Chromosomal localization of four human zinc finger cDNAs

cDNA clones encoding zinc finger motifs were isolated by screening human placenta and T-cell (Peer) cDNA libraries with zinc finger (ZNF) consensus sequences. Unique cDNA clones were mapped in the human genome by rodent-human somatic cell hybrid analysis and in some cases in situ chromosomal hybridization. ZNF 80 mapped to 3p12-3qter, ZNF 7 was previously mapped to 8q24 and is here shown by in situ hybridization and use of appropriate hybrids to map telomeric to the MYC locus. ZNF 79 mapped to 9q34 centromeric to the ABL gene and between a constitutional chromosomal translocation on the centromeric side and the CML specific ABL translocation on the telomeric side. ZNF77 mapped to 19p while ZNF 78L1 (pT3) mapped to 19q. Chromosome 19 carries many ZNF loci and other genes with zinc finger encoding motifs; the pT3 clone additionally detected a locus designated ZNF 78L2, which mapped to chromosome region 1p, most likely in the region 1p32 where the MYCL and JUN loci map.     

Translocation t(11;14) and trisomy 11q13----qter in multiple myeloma

A 14q+ marker with extra material derived from chromosome 11 long arm, i.e. segment q13----qter, has been found in cells from a pleural effusion in a patient with highly malignant multiple myeloma. The segment 11q13----qter was trisomic because of the presence of both apparently normal homologous chromosomes 11.     

Trisomy 6p22→6pter due to familial t(6;13)(p22;q34 or 33) translocation

Summary 235 cases of Down's syndrome were ascertained in a 10-year study of Down's syndrome in Western Australia. Although cytogenetic studies performed on 222 subjects confirmed that 95% of cases were trisomic due to nondisjunction, 4% were trisomic due to translocation, and 1% were mosaic, the ratio of inherited/sporadic translocations differed from that usually reported. Comparison of the results with those of an earlier Australian survey of Down's syndrome demonstrated a real fall in the incidence of Down's syndrome in Australia but no significant change in maternal age-specific incidences.     

Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress

Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration—defects in mitochondrial function and aberrant Rhodopsin trafficking. Although mitochondrial defects are often associated with oxidative stress, they have not been linked to Rhodopsin trafficking. In an unbiased forward genetic screen designed to isolate mutations that cause photoreceptor degeneration, we identified mutations in a nuclear-encoded mitochondrial gene, ppr, a homolog of human LRPPRC. We found that ppr is required for protection against light-induced degeneration. Its function is essential to maintain membrane depolarization of the photoreceptors upon repetitive light exposure, and an impaired phototransduction cascade in ppr mutants results in excessive Rhodopsin1 endocytosis. Moreover, loss of ppr results in a reduction in mitochondrial RNAs, reduced electron transport chain activity, and reduced ATP levels. Oxidative stress, however, is not induced. We propose that the reduced ATP level in ppr mutants underlies the phototransduction defect, leading to increased Rhodopsin1 endocytosis during light exposure, causing photoreceptor degeneration independent of oxidative stress. This hypothesis is bolstered by characterization of two other genes isolated in the screen, pyruvate dehydrogenase and citrate synthase. Their loss also causes a light-induced degeneration, excessive Rhodopsin1 endocytosis and reduced ATP without concurrent oxidative stress, unlike many other mutations in mitochondrial genes that are associated with elevated oxidative stress and light-independent photoreceptor demise.     

Prenatal diagnosis of a de novo satellited chromosome 18 (18ps) associated with 18p deletion

De novo satellited non-acrocentric chromosomes are very rare findings in prenatal diagnosis. Here we report the first case of a de novo 18ps, associated with del(18p), detected at prenatal diagnosis. A 37 years old woman underwent Chorionic Villus Sampling (CVS) for advanced maternal age. Cytogenetic analysis on direct CVS preparation (CVSc) revealed a male karyotype with a nonfamilial satellited 18ps and a reciprocal translocation t(17;19)(P11.1;q11) of maternal origin. The mesenchimal CVS culture (CVSm) showed a mosaic of cell lines with various involvement of chromosome 18: 18ps [36/70]/ r(18) [25/70]/ del(18p) [3/70]/ -18 [6/70]. Amniotic fluid cells (AFC) confirmed the homogeneous karyotype found at CVSc. The molecular cytogenetic characterization, performed on AFC, allowed the following diagnosis: 46,XY, +15, dic(15;18)(p11.1;p11.2), t(17;19)(p11.1;q11)mat. ish dic(15;18)(tel 18p-, D15Z1+, wcp18-, wcp 18+, D18Z1+, tel 18q+). The foetal autopsy disclosed subtle facial dysmorphisms and corpus callosum hypoplasia. In case of prenatal detection of de novo terminal ectopic NORs an accurate cytogenetic and molecular analysis should be performed in order to rule out subtle unbalancements.     

Human bone cell cultures: a new model for studying the mechanism of action of calcitonin

An investigation on cell cultures obtained from temporal human bone fragments showed that they provide a suitable model for studying the mechanism involved in calcitonin action on bone cells. Furthermore they demonstrated: a transitory increase in 45Ca uptake that returned to control values ten minutes after the hormone was added; a relation between 45Ca uptake and increased cAMP concentrations when these were measured at the same time intervals; a reproduction of the salmon calcitonin (sCT) effect after incubation of the cultures with either db-cAMP or db-cGMP and inhibition of 45Ca uptake and parallel decrease in cAMP levels with propanol. These results suggest that in human bone cell cultures, sCT acts as a temporary promoter of 45Ca uptake, probably by activating an adenylate-cyclase system through a beta-receptor.     

Characterization of the cytoskeleton in human normal and otosclerotic osteoblast-like cells.

The localization and distribution of some cytoskeletal protein components were studied by immunostaining methods in normal and ostosclerotic osteoblast-like cells. The protein components investigated were microtubules (beta-tubulin), intermediate filaments (vimentin), microfilaments (actin and myosin) and structural proteins (alpha-actinin and fibronectin). Although the mechanism is not yet clear, the alterations observed in the pathological cells could well play a role in the expression of otosclerosis.     

Stem cells from human amniotic fluid exert immunoregulatory function via secreted indoleamine 2,3‐dioxygenase1

Although human amniotic fluid does contain different populations of foetal‐derived stem cells, scanty information is available on the stemness and the potential immunomodulatory activity of in vitro expanded, amniotic fluid stem cells. By means of a methodology unrequiring immune selection, we isolated and characterized different stem cell types from second‐trimester human amniotic fluid samples (human amniotic fluid stem cells, HASCs). Of those populations, one was characterized by a fast doubling time, and cells were thus designated as fHASCs. Cells maintained their original phenotype under prolonged in vitro passaging, and they were able to originate embryoid bodies. Moreover, fHASCs exhibited regulatory properties when treated with interferon (IFN)‐γ, including induction of the immunomodulatory enzyme indoleamine 2,3‐dioxygenase 1 (IDO1). On coculture with human peripheral blood mononuclear cells, IFN‐γ–treated fHASCs caused significantly decreased T‐cell proliferation and increased frequency in CD4⁺ CD25⁺ FOXP3⁺ regulatory T cells. Both effects required an intact IDO1 function and were cell contact‐independent. An unprecedented finding in our study was that purified vesicles from IFN‐γ–treated fHASCs abundantly expressed the functional IDO1 protein, and those vesicles were endowed with an fHASC‐like regulatory function. In vivo, fHASCs were capable of immunoregulatory function, promoting allograft survival in a mouse model of allogeneic skin transplantation. This was concurrent with the expansion of CD4⁺ CD25⁺ Foxp3⁺ T cells in graft‐draining lymph nodes from recipient mice. Thus fHASCs, or vesicles thereof, may represent a novel opportunity for immunoregulatory maneuvers both in vitro and in vivo.     

Karyotype 46,XY,22p+ in a male patient (author's transl)

The authors report the case of a 2-month-old infant with psychomotor retardation and several physical stigmata. Cytogenetic studies of the patient using the normal technique show in all the cells a karyotype 46,XY with a G group chromosome substituted by an F-like mediocentric element with satellites. The R, G and C-banding methods reveal that it is the 22 with too developed short arms (22p+). This element was found in the mother's and maternal grandfather's karyotypes although they both present normal phenotypes. The authors advance two hypotheses concerning the origin of the alteration but cannot exclude a possible connection between this particular chromosome and the proband's anomalies. The difficulties of genetic counselling in this case are evident.