Associations between blood groups, blood protein polymorphisms and breeding values for production traits in Swedish Red and White Dairy bulls

The relationships of nine blood group systems and two blood protein polymorphisms with breeding values for several production traits were examined in dairy cattle of the Swedish Red and White (SRB) breed. The material consisted of 2212 bulls; the bulls were performance tested for growth rate and their breeding values for milk yield, fat and protein content in milk were estimated from progeny tests. The direct effect of marker alleles or marker phenotypes was analysed in a multiple regression model. Several significant associations were found; many supported earlier findings. However, the contribution of the markers to the total variation of the breeding values was very small. Linkage between marker loci and production loci was studied in offspring from heterozygous sires by estimating the interactions between sire and marker alle using a model eliminating the direct effects of sire and marker alle. There were strong indications of linkage between some marker loci (e.g. B, J and Am-1 loci) and loci with large effects on production traits.     

Genetic variation and distances of five Italian native sheep breeds

Genetic distances among five of the most important Italian native sheep breeds were estimated by using gene frequencies of four blood group and seven blood protein loci and by three different computing methods. The values of the three distance matrices were highly correlated. Genetic distances were found within the range values reported in the literature for local breeds. Shorter distances fitted the historical evidence of migrations.     

Hydrocortisone regulates arylsulfatase A (cerebroside-3-sulfate-3-sulfohydrolase) by decreasing the quantity of the enzyme in cultures of cells dissociated from embryonic mouse cerebra

Previous work from our laboratory (Biochem. J. 219:689–697 (1984) had shown that hydrocortisone stimulated the net accumulation of the myelin-specific sulfolipid in cultures of cells dissociated from embryonic mouse cerebra. This accumulation caused by hydrocortisone was shown to be due to a decrease of sulfolipid degradation by arylsulfatase A (ASA) and not due to a stimulation of its synthesis by a sulfotransferase. Both ASA activity and the turnover of sulfolipid were decreased by hydrocortisone to 60–62% of untreated cells. In current work the same decrease in enzyme activity was obtained and enzyme linked immunosorbent assays demonstrate that hydrocortisone decreased the number of ASA protein molecules to 61% of untreated cells [(-)hydrocorcortisone 0.31±0.06 ng ASA/g protein; (+)hydrocortisone: 0.18±0.04 ng ASA/g protein]. This decrease in the number of ASA molecules correlates well with the decrease in both the enzyme activity and the sulfolipid turnover, which suggests that the major mode of inhibition of ASA activity by hydrocortisone involves a decrease in the concentration of ASA in the cells rather than some other mechanism of inhibition.The material in this paper has been included in a dissertation submitted by A.J.M. in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Temple University.     

Ischemic flow threshold for striatal dopamine release in rats

To determine the level of cerebral blood flow reduction which causes striatal dopamine release, extracellular dopamine and cerebral blood flow was simultaneously determined using in vivo brain dialysis and a hydrogen clearance method, respectively, in the striatum of spontaneously hypertensive rats, before and during experimental cerebral ischemia. The ischemic flow threshold for neurotransmitter dopamine release was found to be 20% of the resting value or 8–10 ml/100g/min of cerebral blood flow, being similar to those for energy and membrane failures.     

Effect of short-and long-term exposure to low environmental temperature on brain regional GABA metabolism

Single exposure of adult male rats to low environmental temperature (LET, 12 ± 0.5°C) for 2 h significantly increased the hypothalamic and striatal GABA levels without affecting those in other regions of brain. The activity of glutamate decarboxylase (GAD) was elevated in hypothalamus (H) and corpus striatum (CS) under these conditions. GABA accumulation rate (measured with ethanolamine-O-sulfate, an inhibitor of GABA-transaminase) was also increased in both H and CS of rats exposed to LET for 2 h. Unlike after a single exposure, the repeated exposure (2 h/day) for 7, 15, and 30 onsecutive days did not change the hypothalamic GABA metabolism. No change in GABA metabolism was observed in CS when rats were repeatedly exposed to LET for 7 consecutive days. Prolongation of repeated exposure to LET (2 h/day) for 15 and 30 consecutive days decreased the striatal GABA level and increased the activity of GABA-transaminase, although GAD activity was not altered under these conditions. These results suggest that single exposure to LET accelerates GABA synthesis and may reduce the GABAergic activity in both H and CS; whereas repeated exposure to LET for 15 or 30 consecutive days enhances GABAergic activity with the stimulation of GABA utilization only in CS without affecting its synthesizing process. Thus, it may be suggested that the hypothalamic and striatal GABA system may play a characteristic role in response to short-and long-term exposure to LET.     

Studies on new,centrally active and reversible acetylcholinesterase inhibitors

We have synthesized the tertiary amines of pyridostigmine and neostigmine, 3-pyridinol dimethylcarbamate (norpyridostigmine) and 3-dimethylaminophenol dimethylcarbamate (norneostigmine) respectively, and we have tested their abilities to cross the blood-brain barrier and inhibit mouse brainAChE activity. The in vivo inhibition of AChE activity by norpyridostigmine reaches 72% at 10 minutes which is comparable to that seen with physostigmine (73% at 10 minutes). Inhibition by norneostigmine is less effective (50% at 10 minutes) and approaches that obtained with tetrahydroaminoacridine (57% at 10 minutes). These data show that both norpyridostigmine and norneostigmine cross the blood-brain barrier and that they are effective inhibitors of mouse brain AChE activity. These drugs could be useful in the treatment of memory, impairment associated with Alzheimer's disease, and other memory disorders.     

65Zinc uptake from blood into brain and other tissues in the rat

Zinc is essential for normal growth, development and brain function although little is known about brain zinc homeostasis. Therefore, in this investigation we have studied⁶⁵Zn uptake from blood into brain and other tissues and have measured the blood-brain barrier permeability to⁶⁵Zn in the anaesthetized rat in vivo. Adult male Wistar within the weight range 500–600 g were used.⁶⁵ZnCl₂ and [¹²⁵I]albumin, the latter serving as a vascular marker, were injected in a bolus of normal saline I.V. Sequential arterial blood samples were taken during experiments that lasted between 5 min and 5 hr. At termination, samples from the liver, spleen, pancreas, lung, heart, muscle, kidney, bone, testis, ileum, blood cells, csf, and whole brain were taken and analysed for radio-isotope activity. Data have been analysed by Graphical Analysis which suggests⁶⁵Zn uptake from blood by all tissues sampled was unidirectional during this experimental period except brain, where at circulation times<30 min,⁶⁵Zn fluxes were bidirectional. In addition to the blood space, the brain appears to contain a rapidly exchanging compartment(s) for⁶⁵Zn of about 4 ml/100g which is not csf.     

A new approach to biochemical evaluation of brain dopamine metabolism

1. Dopaminergic neurotransmission in brain is receiving increased attention because of its known involvement in Parkinson's disease and new methods for the treatment of this disorder and because of hypotheses relating several psychiatric disorders to abnormalities in brain dopaminergic systems. 2. Chemical assessment of brain dopamine metabolism has been attempted by measuring levels of its major metabolite, homovanillic acid (HVA), in cerebrospinal fluid, plasma, or urine. Because HVA is derived in part from dopamine formed in noradrenergic neurons, plasma levels and urinary excretion rates of HVA do not adequately reflect solely metabolism of brain dopamine. 3. Using debrisoquin, the peripheral contributions of HVA to plasma or urinary HVA can be diminished, but the extent of residual HVA formation in noradrenergic neurons is unknown. By measuring the levels of methoxy-hydroxyphenylglycol (MHPG) in plasma or of urinary norepinephrine metabolites (total MHPG in monkeys; the sum of total MHPG and vanillyl mandelic acid (VMA) in humans) along with HVA, it is possible to estimate the degree of impairment by debrisoquin of HVA formation from noradrenergic neuronal dopamine and thereby better assess brain dopamine metabolism. 4. This method was applied to a monkey before and after destruction of the nigrostriatal pathway by the administration of MPTP.     

Insulin: Its binding to specific receptors and its stimulation of DNA synthesis and 2′,3′-cyclic nucleotide phosphohydrolase activity in cerebral cells cultured from embryonic mouse brain

The presence and specificity of insulin receptors was investigated in cultured cells obtained from 15–16 days old embryonic mouse cerebra. Developmental studies suggested that the maximum insulin binding occurred at about 11 days in vitro (DIV). Scatchard analysis of binding data revealed two types of binding sites. One type of receptor was the high affinity type (K _d=7.77×10^–9 M; number of receptor sites,B _max=350 fmol/mg protein) while the other type was of low affinity type (K _d=5.75×10^–8 M;B _max=1150 fmol/mg protein). The specificity of receptors for insulin was also confirmed by showing that [¹²⁵I]insulin was displaced by non-radioactive insulin but not by glucagon or growth hormone. Insulin displayed a clear dose-dependent stimulation of thymidine incorporation. It also stimulated the activity of the enzyme 2,3-cyclic nucleotide phosphohydrolase (CNPase), which is specifically associated with myelin produced from oligodendroglia. Thus insulin has a positive influence on the proliferation and differentiation of brain cells.     

电刺激兔延髓腹侧化学敏感区和压力敏感区对呼吸、血压,的影响及其中枢递质机制

电刺激麻醉兔延髓腹侧化学敏感区头端区引起潮气量(V_T)增加,呼吸频率(f)增快;电刺激压力敏感区(中间区)则使V_T减小,f亦增快。弱刺激时,两者均产生降压反应;刺激增强可诱发双相或升压反应。在出现周期性呼吸时,电刺激化学敏感区可使呼吸节律正常化、V_T增大,而电刺激压力敏感区则导致呼吸暂停。电刺激压力敏感区时,吸气时间(TI)和呼气时间(T_E)均缩短,以T_E变化更明显;由于V_T减小和T_I缩短,V_T/T_I保持相对不变,提示吸气终止的中枢阈值降低。在准备刺激的相应局部预先应用阿托品,可使电刺激化学敏感区产生的通气增强效应翻转,而对电刺激压力敏感区引起的通气抑制无明显影响;用印防己毒素则可选择性消除电刺激压力敏感区的通气抑制和降压效应。本工作表明延髓腹侧存在两个不同的中枢机制,其中化学敏感区产生的通气增强与胆碱能系统有关;压力敏感区产生的通气减弱效应与GABA系统有关。