乳腺浸润性导管癌患者中FHIT、Bcl-2、Bax的表达及其临床病理意义

目的探寻生物标志物FHIT、Bcl-2、Bax对术后化疗的选择及化疗患者预后的提示作用。方法用HE及sP免疫组化染色法对100例乳腺浸润性导管癌作回顾性分析。研究生物标志物在乳腺浸润性导管癌的表达与肿瘤生物学特点及患者无瘤生存时间和总体生存时间的关系。结果各生物标志物的阳性率分别为FHIT73％,Bcl-250％,Bax34％,其中FHIT和Bcl-2的表达正相关（r=0．3290）,FHIT和Bcl-2的表达与组织学分级负相关,分级越高,表达越低。FHIT和Bcl-2的阳性表达的患者无瘤生存时间和总体生存时间均长于阴性者。FHIT为阳性表达者,化疗后平均无瘤生存时间（56．8个月）长于FHIT阴性者（35．8个月）,Bcl-2为阳性表达者,化疗后平均无瘤生存时间（54．8个月）长于Bcl-2阴性者（41．6个月）,Bcl-2为阴性时,单独使用CAF的患者平均无瘤生存时间55个月和总体生存时间58．8个月均长于使用其他化疗方案的患者,其无瘤生存时间和总体生存时间分别为27个月和36个月。Bax表达与患者的预后无关。结论FHIT和Bcl-2的表达与患者的无瘤生存时间和总体生存时间相关。FHIT为阳性表达,患者化疗后无瘤生存时间较长,复发率较低。患者的Bcl-2为阴性时,单独使用CAF组比使用其他化疗方案组的患者的无瘤生存时间和总体生存时间更长,预后更好。     

The generation of antibody diversity

By their nature, antibody molecules exhibit a wide range of binding specificities. The antigen-binding properties of the antibody reside entirely in the amino-terminal portion of the molecule, termed the variable domain. Structurally, the combining site specificity is determined by the amino-acid residues within 6 short lengths, 3 each in the heavy and light chains, of usually variable sequence. The hypervariability of 2 of these lengths arises from the somatic recombination of short gene segments into a single stretch of mRNA which encodes the entire variable region of 1 polypeptide chain. For example, a V gene segment that codes for most of the variable portion of a light chain, can combine with one of a number of much shorter J gene segments to create the complete variable region gene. In heavy chain genes, a third element, the D gene segment, increases the potential for diversity even further. A mechanism has been proposed by which variability occurs at the point where 2 gene segments join. Thus, a large part of the generation of antibody diversity occurs in the somatic recombination of small genetic elements.     

Recovery of rat brain from a brief hyperphenylalaninemic insult early in development

Mice 14 or 60 days of age were injected intraperitoneally with [³H]leucine and were decapitated 10, 20, 40, and 80 days later. A crude fraction of brain myelin was isolated on a discontinuous sucrose gradient. Myelin was separated from the associated myelin-like material by osmotic shock and the two fractions were purified by differential centrifugation and isolated on a continuous CsCl gradient. Proteins of each subcellular fraction were separated by discontinuous gel electrophoresis in buffers containing sodium dodecyl sulfate and the specific activity of individual proteins determined. Myelin contained (in order of increasing molecular weight) two basic proteins, a protein doublet, proteolipid protein and a group of high molecular weight proteins. When animals were labeled at 14 days of age the radioactivity incorporated into the basic and proteolipid proteins of myelin was very stable metabolically (half-life much greater than 100 days), while the high molecular weight myelin proteins turned over with a half-life of about 70 days. The proteins of myelin labeled at 60 days of age turned over more rapidly, the half-life of basic and proteolipid proteins being about 95 days and that of the high molecular weight proteins about 40 days.The myelin-like material consisted primarily of high molecular weight proteins, although small amounts of basic and proteolipid protein also appeared to be intrinsic components. All the proteins of myelin-like materials turned over with a half-life of about 20 days, regardless of whether label was incorporated at 14 or 60 days of age. Thus, whereas the myelin basic and proteolipid proteins of both young and mature animals turn over very slowly as compared to the high molecular weight protein, all proteins in the myelin-like material turn over at the same, much faster rate in both young and mature animals.     

Trichloro-compounds in the urine of humans exposed to methyl chloroform at sub-threshold levels

Summary Survey was carried out in 4 intaglio printing factories where methyl chloroform, the sole organic solvent in the entire process, was employed to remove excess ink. The medical interview and clinico-laboratory examinations revealed no dose-consistent adverse effects among the four groups of workers who had been exposed at the average concentrations of 4, 25, 28 and 53 ppm, respectively. Linear relationship was observed between environmental vapour concentrations and total trichloro-compounds levels in the urine of workers exposed. Increased levels of urinary metabolites towards the week-end, together with the biological half-life of 8.7 hrs as measured from the decrease in the urinary metabolites, suggested the storage of methyl chloroform in the body after repeated exposures. Perusal of previous reports as well as present results regarding toxic potency of methyl chloroform supports, with emphasis of possible accumulation, the German threshold of 200 ppm as a tentative value of choice for the time being.A part of this work was presented at the 46th Annual Meeting of the Japanese Association of Industrial Health, Osaka, April 6–8, 1973.     

Urinary mercapturic acid excretion as a biological parameter of exposure to alkylating agents

Summary Mercapturic acid derivatives or other thioethers can be considered as the endproducts of the metabolic detoxification of possibly alkylating agents. It is proposed that the appearance of these metabolites in the urine can be used as an indicator of exposure of the organism to such toxic compounds. A simple, practical procedure for determination of thioethers in urine samples is described. Employees of chemical and metal industries have been compared with respect to their urinary thioether concentrations. It was found that chemical workers excreted more thioether compounds than persons engaged in metal industry.     

Der einfluß technischer elektrischer wechselfelder hoher feldstärke auf den organisms

Summary The effect of high voltage 50 Hz electric. fields of a gradient up to 80 kV/m on rats and cats has been investigated.Only rats enclosed in a narrow teflon tube developped a hyperthermic shock, obviously elicited by an increase in the reflectoric tonic muscular activity. Permanent damage and irreversible changes in the EEG could not be observed. All acute changes in the EEG that have been recorded can be interpreted as the result of vibration of hairs.In the literature no observations have been described, which could be taken as an indicator of impaired health.The alternating electric field obviously produces reactions only in sensory cutaneous receptors, but no changes of autonomic processes of importance.Der Beitrag zur physikalischen Problematik und die dazugehdrigen experimentellen Untersuchungen wurden von J. Silny am Helmholtz-Institut für Biomedizinische Technik an der RWTH Aachen bearbeitet. Die Untersuchungen wurden auf Veranlassung und mit Unterstützung der Berufsgenossenschaft der Feinmechanik und Elektrotechnik, Köln, durchgeführt.     

The role of cyclic GMP in the regulation of cyclic AMP hydrolysis.

A rat-heart cyclic nucleotide phosphodiesterase has been chromatographically separated from related enzymes and its kinetic properties have been studied. The enzyme can hydrolyze both cyclic AMP and cyclic GMP and has about the same maximum velocity and apparent KM (greater than 10-5 M) for the two nucleotides. Kinetic plots indicate positive cooperative behavior for both substrates. Cyclic GMP at low concentrations is a potent activator of cyclic AMP hydrolysis and this activation, as well as the cooperativity, can be abolished by treatment with solvents or sulfydryl reagents under conditions which do not destroy the catalytic function. A kinetic model for this enzyme is porposed and the physiologic role is discussed.     

A necessary and sufficient condition of global structural identifiability of compartmental models

For fixed structure compartmental deterministic model of the biological system, the problem of global- and local-structural identifiability is studied. Conditions for structural identifiability are reviewed and a necessary and sufficient condition for global identifiability for a particular case of linear time-invariant compartmental model is developed. The proposed condition provides a computationally attractive form.