Molecular Characterization of the Cytidine Monophosphate-N-Acetylneuraminic Acid Hydroxylase (CMAH) Gene Associated with the Feline AB Blood Group System.

Cat's AB blood group system (blood types A, B, and AB) is of major importance in feline transfusion medicine. Type A and type B antigens are Neu5Gc and Neu5Ac, respectively, and the enzyme CMAH participating in the synthesis of Neu5Gc from Neu5Ac is associated with this cat blood group system. Rare type AB erythrocytes express both Neu5Gc and Neu5Ac. Cat serum contains naturally occurring antibodies against antigens occurring in the other blood types. To understand the molecular genetic basis of this blood group system, we investigated the distribution of AB blood group antigens, CMAH gene structure, mutation, diplotypes, and haplotypes of the cat CMAH genes. Blood-typing revealed that 734 of the cats analyzed type A (95.1%), 38 cats were type B (4.9%), and none were type AB. A family of three Ragdoll cats including two type AB cats and one type A was also used in this study. CMAH sequence analyses showed that the CMAH protein was generated from two mRNA isoforms differing in exon 1. Analyses of the nucleotide sequences of the 16 exons including the coding region of CMAH examined in the 34 type B cats and in the family of type AB cats carried the CMAH variants, and revealed multiple novel diplotypes comprising several polymorphisms. Haplotype inference, which was focused on non-synonymous SNPs revealed that eight haplotypes carried one to four mutations in CMAH, and all cats with type B (n = 34) and AB (n = 2) blood carried two alleles derived from the mutated CMAH gene. These results suggested that double haploids selected from multiple recessive alleles in the cat CMAH loci were highly associated with the expression of the Neu5Ac on erythrocyte membrane in types B and AB of the feline AB blood group system.

The role of noradrenergic and dopaminergic hyperactivity in the development of spontaneous recurrence of methamphetamine psychosis and susceptibility to episode recurrence.

The role of dopaminergic activity in susceptibility of methamphetamine (MAP) psychosis (flashbacks) to subsequent spontaneous recurrences was studied. Plasma monoamine metabolite levels were assayed in 23 flashbackers, of whom 10 experienced a single flashback, 8 exhibited subsequent flashbacks and 5 with the last episode; 18 nonflashbackers with a history of MAP psychosis; 9 subjects with persistent MAP psychosis; and 19 MAP user and 10 nonuser controls. All flashbackers had undergone frightening stressful experiences during previous MAP use. Their flashbacks were triggered by mild psychosocial stressors. Plasma norepinephrine (NE) levels increased with the increase in plasma levels of 3-methoxytyramine (3-MT), an index of dopamine release, during flashbacks in the 23 flashbackers. Of these, the 8 with subsequent episodes had markedly increased NE levels and increased 3-methoxytyramine levels during flashbacks. However, the 5 flashbackers with the last episode had moderately increased NE levels, and the 10 with a single episode displayed small increases in NE levels during flashbacks. Their 3-MT levels did not significantly differ from the levels in the control groups. Thus, increased DA release in addition to robust noradrenergic hyperactivity in response to mild psychosocial stressors may be important in susceptibility to subsequent flashbacks.

Factors for susceptibility to episode recurrence in spontaneous recurrence of methamphetamine psychosis.

The relation between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (flashbacks) was examined. Plasma monoamine metabolite levels were assayed in 19 flashbackers, of whom 10 experienced a single flashback and 9 exhibited subsequent flashbacks, 18 nonflashbackers with a history of MAP psychosis, 9 subjects with persistent MAP psychosis, and 22 MAP user and 10 nonuser controls. All flashbackers had undergone frightening stressful experiences during previous MAP use. They exhibited flashbacks in response to mild psychosocial stressors. There was no significant difference in the number of stressful experiences and having mild psychosocial stressors between the two flashbacker subgroups. Plasma norepinephrine (NE) levels increased with a small increase in plasma levels of 3-methoxytyramine (3-MT), an index of dopamine release, during flashbacks in the 19 flashbackers. Of the 19 flashbackers, the 9 with subsequent episodes had markedly increased NE levels and slightly increased 3-MT levels during flashbacks, while the 10 with a single episode displayed small increases in NE and 3-MT levels during flashbacks. The 9 flashbackers with subsequent episodes had a longer duration of imprisonment than the 10 flashbackers with a single episode. Thus, robust noradrenergic hyperactivity with slightly increased DA release in response to mild stress may predict subsequent flashbacks. Long-term exposure to distressing situations appears to contribute to susceptibility to subsequent flashbacks.

[Stress sensitization induced by stressor and methamphetamine].

Repetitive or acute treatment of methamphetamine (MAP) or amphetamine (AMP) induces sensitization to both subsequent challenge treatment of the drugs, and exposure to emotional and physiological stress. In addition, chronic treatment of AMP enhanced DA utilization/release in striatum. Similarly, repetitive exposure to footshock or tail shock stress induces sensitization of noradrenaline or 3-methoxy-4-hydroxyphenylglycol (MHPG) to subsequent mild stress and to small amounts of AMP or MAP injection. Striatum, nucleus accumbens and prefrontal dopaminergic systems have an important role in the development of this sensitization. Immediate early gene (IEG) expression in the hypothalamus, nucleus accumbens and striatum may be involved in this process. Neurobiological vulnerability to schizophrenia may be induced by the interaction of multiple gene disposition and environmental insult, and schizophrenia onset and/or relapse in response to mild, non-specific stress. Stress-sensitive systems therefore are postulated in the pathophysiology of schizophrenia. In this regard, mesolimbic DA systems may be involved in the pathophysiology of schizophrenia. In contrast to MAP- or AMP- and stress-induced sensitization, haloperidol and clozapine induce IEG expression in the caudate-putamen and amygdala. Collectively, MAP- or AMP-induced sensitization may, in part, share an early functional process of neurobiological mechanisms.