Imaging of huge lingual thyroid gland with goitre

One year after a nonspecific trauma and with a history of pain of four weeks only, an osteoid osteoma of the first phalanx of the left thumb was diagnosed in a 31-year-old man. The radiologic appearance as well as a bone scan were suggestive for an osteoid osteoma. The diagnosis was confirmed histologically after resection of the tumor. As indicated in the literature, osteoid osteoma of the hand is relatively rare. The symptoms and radiologic features (osteolytic nidus and sclerosis) of osteoid osteomas are independent of the tumor location. Surgery with resection of the nidus is the only known curative therapy. The etiological role of trauma is discussed and a review of the literature is done with 15 other cases of posttraumatic osteoid osteoma having been reported.     

Distinct exocytotic responses of intact and permeabilised chromaffin cells after cleavage of the 25-kDa synaptosomal-associated protein (SNAP-25) or synaptobrevin by botulinum toxin A or B

Botulinum neurotoxin (BoNT) types A and B are Zn2+-requiring endoproteases which potently block neurotransmitter release by cleavage of a 25-kDa synaptosomal-associated protein (SNAP-25) and synaptobrevin, respectively. Synaptobrevin is important for the exocystosis of catecholamines from dense-core granules and evidence is presented here for the involvement of SNAP-25 in this process in neuroendocrine cells. The effects of BoNT/A and BoNT/B on regulated secretion were compared in intact bovine chromaffin cells to investigate the consequences of cleavage of the different targets. Catecholamine secretion elicited by Ba2+, by elevated K+ concentrations or by nicotine was prevented by each toxin. A very good correlation was observed between the extents of SNAP-25 cleavage or synaptobrevin cleavage and inhibition of secretion by BoNT/A or BoNT/B, respectively, which indicates the importance of SNAP-25 and synaptobrevin in regulated exocytosis. Despite truncation of almost the entire SNAP-25 pool by exposure of the cells to BoNT/A, a residual fraction of secretion persisted that was induced by 20microM Ca2+ (and to a lesser extent by 1 mM Ba2+) following permeabilisation. Addition of more BoNT/A failed to reduce this level of secretion. Inclusion of Mg.ATP, which greatly enhanced secretion from permeabilised cells, was required for Ca2+-stimulated or Ba2+-stimulated BoNT/A-resistant secretion. Furthermore, synaptobrevin is essential for this response because the response was not observed in BoNT/B treated cells. In view of the ability of BoNT/E to abolish secretion from permeabilised cells and to delete 26 amino acids from the C-terminus of SNAP-25, it can be deduced that cleavage of only nine residues by BoNT/A does not prevent the resultant truncated form exhibiting attenuated activity under the conditions created by permeabilisation. This identification of a novel component of secretion from permeabilised cells should facilitate investigation of the functional interaction of SNAP-25 with other proteins involved in regulated exocytosis.     

Tolerance to rat liver allografts: IV. Acceptance depends on the quantity of donor tissue and on donor leukocytes

Liver allografts in some rat strains are often spontaneously accepted across a complete major histocompatibility barrier without the requirement for immunosuppression while other nonliver allografts are rejected. In previous studies, we have shown that spontaneous acceptance is dependent on liver passenger leukocytes. Depletion of passenger leukocytes by donor irradiation allows rejection, with DA recipients of irradiated PVG livers having a median survival time (MST) of 16 days. Here we show that, in this model, spontaneous acceptance is reconstituted by intravenous injection of donor leukocytes. Intravenous injection of 3-5x10(7) PVG liver leukocytes significantly prolonged DA survival time (MST=96 days, P=0.026), as did 5x10(7) spleen leukocytes (MST>100 days, P=0.002). Deletion of T cells from the reconstituting inoculum reduced survival time (MST=78 days, P=0.039), whereas deletion of B cells or monocytes/macrophages had no effect on survival time. In contrast, PVG hearts are regularly rejected by DA recipients, and PVG liver or spleen leukocytes, even at doses of greater than 3x10(8) cells/recipient, were unable to induce heart acceptance. To investigate the possibility that acceptance of the irradiated liver but not the heart might be due to the large mass of the liver, two kidneys and two hearts of PVG origin were transplanted to each DA recipient together with 1.5x10(8) PVG leukocytes. These organs survived for greater than 200 days, thereby showing that a large mass of donor tissue, in association with donor leukocytes, leads to acceptance of organs that are rejected if transplanted singly. It appears likely that spontaneous liver transplant tolerance is a high-dose or activation-associated immune phenomenon.     

A peptide derived from a neurite outgrowth-promoting domain on the gamma 1 chain of laminin modulates the electrical properties of neocortical neurons

Laminins form a family of large multidomain glycoproteins of the extracellular matrix. The cellular distribution of laminin immunoreactivity in the adult mammalian central nervous system suggests an important role for laminins in mature brain function in addition to their role during brain development. To characterize the effects of this group of extracellular matrix molecules on mature brain function, intracellular recording techniques were applied to in vitro slice preparations of the rat neocortex. The experiments show that a peptide homologous to the C-terminal part of the gamma 1 chain of laminin modulates the electrical activity of pyramidal neurons in the adult neocortex of the rat. The peptide is part of the neurite outgrowth-promoting domain of the gamma 1 chain on the E8 fragment of laminin and it displays the neurite outgrowth-promoting activity of the native laminin molecule. Perfusion of in vitro brain slices with the peptide increased the input resistance of the neuronal membrane. In addition, a rise in inward rectification could be observed. These events were accompanied by a strong increase in direct excitability of the treated neurons. Immunohistochemistry techniques were applied to sections of the adult rat neocortex and hippocampus to demonstrate the presence of both the neurite outgrowth-promoting domain and the native laminin in the adult brain. An antiserum raised against the neurite outgrowth-promoting domain on the gamma 1 chain of laminin, which also recognized the free synthetic peptide, showed immunoreactivity on neurons. In addition, a population of glial fibrillary acidic protein-positive astrocytes in the hippocampus displayed immunoreactivity for this antibody. These results were confirmed by using several antibodies directed against the whole laminin-1 molecule. Neurons in the neocortex and hippocampus, as well as astrocytes in the hippocampus, demonstrated immunoreactivity for antibodies directed against the whole laminin-1 molecule. The results suggest that laminins containing the gamma 1 chain have the potential to modulate neuronal activity. This effect may be mediated either by direct cell-cell contact from surrounding cells, or through the neuronal expression of laminin or laminin-like molecules which are inserted into the neuronal cell membrane.     

Regulation of thrombospondin in the regenerating mouse facial motor nucleus

Thrombospondin (TSP) is a multifunctional extracellular matrix protein that plays a role in neuronal migration and axonal outgrowth in the developing central nervous system. In the current study we have examined the localization and regulation of TSP immunoreactivity (TSP-IR) during neuronal regeneration in the axotomized facial motor nucleus using Western blotting and light and electron microscopy. Transection of the facial nerve led to a gradual increase in TSP-IR in the regenerating motoneurons, peaking 4-7 days after injury (DAI). In addition to regenerating neurons, axotomy also caused a rapid upregulation of TSP-IR on activated microglia throughout the facial nucleus, with a maximum of 2-3 DAI, and a second increase at 14-21 DAI on microglial aggregates surrounding degenerating motoneurons and in neuronophagic microglia. In summary, injury leads to the induction of thrombospondin on axotomized neurons and activated microglia, peaking at the times of maximal posttraumatic microglial proliferation and during neuronal phagocytosis. Since thrombospondin is a multimodal extracellular matrix protein with a variety of cell attachment sites, thrombospondin might serve to link microglia and injured neurons, followed by microglial proliferation and removal of the neuronal debris.     

Metabolic activation of aromatic amines by human pancreas

Epidemiologic studies have suggested that aromatic amines (and nitroaromatic hydrocarbons) may be carcinogenic for human pancreas. Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were examined for their ability to metabolize aromatic amines and other carcinogens. Microsomes showed no activity for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following activities (and associated P450s): aminopyrine N-demethylation and ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O-deethylation (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol hydroxylation and N-nitrosodimethyl-amine N-demethylation (P450 2E1); lauric acid omega-hydroxylation (P450 4A1); and 4-(methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450 1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/4/5/7 and epoxide hydrolase. Immunoblots detected only epoxide hydrolase at low levels; P450 levels were <1% of liver. Microsomal benzidine/prostaglandin hydroperoxidation activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were present at levels comparable to human liver. The O-acetyltransferase activity (AcCoA-dependent DNA-binding of [3H]N-hydroxy-ABP) of pancreatic cytosols was high, about twothirds the levels measured in human colon. Cytosols showed high activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue. Cytosolic sulfotransferase was detected at low levels. Using 32P-post-labeling enhanced by butanol extraction, putative arylamine-DNA adducts were detected in most samples. Moreover, in eight of 29 DNA samples, a major adduct was observed that was chromatographically identical to the predominant ABP-DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in the etiology of human pancreatic cancer.     

Laparoscopic cholecystectomy during pregnancy is safe for both mother and fetus

The use of laparoscopic cholecystectomy in pregnant women has been slow to gain wide acceptance for two reasons: one is the potential for mechanical problems related to the pregnant uterus and the other is fear of fetal injury resulting from instrumentation or the pneumoperitoneum. To assess the effects of laparoscopic cholecystectomy on both the mother and the unborn fetus, we reviewed our surgical experience over a 5-year period analyzing indications for the procedure along with complications and outcome. During this 5-year period, 22 patients ranging in age from 17 to 31 years underwent laparoscopic cholecystectomy during pregnancy. Gestational ages ranged from 5 to 31 weeks with two patients being in the first trimester, 16 in the second, and four in the third. The primary indications for surgical intervention were persistent nausea, vomiting, pain, and inability to eat in 17 patients, acute cholecystitis in three, and choledocholithiasis in two. In all patients a pneumoperitoneum was established by means of a closed technique starting in the right upper quadrant of the abdomen. Two of the 22 patients also underwent successful transcystic common bile duct exploration with removal of common duct stones. All 22 patients survived the surgical procedure without complications, and there were no fetal deaths or premature births related to the procedure. Based on the preceding results, it would appear that laparoscopic cholecystectomy during pregnancy is safe for both the mother and the unborn fetus. Indications for this procedure should include stringent criteria such as unrelenting biliary tract symptoms or the complications of cholelithiasis. If at all possible, when laparoscopic cholecystectomy is indicated, it should be performed either in the second trimester or early in the third.