Uneinheitlicher Phänotyp bei Partialtrisomie 4q

Zusammenfassung Es wird über die klinischen und cytogenetischen Befunde bei 3 nichtverwandten Patienten mit Partialtrisomie 4q berichtet. In 2 Fällen ist die Chromosomen-aberration durch eine balancierte elterliche Translokation entstanden (t(3p+;4q-) und t(4q-;18q+)) während im 3. Fall eine spontane invertierte Insertion von 4q22q34 in 4q34 angenommen wird.Ein Vergleich der Symptomatik dieser Patienten mit 7 Fällen aus der Literatur läßt keinen einheitlichen Phänotyp erkennen.

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Phenotypic variation in partial trisomy 4q

Summary The clinical and cytogenetic data of 3 non-related patients who have a partial trisomy 4q in common are reported. The chromosome aberration originated from a parental balanced translocation in 2 cases (t(3p+;4-) and t(4q-;18q+)); in the 3rd case an inverted insertion of 4q22q34 into 4q34 occured spontaneously.A comparison of the symptoms exhibited by these probands and 7 cases from the literature gives no indication of an uniform phaenotype of this aberration.

     

Lymphokine production by human melanoma tumor-infiltrating lymphocytes

Summary Lymphokine production by human melanoma tumor-infiltrating lymphocytes (TIL) was studied. Uncultured TIL produced interferon (IFN), but not interleukin-2 (IL-2) or IL-4, in response to anti-CD3 mAb or IL-2. In bulk cultures, IL-2-activated TIL displaying autologous tumor-specific cytotoxicity (CTL-TIL) produced IFN in culture with medium alone, whereas IL-2-activated noncytotoxic TIL did not. Addition of anti-CD3 mAb or autologous tumor cells up-regulated IFN production in IL-2-activated TIL from 10 of 12 or 6 of 12 cases respectively. Those from 4 of 12 cases (2 CTL-TIL and 2 noncytotoxic TIL) produced IL-2 in culture with medium alone. At the clonal level, 5 (4 CD4⁺ and 1 CD8⁺) of 7 autologous tumor-specific CTL clones derived from TIL and 3 (2 CD4⁺ and 1 CD8⁺) of 7 noncytotoxic TIL clones produced IFN in culture with medium alone, which was up-regulated by adding anti-CD3 mAb. Two IFN-producing CTL clones tested produced IL-2 in 4 ×-concentrated supernatants from a 3.5-h culture with medium alone. Furthermore, 2 IFN-producing CTL clones tested expressed mRNA for both IFN and IL-2. IL-2 production and its mRNA expression were up- or down-regulated, respectively, by adding anti-CD3 mAb or autologous tumor cells. IL-4 production was not observed in culture either with medium alone or with IL-2 in any of the cells described above. Anti-CD3 mAb was required for IL-4 production in 3 of 12 IL-2-activated TIL, 2 of 6 CTL clones, and none of 5 noncytotoxic TIL clones. In summary, IFN production was characteristic of melanoma TIL. Some autologous tumor-specific CTL in TIL are suggested to be productive of IL-2 and IFN under unstimulated conditions, both being required for self-activation in an autocrine loop.This work was supported in part by grant CA-47891 from the National Cancer Institute     

Complex translocations,simple variant translocations and Ph-negative cases in chronic myelogenous leukaemia

Summary A proportion of cases of chronic myelogenous leukaemia (CML) has been described either (1) with a variant translocation, or (2) without the apparent involvement of both 9q34 and 22q11 (Ph-negative CML). All variant translocations have been further demonstrated to be complex implicating 9q34,22q11, plus another breakpoint on a variable chromosome. Complex translocations may be due to two successive events. Some of the breakpoints on the variable chromosome appear to be recurrent, and these remain to be studied for prognostic significance. Ph-negative CML comprises (1) cases of submicroscopic (hidden) insertion of 9q34-ABL within 22q11-BCR, and (2) cases without BCR-ABL rearrangement. We propose this last category to be called CML-like disease, not to be confused anymore with true CML, and consequently to be studied as a separate entity.     

A termination mutation (2143delT) in the CFTR gene of German cystic fibrosis patients

German patients with cystic fibrosis (CF) were screened for molecular lesions in exon 13 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by single strand conformation polymorphism (SSCP) and chemical cleavage of mismatch analyses. Direct sequencing of four samples that displayed the same SSCP pattern and that were susceptible to cleavage of heteroduplexes by osmium tetroxide revealed, in all cases, a deletion of a single T residue at nucleotide position 2143 within codon 671 of the CFTR gene. As a result, leucine codon 671 is changed into a termination codon. In total, the 2143delT mutation was confirmed in 6 out of 271 German non-F508 CF chromosomes by artificial restriction fragment length polymorphism analysis, indicating that this frameshift mutation accounts for about 2% of German non-508 mutations. The 6 pancreas insufficient patients who are compound heterozygous for 2143-delT suffer from the typical features of pulmonary and gastrointestinal CF disease. The 2143delT mutation completes the panel of the more frequent CFTR mutations that reside on the F508 haplotype and that contribute to its overpresentation among German non-F508 alleles that are associated with severe forms of disease.     

Relationships of Agropyron intermedium chromosomes determined by chromosome pairing and alcohol dehydrogenase isozymes in common wheat background

Summary The relationships of Agropyron intermedium chromosomes in two wheat-Agropyron addition series were determined. Chromosome pairing behaviour revealed that the alien chromosome in lines TAF-2 and L7 of Vilmorin-A. intermedium set are homologous to the alien chromosomes in lines P and C of the Caribo-A. intermedium set respectively. Localization of alcohol dehydrogenase isozyme genes in Vilmorin-Agropyron addition line L4 and in Caribo-Agropyron line O indicated relationships with wheat chromosomes of homoeologous group 4.     

Primary structure of the hemoglobin beta-chain of rose-ringed parakeet (Psittacula krameri)

The primary structure of Rose-ringed Parakeet hemoglobin -chain was established, completing the analysis of this hemoglobin. Comparisons with other avian -chains show variations smaller than those for the corresponding -chains. There are 11 amino acid exchanges in relationship to the only other characterized psittaciform -chain, and a total of 35 positions are affected by differences among all avian -chains analyzed (versus 61 for the -chains). At three positions, the Psittacula -chain has residues unique to this species. Three ₁₁ contacts are modified, by substitutions at positions 51, 116, and 125.     

Evidence for methylation as a regulatory mechanism in HLA-DR x gene expression

We examined the possibility that one mechanism for controlling HLA-DR gene expression occurs through DNA hypomethylation. We employed the restriction enzyme Hpa II, which recognizes the sequence 5CCGG3 but not 5C^mCGG3, to study DNA methylation. We first compared a DR-positive B lymphoblastoid cell line (LCL) with an isogenic DR-negative T-LCL. Using a genomic probe for the DR gene, we showed that an Hpa II digestion of DNA from the B-LCL resulted in bands of lower molecular weight than that of the T-LCL. This indicates that the B-LCL DR gene is hypomethylated relative to the T-LCL gene. Demethylation of the gene from the B-LCL is incomplete, suggesting that complete demethylation is not required for its expression. We also examined somatic cell hybrids of T-LCL and B-LCL since the DR gene, which is inactive in the T-LCL, is expressed in the hybrids, providing a system to study DR gene induction. We examined the hybrid line 174 × CEM.T1, which contains and expresses solely the DR gene from the T-LCL parent since both copies of the DR gene from the B-LCL parent, 174, are deleted. The expressed DR gene from the hybrid was compared with the unexpressed gene from the T-LCL parental line, and again an association between DR gene expression and DNA hypomethylation was observed. In contrast to the DR gene from B-LCL, which is not completely demethylated, the DR gene in this hybrid line is not methylated at either of the Msp I sites covered by our probe. This suggests that different regulatory mechanisms operating through DNA methylation may be involved in the expression of DR genes from T-LCL and B-LCL. Examination of another hybrid line which has DR genes from both parental lines supports this contention. The implications of these findings are discussed.     

Inhibitory effect of menaquinone-7 (vitamin K2) on osteoclast-like cell formation and osteoclastic bone resorption in rat bone tissues in vitro

Heme oxygenase1, the major inducible isoform of heme oxygenase (HO), can be induced by heme and numerous other physical and chemical factors, many of which cause cellular stress. This has led to the realization that HO1 is a major highly conserved stress or heat shock protein. Recent work has implicated activation of mitogenactivated protein kinases and other kinases in the mechanism of induction of HO1, and suggested that signal transduction pathways through tyrosine kinases are involved in induction of HO1 gene expression by stress inducers. We hypothesized that phenylarsine oxide (PAO), an inhibitor of protein tyrosine phosphatases (PTPs), might up-regulate the HO1 gene. Here, we show that a remarkably brief (1–15 min) exposure of normal hepatocytes to low concentrations (0.5–3 M) of PAO produces a marked increase in mRNA and protein of HO1. This increase is comparable to the level obtained by addition of heme (20 M), and occurs without producing changes in cellular glutathione levels or stabilization of HO1 message. Preincubation of cells with inhibitors of protein synthesis decreased the ability of PAO to increase levels of HO1 mRNA, suggesting that the inductive effect requires de novo protein synthesis. Addition of thiol donors abrogated the PAOmediated induction of HO1 in a dose dependent fashion. Addition of genistein, a tyrosine kinase inhibitor, blunted the induction produced by both PAO and heme. After brief incubations with PAO or heme, cell extracts showed comparable increases in levels of protein tyrosine phosphorylation in general, and specifically in ZAP70 kinase. Our results are consistent with the proposition that induction of HO1 by PAO involves inhibition of specific PTP(s), and that the mechanisms of induction of HO1 by PAO and by heme may share some common pathways.     

Bacterial symbionts on green hydra and their effect on phosphate uptake

Gram-negative rod-shaped bacteria (1.5–2m long and 0.5m wide) have been found associated with green hydra. They are always present on the hydra surface delineating the ectodermal cells, on animals in culture, and also on those sampled from a natural habitat. The bacteria could be removed by a 30-min treatment with antibiotics (50/ml polymyxin B and 50/ml streptomycin). Antibiotic-treated hydra took up 55% less phosphate from the medium than control hydra. The nutritional relationship between the bacteria and green hydra and possible routes of infection of the hydra by these prokaryotic symbionts are discussed. Their importance in interpreting results of certain types of physiological experiments using aquatic organisms is emphasized.     

Haemoglobin synthesis in 28 obligatory cases for α-thalassemia traits

Summary In the Far East two types of -thalassemia genes, namely -thalassemia₁ (-thal₁) and -thalassemia₂ (-thal₂) exist. Definite diagnosis of the -thal₁ and -thal₂ traits is very difficult because their hematological findings are minimally abnormal or normal. This study attempts to characterize the heterozygotes by hemoglobin chain synthesis in reticulocytes from obligatory cases of the -thal₁ and -thal₂ traits. Twelve parents of babies with hemoglobin Bart's hydrops fetalis (obligatory -thal₁ trait) had the mean total radioactivity / ratio of 0.76±SD 0.04, while that of 7 normal controls was 1.06±SD 0.04. The / globin chain ratios of 16 cases, who were either parents or offspring of patients with hemoglobin H disease, were found to segregate into 2 groups, i.e. 0.78±SD 0.03 (10 cases) and 0.92±SD 0.03 (6 cases), probably representing the -thal₁ and -thal₂ traits respectively. The hematological data of the first group showed definite hypochromic microcytic red cells, similar to thoseof the parents of the hydrops. The second group had significantly higher mean corpuscular hemoglobin than the first group, compatible with -thal₂ trait. Our globin chain synthesis study thus appears to be capable of discriminating normal, -thal₁ and -thal₂ traits.A preliminary report of the results was presented at the XV Congress of the International Society of Haematology, Israel, September, 1974.     

Preferential maternal derivation in inv dup(15)

Summary Eight patients are reported with a de nov extra inverted duplicated chromosome 15. The abnormal chromosome was considered to be the same in all cases, but its precise delineation remained uncertain and was defined as either 15qter15q12::15q1215pter or 15pter15q11::15q1315pter. Analysis with various techniques of the satellite regions of the bisatellited chromosomes demonstrated maternal derivation in six and paternal derivation in one of the seven families. A nonsister chromatid exchange between the two homologous chromosomes 15 is considered a likely origin of the inv dup(15) in the cases with maternal derivation; in the only case of paternal derivation, however, the abnormal chromosome originated from one single chromosome 15. The clinical findings confirm that patients with inv dup(15) have mental and developmental retardation and are frequently affected by seizures, while severe physical malformations are absent.     

On the sufficiency of the velocity field for perception of heading

All models of self-motion from optical flow assume the instantaneous velocity field as input. We tested this assumption for human observers using random-dot displays that simulated translational and circular paths of movement by manipulating the lifetime and displacement of individual dots. For translational movement, observers were equally accurate in judging direction of heading from a velocity field with a two-frame dot life and a direction field in which the magnitudes of displacement were randomized while the radial pattern of directions was preserved, but at chance with a speed field in which the directions were randomized, preserving only magnitude. Accuracy declined with increasing noise in vector directions, but remained below 2.6° with a 90° noise envelope. Thus, the visual system uses the radial morphology of vector directions to determine translational heading and can tolerate large amounts of noise in this pattern. For circular movement, observers were equally accurate with a 2-frame velocity field, 3-frame acceleration displays, and 2-frame and 3-frame direction fields, consistent with the use of the pattern of vector directions to locate the center of rotation. The results indicate that successive independent velocity fields are sufficient for perception of translational and circular heading.     

X-chromosome methylation in manifesting and healthy carriers of dystrophinopathies: concordance of activation ratios among first degree female relatives and skewed inactivation as cause of the affected phenotypes

The X-chromosome activity states of 11 manifesting carriers of dystrophinopathies, all with normal karyotypes, were estimated by restriction fragment length polymorphism (RFLP)-methylation analysis with the probes M27 (DXS255), p2-19(DXS605) and pSPT/PGK (PGK1) to test the role of skewed X-inactivation ratios as the cause of their affected phenotypes. In eight cases preferential inactivation of the putative X chromosome carrying the normal dystrophin allele in 90% of their peripheral lymphocytes was observed, two cases showed non-appparent deviant ratios (6040 and 7030) from the theoretically expected values around the mean of 50% and in one case the three markers employed yielded no information. The analysis of the X-inactivation ratio in six mother-daughter pairs, all non-manifesting Duchenne muscular dystrophy (DMD) carriers, and in the close female relatives of the patients showed: (a) neither of the two X chromosomes was preferentially inactivated with respect to their parental origin; (b) a high concordance among the activation ratios of mothers and daughters, a result difficult to explain just in terms of random X-chromosome inactivation.     

Polygynie des Trauerschn?ppers(Ficedula hypoleuca) am Westrand seines Areals in Mitteleuropa

Zusammenfassung 1974–1983 waren in einem mit 600 künstlichen Nisthöhlen ausgestatteten Lärchen-Versuchsforst (52.27 N, 7.15 E) bei Lingen/Emsland beim Trauerschnäpper 20,7% der nachweislich mit einem polygamen verpaart. Neben 51 Bigynie-Fällen konnte auch 4mal Trigynie nachgewiesen werden. mit Polygamie-Nachweis waren im Mittel älter als die übrigen (2,71 bzw. 2,18 Jahre). Polygame hatten im Durchschnitt längere Flügel und ein größeres Gewicht als ohne Polygamie-Nachweis, was als Folge der unterschiedlichen Altersstruktur zu deuten ist. Brutkästen der Bigamisten waren im Mittel 258 m voneinander entfernt (Maximum 750 m). Bei Bruten ohne Nachweis eines fütternden lag die Anzahl ausgeflogener Junge (im Mittel 2,9) gesichert unter dem Bruterfolg von zwei anderen Gruppen (fütterndes bei einer Brut festgestellt 4,7; fütterndes bei 2–3 Bruten festgestellt 4,5). Zwischen den Schlüpfterminen von Bigamisten-Bruten lagen 1–16 Tage. Das Durchschnittsalter der in den jeweils früheren Bruten betrug 2,67, in den jeweils späteren Bruten 1,67 Jahre.

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Polygyny in the Pied Flycatcher (Ficedula hypoleuca) at the western border of its Central European range

Summary 1974–1983 in a study area of larch forest (52.27 N, 7.15 E), with 600 nestboxes, near Lingen/Emsland in western Lower Saxony, polygyny among Pied Flycatchers was identified as participation of in feeding at 2 or 3 nestboxes (bigyny or trigyny). 20.7% of were shown to be paired with a polygamous . Beside 51 cases of bigyny 4 cases of trigyny were identified. The incidence of polygyny was also considered in relation to the border situation of the study area. Proven polygamous were on average older than other (2.71 as compared to 2.18 years). On average polygamous had longer wings and greater bodyweight than without polygamous record, which is to be interpreted as a result of differing age structure. On average the mean distance between nestboxes of bigamists was 258 m (max. 750 m). In cases of broods without recorded feeding (generally this would occur in cases of secondary broods of polygamous in which the assisted only rarely or not at all) the number of reared young (on average 2.9) was significantly lower than the breeding success realised by 2 other groups ( recorded as assisting in rearing one brood only 4.7; recorded as assisting in rearing 2–3 broods 4.5). A period of 1–16 days (on average 7) elapsed between the hatching dates of broods of bigamists. The average age of in the earlier broods was 2.67 yrs, in the later broods 1.67 yrs.

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Gefördert mit Hilfe von Forschungsmitteln des Landes Niedersachsen.     

Weather and the incidence of urinary stone colics in the Province of Florence

The present study analyses the case histories of urinary stone colics recorded at the hospital Val di Sieve (Florence) during the period 1962–1971 by comparing the weather conditions of the 353 days during which the cases occurred, with the weather conditions of a sample of normal reference days.From the analysis it seems to emerge that a hot and — at the same time — dry weather, as well as wide changes in air pressure, may favour in predisposed individuals the onset of urinary stone colics.     

Substitutions of the Conserved Thr42 Increased the Roles of the ε-Subunit of Maize CF1 as CF1 Inhibitor and Proton Gate

The conserved residue Thr42 of -subunit of the chloroplast ATP synthase of maize (Zea mays L.) was substituted with Cys, Arg, and Ile, respectively, through site-directed mutagenesis. The over-expressed and refolded -proteins were purified by chromatography on DEAE-cellulose and FPLC on mono-Q column, which were as biologically active (inhibiting Ca²⁺-ATPase activity and blocking proton gate) as the native subunit isolated from chloroplasts. The T42C and T42R showed higher inhibitory activities on the soluble CF₁(–) Ca²⁺-ATPase than the WT. The T42I inhibited the Ca²⁺-ATPase activity of soluble CF₁ and restored photophosphorylation activity of membrane-bound CF₁ deficient in the most efficiently. Far-ultraviolet CD spectra showed that the portions of -helix and -sheet structures of the three mutants were somewhat different from WT. Thus the conserved residue Thr42 may be important for maintaining the structure and function of the -subunit and the basic functions of the -subunit as far as an inhibitor of Ca²⁺-ATPase and the proton gate are related.     

Molecular characterization of β-thalassemia mutations in Egypt

Summary The relative frequency of different -thalassemia mutations and their association with -globin haplotypes were studied in patients from the Nile delta region, Egypt, by means of the polymerase chain reaction, oligonucleotide hybridization and restriction analysis. We found that 8 mutations account for 77% of -thalassemia chromosomes in this population, the commonest being IVS-1 nt 110, IVS-1 nt 6 and IVS-1 nt 1. Each mutation was associated with a specific haplotype, with the exception of IVS-1 nt 110, found on 3 different chromosomal backgrounds. Our data show that testing for the 8 detectable mutations makes feasible prenatal diagnosis in 65% of at risk couples and exclusion testing in an additional 25% of cases.     

Porosity and available water of temporarily waterlogged soils in a Quercus robur (L.) declining stand

Pedunculate oak (Quercus robur L.) is particularly sensitive to decline in clayey soils presenting a high-perched temporary water table. These soils induce two successive constraints in one-year cycle: water excess (and hypoxy) in winter and early spring, and water shortage in summer (water stress being more restrictive to oak). We determined the porosity and water properties of temporarily waterlogged clayey soils supporting forest stands of decliningQuercus robur trees in a 101yr-old oak stand in Belgium (50°06N, 4°16E). Roots unevenly colonized the soil down to 1.6m: fine roots (diameter<5mm) were mostly distributed on the surface horizons (0–0.3 m) and around 1.3m deep, despite dense clayey horizons appearing at 0.35m depth. Clay content below this depth reached 46–51. Illite and vermiculite were the dominant clay minerals. The clayey horizons exhibited marked shrink–swell properties: bulk density at 30kPa increased from 1.41 to 1.88gcm^–3 from the surface to 2m depth. There was also evidence of hypoxic conditions caused by water saturation of pore space in the rooting zone from October to mid-April. Extractable water (EW), calculated between moisture tensions of 5 and 1600kPa was 152.8mm. The level of perched temporary water table strongly depended on the seasonal rhythm of water uptake by trees and on the shrink–swell behaviour of soil.     

Involvement of abscisic acid in bulb dormancy of Allium wakegi Araki. II. A comparison between dormant and nondormant cultivars

The content of abscisic acid (ABA) in bulbs of two Allium wakegi Araki cultivars, Kiharabansei No. 1 (dormant type) and Ginoza (nondormant type), was similar and changed similarly during the development and storage of the bulbs. It increased during bulb development, reached a maximum shortly after bulb harvesting, and gradually decreased during bulb storage. The bulbs of Kiharabansei No. 1 showed dormancy correlated with the change in ABA content, but those of Ginoza did not show significant dormancy throughout the experimental period. The ABA content in the buds of dormant bulbs of Kiharabansei No. 1 did not change after planting of bulbs, but that of nondormant bulbs of Ginoza planted on the same day rapidly decreased after planting. Application of ABA to bulbs delayed sprouting of both cultivars, but dormant bulbs of Kiharabansei No. 1 had higher sensitivity to ABA than the bulbs of Ginoza or the bulbs of Kiharabansei No. 1 partly released from dormancy. These results suggest that the decrease in the ABA content after planting (watering) and low sensitivity to ABA are correlated with the nondormancy of Ginoza.     

Molecular detection of a translocation (Y;11)(q11.2;q24) in a 45,X male with signs of Jacobsen syndrome

Summary A 45,X karyotype was found in a boy with dysmorphic features, hypoglycaemia and pancytopenia. DNA analysis showed the presence of the Y-chromosomal DNA sequences SRY, ZFY, DYZ4, DYZ3 and DYS1. Using fluorescent in situ hybridization, we located DYZ4 and DYZ3 on chromosome llqter and concluded that a de novo translocation (Y;11)(q11.2;q24) with a deletion of 11q24qter and a deletion of Yq11.2Yqter were present; Jacobsen syndrome and azoospermia are associated with these deletions. Signs of Jacobsen syndrome were observed in the patient.