Ex vivo rapamycin generates Th1/Tc1 or Th2/Tc2 Effector T cells with enhanced in vivo function and differential sensitivity to post-transplant rapamycin therapy.

Rapamycin prevention of murine graft-versus-host disease (GVHD) is associated with a shift toward Th2- and Tc2-type cytokines. Recently, we found that use of rapamycin during ex vivo donor Th2 cell generation enhances the ability of adoptively transferred Th2 cells to prevent murine GVHD. In this study, using a method, without antigen-presenting cells, of T-cell expansion based on CD3,CD28 costimulation, we evaluated whether (1) rapamycin preferentially promotes the generation of Th2/Tc2 cells relative to Th1/Tc1 cells, (2) rapamycin-generated T-cell subsets induce cytokine skewing after allogeneic bone marrow transplantation (BMT), and (3) such in vivo cytokine skewing is sensitive to post-BMT rapamycin therapy. Contrary to our hypothesis, rapamycin did not preferentially promote Th2/Tc2 cell polarity, because rapamycin-generated Th1/Tc1 cells secreted type I cytokines (interleukin [IL]-2 and interferon-gamma) did not secrete type II cytokines (IL-4, IL-5, IL-10, or IL-13) and mediated fasL-based cytolysis. Rapamycin influenced T-cell differentiation, because each of the Th1, Th2, Tc1, and Tc2 subsets generated in rapamycin had increased expression of the central-memory T-cell marker, L-selectin (CD62L). Rapamycin-generated Th1/Tc1 and Th2/Tc2 cells were not anergic but instead had increased expansion after costimulation in vitro, increased expansion in vivo after BMT, and maintained full capacity to skew toward type I or II cytokines after BMT, respectively; further, rapamycin-generated Th1/Tc1 cells mediated increased lethal GVHD relative to control Th1/Tc1 cells. Rapamycin therapy after BMT in recipients of rapamycin-generated Th1/Tc1 cells greatly reduced Th1/Tc1 cell number, greatly reduced type I cytokines, and reduced lethal GVHD; in marked contrast, rapamycin therapy in recipients of rapamycin-generated Th2/Tc2 cells nominally influenced the number of Th2/Tc2 cells in vivo and did not abrogate post-BMT type II cytokine skewing. In conclusion, ex vivo and in vivo usage of rapamycin may be used to modulate the post-BMT balance of Th1/Tc1 and Th2/Tc2 cell subsets.     

Vereinfachte enzymatische Bestimmung der Blut-Glucose mit 20 Mikroliter Blut

Ohne Zusammenfassung     

Lexical priming deficits as a function of age

The effects of age on implicit memory were assessed in elderly young adults using 2 priming procedures. Subjects also completed the WAIS-R, 3 tests to assess frontal lobe function, and 2 recall and 2 recognition tests of explicit memory. In Experiment 1, subjects were exposed to the low-frequency member of a homophone pair in a test purported to assess general knowledge. Subsequently, subjects completed a spelling test that contained the previously presented homophones to assess priming. Young subjects demonstrated priming (p less than .01). Elderly subjects demonstrated a high baseline that may have obscured priming. In Experiment 2, subjects from each decade of life from the 20s through the 80s were given a word-stem completion test of priming. All age conditions demonstrated an effect of priming (p less than .01). However, subjects in their 70s and 80s demonstrated lower priming scores (p less than .05). Elderly subjects were also impaired on immediate-and delayed-recall tests. These results suggest an age-related decline in both implicit and explicit memory.     

Etherification of poly(oxymethylene)-diol [α-hydro-ω-hydroxypoly(oxymethylene)] with orthoesters in the presence of Lewis acids

Attempts were made to elucidate experimentally the behaviour of poly(oxymethylene)-diol [α-hydro-ω-hydroxypoly(oxymethylene)] in the etherification reaction in order to explain the decrease of the polymer molecular weight compared with that of the starting product and in order to determine the type of terminal groups and how the thermal resistance and alkali stability can be affected. In fact one finds that, in addition to the wanted terminal ether groups, formyl and orthoformyl (dialkoxymethyl) groups are formed having a different chemical resistance in comparison to that of the pure ethers, particularly in basic media.     

Immunogenicity of a yeast-recombinant hepatitis B vaccine in high-risk children

Horizontal transmission of hepatitis B virus (HBV) from illicit drug users to their contacts, including young children, can be prevented by active immunization against HBV. Yeast-recombinant hepatitis B vaccines are now available for this purpose, but their potential efficacy in such high-risk contacts has not yet been evaluated. Therefore we gave 20 mcg of a recombinant yeast-derived hepatitis B vaccine to 38 children who were at high risk for HBV infection because they had been institutionalized in a community for drug users in which 8.7% of the occupants are carriers. After third dose of vaccine (at 0, 1, and 6 months), all children had anti-HBs responses with titers of 10 mIU/ml or more, with 81% showing responses greater than 1,000 mIU/ml. At 12 months, the percentage of anti-HBs-positive children was 100%, and the percentage of children with anti-HBs higher than 1,000 mIU/ml was 56%. None of the children developed HBV infection during follow-up. Hence the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers comparable with those attained in other categories of high-risk children with plasma-derived vaccines.     

Angiomorphology of the ciliary body in diabetic disease

The authors describe the pathological changes in the vascular structures of the ciliary body occuring in diabetes mellitus. The lesions consist of a quantitative reduction in the number of vessels and in modifications of diameter and arborisation. Changes include sectoral thinning, isolated and grouped aneuryms and marked tortuosity. These findings are thought to be constant in the diabetic patient and are probably involved in the various aspects of diabetic eye disease affecting other structures besides the ciliary body. The group of vascular changes in the ciliary body in diabetes may aptly be termed "diabetic ciliopathy".     

Neural projections of the preoptic-suprachiasmatic region to the median eminence in the rat: A quantitative autoradiographic study

The possibility of a preferential distribution of projections from the preoptic-suprachiasmatic region (POA-Sch) to the median eminence in the male rat was studied using autoradiographic and computer procedures. A cocktail of [3H]leucine-[3H]proline was injected into the POA-Sch. Animals were killed after either 1, 4, or 24 h of incorporation time (IT). The number of silver grains per 25-micron square was counted throughout the median eminence. Squares with silver grain densities at or above the 75 percentile of the population for any given IT group were labeled as "concentrating areas." The distribution of these concentrating areas in median eminence tissue was analyzed utilizing univariate procedures. Visual inspection of the distribution of silver grain densities in a rostrocaudal fashion indicated the likelihood of uneven distribution; however, these differences were not statistically significant. In the dorsoventral plane, results indicated that the highest silver grain density was at 50 to 75 micron from the floor of the 3rd ventricle. Such distribution was apparent both ipsi- and contralateral to the injection site, but was greater on the ipsilateral side.     

Autosomal-dominant dystrophy with humeroperoneal weakness and cardiopathy: a genetic variant of Emery-Dreifuss disease?

Two females mother and daughter, were affected by a neuromuscular disorder, characterized by slow progression, humeroperoneal weakness and wasting, limited neck flexion, elbow and ankle joint contractures, cardiopathy and myopathic pattern on EMG. Muscle histology and histochemistry showed type I fiber atrophy and predominance in both. Cardiac abnormalities, in the first case, were suggestive of a hypertrophic cardiomyopathy while in the second hypotension and chronic bradycardia were present.Neurological signs, EMG and morphology seemed to point to a genetic variant of the form of dystrophy named Emergy-Dreifuss disease.The mode of transmission and cardiac abnormalities, however, raise the problem of variability even in this well-defined, usually X-linked, disorder.

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Sommario Questa è la prima descrizione di madre e figlia affette da una infrequente malattia muscolare, caratterizzata da progressione lenta, ipostenia con atrofia a distribuzione omero-peroneale, presenza di contratture articolari, cardiopatia e pattern miopatico dell'EMG.Istologia e istochimica muscolare hanno mostrato in entrambi i soggetti atrofia e predominanza delle fibre del I tipo. Le anormalità cardiologiche rilevate nel 1° caso, erano a favore di una cardiomiopatia ipertrofica, mentre nel secondo caso erano presenti ipotensione e bradicardia.Segni neurologici, elettromiografici, reperti istologici ed istochimici sembrano configurare nelle nostre pazienti una variante genetica della forma di distrofia muscolare chiamata Emery-Dreifuss disease. Tuttavia, la modalità di trasmissione e il tipo delle anormalità cardiologiche, diverse nelle due pazienti, sollevano il problema di variabilità fenotipiche, anche in entità clinico-genetiche usualmente ben definite quali la malattia di Emery-Dreifuss.

     

Stereotaxic irradiation with a linear accelerator

At least two fundamental requirements must subsist for every stereotaxic radiotherapy treatment: 1) a capacity to administer extremely high doses of radiation to small areas which have been precisely defined in three dimensions; 2) the presence of a steep gradient between adjacent isodose curves so that damage to the tissues close to the target may be reduced to the minimum. The authors have built a special stereotaxic device for the fixing of the head of the patient (together with the chosen intracranial target), once the indispensable neuroradiological evaluations and bioptic controls have been effected, at the isocenter of a linear accelerator (Varian Clinac 4). Once the dimensions of the collimator have been chosen in accordance with the volume and the three dimensional conformation of the target and the dose to be administered has been decided upon in accordance with the histological nature of the lesion, both the linear accelerator and the patient are rotated about the isocenter of the therapy unit. It this way it is possible to reach extremely high dosages with very steep isodose gradients, centered exclusively upon the target ("gamma knife"). The procedure employed is described in full. The dosimetric evaluations which preceded the use of the set-up in clinical practice are illustrated as well. The advantages that this technique offers when compared with interstitial brachytherapy and/or Leksell's radiosurgical procedures are stressed. The described procedure, which is entirely bloodless and thus applicable also to high vascularized lesions, has so far been used in a limited series of cases.     

Polyphenols and Human Health: The Role of Bioavailability

Polyphenols are a group of phytochemicals with potential health-promoting effects. They are classified as flavonoid (flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins) and non-flavonoid molecules (phenolic acids, hydroxycinnamic acids, lignans, stilbenes, and tannins). Although an increasing number of trials have shown a correlation among polyphenol consumption and a reduction in risk factors for chronic diseases, discrepancies in explaining their positive effects have been found in terms of the bioavailability. In fact, polyphenols show a low bioavailability due to several factors: interaction with the food matrix, the metabolic processes mediated by the liver (phase I and II metabolism), intestine and microbiota. On the other hand, the biological activities of phenol compounds may be mediated by their metabolites, which are produced in vivo, and recent studies have confirmed that these molecules may have antioxidant and anti-phlogistic properties. This review discusses the studies performed in vivo, which consider the polyphenol bioavailability and their different food sources. Factors influencing the biological effects of the main classes of polyphenols are also considered.