Assisted reproductive technology and congenital overgrowth: some speculations on a case of Pallister-Killian syndrome.

We report on a boy with Pallister-Killian syndrome (PKS) who was conceived by assisted reproductive technology (ART), specifically in vitro fertilization (IVF) with parents' gametes. A prenatal diagnosis performed elsewhere by CVS failed to detect the presence of the isochromosome 12p that was demonstrated postnatally in approximately 50% of cultured skin fibroblasts. Given that the patient did not show the congenital overgrowth typical of PKS, we speculate that ART might have restricted overgrowth in this particular case. More broadly, we hypothesize that overgrowth might protect from early demise fetuses conceived by ART, a technology known to cause low and very low birth weight.

Constitutional trisomy 8 and myelodysplasia: report of a case and review of the literature.

A diagnosis of myelodysplastic syndrome was made in an 18-year-old patient with Warkany syndrome due to constitutional trisomy 8 mosaicism. The possible causal role of this particular chromosome constitution with respect to myelodysplasia and embryonal childhood tumors is discussed.

Trisomy 4 as the sole karyotypic anomaly in acute biphenotypic leukemia with B lineage markers and in acute minimally differentiated myeloid leukemia (M0).

Trisomy 4 is a recently defined chromosomal aberration in acute leukemia. The first reports suggested that this cytogenetic anomaly belongs to the M4 leukemia subtype of the FAB classification, but recent reports have described this alteration in a wider spectrum of leukemia subtypes. Here we report two cases of trisomy 4 as the sole chromosome anomaly: one was observed in a patient with acute biphenotypic leukemia with B-lineage markers and the second in a patient diagnosed with acute minimally differentiated myeloid leukemia (M0) with myelodysplastic features. To our knowledge these are, respectively, the first and second reports of trisomy 4 as the sole chromosomal anomaly in these leukemia subtypes.

First report of t(8;21)(q22;q22) in a case of de novo acute monoblastic leukemia.

Here we describe the case of a 30-year-old man with a diagnosis of de novo acute monoblastic leukemia (FAB M5a), whose karyotype analysis revealed the presence of the translocation (8;21)(q22;q22) as the sole chromosome anomaly. In spite of the rather good prognosis patients suffering from acute leukemia and carrying this translocation are supposed to have, our patient had a very poor outcome, including an early relapse resistant to any treatment and meningeal localization. Death occurred within 5 months from diagnosis. To our knowledge this is the first report of t(8;21)(q22;q22) in de novo acute monoblastic leukemia.

Trisomy 4 in acute myeloblastic and acute lymphoblastic leukemia.

We report three cases of trisomy 4 in acute leukemia. This alteration was detected as the sole cytogenetic abnormality in a case of FAB M4 leukemia; it occurred in association with 5q deletion in a case of M1, and concomitant with Ph chromosome and trisomy 17 in a case of L2 leukemia. The latter case represents the fourth report of trisomy 4 in acute lymphoblastic leukemia.

UV microbeam irradiations of the mitotic spindle. II. Spindle fiber dynamics and force production.

Metaphase and anaphase spindles in cultured newt and PtK1 cells were irradiated with a UV microbeam (285 nM), creating areas of reduced birefringence (ARBs) in 3 s that selectively either severed a few fibers or cut across the half spindle. In either case, the birefringence at the polewards edge of the ARB rapidly faded polewards, while it remained fairly constant at the other, kinetochore edge. Shorter astral fibers, however, remained present in the enlarged ARB; presumably these had not been cut by the irradiation. After this enlargement of the ARB, metaphase spindles recovered rapidly as the detached pole moved back towards the chromosomes, reestablishing spindle fibers as the ARB closed; this happened when the ARB cut a few fibers or across the entire half spindle. We never detected elongation of the cut kinetochore fibers. Rather, astral fibers growing from the pole appeared to bridge and then close the ARB, just before the movement of the pole toward the chromosomes. When a second irradiation was directed into the closing ARB, the polewards movement again stopped before it restarted. In all metaphase cells, once the pole had reestablished connection with the chromosomes, the unirradiated half spindle then also shortened to create a smaller symmetrical spindle capable of normal anaphase later. Anaphase cells did not recover this way; the severed pole remained detached but the chromosomes continued a modified form of movement, clumping into a telophase-like group. The results are discussed in terms of controls operating on spindle microtubule stability and mechanisms of mitotic force generation.

Autoantibodies from a patient with scleroderma CREST recognized kinetochores of the higher plant Haemanthus.

Human autoantibodies from a patient with scleroderma CREST (calcinosis, Raynaud phenomenon, esophageal dismotility, sclerodactyly, telangiectasia) were used to immunostain kinetochores on chromosomes in endosperm of the seed of the monocot Haemanthus katherinae Bak. Kinetochores of mitotic chromosomes and prekinetochores of interphase cells were specifically stained using conventional indirect immunofluorescence procedures as well as a nonfading immunogold-silver-enhanced technique and analyzed by fluorescence and video microscopy. In interphase, prekinetochores were either single or double structures depending on the stage of the cell cycle but became quadruple (two distinct stained dots on each chromatid) in mid-to-late prophase. In favorable preparations of prometaphase chromosomes, multiple subunits could be resolved within each sister kinetochore suggesting a compound organization. Western blot analysis demonstrated common epitopes in centromeric peptides of HeLa and Haemanthus cell extracts. Although the molecular mass of individual polypeptides differed in the two species, the presence of shared epitopes indicates striking conservation of centromere/kinetochore components throughout evolution.

Catalase and glutathione peroxidase activity in cells with trisomy 21.

CuZnSOD is produced in overdose in cells with trisomy 21. This has been considered to be a cause of increased oxidative stress. In the present work we have studied the catalase and glutathione peroxidase activity in fibroblasts from 6, and blood cells from 30, subjects affected by Down syndrome. In the fibroblasts, catalase and glutathione peroxidase activities did not differ significantly from control cells. In platelets, lymphocytes, polymorphs and erythrocytes, no significant increase of catalase activity was found while glutathione peroxidase activity appeared significantly increased in platelets, polymorphs and erythrocytes but not in lymphocytes. These data seem to indicate that the increase of CuZnSOD in trisomy 21 cells does not affect the production of catalase. An increase, instead, of glutathione peroxidase has been detected in all blood cells, except in lymphocytes; this is a sign of a greater need for protection against the risk of lipoperoxidation. The fact that the enhancement of glutathione peroxidase activity could be assessed only in some types of cells examined suggests that the observed increase in those cells is probably a result of an additive effect of the overproduction of CuZnSOD due to gene dosage and the ordinarily higher content of oxygen radicals and peroxides.

Three-dimensional localization and redistribution of F-actin in higher plant mitosis and cell plate formation.

The distribution of F-actin cables in dividing endosperm cells of a higher plant, Haemanthus, was visualized with the immunogold-silver-enhanced method and compared with the arrangement of immunogold-stained microtubules in the same cells. The three-dimensional distribution of F-actin cables and microtubules during mitosis and cell plate formation was analyzed using ultrathin optical sectioning of whole mounts in polarized light video microscopy. F-actin cables form a loose irregular network in the interphase cytoplasm. Much of this network remains outside of the spindle during mitosis. A few F-actin cables were detected within the spindle. Their pronounced rearrangement during mitosis appears to be related to the presence and growth of microtubule arrays. During prometaphase, actin cables located on the spindle surface and those present within the spindle tend to arrange parallel to the long axis of the spindle. Cables outside the spindle do not reorient, except those at the polar region, where they appear to be compressed by the elongating spindle. Beginning with mid-anaphase, shorter actin cables oriented in various directions accumulate at the equator. Some of them are incorporated into the phragmoplast and cell plate and are gradually fragmented as the cell plate is formed and ages. Actin cables adjacent to microtubule arrays often show a regular punctate staining pattern. Such a pattern is seldom observed in the peripheral cytoplasm, which contains few microtubules. The rearrangement of F-actin cables mimicks the behavior of spindle inclusions, such as starch grains, mitochondria, etc., implying that F-actin is redistributed passively by microtubule growth or microtubule-related transport. Thus F-actin or actomyosin-based motility does not appear to be directly involved in mitosis and cytokinesis in higher plants.

Modification of the 6-hydroxydopamine technique for the correct determination of superoxide dismutase.

Heikkila & Cabbat (Anal. Biochem. 75, 356-362 (1976] have proposed the autoxidation of the 6-hydroxydopamine as a method to test superoxide dismutase activity in biological samples. This method has several advantages but in some instances leads to incorrect determinations. We present here a necessary modification of the method to avoid bias.