大鼠局灶性脑缺血模型及其与C反应蛋白变化的关系

目的 改进大鼠大脑中动脉梗塞法,建立更接近于临床缺血性脑卒中及其再扩灌注的可靠模型,并观察其与血甭Ｃ反应蛋白变化的。方法沿大鼠右颈内动脉插入长２．１￣２．３ｃｍ直径０．２０５ｍｍ的单股尼龙丝,直达大脑中动脉起始部开口,阻断其血流,观察大鼠神经病学改变及脑组织形态学变化,并测定血清Ｃ反应蛋白含量。结果 术后大鼠表现特殊体态及典型追尾征,６ｈ大脑中动脉供血区出现缺血性外观（ＴＴＣ染色）及相应组织学变化     

GABA(A) receptors mediate inhibition of T cell responses

We describe the presence of functional GABA(A) receptors on T cells. GABA inhibited anti-CD3 and antigen-specific T cell proliferation in vitro in a dose-dependent manner that was 1) mimicked by the GABA(A) receptor agonist muscimol (but not the GABA(B) receptor agonist baclofen), 2) blocked by GABA(A) receptor antagonists and a GABA(A) receptor Cl- channel blocker (picrotoxin) and 3) enhanced by pentobarbital. These data suggest that GABA(A) receptors mediate this immune inhibition and that these receptors can be modulated in a similar fashion to their neuronal counterparts. Finally, GABA inhibited DTH responses in vivo. Thus, pharmacological modulation of GABA(A) receptors may provide new approaches to modulate T cell responses in inflammation and autoimmune disease.     

Effects of TGFbeta on bone ingrowth in the presence of polyethylene particles

We implanted bone harvest chambers (BHCs) bilaterally in ten mature male New Zealand white rabbits. Polyethylene particles (0.3+/-0.1 microm in diameter, 6.4 x 10(12) particles/ml) were implanted for two, four or six weeks bilaterally in the BHCs, with subsequent removal of the ingrown tissue after each treatment. In addition to the particles, one side also received 1.5 microg of recombinant transforming growth factor beta1 (TGFbeta1). At two weeks, the bone area as a percentage of total area was less in chambers containing TGFbeta compared with those with particles alone (7.8+/-1.3% v 16.9+/-2.7% respectively; 95% confidence interval (CI) for difference -14.0 to -4.30; p = 0.002). At four weeks, the percentage area of bone was greater in chambers containing TGFbeta compared with those with particles alone (31.2+/-3.4% v 22.5+/-2.0% respectively; 95% CI for difference 1.0 to 16.4; p = 0.03). There were no statistical differences at six weeks, despite a higher mean value with TGFbeta treatment (38.2+/-3.9% v 28.8 +/-3.5%; 95% CI for difference -4.6 to 23.3; p = 0.16). The number of vitronectin-receptor-positive cells (osteoclast-like cells) was greater in the treatment group with TGFbeta compared with that with particles alone; most of these positive cells were located in the interstitium, rather than adjacent to bone. TGFbeta1 is a pleotropic growth factor which can modulate cellular events in the musculoskeletal system in a time- and concentration-dependent manner. Our data suggest that there is an early window at between two and six weeks, in which TGFbeta may favourably affect bone ingrowth in the BHC model. Exogenous growth factors such as TGFbeta may be a useful adjunct in obtaining osseointegration and bone ingrowth, especially in revisions when there is compromised bone stock and residual particulate debris.     

Synaptic connectivity of two types of recoverin-labeled cone bipolar cells and glutamic acid decarboxylase immunoreactive amacrine cells in the inner plexiform layer of the rat retina.

We investigated the synaptic connectivity of two populations of recoverin-labeled bipolar cells and GABAergic neurons in the inner plexiform layer (IPL) of the rat retina. Two types of cone bipolar cells, type 2 and type 8, were stained with anti-recoverin antibodies, and GABAergic neurons were stained with anti-glutamic acid decarboxylase (GAD) antibodies. Type 2 cone bipolar axons received synaptic input from amacrine cell processes in 177 cases; among these amacrine cell processes, 92 processes (52.0%) were GAD-like immunoreactive. A total of 159 amacrine cell processes, which are presynaptic to type 8 cone bipolar cells, were observed. Among these processes, 117 processes (73.6%) were GAD-like immunoreactive. The postsynaptic elements at the ribbon synapses of recoverin-labeled cone bipolar cells were observed in 482 processes. In both type 2 and type 8 cone bipolar cells, the major output was to amacrine cell processes. At the ribbon synapses of the type 2 cone bipolar cells, 224 of the postsynaptic profiles were amacrine cell processes, 97 processes (43.3%) were GAD-like immunoreactive. In type 8 cone bipolar cells, 45 processes (30.2%) of 149 amacrine cell processes were GAD-like immunoreactive. Our results provide morphological evidence that GABA is a major transmitter involved in the visual processing of type 2 and 8 cone bipolar cells and GABA may have a stronger influence on type 8 cone bipolar cells than type 2 cone bipolar cells in the IPL of the rat retina.     

Disorders of pyruvate carboxylase and the pyruvate dehydrogenase complex

Summary The most common defect associated with deficiency of the pyruvate dehydrogenase (PDH) complex occurs in the E₁ component, specifically due to mutations in the X-linked E₁ gene. Clinical sequelae of these mutations, which range from severe neonatal lactic acidosis to carbohydrate-sensitive ataxia, can be different in males and females depending on the nature of the mutation and, in the case of females, on the X-inactivation pattern in different tissues. Males have a high representation of missense mutations among the patient cohort, while females are much more likely to have DNA rearrangements, particularly toward the 3 end of the coding sequence of the gene. Missplicing mutations involving exon 6 deletion have been reported, as has a missense mutation conferring true thiamin-responsiveness of the enzyme and the patient's clinical symptoms.Pyruvate carboxylase deficiency, on the other hand, is a true autosomal recessive disease, though it has high occurrences in particular ethnic groups, especially in Algonkian-speaking Amerindians and in Arabs. In the former group the defect is a simple type in which material cross-reactive to pyruvate carboxylase antibody is present in cultured cells (CRM^+ve). In the latter group, cross-reacting material is rarely present (CRM^–ve). The CRM^+ve patients can survive into teenage years with careful supervision, while the CRM^–ve patients have complications due to hyperammonaemia and dysfunction of the urea cycle and rarely survive beyond 3 months of life.     

The trough: peak ratio and the normalization of blood pressure profiles

Experts from the Food and Drug Administration (FDA) of the USA have assumed that hypertensive patients are likely to achieve greatest benefit from therapy in which the antihypertensive effects do not vary excessively during the course of the day. They suggested that the ratio of the minimal (trough) effect to the maximal (peak) effect of the drug should be no lower than 0.5. The concept of the trough: peak ratio (TPR) raises many practical problems. Using actual data, the effect of a drug often shows erratic fluctuations with several local minima and maxima. Mean blood pressure levels for several hours have been used to estimate the trough and peak effects. Blood pressure averages over 4 h may e a good choice, because blood pressures measured 4 h apart are not correlated. The statistical distribution of the TPR is not Gaussian. Negative and very low or positive and very high individual ratios are frequently observed. Therefore, the individual TPR is of questionable clinical value, except when the ratio is applied for responders only. The TPR can be calculated for a sample. In that case, the bootstrap method can be used to estimate the error of the TPR. Most important is the question of why the TPR should be higher than 0.5. We introduced the concept of 'normalization of the blood pressure profile', namely 'reducing the blood pressure profiles in hypertensives to match those profiles in normotensives'. This concept leads very naturally to the TPR and justifies the lower limit of 0.5 for the TPR.     

Headache and family history

In two headache questionnaire surveys we inquired about the occurrence of headache in the mothers, fathers, siblings and children of the respondents. In total, 633 people completed valid questionnaires, 260 in the first survey and 373 in the second. The hypothesis was that familial headache occurrence would be positively associated with headache frequency. In each survey, the regression of headache frequency on the number of parents having headache was highly significant. Neither sex nor the sibling and children variables were significant predictors. In the cross-tabulations of the parental occurrence of headache with headache frequency we saw a clear "break-point" between the "no headache" and the headache frequency categories studied. For the final analyses the dichotomy "headache/no headache" was related in fourfold tables to headache occurrence in the father and the mother separately, and to the number of headache parents. The positive associations were not simply due to the large number of migraine cases since they remained after removing the migraineurs.