Acute lymphoblastic leukemia, hand-mirror variant. A detailed ultrastructural study.

The hand-mirror cell in acute lymphoblastic leukemia may have important immunologic, pathogenic, and prognostic implications. To learn more about this cell, a detailed ultrastructural analysis was performed. Fifty electronmicrographs of lymphoblasts from an untreated patient with acute lymphoblastic leukemia with numerous hand-mirror cells in the bone marrow were compared with 60 electronmicrographs of lymphoblasts from six patients with classic acute lymphoblastic leukemia. The unique qualitative ultrastructural features of the hand-mirror cells were the presence of undamaged mitochondria and uropods (handles) with terminal microspikes containing circular organized arrangement of 50-A microfilaments. Quantitative differences between hand-mirror cells and lymphoblasts were observed in nuclear perimeters (P less than 0.0001), nuclear lengths (P less than 0.001), cytoplasmic lengths (P less than 0.0002), nuclear-cytoplasmic length ratios (P less than 0.0001), and numbers of mitochondria (P less than 0.002). These findings indicate that hand-mirror cells contain ultrastructural components that are related to cell motility and the immunologic process. These results are significant in that the hand-mirror cells may be associated with an immunologic mechanism that is involved in leukemogenesis.

Acute lymphoblastic leukemia: hand mirror variant.

The presence of numerous hand mirror cells in the bone marrow of patients with acute leukemia may be related to a good prognosis. To further evaluate this relationship, the bone marrows of 21 consecutive patients with a diagnosis of acute lymphoblastic leukemia were reviewed for the presence of greater than 40% hand mirror cells. Four of these 21 patients (19%) demonstrated this finding during the course of their illness. These patients were characterized by ease of remission and/or prolonged survival. Three (75%) patients are alive and well at the time of this writing. At the present time, of the 17 patients without hand mirror cells, seven (41%) are alive and ten (59%) are dead. Although not statistically significant, our findings suggest a positive relationship between the presence of greater than 40% hand mirror cells in the bone marrow ans a favorable prognosis. Future larger prospective studies are indicated to further understand the importance of this complex, apparently immunologically stimulated cell.

Male--female variability in the dietary cholesterol-induced hyperlipoproteinemia of cynomolgus monkeys (Macaca fascicularis).

The characteristics of dietary cholesterol-induced hyperlipoproteinemia were studied in adult Macaca fascicularis to determine if significant male--female differences could be identified. The plasma lipoproteins from individual animals were separated by agarose column chromatography and the resulting size populations of lipoproteins were chemically characterized. The distribution of constituents among the lipoprotein classes was determined. The lipoproteins that increased most significantly in response to dietary cholesterol were the low density lipoproteins (LDL) which were those of region III of the column elution profile. The LDL mass concentrations (in mg/dl of plasma) were not different between males and females. However, these lipoproteins showed a characteristic difference between males and females in response to dietary cholesterol. The primary response in the males was an increased LDL molecular weight. In females, the primary response was an increased number of LDL particles (measured as mumolar concentration). Thus, at the same LDL mass concentration, males had significantly larger LDL particles and yet fewer of them. Analysis of the chemical composition data showed that size differences between LDL of males and females was due primarily to the incorporation of more cholesteryl ester into the LDL particles from male animals; the content per LDL particle of free cholesterol, phospholipid, and protein showed the same proportionality to size for both sexes. Another significant difference between lipoproteins of males and females was in the extent to which the plasma HDL (identified in these studies as the lipoproteins of region IV of the elution profile) decreased in response to dietary cholesterol. Chemical composition differences were also noted. The HDL particles of males and of cholesterol-fed animals contained more cholesteryl ester than did HDL of females and control animals, respectively.

Characterization of plasma low density lipoproteins on nonhuman primates fed dietary cholesterol.

LDL from animals of three nonhuman primate species, Macaca mulatta, Macaca fascicularis, and Cercopithecus aethiops, were studied. A standard preparation of 125I-LDL was added to isolated lipoprotein mixtures just prior to separation of plasma lipoproteins by agarose gel chromatography. A relative size index, rI, was determined by dividing the elution volume of the iodinated LDL by the elution volume of the sample LDL, both volumes being determined simultaneously during chromatographic elution. Comparison of rI with molecular weights measured by flotation equilibrium analysis in the analytical ultracentrifuge showed a linear relationship across a molecular weight range of 2.5-8.0 X 10(6), r = 0.985. A regression equation describing this relationship was used to calculate molecular weights of LDL from a group of M. fascicularis that were fed cholesterol-containing diets. In these animals, plasma cholesterol concentration ranged from 100 to over 700 mg/dl and was highly correlated with LDL molecular weight and with the micromolar concentration of the LDL. Using multiple regression analyses, the two variables of plasma LDL could be shown to account for 94% of the variation in plasma cholesterol concentration in the M. fascicularis of this study. Micromolar concentration and molecular weight of LDL were not correlated with each other, suggesting that in M. fascicularis at least two independent types of controls are operative in the response of plasma LDL to dietary cholesterol. The increase in LDL molecular weight was associated with a large increase in cholesteryl ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. As molecular weight increased, these components appeared to be added to the LDL particles together as discrete increments of fixed composition. The data are consistent with a spherical model of LDL structure with a core of cholesteryl ester and triglyceride and a 21.3 A-thick coat of phospholipid, free cholesterol, and protein.

Infectious mononucleosis and acute lymphoblastic leukemia--hand mirror cells: a qualitative and quantitative ultrastructural study.

The hand mirror cell (HMC) in infectious mononucleosis (IM) is a T cell which appears at the time of improvement and apparently has an important role in immune surveillance. Fifty electron micrographs of HMC from an unusual untreated patient with ALL-HMC variant were compared to 50 electron micrographs of HMC from five patients beginning to recover from IM. Quantitative differences between the IM-HMC and ALL-HMC were observed in multivariate analysis of variance (p < 0.001), nuclear perimeter (p < 0.0001), nuclear length (p < 0.0001), cytoplasmic length (p < 0.0001), total cell area (p < 0.0001), cytoplasmic area (p < 0.0001) and nuclear cytoplasmic ratio (p < 0.004), and numbers of mitochondria (p < 0.001). The qualitative differences included greater nuclear irregularity in the IM-HMC, and prominent nucleolonema in some of the ALL-HMC. In addition, the IM-HMC showed more polyribosomes, parallel tubular arrays and microtubules, but much less glycogen. Since the IM-HMC apparently enter effectively into immune surveillance, and some cases of ALL have HMC, the ultrastructural similarities and differences above contribute to a better understanding of the importance of this unique cell configuration in benign and malignant disorders.

Spectrophotometric measurement of carboxyhemoglobin and methemoglobin in blood.

This paper describes separate spectrophotometric procedures for rapidly measuring carboxyhemoglobin (COHb) and methemoglobin (MetHb) in blood. Absorbance measurements are made in the Soret region at a blood dilution near 1000-fold. For COHb estimation, the diluent contains sodium hydrosulfite, providing the two-component system COHb--Hb for absorbance measurements at 420 and 432 nm. The NA2S2O4 effectively prevents dissociation of COHb by oxygen. For MetHb estimation, the diluent contains KCN and carbon monoxide, providing the two-component system COHb--CNMetHb. Absorbance measurements are made at 420 nm, before and after addiely analyzed for the total of all MetHb forms present. Each procedure requires about 3 muL of blood and can be applied to human or animal blood. Results obtained by the present methods are in satisfactory agreement with currently accepted procedures, which require much larger samples or more elaborate equipment.

Acute lymphoblastic leukemia--hand mirror variant. An analysis of a large group of patients.

One hundred and thirty-four initial bone marrows and 102 peripheral blood smears were evaluated for hand mirror cells (HMC) on pediatric patients with acute lymphoblastic leukemia (ALL). Twenty (15%) of the 134 patients were found to have greater than 5% HMC in their bone marrows. Only rarely were a few HMC noted in the peripheral blood. Survival did not appear to be related to the number of HMC in the bone marrow. Also, the median survival was not significantly greater in those HMC patients with greater than 40% HMC in their bone marrows when compared to the non-HMC group. From the available data in this study, it would appear that the number of HMC does not affect prognosis in the bone marrows of children with ALL. However, the prognostic significance of the HMC has not been clearly established in adults.