for advanced Hodgkin's disease (HD) is conventional dose multiagents chemotherapy. As HD is not common in Japan, we conducted a phase II study of the commonly used combination chemotherapy (CCT) regimen established in the West for Japanese patients with advanced HD to confirm the efficacy and safety. METHOD: Between October 1989 and February 1993, a multicenter phase II study of alternating CCT C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, vinblastine, bleomycin, dacarbazine) to evaluate its clinical usefulness for clinical stage (cS) II-IV HD was conducted by the Lymphoma Study Group of the Japan Clinical Oncology Group. RESULTS: Seventy-nine previously untreated patients were enrolled in the study. For 67 eligible patients, the response rate was 92.5% with 83.6% complete response (CR). For 40 cS II and 27 cS III/IV patients the response rate was 95.0% with 90.0% CR and 88.9% with 74.1% CR, respectively. The overall 5-year survival rate was 84.8%. Those of cS II and cS III/IV were 92.5 and 73.1%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.1025). The progression-free 4-year survival rate was 72.8%. Those of cS II and cS III/IV were 77.5 and 65.7%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.2483). Grade 4 toxicity by the criteria of the World Health Organization consisted of leukocytopenia in 28.4% of patients. There was GPT elevation in 4.5%, nausea/vomiting in 11.9% and CNS in 1.5% of patients, but there was no treatment-related death. CONCLUSION: The C-MOPP/ABVd regimen for Japanese patients with advanced HD is considered to be one of the effective CCTs according to the results of the present phase II study.

Analysis of 500 bone marrow transplants from unrelated donors (UR-BMT) facilitated by the Japan Marrow Donor Program: confirmation of UR-BMT as a standard therapy for patients with leukemia and aplastic anemia.

In December 1991, the Japan Marrow Donor Program (JMDP) was established with the cooperation of the Japanese Red Cross and Japan Marrow Donor Foundation under the auspices of the Ministry of Health and Welfare in Japan. By December 1998, 122365 HLA-A,B typed volunteer marrow donors and 7207 patients had been cumulatively registered in the JMDP. The results of HLA-matching between donors and patients revealed that 5684 out of 7207 (78.9%) patients could have at least one HLA-A,B,DR serologically matched donor. Among these matched pairs, 1829 unrelated bone marrow transplants (UR-BMT) were performed. The initial 500 UR-BMT transplanted from January 1993 to October 1995 were analyzed as of July 1998. Engraftment was achieved in 95% of cases. Probability of the occurrence of grade III and IV acute GVHD was 18.4%. The rate of disease-free survival (DFS) of the patients who had standard-risk leukemia and did not suffer from grade III or IV acute GVHD (n = 154) was 60-71% and the rate of survival of patients with aplastic anemia was 56%. It can be stated that UR-BMT is a modality of treatment which is as effective as related BMT if the occurrence of grade III or IV acute GVHD is predicted and prevented.

Synthesis of an artificial glycoconjugate polymer carrying Pk-antigenic trisaccharide and its potent neutralization activity against Shiga-like toxin.

Fluorescence-labeled glycoconjugate polymers carrying carbohydrate segments of a globotriaosyl ceramide (Gb3) were synthesized and subjected to biological assays using Escherichia coli O-157 strains and Shiga-like toxins (Stx-I and Stx-II). For the fluorescence labeling, a new polymerizable fluorescent monomer with a TBMB carbonyl chromophore (Ex. 325 nm, Em. 410 nm) was designed. A glycosyl monomer of the trisaccharide segment of Gb3 was prepared from p-nitrophenyl beta-lactoside and copolymerized with acrylamide and the fluorescent monomer to prepare a fluorescence-labeled glycoconjugate copolymer carrying [alpha-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyl]-(1-->4)-beta- D-glucopyranoside. The polymer showed potent neutralization activity against Stx-I and also binding activity onto E. coli O-157 strains.

Separation of deterrents to ingestive behavior of cattle from cattle feces.

Feeding-deterrent chemicals were extracted from cattle feces and then separated with three chromatographic methods. Behavioral two-choice test bioassays with cattle were used to examine the deterrent properties of the fractions. Cattle feces were extracted with diethyl ether, and the extracts were separated into neutral, acidic, and basic fractions. Of the three fractions, only the neutral fraction was a deterrent. Separation of the ether-soluble neutral chemicals was conducted with an open column of silica gel using four carrier solutions consisting of pentane and ether. Fraction B (eluted with the carrier solution; pentane:ether = 90:10) was the most effective deterrent among the four fractions. This fraction was divided into 10 fractions by liquid chromatography. Fractions 6, 7, and 8 seemed to deter cattle from feeding. The combined Fractions 6, 7, and 8 were separated into 15 fractions with HPLC. Deterrent activities were detected in Fractions 2, 3, 9, 10, 11, 12, 13, and 14, suggesting that deterrents were separated into two groups using HPLC. These results suggested that several specific chemicals in feces are involved in inhibiting cattle from ingesting grass near cattle feces.

Intake stimulants in perennial ryegrass (Lolium perenne L.) fed to sheep.

Few studies exist on intake stimulants in forage plants, although a large amount of research has been conducted on deterrents to the feeding behavior of herbivore livestock. To study intake stimulants in plants, chemical components of perennial ryegrass were extracted, fractionated, and examined for their effects on the feeding behavior of sheep. Methanol extracts were found to be stimulants, and pentane extracts tended to be deterrents. The ethyl acetate fraction of the methanol extracts stimulated feeding, and the basic ethyl acetate-soluble fractions of the methanol extracts were bioactive. These results suggest that the basic and less volatile chemicals in perennial ryegrass stimulate feeding in sheep in the absence of other cues.

[A nonparametric estimation of survival curve with interval censored data].

Although survival analysis dealing with right-censored data has enjoyed wide use, analysis of data with left-censored and interval censored cases is available only to a very limited number of clinical researchers because of the difficulty in understanding the concepts and performing the calculations. This paper applies Turnbull's self-consistency algorithm, which he applied in his paper on survival data with only left-censored cases, for nonparametric estimation of survival curve including both left and interval censored data. A difference in the estimates of survival rate among different modes of calculation was demonstrated using the data from the Hematopoietic Cell Transplantation Registry of the Japan Society for Hematopoietic Cell Transplantation, which illustrated the necessity of a correct analysis.

Preference of sheep and goats for extracts from high-grain concentrate.

Appetite stimulants were extracted and partially isolated from high-grain concentrate. The stimulants were fed daily and were palatable to sheep and goats used in the experiments. The stimulative effects were tested by comparing the intake of two types of hay: with or without the extracts. Diethylether and n-pentane extracts of the concentrate stimulated feeding in sheep (P < .01 and P < .05, respectively). However, methanol extracts had no significant stimulative effect on selective feeding in sheep. Goats also preferentially fed on hay sprayed with the diethyl ether extracts (P < .01). The diethyl ether extracts were divided into acid, neutral, and basic fractions. Sheep and goats had a marked preference for the acid fraction only (P < .01 and P < .05, respectively). These results suggest that specific chemicals to increase palatability of hay are present in high-grain concentrate and that the chemical are nonpolar, acidic substances.

Effects of organic solvent extracts from herbage on feeding behavior in goats.

The effects of organic solvent extracts from perennial ryegrass (Lolium perenne L. cv. Friend), orchardgrass (Dactylis glomerata L. cv. Akimidori) andLolium ×Festuca hybrid on the hay consumption of goats were measured by simple two-choice feeding assays. Orchardgrass hay treated with methanol extracts (resuspended in water) of perennial ryegrass showed an increased intake by goats compared to untreated hay (P < 0.01). The palatability of hay tended to be slightly decreased by spraying it with pentane extract of perennial ryegrass and orchardgrass. Furthermore, extracts of hybrid with pentane inhibited goats from feeding (P < 0.05). Methanol extract stimulated hay consumption whereas the pentane extracts did not change or reduce intake.

GeneView: multi-language human gene mapping library with a graphical user interface.

GeneView is a newly developed human gene mapping library system that works on an X-Window platform. This system is designed for researchers who routinely utilize gene mapping data in the laboratory but are unfamiliar with computer technology. GeneView offers various features, including friendly user interface, fast operation and visualization facility. Genetic loci are displayed graphically with an idiogram. This system can be operated in multiple languages. A current version supports Japanese and English, and can be easily expanded to include other languages. A prototype of GeneView is now installed on a SPARC (Sun4) workstation. Because of the X-Window platform, GeneView should be compatible with various types of workstations.

Technical note: a pressure-sensitive sensor for measuring the characteristics of standing mounts of cattle.

A pressure-sensitive sensor that reacts to pressure by changing its electrical resistance was used to measure the characteristics of standing mounts of estrous cattle. While an estrous heifer fitted with a sensor on the rump was standing when mounted by a bull (i.e., during a standing mount), the sensor reacted to the addition and removal of pressure against it by the bull. The times of electric contact signals produced by these pressure changes were recorded to pinpoint the time of the mounted response and the duration of the mount. To detect the characteristics of standing mounts accurately, three types of sensors with different sensitivities and various positions on the rump of heifers were examined. When 13.5-cm sensors that operated with a pressure of 1,000 g/cm2 were fitted on the line combining the highest points of the left and right hip bones toward the tail, or 6.5 cm behind this position, on the rump of heifers (200 to 225 kg), mounts by vasectomized bulls (278 to 556 kg) were accurately recorded with the sensors more than 85% of the time. However, the correlation between the observed and automatically recorded lengths of mounting varied with combinations of the mounted and mounting animals or with locations of the sensor (r = .19 to .86). The pressure-sensitive sensor proved to be a promising device for continuously measuring the characteristics of standing mounts, especially the exact time at which a mount occurs.

[Analysis of breakpoints on BCR gene in acute leukemia patients with Ph1 chromosome].

Eight cases with Ph1 positive acute leukemia (7 of acute lymphocytic leukemia: ALL, and one of acute myelocytic leukemia: AML) were studied molecular biologically to identify location of breakpoints on BCR gene in each patient. Six of the 8 patients (5 of ALL and 1 of AML) had rearrangements at bcr (M-BCR) region. Their locations of the breakpoint in M-BCR were similar to those of 59 chronic myelocytic leukemia patients. One of the remaining two patients had gene rearrangements at m-BCR-1 region in BCR intron 1, and the last patient did not have gene rearrangements at any site of m-BCR-1 and IgL C lambda region. Two cases had gene deletion at either 3' or 5' side of the bcr. A patient with bcr rearrangement was also analyzed by PCR method with reverse transcriptase (RT-PCR) and had simultaneous expressions of bcr3-abl and bcr2-abl chimeric mRNAs. These results indicate that Ph1 positive acute leukemia have heterogeneous characteristics in terms of the molecular biology. The molecular analysis will help for classifying the leukemic types and for elucidating the pathogenesis in Ph1 positive acute leukemia.

Cattle feeding deterrents emitted from cattle feces.

Cattle avoid grazing forage near their feces on pasture for more than a month. The relation of cattle feces odor to the rejection was studied in feeding choice tests using cattle. The feeding deterrent of feces odor was investigated using a trough partitioned to allow passage of feces odor through test food to the cattle. The cattle did not feed from the trough containing feces 0-35 days after excretion. Volatile chemicals isolated from feces 0-35 days after excretion by a cold trap method also inhibited cattle from feeding. These results demonstrated that feces odor is a major cause of the unpalatability of forage around cattle feces. The volatile chemicals were separated into ether and aqueous fractions. The ether fraction inhibited the feeding behavior of cattle. Furthermore, the ether fraction was separated into neutral, acidic, and basic fractions. The neutral fraction of the three was bioactive. These results suggested that specific volatile chemicals emitted from cattle feces were deterrents to the feeding behavior of cattle.

[Late appearance of Philadelphia chromosome with bcr gene rearrangement in an acute myelocytic leukemia patient].

A case of acute myelocytic leukemia (AML-M2) with a late appearance of Philadelphia chromosome (Ph1) is presented. Chromosome analysis revealed a normal karyotype at the time of diagnosis and for 23 months, when hematological relapse occurred, accompanied by abnormal clones, 46, XX, t(9;22) (q34;q11) (78%) and 45,XX, -16, t(9;22) (q34;q11), del (5) (q13q31) (22%). The patient died of GVHD after bone marrow transplantation. Molecular analysis confirmed bcr gene rearrangement in the cells with Ph1 chromosome. Acquisition of Ph1 chromosome during the course of hematological malignancies other than CML is extremely rare. This case is undoubtedly important for the understanding of leukemogenesis and the evolution of leukemia clones. The authors discussed possible mechanisms of Ph1 acquisition in the late stages of AML.

[Familial spontaneous pneumothorax in three siblings including identical twins].

Two identical twin brothers and their sister who suffered from spontaneous pneumothorax (ages at onset, 18, 22 and 20 years) were admitted to our hospital. Their symptoms and clinical courses were similar and all three were finally treated by thoracotomy. No other members of their family had any history of spontaneous pneumothorax. None of these cases presented any abnormal level of serum ACE or alpha 1-antitrypsin. In order to establish the monozygosity of the brothers more accurately, we examined restriction fragment length polymorphisms (RFLPs) which were shown as the band patterns of hypervariable minisatellite regions in human genomes. However there have been few reports of spontaneous pneumothorax in identical twins, but the onset of the disease tends to be the same as in our cases, suggesting a genetical background of spontaneous pneumothorax.

[A case of chemotherapy induced necrosis of primary mediastinal germ cell tumor].

A 17 year old male with mediastinal yolk sac tumor is herein reported. His chief complaint was anterior chest pain. Chest X-ray and chest CT indicated a 8 cm diameter mass in the anterior mediastinum. Laboratory analysis revealed 2,578 ng/ml for AFP and 54% for LDH I. HCG and CEA values were normal. Yolk sac tumor was cytologically suspected on needle aspiration specimen. Combined chemotherapy with CDDP, VP16, and PEP brought the AFP and LDH 1 values down to 10 ng/ml and 27%, respectively. The diameter of the mass decreased to 6 cm. The mass was removed together with the thymus and the right upper lobe of the lung. A post operative histological examination of the mass revealed total necrosis. Nine months after the initiation of the therapy, his AFP level was within normal limits. The patient is doing well.

[Aggressive natural killer cell leukemia/lymphoma--possible existence of a new clinical entity originating from the third lineage of lymphoid cells].

The morphologic, immunologic, genotypic, and functional properties of peripheral blood and bone marrow cells or cultured cells from two patients with a clinically aggressive non T, non B natural killer cell lymphoma/leukemia (ANKL/L) were described. The leukemic cells possessed medium to large granules in the cytoplasm, antigens against CD 38, CD 2, OKIal, and NKH-1 (N 901) monoclonal antibodies on their cell-surface, and also showed a high natural killer (NK) activity. In addition, these ANKL/L belonged to neither T-nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta and T gamma receptor, and immunoglobulin. After we compared and investigated them with 9 cases of ANKL/L reported in other institutions, concerning immunophenotype, genotype and function, we reached the conclusion that the existence of ANKL/L originating from the third lineage in lymphoid cells is an obvious fact, suggesting this new clinical entity. It is important that all patients who have this type of a clinical disorder be diagnosed that there is no effective form of therapy at present.