THE ETIOLOGY OF SCHIZOPHRENIA—A Review

The causes and the nature of the psychiatric disorder labeled schizophrenia remain vexingly obscure. Perhaps as an expression of a still extant body-mind controversy, most of the experiments and statements made toward an elucidation of the problem follow one or the other of two opposing postulations: (a) That its origin is genetico-organic; (b) that it is environmental. In a review of the outstanding “facts” for either argument, it is notable that they presuppose not only a difference in theoretical frameworks, but two radically distinct outlooks. This is reflected in therapy, a field in which organicists and environmentalists stand even further apart; the organicist, relying heavily on electroshock and drugs, hopes to counteract a hypothetical body malfunction, and the environmentalist, through psychotherapy, attempts to make it possible for the patient to disentangle his own conflicting feelings and reaction patterns.Between the two an eclectic position seems hardly tenable. For, in spite of voluminous research and speculation, it has not been possible to build a bridge between the two camps and integrate different outlooks which, at times, have brought psychiatry almost to the point of schism.     

Inhibition of lipolysis by hydrocarbons and fatty alcohols

The hydrolysis of long-chain triglyceride by pancreatic lipase (EC 3.1.1.3) is inhibited by hydrophobic solutes that are dissolved in the fat. Solutes tested included n-alkanes (C10-C16), aromatic and chlorinated aromatic hydrocarbons (including a PCB and DDT), n-alcohols (C10-C16), and cholesterol. Except for cholesterol, which stimulated lipolysis at low concentrations, all compounds produced roughly similar inhibition curves that followed the pattern of a typical Langmuir adsorption isotherm (Mattson, F. H., R. A. Volpenhein, and L. Benjamin, 1970. J. Biol. Chem. 245: 5335-5340). According to this interpretation, hydrophobic solutes dissolved within fat droplets partition between the interior oil phase and the surface monolayer where lipolysis occurs. Although the aromatic and chlorinated aromatic hydrocarbons were approximately 25% more inhibitory than the long-chain aliphatic hydrocarbons, as a single class, hydrocarbons were 7-10 times weaker inhibitors of lipolysis than fatty alcohols. In contrast to the alcohols whose inhibitory action may involve several mechanisms, the hydrocarbons behaved like simple dilution inhibitors; i.e., at 50% inhibition the mass ratio of hexadecane to triglyceride was 0.42. The lack of a chain length effect indicates that the hydrocarbons are not adsorbed at the interface but interdigitate the triglyceride molecules and align parallel to the lipid acyl chains. Inhibition by hydrophobic solutes was not reversed by the presence of 4 mM taurodeoxycholate and pancreatic procolipase or colipase.     

Identification of a common molecular basis for combined 17α-hydroxylase/17,20-lyase deficiency in two Mennonite families

Summary During the course of studies to characterize mutations of the CYP17 gene that cause the 17-hydroxylase-deficient form of congenital adrenal hyperplasia we have discovered two ostensibly unrelated Mennonite families in which affected individuals are homozygous for the same mutation. The defect is a four-base duplication in exon 8 of the CYP17 gene, which alters the reading frame encoding the C-terminal 26 animo acids of cytochrome P450₁₇.     

Effects of pollen donors on seed formation inEspeletia schultzii (Compositae) populations at different altitudes

The influence of different pollen donors on seed formation was investigated in three populations ofEspeletia schultzii that differ in environmental conditions and life history characteristics. Self pollen and pollen from different donors (< 15m apart) within each population was used in a diallel design in order to test the genetic base of seed set variation. Three measures of seed formation were used: (1) achene number; (2) proportion of filled achenes (fruits) that distinguishes between achenes with seeds and empty achenes; (3) proportion of aborted seeds that distinguishes between viable and aborted seeds. Self-pollinations resulted in empty achenes. Achene number did not vary between the different pollen donors. A bimodal pattern of filled achenes was found in two populations in two consecutive years. On the other hand, a unimodal pattern was found in crosses between more distant donors (> 30m). These patterns seems to be the results of a sporophytic incompatibility system. Seed abortion was highest at the higher elevations and seems to be correlated with elevation rather than with any genetic effect.     

Hypervariability of intronic simple (gt)n(ga)m repeats in HLA-DRB genes

We have investigated the extent of DNA variability in intronic simple (gt)_n(ga)_m repeat sequences and correlated this to sequence polymorphisms in the flanking exon 2 of HLA-DRB genes. The polymerase chain reaction (PCR) was used to amplify a DNA fragment containing exon 2 and the repeat region of intron 2. The PCR products were separated on sequencing gels in order to demonstrate length hypervariability of the (gt)_n(ga)_m repeats. In a parallel experiment, the PCR products were cloned and sequenced (each exon 2 plus adjacent simple repeats) to characterize the simple repeats in relation to the HLA-DRB sequences. In a panel of 25 DRB1, DRB4, and DRB5 alleles new sequences were not detected. Restriction fragment length polymorphism (RFLP) subtyping of serologically defined haplotypes corresponds to translated DNA sequences in 85% of the cases, the exceptions involving unusual DR/DQ combinations. Many identical DRB1 alleles can be distinguished on the basis of their adjacent simple repeats. We found group-specific organization of the repeats: the DRw52 supergroup repeats differ from those of DRB1*0101, DRB4*0101, and DRB5*0101 alleles and from those of pseudogenes. Finally, we amplified baboon DNA and found a DRB allele with extensive similarity to DRB1 sequences of the DRw52 supergroup. The simple repeat of the baboon gene, however, resembles that of human pseudogenes. In addition to further subtyping, the parallel study of polymorphic protein and hypervariable DNA alleles may allow conclusions to be drawn on the relationships between the DRB genes and perhaps also on the theory of trans-species evolution.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M 34258.     

Adsorption of 5′-adenosine monophosphate onto precipitated calcium phosphate: Effects of inorganic polyphosphates and carbamyl phosphate

In this paper it is shown that the adsorption of 5-adenosine monophosphate (5-AMP) onto precipitated calcium phosphate exhibits a sigmoidal profile as revealed by isotherms at 45 °C. This result indicates a cooperative behavior in the adsorption of 5-AMP. The relationship between adsorption capacity and surface area of the sedimented matrix may be interpreted as an indication that there is a monolayer of the adsorbed nucleotide on the solid surface. The pH dependence of adsorption suggests that the negatively charged phosphoryl group of 5-AMP interacts with a positively charged site (possibly Ca²⁺) on the matrix surface. The adsorption of the nucleotide is markedly decreased at pH values above 8.0. The Dixon-like plot of the effect of pH suggests an inhibitory role of hydroxyl ions in the adsorption of 5-AMP. At pH 7.5, other anions such as pyrophosphate, tripolyphosphate and carbamyl phosphate also inhibit the adsorption of the nucleotide, probably by interacting with its adsorption site. We suggest that these phosphorylated molecules could have played a role in chemical evolution by modulating the amount of nucleotides adsorbed onto mineral surfaces. The significance of these phenomena in chemical evolution is discussed.     

Divalent cations modify adsorption of 5′-AMP onto precipitated calcium phosphate: A model for cation modulation of adsorptive processes in primitive aqueous environments

The adsorption of 5′-AMP onto precipitated calcium phosphate (CaPi) requires the presence of soluble calcium and this dependence exhibits a Michaelian-like behavior. This result suggests that the formation of a complex between 5′-AMP and free Ca²⁺ (CaAMP) is a prelude to the adsorption of the nucleotide in the solid matrix. At concentrations one order of magnitude higher, Mn²⁺ and Mg²⁺ can substitute for soluble Ca²⁺ in the adsorption of 5′-AMP onto solid CaPi. However, when added simultaneously with 5′-AMP to a heterogeneous mixture that contains CaPi and soluble Ca²⁺, Mn²⁺ and Mg²⁺ inhibit the adsorption of 5′-AMP in a concentration-dependent manner. This suggests the formation of complexes that are much less effective for 5′-AMP adsorption than the CaAMP complex. On the other hand, Mn²⁺ and Mg²⁺ cannot promote desorption of the nucleotide attached to the precipitate in the presence of soluble Ca²⁺ if they are added after adsorption has attained equilibrium. Although desorption of 5′-AMP can be obtained by a sequential dilution of the soluble phase with buffer and no nucleotide in a process that obeys a Langmuir equation, the lack of effect of Mn²⁺ or Mg²⁺ when adsorption has attained its maximal value suggests strong interactions between the CaAMP complex and the solid matrix when adsorption equilibrium is reached. The divalent cations present in the matrix also participate with different selectivity in the attachment of the CaAMP complex, indicating that a cation-exchange mechanism could have acted in the modulation of adsorptive/desorptive processes involving biomonomers and phosphate surfaces in primitive aqueous environments. Received: 11 December 1995 / Accepted: 5 April 1996