Evidence for Linkage of Bipolar Disorder to Chromosome 18 with a Parent-of-Origin Effect

A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study.     

Genetic variability of plant characters in the partial inbreeder Collinsia heterophylla (Scrophulariaceae)

Quantitative genetic variability for six characters was estimated in four populations of the annual plant, Collinsia heterophylla, with estimated selling rates ranging from 0.36 to 0.68. Based on large samples of parental plants, all four populations showed significant genetic variation for two or more characters, and there was no sign that the more selfing populations had lower amounts of genetic variance or lower heritability values. Autogamous fruit set rates in the absence of pollinators also showed significant heritability in one population.     

Complex interaction between different proteinaceous components within the cell-wall structure ofCandida albicans

We have previously described a monoclonal antibody, MAb DC3:H10, which recognized an epitope preferentially expressed on the surface ofCandida albicans germ tubes. In the present study we examined the MAb-reactive material further. Immunoblot analysis of the material purified partially by Sephadex G-200 and DEAE-Sephacel chromatography reacted with antibodies to theC. albicans C3d receptor (CR2). In an ELISA, MAb DC3:H10 captured antigen that was recognized by both anti-CR2 and anti-mp58 fibrinogen binding mannoprotein polyclonal antibodies. The MAb DC3:H10 failed to compete with either of these antisera in an ELISA. Indirect immunofluo-rescence (IIF) analysis showed differences in surface distribution for the MAb DC3:H10, the CR2, and the mp 58 epitopes. Dual labeling IIF experiments showed MAb DC3:H10 binding to be unaffected by binding of fibrinogen or anti-mp58 antibody. However, the binding patterns of MAb DC3:H10 were modified in the presence of anti-CR2 antibody, suggesting a complex interaction between these cell wall components.     

Structure of Leu5-enkephalin bound to a model membrane as determined by high-resolution NMR

Summary Opioid peptides are thought to interact with the cell membrane in their biological journey to the membrane-bound receptor. Both organic solvents and model membranes have been used previously to determine the stable solution conformations of peptide hormones. Leucine enkephalin has been studied in a number of different environments, but with limited resolution. Here it is shown that leucine enkephalin forms a stable type IV -turn structure in dodecylphosphocholine micelles. We have observed a highly solvent-shielded amide proton with no evidence for a complementary hydrogen bond acceptor. The structural details of the peptide as determined by NMR spectroscopy in solution are described.     

Diacytosis of 125I-asialoorosomucoid by rat hepatocytesa. A non-lysosomal pathway insensitive to inhibition by inhibitors of ligand degradation

Diacytosis of ¹²⁵I-asialoorosomucoid by rat hepatocytes was studied by preincubating the cells with the labelled ligand at 37°C for 30 min or 18°C for 2 h, washing free of cell surface receptor-bound tracer at 4°C and then reincubating at 37°C. The cells preloaded at 37°C released a maximum of 18% of the total intracellular ligand as undegraded molecules after 1 h of incubation with an apparent first-order rate constant of 0.018 min^?1 ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{= 39}\text{min}$). When the preloaded cells were incubated in the presence of 100 μg/ml unlabelled asialoorosomucoid or 5 mM ethylene glycol bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid, the amount of the released ligand increased to 32 and 37%, respectively, without apparent change in kinetics, indicating that these agents prevented rebinding of the released ligand. In the presence of 5 μM colchicine, 20 μM cytochalasin B, 20 μM chloroquine, 10 mM NH₄Cl, 10 μM monensin or 20 μM leupeptin, degradation of the preloaded ligand was inhibited, whereas the release of the ligand was either slightly increased or unchanged. Similar effects of leupeptin, colchicine and asialoocrosomucoid were observed with cells preloaded at 18°C. These results indicate that diacytosis of ¹²⁵I-asialoorosomucoid occurs from a prelysosomal compartment via a route insensitive to inhibition by the inhibitors of ligand degradation.     

THE PERMISSIVE ROLE OF HYPERTHERMIA IN THE DISAGGREGATION OF BRAIN POLYSOMES BY l-DOPA OR d-AMPHETAMINE1

Abstract— l -DOPA or d -amphetamine administration disaggregates brain polyribosomes in animals maintained in an environment warm enough (26°C) so that the drugs concurrently elevate their body temperatures to above 39°C. The production of equivalent hyperthermia (by keeping control rats at ambient temperatures of 40–44° C) does not cause similar disaggregation of brain polysomes. Hence, the role of hyperthermia in the drug-induced disaggregation is permissive.     

Effects of enkephalins on perfusion pressure in isolated hindlimb preparations

A series of studies were conducted to determine the effects of leucine-(leu-) enkephalin and methionine-(met-) enkephalin on perfusion pressure. These experiments utilized isolated perfused femoral arterial preparations in pentobarbital-anesthetized cats. The enkephalins were administered intraarterially into the femoral artery and changes in perfusion pressure recorded. Leu-enkephalin in doses of 1 μg to 320 μg produced significant dose-dependent decreases in perfusion pressure (4.0 ± 1.3% with 1 μg to 19.1 ± 2.1% with 320 μg). Similar declines in perfusion pressure (5.2 ± 2.4% with 1 μg to 21.7 ± 4.1% with 320 μg) were observed following the administration of met-enkephalin. Pretreatment with naloxone (3 mg/kg) antagonized the effects of both enkephalins. Diphenhydramine (2 mg/kg) effectively antagonized the leu-enkephalin elicited decline in perfusion pressure but blocked the effects of met-enkephalin only at lower agonist doses. Propranolol treatment (4 mg/kg) did not alter the pressure responses to either enkephalin. The results of the study show that intraarterially administered enkephalins exert a vasodilatory effect on vasculature in skeletal muscle which may be direct, indirect or both. The differential antagonism of the effects of the two enkephalins suggest that the two opioids act through different receptors or multiple receptors.     

Origin of cholesterol transported in intestinal lymph: studies in patients with filarial chyluria

In subjects fed a cholesterol-free diet there are three possible sources of intestinal lymph cholesterol: a) mucosal synthesis; b) absorption of endogenous (biliary) cholesterol; and c) transudation of plasma lipoproteins into the lacteals of the intestinal wall. To test these possibilities, the extent of transudation was measured by means of [3H]beta-sitosterol administered intravenously as a marker. Absorption of biliary cholesterol was reduced by oral administration of beta-sitosterol (9 g/day), and mucosal synthesis of cholesterol was evaluated by comparisons of plasma/lymph [14C]cholesterol specific activity ratios after intravenous administration of a single dose of labeled cholesterol. Studies were carried out on six patients with filarial chyluria. In five patients fed a cholesterol-free diet the results indicated that lymph cholesterol was largely derived by transudation of plasma lipoproteins into the lacteals from the intestinal blood supply, without contribution from de novo mucosal synthesis or from absorption of endogenous cholesterol. The intestinal lymph of one patient fed cholesterol (2 g/day) contained cholesterol originating mostly from plasma transudation and from dietary absorption, with little contribution from absorbed endogenous cholesterol. In all experiments the larger part of the cholesterol transported away from the intestine in the lymph was carried in chylomicrons, even though it had its origin in plasma lipoproteins.     

F plasmid replication and the division cycle of Escherichia coli B/r

A terminal stage in the duplication of many bacterial plasmids involves the transient formation of catenated molecules containing two interlocked monomeric plasmid units. This property of plasmid replication was exploited to examine the relationship between F replication and the division cycle of Escherichia coli B/r cells growing in undisturbed, exponential-phase cultures. Various cultures of F′lac- or FKm^r-containing cells were briefly exposed to [³H]thymidine, and then the transfer of radioactivity into, and out of, a catenated dimer consisting of two closed circular monomers was measured during a chase period. The fraction of plasmid molecules present in this dimer form was determined by separating cellular DNA in alkaline sucrose gradients. In addition, plasmid replication was studied in synchronously growing cultures by measuring both [³H]thymidine incorporation into covalently closed circular DNA and β-galactosidase inducibility. The results suggest that replication of F plasmids can take place throughout the cell division cycle, with the probability of replication increasing toward the end of the cycle. The presence of DNA homologous to the chromosome on the F′lac did not alter the replication pattern of the plasmid during the division cycle.     

The alleles of theH-13 locus

Seven congenic strains differing from C57BL/10Sn at theH-13 locus have been produced which define fourH-13 alleles. Isografting, exchanging of grafts between sublines, F(1) testing, and linkage testing demonstrate the presence of additionalH genes in four of these strains. The medial survival times (MSTs) of skin grafts fromH-13(a) to unimmunizedH-13(b) recipients ranged from 69 to 83 days. Rejection across all other barriers was extremely weak with most MSTs being > 100 days. Preinjection of donor strain thymocytes caused accelerated rejection of skin grafts fromH-13(a) toH-13(b) mice, but had only minimal effect on skin grafts across other barriers. Rejection ofH-13 incompatible grafts was significantly stronger when the donor and host areH-3(a) than when they wereH-3(b).