Establishment and characterization of "biphenotypic" acute leukemia cell lines with a variant Ph translocation t(9;22;10) (q34;q11;q22).

We established two novel PH-positive acute leukemia cell lines with "biphenotypic" feature, NALM-27 and NALM-28, with t(9;22;10)(q34;q11;q22) from a patient with biphenotypic acute leukemia(BAL). The breakpoint cluster region (bcr) of the BCR gene was found to be rearranged in these cells by Southern blot analysis using a major 3'-side bcr probe. Polymerase chain reaction (PCR) results showed differences in the pattern of expression of the abl-bcr fusion gene in comparison with the diagnosis. In the case of variant Ph translocations, reports have appeared concerning mainly chronic myelogenous leukemia (CML), but there have been few concerning acute leukemia with lymphoid feature. This study thus identifies nonrandomly involved chromosome sites which can then be targeted for detailed molecular analysis to obtain an understanding of abl-bcr fusion in the cells with lymphoid feature. In addition, chromosome band 10q22, involved in this translocation, is the site for several neoplasia. Furthermore, this site is non-randomly involved in the formation of variant Ph translocations in acute lymphoblastic leukemia (ALL). This is the first report on the t(9;22;10)(q34;q11;q22) rearrangement in NALM-27 and NALM-28 cell lines which should prove useful for understanding the translocation of molecular breaks within the bcr of the complex translocation site.

Low-dose melphalan for treatment of high-risk myelodysplastic syndromes.

Twenty-one consecutive patients with high-risk myelodysplastic syndromes (MDS) including six with refractory anemia with excess blasts (RAEB) and 15 with RAEB in transformation (RAEBt) were treated with daily oral low-dose melphalan (2 mg/day). Seven patients achieved complete remission (CR), one patient partial response, and four minor response while the remaining eight did not respond. The median age of the patients was 65 (range 56-83 years). The mean total amount of melphalan given was 140+/-19 mg in patients who achieved CR. The median duration of CR was 14.5 months. Serious toxicity was not encountered in any of the cases. Neither marrow suppression nor pancytopenia was observed during the administration of melphalan in patients who achieved CR. The clinical features of CR patients included normal karyotype and hypocellular marrow in biopsied specimen from the lilac bone. These observations suggest that melphalan may exert some differentiation effects on leukemic cells in addition to cytotoxic effects. Our study indicates that daily administration of low-dose melphalan is worth trying in the treatment of elderly patients with high-risk MDS.

[Successful treatment of refractory anemia with excess of blasts in transformation with cytarabine ocfosfate].

A 58-year-old female was diagnosed as myelodysplastic syndrome (MDS) [refractory anemia with excess of blasts (RAEB)]. Although melphalan was administered, no response was obtained in the peripheral blood. Sixteen months after diagnosis, she developed RAEB in transformation (RAEB-t), and then overt leukemia. White blood cell (WBC) count elevated to 28,600/microliters with 34% of blasts. She was administered cytarabine ocfosfate (200 mg-->300 mg/day) orally, resulting in decrease of WBC count and blasts in peripheral blood. The drug has been given for 11 months, and her hematological data have now remained stable in RAEB. Cytarabine ocfosfate might be a useful drug for the treatment of high risk MDS such as RAEB and RAEB-t.

Prognostic factors of peripheral T-cell lymphoma (PTL): statistical analysis on 30 patients.

Peripheral T-cell lymphoma (PTL) is a distinctive clinical entity, albeit it comprises several diseases with histologically heterogeneous diagnoses. We studied prognostic factors on 30 patients diagnosed and treated at Shikoku Cancer Center Hospital. Clinical findings and laboratory data were evaluated by statistical analysis to investigate the important factors influencing survival duration. Variables influencing survival were stage, leukemic change, bone marrow infiltration (BMI), anti-human T-lymphocyte virus-type I antibody, white blood cell count, and lactate dehydrogenase (LDH). Multivariate analysis revealed high level of LDH and positive BMI as the important factors for short survival. Histological classifications of the Working Formulation and the T-lymphoma classification by Suchi et al. were also evaluated whether these were related with prognosis. Our data revealed that there was no significant relationship between histological subtype and survival duration. The study of prognostic factors provides valuable aids for us to understand the clinical characteristics of PTL patients with various backgrounds.

Diurnal variation of thermal resistance in rats.

Effects of photoperiod on heat resistance were studied in 88 rats by observing their survival times in a hot environment (42.5 degrees C). Prior to the experiments individual rats were exposed to a given heat (42.5 degrees C) at a definite time of day and a "predicted survival time" in a given heat in individual rats was obtained. Rats were then divided into eight groups (with nine rats in each group) so as to ensure intergroup homogeneity regarding their predicted survival time and were exposed to heat at different times of day (every 3 h) until they were exhausted. It was found that the heat resistance varied with the time of day. In the eight groups kept under a normal light-dark cycle (L, 0700-1900;D, 1900-0700), heat resistances were observed to be significantly higher in the light phase than in the dark phase. Lethal body temperature was not correlated with the heat resistance. In two other groups (n = 8) kept under conditions reversed from the normal lighting cycle, resistance was higher in the nighttime (corresponding to the light phase when the rats were kept in the reversed lighting cycle) than in the morning (corresponding to the dark phase), these changes being accompanied by a phase shift of the diurnal changes in body temperature.

Effects of heat acclimation of distance runners in a moderately hot environment.

Five distance runners (H groups) performed a 60 min bicycle exercise at a load of 60--70% VO2max in a moderately hot environment (Ta: 33.5 degree C, 60% RH). Following a period of heat acclimation with bench-stepping at a load equal to about 25--30% VO2max, in a hot environment (Ta: 45--50 degree C, 30--40% RH) for 9 days, the work test was repeated. Two control subjects (R) performed the same work tests with no heat acclimation. Heat acclimation increased performance time. Rectal temperature, mean skin temperature, heart rate, and Na+ concentrations in sweat were lower in H and, with one exception, sweat rate was higher after heat acclimation. All H subjects demonstrated that the linear relationship between sweat rate and rectal temperature was shifted to a lower temperature (threshold shift). This shift correlated with a lowering of resting rectal temperature. The magnitude of the reduction in those two temperatures due to heat acclimation was identical. The observed improvement of work performance in moderate heat following heat acclimation to a higher temperature is attributed to a more efficient thermoregulatory mechanism.

Effects of endurance training on thermoregulation in females.

Thermoregulatory responses to heat have been evaluated at rest in 27 university students; 11 female competitive athletes, 8 male non-athletes, and 8 female non-athletes. They rested for 2 h in an ambient temperature of 32 degrees C, 40% RH with their legs immersed up to the knees in a stirred water bath of 42 degrees C. Sweat rates of the female athletes were higher than the female non-athletes, but lower than the male non-athletes. Core temperature threshold for sweating was significantly lower in the female athletes than in the male and female non-athletes. The slope in sweat rate/core temperature relationship of the female athletes was nearly parallel to that of the female non-athletes. The thermoregulatory responses observed in the female athletes are thought to be comparable to those produced by heat adaptation. Comparing the heat responses in male and female non-athletes, no distinct sexual differences were observed in the rise in core temperature, mean skin temperature, and the core temperature threshold for sweating. On the other hand, the slope in the sweat rate/core temperature relationship was significantly steeper in males than in females. The beneficial modifications of heat responses demonstrated in the present study in female athletes are similiar to those observed in male athletes.