Rat mature sympathetic neurones derive neurotrophin 3 from peripheral effector tissues

In a previous study we have demonstrated that endogenous neurotrophin 3 (NT3) is required for the survival of most sympathetic neurones in postnatal rats. However, the mechanisms underlying the action of NT3 on sympathetic neurones is not known. Neither is it understood whether NT3 is retrogradely transported from peripheral tissues or acts locally in an autocrine fashion. In the present study, NT3-mRNA was quantified in sympathetic effector tissues and NT3 protein was localized in intact and lesioned sympathetic nerves in rats. NT3-mRNA is expressed and developmentally regulated in many effector tissues including mesenteric arteries, salivary gland, heart and kidney but hardly detectable in the superior cervical ganglia of adult animals. The majority of sympathetic neurones express immunoreactivity for TrkA and TrkC in both neonatal and adult rats. Sympathetic somata are normally immunoreactive for NT3, but the immunoreactivity is abolished by systemic administration of NT3 antibodies or axotomy of postganglionic neurones, suggesting an accumulation of NT3 from extraneuronal sources. Furthermore, the detection of NT3-immunoreactivity in the internal carotid nerve as early as 3 h following a compression and only on the distal side indicates endogenous NT3 is retrogradely transported by sympathetic neurones. These studies provide evidence indicating that NT3, like nerve growth factor, is an effector tissue-derived neurotrophic factor for sympathetic neurones both during development and in the adult animal. Thus, we have provided a clear example that one type of neurone derives, through a retrograde transport mechanism, two neurotrophic factors simultaneously from its peripheral effector tissues.     

Antibody-IL-2 fusion proteins: a novel strategy for immune protection

Advances in genetic engineering and expression systems have led to a rapid progress in the development of immunoglobulins fused to other proteins. These 'antibody fusion proteins' have novel properties and include antibodies fused to the cytokine interleukin-2. In the present review we describe strategies for construction of these antibody-interleukin-2 fusion proteins and discuss their in vitro and in vivo properties. Antibody-interleukin-2 fusion proteins retain both antibody associated functions such as antigen binding, complement activation and Fc gamma receptor binding as well as interleukin-2 associated functions such as the stimulation of proliferation of CTLL2 cells. In vivo, they produce strong potentiation of the host immune response against any associated antigen. In addition, these novel molecules are able to target tumor cells and produce a specific and effective T cell response capable of eliminating the tumor. These properties suggest that antibody-interleukin-2 fusion proteins will be useful in the diagnosis and/or treatment of human cancer as well as in the potentiation of human response against any associated antigen.     

Morphological and functional polymorphism within clonal thyroid nodules

Thirty-nine thyroid nodules, removed because of recent growth, were analyzed morphologically by serial histological sections for the classical histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-associated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27 beta that detects polymorphisms on the locus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of poly-clonal origin. Only 3 out of the 24 clonal nodules were histomorphologically uniform. In all others, the structural hallmarks of active growth and the P21ras growth-marker expression were remarkably heterogeneous throughout the tumors. There were no histomorphological characteristics distinguishing these clonal tumors from polyclonal nodules. Even if a clonal thyroid tumor may be originally homogeneous in respect to the parameters studied here, mechanisms must exist that create wide heterogeneity of growth and of morphogenetic potential among the individual follicular cells during further expansion of the nodule. Thus, clonal nodules are much more common in nodular goiters than hitherto assumed on grounds of the classical morphological criteria. The diagnosis of a true monoclonal nodule can no longer rely on morphological and functional criteria alone but requires molecular or cytogenetic analysis of clonality.     

Sympathetic nervous system activity and resting metabolic rate in vegetarians

We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.     

In situ bypass and diabetes

From 1986 through to 1990 a total of 483 in situ bypass procedures were performed in 444 patients. Preoperative risk-factors were equally distributed among diabetic (DM) and non-diabetic (NDM) patients, except for smoking habits (DM:48%, NDM:64%, p = 0.002) and cardiac disease (DM:45%, NDM:29%, p = 0.005). Critical limb-ischaemia was more often present in diabetic than non-diabetic patients (DM:57%, NDM:36%, p = 0.0002). Diabetic patients had a significantly lower distal anastomosis than non-diabetic patients (p = 0.00001). There were no differences among diabetic and non-diabetic patients regarding three years primary and secondary patency (58% and 64% respectively), and regarding major amputations. However, the rate of minor amputations was higher in insulin-dependent compared with non-insulin-dependent diabetics, who in turn had a higher rate than non-diabetics (p < 0.00001). A markedly decreased survival rate was found in diabetics (p < 0.00005). We found the in situ bypass technique very useful in the treatment of critical ischaemia of the lower limb in diabetic patients. The overall results in diabetic patients, whether insulin-dependent or not, were equal to those in non-diabetic patients.     

Fabrication and characterization of planar and channel polymer wave guides. I. Plasma-polymerized HMDS films

Plasma-polymerized hexamethyldisiloxane (HMDS) films have been prepared as both planar and channel wave guides. The optical attenuation results measured in both the planar and channel HMDS wave guides were found to be similar, thus demonstrating that the inherent solvent resistance and chemical inertness of the plasma polymerized films allows the use of common photoresist techniques, including application of the photoresist, photomasking, and subsequent etching. This may be contrasted with wave guides made from conventional polymers, where careful consideration must be given to photoresist/polymer compatibility, because the photoresist solvents may adversely affect the underlying polymer and lead to degradation of the material during processing. © 1995 John Wiley & Sons, Inc.