Studies of small GTPase Rab7 association with endosomes of cells expressing normal and mutant forms of epidermal growth factor receptors

A study was made of an association of small GTPase Rab7, commonly considered as a marker of late endosomes, with endosomal compartments of cells expressing EGF receptor with different ability to be sorted for degradative pathway. It was found that in cells HER14, expressing normal EGF receptor, Rab7 was associated with both early and late endosomes and the extent of association correlated with the number of EGF-receptor complexes in the specific endosomal fraction. Cels with a receptor, lacking major sites of autophosphorylation by deletion of 126 C-terminal residues (CD126), demonstrated a low efficiency of EGF-receptor sorting to late endosomes and decreased association dynamics with Rab7. Interaction of Rab7 with endosomes of cells expressing kinase negative receptors (K721) was found to be minimal. At the same time, in cells Cd126 and K721 with a low sorting efficiency Rab7 was mainly associated with early endosomes. These data favor Rab7 involvement in mediating early-to-late endosomal transition.     

Linkage of DFNB1 to non-syndromic neurosensory autosomal-recessive deafness in Mediterranean families

A study involving the immediate loading of Br?nemark implants in the edentulous mandibles of 10 patients is reported. The design involved the immediate loading of four widely distributed implants with a transitional fixed implant-supported prosthesis at first-stage surgery, avoiding the need for a removable prosthesis. A sufficient number of additional implants are allowed to heal in the conventional manner to provide sufficient support for a definitive fixed prosthesis even if all of the immediately loaded implants fail. Preliminary results have been favorable, with all patients functioning with a fixed implant prosthesis from the day of first-stage surgery.     

Constitutive activation of the m5 muscarinic receptor by a series of mutations at the extracellular end of transmembrane 6

The m5 muscarinic acetylcholine receptor was constitutively activated by a wide range of amino acid substitutions at a residue (serine 465) that is positioned at the junction of the sixth transmembrane domain and the extracellular loop. Of 13 substitutions tested, 11 produced significant increases in constitutive activity. Replacement of serine 465 with large (phenylalanine and valine) or basic residues (arginine and lysine) increased the constitutive activity of the receptor to between 55 and 110% of the maximum response of the wild-type receptor to the agonist carbachol. Other substitutions (e.g., cysteine and leucine) increased the constitutive activity to an intermediate level (30%), while small and acidic residues (glycine, aspartate, and glutamate) caused small or insignificant increases. The increase in the constitutive activity of each mutant receptor correlated with an increase in the potency of carbachol in both binding and functional assays, with the most constitutively activated receptors showing a 40-fold decrease in the EC50 of carbachol. The negative antagonist atropine bound to and reversed the constitutive activity of all mutant receptors with equal potency. These data were fitted to a two-state model of receptor function. The data are consistent with the primary effect of substitutions to serine 465 being to selectively destabilize the inactive state of the receptor, thus favoring formation of the active state in the absence of agonists. Our data strongly support this two-state model of receptor function and identify a critical role of this domain in the activation of muscarinic receptors.     

Eccrine syringofibroadenoma surrounding a squamous cell carcinoma: a case report

In adult mammals fever is associated with the reduction of blood plasma iron level. Immature mammals, however, show either a decrease (precocial animals such as guinea pig neonates) or a lack of reduction (altricial animals such as human neonates) of plasma iron in response to endotoxin. In order to determine whether this difference is connected with maturity just after delivery, plasma iron concentration, hematocrit, body temperature and body mass were measured in rat pups injected with E. coli endotoxin in doses of 50 or 200 micrograms kg-1. Rat pups, like human neonates, are altricial animals. In 7-day-old rats injection of LPS led to a dose-dependent decrease in plasma iron level. The fall in plasma iron was accompanied by changes in body temperature and body mass. The results showed that plasma iron response to endotoxin in altricial rat neonates is similar to that observed in precocial guinea pig pups.     

A cohort mortality study of foundry workers

The present study aimed to demonstrate conditioned inhibition of Pavlovian conditioning of autonomic responses in humans. Subjects (N = 21) were presented initially with four geometric shapes (A, B, C and D). An electric shock served as the unconditioned stimulus (US) during acquisition. Conditional stimuli lasted for 8 s and US onset coincided with CS offset. Subjects were trained with A-US, C-US, and AC-US pairings and AB alone and B alone presentations. The subsequent summation test consisted of C-US pairings and CB alone and CD alone presentations. Conditioning was evident in self-reported US expectancy and first and second interval electrodermal responses. Evidence for conditioned inhibition during the summation test was found in US expectancy and second interval electrodermal responses.