Clinical and Molecular Characterization of Patients with Distal 11q Deletions

Jacobsen syndrome is caused by segmental aneusomy for the distal end of the long arm of chromosome 11. Typical features include mild to moderate psychomotor retardation, trigonocephaly, facial dysmorphism, cardiac defects, and thrombocytopenia, though none of these features are invariably present. To define the critical regions responsible for these abnormalities, we studied 17 individuals with de novo terminal deletions of 11q. The patients were characterized in a loss-of-heterozygosity analysis using polymorphic dinucleotide repeats. The breakpoints in the complete two-generation families were localized with an average resolution of 3.9 cM. Eight patients with the largest deletions extending from 11q23.3 to 11qter have breakpoints, between D11S924 and D11S1341. This cytogenetic region accounts for the majority of 11q⁻ patients and may be related to the FRA11B fragile site in 11q23.3. One patient with a small terminal deletion distal to D11S1351 had facial dysmorphism, cardiac defects, and thrombocytopenia, suggesting that the genes responsible for these features may lie distal to D11S1351. Twelve of 15 patients with deletion breakpoints as far distal as D11S1345 had trigonocephaly, while patients with deletions distal to D11S912 did not, suggesting that, if hemizygosity for a single gene is responsible for this dysmorphic feature, the gene may lie distal to D11S1345 and proximal to D11S912.     

Molecular basis and PCR-DNA typing of the Fya/fyb blood group polymorphism

Spondyloepiphyseal dysplasia tarda (SEDL) is an X-linked recessive disorder characterized in affected males by short stature resulting from a growth defect of the vertebral bodies. We have extended our earlier studies by analyzing 15 families with newly identified microsatellite DNA markers; analysis of recombination events with these markers indicates that the gene responsible for SEDL is located in Xp22 between DXS 16 and DXS 987 on an interval spanning approximately 2 Mb.     

Gavaserin and saltavalin, new peptide antibiotics produced by Bacillus polymyxa

Abstract A strain of Bacillus polymyxa (BP1), isolated from cauliflower seeds, inhibited the growth of microbial phytopathogens. Growth of this strain in liquid medium containing lactose, ammonium sulfate, biotin, and amino acids, resulted in optimal inhibition in vitro. Two new antibacterial substances were isolated and purified from culture broth. Their molecular masses were, respectively, 911 and 903 dallons. The first compound was named gavaserin because it contained glutamic acid, alanine, valine, serine and 2,4-diaminobutyric acid, and octanoic acid. No fatty acid was detected in the second compound, which was named saltavalin because it contained serine, alanine, leucine, threonine, valine, and 2,4-diaminobutyric acid.     

In vitro colonization ability of human colon mucosa by exogenous Lactobacillus strains

Abstract A 5.4 kb Hind III DNA fragment carrying the gene encoding raw starch-digesting α-amylase (RSDA), has been previously cloned from Bacillus circulans F-2 and expressed in Escherichia coli [Kim et al. (1990) Biochim. Biophys. Acta 1048, 2233–2238]. Interestingly, when the cell extract of E. coli harboring a plasmid carrying this fragment was incubated with l M NaCl, it exhibited about 10 times higher enzyme activity than when assayed without NaCl. Differential zymograms showed two different amylase activities: one for RSDA and the other for a salt-dependent a-amylase (SDA). Even though RSDA activity was detected without NaCl, SDA activity was detected only in high concentrations of NaCl. SDA activity was fully detected at above l M NaCl. Results from subcloning of the genes, fractionation analysis of cell extracts, and immunological assays clearly suggested that the two amylases are genetically distinct and that genes for both enzymes are closely linked on the 5.4 kb DNA fragment.     

Human prostatic steroid 5α-reductase isoforms—A comparative study of selective inhibitors

The present study describes the independent expression of the type 1 and 2 isoforms of human 5α-reductase in the baculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties and kinetic parameters of the recombinant isozymes were consistent with published data. The type 1 isoform displayed a neutral (range 6–8) pH optimum and the type 2 isoform an acidic (5–6) pH optimum. The type 2 isoform had higher affinity for testosterone than did the type 1 isoform (K_m = 0.5 and 2.9 μM, respectively). Finasteride and turosteride were selective inhibitors of the type 2 isoform (K_i (type 2) = 7.3 and 21.7 nM compared to K_i (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both isozymes (K_i (type 1) = 8.4 nM and 7.2 μg/ml, respectively; K_i (type 2) = 7.4 nM and 4.9 μg/ml, respectively). The three azasteroids were competitive inhibitors vs substrate, whereas LSESr displayed non-competitive inhibition of the type 1 isozyme and uncompetitive inhibition of the type 2 isozyme. These observations suggest that the lipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5α-reductase. Partially purified recombinant 5α-reductase type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5α-reductase.     

An electrogenic proton pump in plasma membranes from the cellular slime mould Dictyostelium discoideum

Plants and fungi possess an outwardly directed plasma membrane proton pump that may regulate intracellular pH. We provide the first demonstration that amoebae of the slime mould Dictyostelium discoideum also possess a similar proton pump. It can be assayed either as an ATPase activity in highly purified plasma membranes or as a proton pump, after solubilization and reconstruction into liposomes. The pump is inhibited by vanadate, diethylstilbestrol (DES) and miconazole but not by azide or ouabain. The proton pump described here may represent the target for the action of DES and miconazole, both of which have previously been shown to induce stalk cell formation during the in vitro development of Dictyostelium.     

Recognition of sodium- and potassium-dependent adenosine triphosphatase on mouse lymphoid cells by means of a monoclonal antibody

Summary Previous evidence has established the similarity between (Na⁺+K⁺)-ATPase (ATP phosphohydrolase, EC.3.6.1.3) and the antigen recognized by the rat antimouse monoclonal antibody anti-BSP-3. This antibody has been used for investigation of the surface expression and biochemical analysis of the enzyme in different mouse lymphoid populations. The BSP-3 determinant is found on almost all thymocytes and concanavalin A-induced thymocytes, to a lesser extent on bone marrow cells and also on a minor population of spleen cells. Spleen cells from athymic mice are negative. The (Na⁺+ K⁺)-ATPase purified from mouse thymus by affinity chromatography migrates in SDS-polyacrylamide gels in the form of two polypeptide chains of 105000 and 51000 daltons. Chains of the same molecular weight, fractionated on SDS-PAGE from microsomes of mouse thymuses, are shown to react with subunit-specific polyclonal antisera against ATPase in immunoblotting experiments. Immunoprecipitation with anti-BSP-3 from surface iodinated thymocytes yields only the small subunit. Comparison of the chains isolated from thymus and brain shows molecular weight differences in both subunits. These results, and variations in the reactivity pattern of the anti-BSP-3 antibody on several cell types, may indicate a possible heterogeneity of the (Na⁺+K⁺)ATPase expressed by various tissues and cells.     

Mortality and sterility induced in Piophila casei by X-ray and neutron irradiation

Different doses of neutrons and X-rays were given to 5-day-old pupae of Piophila casei L. (Diptera, Piophilidae), just before their emergence. The mortality and sterility induced by the different types of radiation were measured. Neutrons are more effective than X-rays in provoking lethal lesions in somatic cells. Females are more resistant than males to the sterilizing action of neutrons, the relative biological efficiency of neutrons being 6 and 3.5, respectively.

---

Iduktion von mortalität und sterilität durch röntgenstrahlen und neutronen bei piophila casei

Zusammenfassung Puppen von Piophila casei im Alter von 5 Tagen wurden mit verschiedenen Dosierungen von Neutronen und Röntgenstrahlen bestrahlt. Dadurch was es möglich, Dosis-Effekt-Kurven für Mortalität und Sterilität zu bilden. Die Neutronen erwiesen sich als wirksamer als die Röntgenstrahlen für die Auslösung von Letalstörungen bei den Puppen. Die Relative Biologische Wirkung (RBE) beider Strahlenarten auf die Mortalität ist nicht im ganzen Mortalitätsbereich gleichartig. Die durch Bestrahlung verursachte Sterilität wurde für beide Geschlechter bestimmt und zwar anhand der Überlebensrate der Eier von Einzelpaaren. Neutronen sind wirksamer als Röntgenstrahlen, um letale dominante Mutationen in Spermatozoen zu verursachen (RBE: 6). Neutronen reduzieren die Fertilität von Weibchen, welche aus bestrahlten Puppen stammen, ebenfalls stärker (RBE: 3,5). Die Fekundität der Weibchen wird wesentlich vermindert bei Neutronenbestrahlung von über 2000 rad und bei Röntgenbestrahlung von 7500–10000 rad. Die strahlenbedingte Schädigung der Ovarien konnte auch histologisch nachgewiesen werden.

---

---

This work has been supported by grant nr. 74.01552.06 from the Consiglio Nazionale delle Ricerche (C.N.R.), Rome, Italy.     

Le fucosterol-24,28 epoxyde,intermediaire dans la biodegradation oxydative du fucosterol en cholesterol par le criquet Locusta migratoria (R. ET F.)

β-Sitosterol 1 is metabolised to cholesterol 5 by phytophagous insects. It has been previously shown that fucosterol-24,28 epoxide 3 is transformed into 5 in Locusta migratoria, desmosterol 4 being an intermediate. It is now established that locusts transform [3-³H] fucosterol propionate into the corresponding labelled epoxide 3, recovered as such or as an oxazoline derivative 11.