Effects of Orally Administered Epidermal Growth Factor on Enteropathogenic Escherichia coli Infection in Rabbits

The increased intestinal absorption induced by epidermal growth factor (EGF) is associated with diffuse lengthening of brush border microvilli. The aim of this study was to examine the in vivo effects of oral administration of EGF during infection with enteropathogenic Escherichia coli. New Zealand White rabbits (4 weeks old) received orogastric EGF daily starting 3 days prior to infection with enteropathogenic E. coli RDEC-1 and were compared with sham-treated infected animals and uninfected controls. Weight gain, food intake, fecal E. coli, and stool consistency were assessed daily. On day 10, segments of jejunum, ileum, proximal, and distal colon were assessed for gram-negative bacterial colonization, disaccharidase activities, and epithelial ultrastructure. Effects of EGF on E. coli RDEC-1 proliferation were studied in vitro. E. coli RDEC-1 caused diarrhea and reduced weight gain. Seven days postinfection, the small and large intestines were colonized with numerous bacteria, brush border microvilli were disrupted, and maltase and sucrase activities were significantly reduced in the jejunum. Daily treatment with EGF prevented the occurrence of diarrhea and reduction of weight gain. These effects were associated with significant inhibition of E. coli colonization in the small and large intestine, improved jejunal maltase and sucrase activities and reduced microvillous injury. EGF did not affect the proliferation of E. coli in vitro. The findings suggest that EGF protects the gastrointestinal tract against colonization by enteropathogenic E. coli.     

我国狂犬病病原学和病理形态学观察

报告四例狂犬病病例及对其尸脑组织的病原学和病理形态学观察。４例病人均有被犬咬伤史；发病后临床病状典型，表现为发热、恐水、怕风等；潜伏期和病程分别在２０～１３２天和７～１４天；临床诊断明确。死亡后尸检脑组织病理改变为病毒性脑炎病变，在感染神经细胞胞浆内均检到内基氏体。从尸脑组织中分离出狂犬病毒４株。又从４例病人血清中和２例病人脑脊液中分别检测出特异性狂犬病毒抗体各１例。     

Interferon Production by Macrophages from Adult and Newborn Rabbits Bearing Fibroma Virus-Induced Tumors

Tumors were induced in adult and newborn rabbits by inoculation of fibroma virus. After 10 to 14 days, oil-induced peritoneal macrophages were harvested, purified, and tested in vitro for interferon synthesis after stimulation with specific and nonspecific viruses. Peritoneal macrophages from adult rabbits that had initiated tumor regression produced high levels of interferon (titers ranged from 160 to 640) after stimulation with fibroma virus, whereas macrophages from normal adult rabbits failed to produce significant levels of interferon under the same conditions (titers ranged from <10 to 10). Furthermore, fibroma-immune macrophages responded to vaccinia virus and Newcastle disease virus with higher levels of interferon than did normal macrophages. In contrast, macrophages from newborn tumor-bearing rabbits that showed no evidence of tumor regression failed to respond to fibroma virus stimulation with higher levels of interferon (titers ranged from <10 to 10). These macrophages did, however, yield significantly more interferon than newborn control macrophages when stimulated with a good interferon inducer, Newcastle disease virus (titers ranged from 10 to 80). These data suggest that interferon production may be an expression of macrophage activation to fibroma antigens and that macrophage activation is impaired in newborn rabbits with progressive growing tumors.     

Intramuscular and/or Intralumbar Postexposure Treatment of Rabies Virus-Infected Cynomolgus Monkeys with Human Interferon

From 9 to 10 of 10 cynomolgus monkeys infected with rabies street virus died of rabies about 20 days postinfection (pI). Symptoms of illness appeared 1 to 4 days before death. In an attempt to protect infected animals from the disease, human leukocyte interferon (HIF) was administered intramuscularly (i.m.) near the site of infection or into the cerebrospinal fluid between the first and second lumbar vertebrae (i.e., intralumbarly [i.l.]). Multiple HIF doses given over a period of several days proved more effective than a single HIF dose. In every experiment, i.m. HIF treatment was started 1 day pI. The best result obtained was a survival rate of 7 of 10 monkeys. The i.l. HIF administration schedules, consisting of multiple doses given over a period of at least 8 days, were started on day 3, 7, or 11 pI. Here the best result noted was the protection of 5 of 10 treated monkeys. The latest successful postexposure i.l. HIF treatment began on day 11 pI. The highest protection rate, 8 survivors of 10 treated monkeys, was achieved by a combined i.m. and i.l. HIF treatment. From these results we conclude that human patients severely bitten by rabid animals should in addition to an active immunization be i.m. and i.l. treated with HIF. Particularly, i.l. HIF administration could be effective, even when given several days pI. Whether an HIF administration starting after the appearance of clinical symptoms of rabies can help cannot be decided upon from the studies made in this monkey model. The most obvious difference between rabies in humans and cynomolgus monkeys is the duration of illness between the outbreak of the disease and death (1 to 4 days only in this animal model). It might have been due to this short period of illness that i.l. and i.m. HIF treatment at the appearance of clinical symptoms failed to help any of the monkeys treated.     

家兔血液流变学参数及其影响因素

目的检测正常家兔血液流变学指标,建立其正常参考值,并对有关影响因素进行探讨。方法采用ＮＸＥ－１型锥板式粘度计。测定５．７５５~(－１)～３０７．２Ｓ~(－１)七个切变率的血液表观粘度、血浆粘度、红细胞硬度指数（ＴＫ）、红细胞聚集指数（ＲＡＩ）和氧释放系数（ＯＤ）。结果雄性组家兔高切变率和低切变率下的血液粘度及ＲＡＩ较雌性组明显增高（Ｐ<０．０５和Ｐ<０．０１）,而ＯＤ较雌性组明显降低（Ｐ< ０．０５）。高体重组家兔高、中、低各切变率下的血液粘度和红细胞压积（Ｈｃｔ）较低体重组明显增高（Ｐ< ０．０５和Ｐ<０．０１）,而ＯＤ明显低于低体重组（Ｐ<０．０５）。高Ｈｃｔ组家兔的血液粘度、ＯＤ较低Ｈｃｔ组明显增高（Ｐ均<０．０１）,而血浆粘度和ＴＫ较低Ｈｃｔ组明显降低（Ｐ＜０．０５和Ｐ<０．０１）。结论家兔不同性别、体重和Ｈｃｔ,其血液流变学指标存在明显差异。     

控制性深低温对家兔血液流变性的影响

目的 通过建立低温家兔模型,探讨低温对家兔血液流变性的影响及其作用机制.方法 20只家兔随机分为2组,每组10只,分别设为对照组和降温组.所有家兔经3%戊巴比妥钠麻醉作气管切开插管后接呼吸机控制呼吸,然后静脉注入芬太尼、哌库溴胺加深麻醉;采用体表降温法将降温组家兔体温降至(25±1)℃,维持3 h.实验组于降温前、深低温、复温开始、复温至37℃时各采动脉血测定血液流变学各项指标.结果 降温组在鼻咽温度从36℃降至25℃后,全血黏度高、中、低切及全血还原黏度低切与降温前比较明显升高(P＜0.05),且低温持续过程中变化不大;复温后高、中、低切全血黏度及全血还原黏度低切显著降低(P＜0.05),与对照组比较,无统计学差异(P＞0.05).降温、低温及复温过程中血浆黏度和HCT变化不明显.结论 低温对家兔血液流变性有明显的影响,主要表现在各种切变率下全血黏度明显升高.     

Eperythrozoon coccoides I. Effect on the Interferon Response in Mice

Eperythrozoon coccoides is a common blood parasite of rodents and the etiological agent of a chronic infection present in many mouse colonies. After primary infection, mice develop a parasitemia and anemia followed by a chronic, latent infection. During the acute phase of infection, mice manifest a striking suppression of interferon production in response to induction with Newcastle disease virus, Chikungunya virus, and poly I:C. These data suggest that the reticuloendothelial system involvement with this agent is associated with impairment of the interferon response. The enhanced susceptibility of E. coccoides-infected animals to certain viral infections may be related to this suppression of interferon production.     

环磷酰胺对家兔血液流变性的影响

观察抗肿瘤药物环磷酰胺（ＣＴＸ）对家兔血液流变性的影响。结果显示：ＣＴＸ给药组（１０只）多项血液流变学指标明显异常，与正常对照组（８只）比较具有显著性差异（Ｐ＜０．０５～０．００１），标志着ＣＴＸ有引起高粘滞血症的作用。提示：恶性肿瘤病人应用ＣＴＸ后，可加重原有的高粘滞血症。这一结果可作为肿瘤化疗并用活血化瘀及抗凝治疗的依据     

Effect of Corynebacterium acnes on Interferon Production in Mice

Exposure to Corynebacterium acnes, the most prominent member of our normal skin flora, produces stimulation of lymphoid tissue and certain reticuloendothelial system functions, as well as the immune response. Alteration of the host response is extended by these studies to include changes in the pattern of interferon production in response to a representative group of inducing agents. Serum interferon levels induced by the injection of endotoxin in mice are enhanced, whereas interferon production after injection of Newcastle disease virus, Chikungunya virus, and polyinosinic:polycytidylic acid is depressed in animals inoculated with viable or nonviable C. acnes organisms.     

干扰素对受照射机体NK细胞活性的调节作用

采用4h51Cr释放法,分别以小鼠脾脏淋巴细胞对YAC-1细胞和肿瘤患者外周血淋巴细胞对K562细胞的体外自然杀伤（NK）活性为指标,研究受电离辐射后小鼠脾脏NK细胞活性的变化以及干扰素（IFN－α）对NK细胞活性的影响;并观察肿瘤患者及其放疗后NK细胞活性的变化以及IFN－α的调节作用。结果表明NK细胞具有较强的辐射耐受性,经16Gy照射后24hNK细胞活性显著降低;肿瘤患者的NK细胞活性明显低于正常对照组（P＜0．01）,放疗后NK细胞活性进一步降低（P＜0．05）。IFN－α处理NK细胞可以显著增强NK细胞活性,这提示IFN-α有可能作为一种生物应答调节剂用于肿瘤患者、肿瘤放、化疗或手术患者。     

The Fate of Intravenously Administered bFGF and the Effect of Heparin

Abstract

The fate and effects of intravascular bFGF are unknown. We have investigated the fate of bFGF administered intravenously to rats in the presence and absence of heparin, and evaluated the effect of a 3-day IV infusion of bFGF on proliferation of endothelial and vascular smooth muscle cells in situ. [¹²⁵I]bFGF, administered as an IV bolus, was rapidly cleared from the circulation (t_1/2 = 1.5 min) by the liver. Nevertheless, it was maintained at a constant, predictable concentration in the blood (9.7 ± 4% of the amount infused) by continuous IV infusion. Heparin consistently altered the pattern: slowing the rate of clearance (t_1/2 = 4.5 min), increasing the plateau concentration in the blood during continuous infusion (32.5 ± 14.3% of the amount infused), and allowing intact (as determined by gel analysis) bFGF to cross from the circulation into the urine. A 3-day infusion of bFGF alone (2.5 ng/kg/min) and with adenosine (11.6 μM/kg/hr) did not increase [³H]thymidine incorporation in either endothelial cells or vascular smooth muscle cells, suggesting that they are refractory to this factor when it is administered intravascularly.     

Effect of Interferon and Interferon Inducers on Infections with a Nonviral Intracellular Microorganism, Rickettsia akari

The effect of mouse interferon (IF) on the multiplication of Rickettsia akari in homologous (L-929) cell cultures and the effect of IF inducers on R. akari infection in mice were investigated. There was a reduction in the proportion of cells containing rickettsiae in IF-treated cultures and in the yield of rickettsiae from these cultures, as compared with those from infected cultures without IF. Trypsin treatment and heating for 1 hr at 65 C destroyed this antirickettsial activity of the IF preparation, whereas ultracentrifugation (105,000 × g for 90 min) and acidification at pH 2.0 did not affect it. There was no evidence that mouse IF inactivated R. akari directly, nor did it have an inhibitory effect on multiplication of R. akari in heterologous chick embryo cell or monkey kidney cell cultures. Susceptibility of R. akari to the action of IF was about 16 times less than that of Chlamydia trachomatis and 256 times less than the susceptibility of vesicular stomatitis virus. Mice were not protected from infection with R. akari by intraperitoneal injection with IF inducers, Newcastle disease virus (10^8.3 plaque-forming units/0.2 ml) or polyriboinosinic acid-polyribocytidylic acid complex (poly I:C, 200 μg/0.2 ml), within 24 hr before or 24 hr after intraperitoneal challenge. The yields of R. akari harvested from the spleens, livers, and peritoneal washings of infected mice treated with IF inducers were similar to those of infected control mice. Titers of IF in peritoneal washings of treated mice, taken 6 hr after administration of Newcastle disease virus or 9 hr after injection of poly I:C, were 1,024 or 320 units/ml, respectively.     

Effect of Interferon and Interferon Inducers on Infections with a Nonviral Intracellular Microorganism, Chlamydia trachomatis

The effect of mouse interferon (IF) on the multiplication of Chlamydia trachomatis (strain MRC-1/G) in homologous (L-929) cell cultures and the effect of the IF inducers Newcastle disease virus (NDV) and polyriboinosinic acid-polyribocytidylic acid complex (poly I:C) on the experimental infection of mice with aerosolized C. trachomatis (strain MoPn) were investigated. Treatment of infected cell cultures with IF reduced the number of cells containing chlamydial inclusions and depressed the yield of chlamydiae as determined by titrations for infectivity. Growth of chlamydiae was reduced when cultures were exposed to IF 6 or 18 hr before infection, and slight reduction of the yield was also detectable in cell cultures treated with IF at early intervals (0 or 4 hr) after chlamydial infection. No effect of IF on penetration of chlamydiae into mouse cells was observed, whether phagocytic cells from peritoneal washings or L-929 cells were used, indicating that the inhibitory effect of IF occurs after chlamydiae enter the host cell. Additional evidence was obtained that a significant effect of IF occurs at an early stage in maturation of the intracellular chlamydiae. In mice exposed repeatedly to NDV aerosols and challenged with aerosolized MoPn 8 hr after the first exposure to NDV, mortality was delayed by 2 to 3 days and lung consolidation was slightly reduced at 3 days after infection. Yields of chlamydiae from lung pools of NDV-treated mice, taken at 3, 6, and 9 days after challenge, were not significantly different from those of controls. Similar results were obtained when mice were challenged with MoPn 8 hr after intranasal injection with 100 μg of poly I:C or 24 hr after intravenous injection with 200 μg of poly I:C. In contrast, administration of 0.2 ml of NDV (10^8.3 plaque-forming units) intravenously 10 hr before or 24 hr after challenge with MoPn accelerated mortality of mice by 2 to 3 days. In all experiments, detectable levels of IF in sera or 20% lung suspensions were found only up to 48 to 72 hr after exposure of mice to IF inducers.     

Relationship between Intracranial Granulomas and Cerebrospinal Fluid Levels of Gamma Interferon and Interleukin-10 in Patients with Tuberculous Meningitis

Cerebrospinal fluid gamma interferon (IFN-γ) and interleukin-10 levels in 39 patients with tuberculous meningitis were serially measured. Cytokine levels did not predict intracranial granuloma (IG) development, but IFN-γ levels in the top quartile after 1 month of therapy were highly associated (odds ratio = 18) with detection of an IG by computed tomography scanning.