肺癌靶向多肽荧光分子探针的研制及其应用

目的:选择能与整合素α3受体结合的小分子多肽cNGQGEQc-L作为靶向载体，将羧基荧光素（FAM）与cNGQGEQc-L连接构建荧光分子探针，通过荧光成像探讨荧光多肽分子探针用于肺腺癌显像的可行性。方法:利用倒置荧光显微镜观察FAM-cNGQGEQc-L与肺腺癌A549细胞结合部位，流式细胞仪检测荧光多肽与A549细胞的竞争抑制实验，观察FAM-cNGQGEQc-L随浓度的增加与肺腺癌A549细胞结合能力的变化情况。通过小动物活体成像仪，观察荧光多肽在荷瘤裸鼠体内的生物分布特点。结果:倒置荧光显微镜显示荧光多肽cNGQGEQc-L能与A549细胞结合，结合部位在细胞膜和细胞质中。流式细胞仪测试结果证明荧光多肽与A549细胞的结合具有特异性和饱和性，当FAM-cNGQGEQc-L浓度为0.125 mmol/L时，荧光多肽与A549细胞的结合趋近饱和。荷瘤裸鼠活体成像显示移植瘤能够摄取荧光多肽，且荧光多肽通过泌尿系统和胆道系统排泄。结论:体外、体内荧光实验结果显示，荧光多肽分子探针FAM-cNGQGEQc-L可与肺腺癌A549细胞、肺癌移植瘤结合，能够特异性靶向肺腺癌。     

An immunohistochemical study of endocrine cells in the alimentary tract of the grass lizard, Takydromus wolteri Fischer (Laceridae)

Distribution patterns and the relative frequency of different types of endocrine cells were demonstrated in the alimentary tract of the grass lizard, Takydromus wolteri, using nine specific antibodies raised against mammalian regulatory peptides. The alimentary tract of the lizard was divided into six portions from the esophagus to the rectum. Most endocrine cells were found in the epithelial lining and were generally spindle shaped with long cytoplasmic processes ending in the lumen (open cell type), whereas cells that were spherical in shape (closed cell type) were occasionally found in gastric, esophageal and intestinal glands. Endocrine cells were stained for the following regulatory peptides: bovine Sp-1/chromogranin (BCG), serotonin, somatostatin, gastrin, cholecystokinin (CCK)-8, glucagon, insulin, human pancreatic polypeptide (HPP) and secretin. Cells stained for BCG and serotonin were present throughout the entire gastrointestinal tract and they occurred with the highest frequency in stomach and pylorus, respectively. Somatostatin-positive cells were detected throughout the entire gastrointestinal tract except for the esophagus and large intestine, and were most predominant in pylorus and duodenum. Cells stained for gastrin were restricted to the pylorus and duodenum and occurred with a relatively low frequency. CCK-8-positive cells were observed from pylorus to small intestine and showed the highest frequency in the pylorus. Glucagon- and insulin-containing cells were located in duodenum and small intestine but were found only rarely. HPP-stained cells were detected in duodenum and small intestine with the highest frequency in duodenum. Cells stained for secretin were restricted to duodenum and were found only rarely. In conclusion, distribution patterns and the relative frequency of these endocrine cells correspond well with previous reports on distribution patterns of endocrine cells in reptile species but some deviating patterns were also observed.     

Latent variable discovery in classification models

The naive Bayes model makes the often unrealistic assumption that the feature variables are mutually independent given the class variable. We interpret a violation of this assumption as an indication of the presence of latent variables, and we show how latent variables can be detected. Latent variable discovery is interesting, especially for medical applications, because it can lead to a better understanding of application domains. It can also improve classification accuracy and boost user confidence in classification models.     

The rheumatic patient''s early needs and expectations

During the last few years, studies have revealed that the need for psychosocial support and concrete social services are great in the early stages of the treatment of rheumatic diseases. The ability to keep a job, to do household chores, to participate in leisure activities and to maintain social relations is clearly impaired. Anxiety and depression are not unusual and often associated with weak support from relatives, loneliness and disturbed family relations. Nevertheless, the patients report resilience and determination to cope with the impacts of illness. Crisis intervention, vocational guidance and counselling about problems concerning the disease should be available and offered to the patients. As the patients seem to be unaccustomed to talking about their psychosocial problems, an empathetic and information-seeking attitude on the part of the health care staff is essential.     

A mathematical simulation of the AIDS patient and extracorporeal detoxification

A simple numerical simulation of AIDS patient detoxification by a hypothetical extracorporeal device for the removal of viruses, infected white cells, and syncytia has been designed. The mathematical model accounts for healthy blood white cells attacking and destroying the viruses, while at the same time the viruses attack and infect certain white cells. The infected white cells serve as a site for viral growth; eventually the cells lyse, releasing a large number of viruses into the blood stream. The healthy white cells and infected white cells combine to form syncytia, where the virus multiplies, and finally the syncytium ruptures releasing all the virus. This model can be used to predict concentrations over a specified period for the patient. This is a mathematical model to be used as a research and design tool only.     

Cannabinoid agonist, CP 55,940, facilitates intake of palatable foods when injected into the hindbrain

Cannabinoids have been shown to influence food intake, and until recently, the neural pathways mediating these effects have remained obscure. It has been previously shown that intracerebroventricular injection of delta-9-tetrahydrocannabinol (Δ⁹-THC) causes increased consumption of palatable foods in rats, and we postulated the involvement of the hindbrain in this cannabinoid-induced food intake. Cannulated rats (both female and male groups) trained to consume sweetened condensed milk received either lateral or fourth ventricle injections of CP 55,940 and were presented with sweetened condensed milk 15 min after injection. Rats were injected over a range of doses between 100 pg and 10 μg per rat. Milk intake was recorded for a total of 3 h. Lateral ventricle injection of CP 55,940 increased milk intake at doses in the microgram range. However, CP 55,940 was effective in increasing food intake at nanogram doses when injected into the fourth ventricle. Finally, male rats appeared to be more sensitive to CP 55,940 than female rats inasmuch as milk consumption was increased at the 1 ng dose in male rats, whereas only the 10 ng dose was effective in females. These results indicate that CP 55,940 may act in the hindbrain to influence feeding behavior in rats.     

Measurement of functional ability and health status in the arthritic patient

Chronic arthritis may have great impact on the patient but also on his or her family, relatives and friends. The assessment of the consequences of chronic arthritis and the effect of therapy not only in terms of physical, but also psychological and social dimensions deserves more attention. Functional ability and health status can be measured using a questionnaire or ‘instrument’, high-lighting important aspects not quantified with more traditional measurements. In this paper, arguments to apply such instruments more frequently are given. Health status instruments can be used not only to assess beneficial but also deleterious (side-)effects of therapeutic interventions. The properties are summarized of the most frequently used instruments assessing functional ability and health status. Many of these instruments have been evaluated sufficiently for validity and reliability; their sensitivity to detect change seems to be satisfactory. Therefore it is advisable to choose an internationally accepted, frequently used instrument, reflecting the area of interest.     

Chondral separation in the trochlear groove - a definite clinical entity

Four patients with unusual femoro-patellar chondral defects are presented. We were unable to find their particular lesion described adequately in the literature. The patients all gave a history of relatively minor non-contact injury and presented with anterior knee pain and persistent swelling. The main features on clinical examination were moderate effusion and marked patello-femoral crepitus. Plain X-rays of the knee were unhelpful. At arthroscopy large full thickness chondral defects were seen on the femoral side of the patello-femoral articulation at the site of patellar contact with the knee in about 60° of flexion. The synovium was found to be prolific and vascular. Multiple 1.6-mm drill holes were made in the defect and chondral debris was washed out. Two patients underwent associated lateral patellar release. When a clear cut mechanical patello-femoral disorder presents unexpectedly with associated effusion and a normal radiograph, we suggest that arthroscopy be advised with particular attention to the femoral trochlea.     

A method for shape optimization of a hip prosthesis to maximize the fatigue life of the cement

The long term success of total joint replacement can be limited by fatigue failure of the acrylic cement and the resulting disruption of the bone-cement interface. The incidence of such problems may be diminished by reduction of the fatigue notch factor in the cement, so that stress concentrations are avoided and the fatigue crack initiation time maximized. This study describes a method for numerical shape optimization whereby the finite element method is used to determine an optimal shape for the femoral stem of a hip prosthesis in order to minimize the fatigue notch factor in the cement layer and at interfaces with the bone and stem.

A two-dimensional model of the proximal end of a femur fitted with a total hip prosthesis was used which was equivalent to a simplified three-dimensional axisymmetric model. Software was developed to calculate the fatigue notch factor in the cement along the cement/stem and cement/bone interfaces and in the proximal bone. The fatigue notch factor in the cement at the cement/stem interface was then minimized using the ANSYS finite element program while constraining the fatigue notch factor at the cement/bone interface at or below its initial level and maintaining levels of stress in the proximal bone to prevent stress shielding. The results were compared with those from other optimization studies.     

Noninvasive method for measuring the electrical properties of deep tissues using an open-ended coaxial probe

A new noninvasive method of measuring the structure and the electrical properties of bilayered biological tissues was evaluated as a potentially useful diagnostic means for detecting changes in subcutaneous tissues. First, the input impedance of an open-ended coaxial probe radiating into a bilayered model was calculated using a full-wave method, the results showed that the evanescen higher order modes do not have a significant influence on the reflection coefficient of muscle layer surface. Then, it was clearly proven that the phase shift and the modulus of the reflection coefficient of muscle layer surface depending on the frequency are useful to estimate the thickness of fat layer and the electrical properties of muscle respectively. The experimental results showed an excellent agreement with the theoretical relationship between the phase shift and the thickness. The sensitivity of estimation of the electrical properties of muscle was shown to be not enough for differentiating between normal and diseased deep tissue because of noises from the experimental systems.