重组人神经营养因子-4/5蛋白抗三氧化二砷神经毒作用

目的初步观察重组人神经营养因子-4／5（hNT－4／5）蛋白对三氧化二砷毒性的抑制作用。方法利用hNT－4／5蛋白具有抗神经毒性的特点,采用本实验室克隆表达及部分纯化的具有天然hNT－4／5蛋白生物学活性的重组hNT-4／5蛋白,以不同水平的重组hNT4／5蛋白（0－100μl）与不同浓度的As2O3（0－160μmol／L）同时加入各组鸡胚前脑神经细胞和PC12细胞培养液中共同孵育24－48小时,观察其对染毒鸡胚前脑神经细胞存活和PC12细胞突起生长的影响作用。结果在鸡胚前脑神经细胞和PC12细胞中与As2O3共同培养48小时后,对照组与实验组的细胞存活率差异有显著性,而且细胞存活率和突起数目随hNT－4／5浓度增高而提高和增加。结论初步观察到重组hNT4／5蛋白具有抑制As2O3的毒性作用,为从基因工程途径寻找抗环境毒物因子提供了依据。     

The effect of separate red blood cells on capillary tissue oxygenation calculated with a numerical model

Author to whom correspondence should be addressed In simplified models that describe large quantities of capillariesthe capillary content is considered to be homogeneous for oxygentransport; but, in reality, the capillaries contain discretered blood cells (RBCs), and this discreteness will affect oxygentransport from the capillary to the tissue. This was previouslyinvestigated with an analytical model, where RBCs were modelledas point-like sources. A numerical approach is used in thisinvestigation, and the results are compared with the analyticalmodel. In both models the effect of the particulate nature ofblood depends on the haematocrit and on the RBC velocity. Thereis only a minor difference between the two models. For rat hearts,the correction factor used in this study, the extraction pressure,can be up to 3 kPa (23 mmHg).     

Heterotopic brain tissue in the submandibular region and lung

Summary Two cases of extracranial heterotopia of the brain are reported. Case 1, in an otherwise normal female baby, had a brain heterotopia in the submandibular region. Case 2, in a still-born female baby with anencephaly, had the heterotopia in the lung. The lesion in case 1 is believed to be an encephalocele that has been pinched off through a cleft in the bone or through a foramen of the skull; the pathogenesis is similar to that of the so-called nasal glioma. Concerning the pathogenesis of case 2, contrary to the generally supported embolism theory, observation of serial sections of the tumor in the lung favors the aspiration theory according to which amniotic brain tissue fragments, which are dislocated into the amnion because of nonclosure of the ventricle or following destruction of the fetal brain, are aspirated by fetal respiratory movements in the 4th to 6th month of intrauterine life.     

Pentose shunt activity in developing chick retina and pigment epithelium: A switch in biochemical expression in cultured pigment epithelial cells

Pentose shunt activity in developing chick retina and pigment epithelium was studied by measuring the rate of ¹⁴CO₂ evolution from glucose selectively labelled in the C-1 and C-6 positions. In the retina, shunt activity declines from appreciable levels at stages 29–31 to minimal activity in the 2-week-old hatched chick. Overall retinal metabolism also declines up to stage 45, but dramatically increases again after hatching. Developing chick pigment epithelium has minimal shunt activity at all stages studied. In contrast, cultured chick pigment epithelium has appreciable shunt activity which is constant over a period of several weeks in culture. This appears to be a switch in biochemical differentiation which could form the basis at least in part for subsequent changes in cell types observed in cultured pigment epithelial cells byEguchi and Okada (1973).     

Dose-incidence curves for tumour control and normal tissue injury, in relation to the response of clonogenic cells

A probit analysis has been made of data from the literature on local control of tumours and injury to normal tissue as a function of dose of radiation. Fifteen series were analysed for local tumour control in man and ten series for complications. The analysis yielded values for the D50 dose (50% incidence of effect) and the probit width (K), a measure of the steepness of the dose-incidence curve. The same analyses were made of data for rodents. Broadly, K was proportional to D50 in the ratio 1:7, with no major differences between tumours and reported complications. D50 was plotted as a function of dose per fraction for four normal tissues and two tumours in rodents. D50 decreased more rapidly with increasing dose per fraction for the normal tissues than for tumours. The probit width, K, varied inversely with increasing dose per fraction for normal tissues and this contrasted with the tumour response. Thus with increasing dose per fraction, the threshold for effect decreased and the steepness of the ensuing dose-incidence curve increased, relatively more rapidly for normal tissue than for tumour. These curves of gross response have been analysed also by the double negative log method of Gilbert [23], in an attempt to estimate the number and survival characteristics of "tissue-rescuing cells". These were calculated to be less than 1 in 10(4) of the numbers of clonogenic cells measured by excision assays. The D0 values of the derived survival curves for these tissue-rescuing cells were higher than those measured by excision assays.     

Breast tumor-derived factors stimulate reduction of estrone to estradiol in nonmalignant breast tissue

Summary This study examines the paracrine influence by human breast carcinoma cells (UISO-BCA-1) on nonmalignant breast tissuein vitro. The 17-OH-SDH-mediated reductive pathway (estroneestradiol) was significantly increased in nonmalignant breast tissue coincubated with human breast carcinoma cells, compared to control tissues incubated in the media alone. No influence on the enzyme activity was noticed in coincubated breast cancer cells. Preincubation of breast cancer cells with estradiol (10^–8 M) significantly decreased the enzyme activity in coincubated nonmalignant breast tissue, which was restored to control levels by addition of R5020 (10^–8 M), tamoxifen (10^–6 M), or a combination of both. In nonmalignant tissues incubated in the presence of growth factor TGF, enzyme activity was reduced to between 46% and 76%. No other growth factors (IGF I, IGF II, PDGF) influenced enzyme activity. In nonmalignant tissues incubated with malignant tumor cytosol, enzyme activity was increased in 16% cases, inhibited in 21%, and not significantly changed in 63%.The data from the present study suggest that factors produced by breast carcinoma cells may influence interconversion of estradiol in nonmalignant tissue. In patients, factors produced by malignant tumor mass may have paracrine influence on surrounding nonmalignant breast tissue and, thereby, may influence the estrogen availability to tumor mass.     

Stimulatory effect of ipriflavone on formation of bone-like tissue in rat bone marrow stromal cell culture

The effects of ipriflavone (IP) (10^–5 M) on bone formation were studied in stromal cells from the femoral bone marrow of young adult rats cultured for 21 days in the presence of -glycerophosphate and dexamethasone. Stereoscopic microscopy showed nodule formation after 14 days of culturing, and both the number and the size of the nodules increased with time. The alizarin-red-stained calcified area in the nodules in the IP group was nearly 4 times as large as that in the control after 21 days. Light and electron microscopy revealed the presence of many osteoblast-like cells with developed rough endoplasmic reticulum and Golgi apparatus in the nodules in the control group after 14 days, and a collagenous fibril network was seen among the cells. After 21 days, calcification of the dense collagenous fibril network and bone matrix-like tissue were observed in many nodules, resulting in the formation of bone-like tissue containing osteocyte-like cells. In the IP group, the collagenous fibril network area in the nodules was greater than that in the control after 14 days, and a further increase in both the dense collagenous fibril network area and calcified bone-like tissue area was observed after 21 days. These findings indicate that IP stimulates bone-like tissue formation in the rat bone marrow stromal cell culture, suggesting that the promotion of collagen production by osteoblasts is involved in the stimulation of bone-like tissue formation by IP.     

Knochenheilung und dynamischer Interferenzstrom (DIC). —Erste vergleichende tierexperimentelle Studie an Schafen Teil II: Physikalische und chemische Ergebnisse

Zusammenfassung Zusätzlich wurden physikalische und chemische Untersuchungen über den Einfluß von dynamischem Interferenzstrom (DIC) auf die Knochenheilung durchgeführt, nachdem bei 24 Schwarzkopfschafen eine Querosteotomie des Radius vorgenommen worden war. Nach instabiler Osteosynthese wurde die Osteotomiezone wiederholt mit DIC verschiedener mA—Stärken behandelt. (Methodische Einzelheiten sind in Teil I beschrieben). Die Behandlung mit dynamischem Interferenzstrom führte im behandelten Gewebe zu steigenden Temperaturen, die von den mA—Stärken abhängig waren. Weiterhin wurden Zusammenhänge zwischen DIC—mA—Intensität und dem Vorkommen von Hydroxyprolin, einer kollagenspezifischen Aminosäure, nachgewiesen, welches eine erhöhte Calcifizierungsaktivität zur Folge hatte. Messungen des Calcium— und Phosphorgehaltes im neugebildeten Knochengewebe wiesen bei den mit DIC behandelten Tieren vollständige Mineralisation zu einem viel früheren Zeitpunkt als bei den unbehandelten, nach gleichem Verfahren operierten Kontrolltieren auf. Ob DIC einen spezifischen Reiz auf die Knochenneubildung heilender Knochen ausübt, ist noch nicht vollständig geklärt.

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Bone healing and Dynamic Interferential Current (DIC)

Summary In the course of supplementary physical and chemical investigations of the influence ofDynamicInterferential Current (DIC) on bone healing 24 black-head sheep were subjected to transversal osteotomy of the radius. After an instable osteosynthesis the site was exposed to repeated therapy with DIC of varying mA intensity. (Methodological details are described in part 1.) DIC therapy resulted in altering the temperatures in the treated tissue, dependent on the mA intensity. Further associations were verified between DIC intensity and the occurrence of hydroxyprolin, an amino acid specific collagen, which also reflected increased calcifying activity. Measurements of the calcium and phosphorus levels in the regenerated (newly forming) bone tissue documented full mineralization in the DIC-treated animals at a much earlier date than in the untreated controls that had undergone similar operations. Whether DIC specifically stimulates osteogenesis within healing bones is still unclear.

     

Bone involvement pattern in hypervascular lesions

The pattern of the focal bone lesion which consists partly or wholly of rounded holes with comparatively smooth edges is discussed.Twenty-two bone lesions were studied by angiography. The hypervascular pattern occurred in five cases of widely different histology, all with strong intraosseous hypervascularity. Different pathogenic mechanisms in the creation of this pattern are discussed. It is probably the result of both destructive and reparative processes in the bone.     

Interaction of phenylbutazone with racemic phenprocoumon and its enantiomers in rats

The interaction of phenylbutazone with the enantiomers and racemic [ ³ H]phenprocoumon was studied in male inbred Wistar-Lewis rats following a single i.v. dose of the three forms of phenprocoumon and chronic oral treatment with phenylbutazone (average plasma concentration of about 60 g/ml). Phenylbutazone augmented the anticoagulant effect of R(+), S(–), and R, S (±) phenprocoumon to a similar extent. The free fraction of drug in the plasma of the enantiomers and racemic phenprocoumon increased in the presence of phenylbutazone. However, the rate of elimination of total drug from plasma and liver and the distribution between liver and plasma of all three forms of phenprocoumon remained nearly unaffected by phenylbutazone. Thus there is no evidence for a stereoselective drug interaction between phenprocoumon and phenyl-butazone. For racemic [ ³ H]phenprocoumon it was possible to follow the kinetics of free drug in plasma and liver along with the time course of anticoagulant activity. In these studies, free drug concentrations in plasma and liver increased during treatment with phenylbutazone, but the elimination rate constant of free racemic phenprocoumon in plasma and liver remained essentially unchanged. Phenylbutazone markedly decreased the volume of distribution referenced to free drug and the clearance of free phenprocoumon (i.e., intrinsic metabolic clearance). Whereas the total (bound and unbound) drug concentration-effect relationship in plasma and liver was shifted to the left in rats treated with phenylbutazone, such shift was not seen in the free drug concentration-response relationship. In conclusion, the increase in the free concentration of phenprocoumon in plasma and liver and the concomitant decrease in the clearance of free drug are the mechanisms responsible for the marked and sustained enhancement of the anticoagulant effect which follows treatment with phenbutazone.This work was supported by the Deutsche Forschungsgemeinschaft.