Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.     

Gastrogastric fistula: a possible complication of Roux-en-Y gastric bypass.

BACKGROUND: Gastrogastric fistula is a communication between the proximal gastric pouch and the distal gastric remnant, rarely described in the realm of bariatric procedures. The aim of this study was to review the existing literature about this topic and to demonstrate its laparoscopic treatment. METHODS: An extensive literature review found several articles reporting this complication. However, no citation was found describing the steps of the laparoscopic management of this situation. RESULTS: Gastrogastric fistula occurs in up to 6% of Roux-en-Y gastric bypasses. Two theories exist for fistula formation: (1) it is a technical complication derived from the incomplete division of the stomach during the creation of the pouch, and (2) it occurs after a staple-line failure, developing a leak with an abscess, which then drains into the distal stomach forming the fistula. Early symptoms include fever, tachycardia, and abdominal pain. Failure in weight loss is a late clinical sign observed in these patients. Diagnosis is based on radiologic study, upper endoscopy and computed tomography. When identified in the acute postoperative course, laparoscopic treatment is easy. Chronic fistulas are difficult to manage, and the laparoscopic approach is an alternative to open surgery. CONCLUSIONS: Gastrogastric fistula is a possible complication of Roux-en-Y gastric bypass and its laparoscopic treatment is feasible.     

Alterations of the levels of glycoproteins Ib-IX and IIb-IIIa in platelets stored at 22°C

Platelets stored in CLX™ blood bags, under normal blood banking conditions, were studied for up to 7 days to determine if changes ocurred in the levels of membrane glycoproteins (GP) Ib-IX and IIb-IIIa. Radiolabeled monoclonal antibodies (MAB) were used to estimate the number of glycoprotein molecules on the surface membrane of intact platelets. GP IX and GP IIb-IIIa levels remained essentially unaltered during storage. In contrast, the content of GP Ib at day 7 decreased by 45% of the total when fresh. The aggregation response to ristocetin, which requires GP Ib, was also diminished after 7 days. Addition of protease inhibitors, leupeptin and/or aprotinin did not appear to influence the degradation of this glycoprotein. We conclude that storage at 22°C has deleterious effects on the GP Ib content of platelets.     

The prostatic capsule: does it exist? Its importance in the staging and treatment of prostatic carcinoma

Pathologic evaluation of tumor extent in a radical prostatectomy specimen for prostatic adenocarcinoma is extremely important in staging and planning further therapy. We studied whole-organ sections of 50 prostate glands, obtained at either radical prostatectomy for adenocarcinoma or cystoprostatectomy for bladder cancer, to evaluate the so-called capsule of the prostate, the prostatic apex, and the surgical margins. The outer surface of the prostatic portion of the specimen was totally inked with different colors for the anterior, posterior, left, and right areas. Cross sections were processed for histologic examination, and the apex (distal 1.5 cm) was amputated and radially sectioned (like a cervical cone). We found that the "capsule" is made up of a band of concentrically placed fibromuscular tissue that is an inseparable component of the prostatic stroma. The outer surface of this tissue gives rise to a few bundles of fibromuscular stroma that penetrate and disappear into the periprostatic connective tissue stroma. The apex is sparse in glandular elements, particularly in the anterior portion, and the outer fibromuscular layer is no longer present. Thus we conclude that the prostate does not have a true capsule, but only an outer fibromuscular band.     

Acidic pH and increasing [Ca(2+)] reduce the swelling of mucins in primary cultures of human cervical cells

BACKGROUND: Cervical mucus is a heterogeneous mixture of water, ions and mucins that form a hydrophilic polymer gel. Mucins, the main components of mucus, are condensed inside secretory granules and swell to become a hydrogel after exocytosis. Using human cervical secretory cell primary cultures, the effect of [Ca(2+)] and [H(+)] on the swelling velocity of mucin granules was investigated in vitro. METHODS and RESULTS: Immunocytochemistry demonstrated that estrogen and progesterone receptors were expressed in cultured secretory cells along with mucins type 1, 4, 5AC and 5B. Exocytosis of secretory cells, recorded by videomicroscopy, showed that during swelling, the radius of the secretory granule matrix followed first-order kinetics. An increase in extracellular [Ca(2+)] from 1 to 4 mmol/l or a reduction in pH from 7.4 to 6.5 was seen to produce a significant decrease in the velocity of swelling of the secretory granule matrix. CONCLUSIONS: The inverse relationship observed between the diffusion of the granular matrix and the extracellular [Ca(2+)] or [H(+)] suggested that changes in cation concentration might drastically affect the swelling characteristics of mucins and provide a control mechanism for the observed viscoelastic properties of mucus.     

Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress

The identification of rare monogenic forms of Parkinson's disease (PD) has provided tremendous insight into the molecular pathogenesis of this disorder. Heritable mutations in alpha-synuclein, parkin, DJ-1 and PINK1 cause familial forms of PD. In the more common sporadic form of PD, oxidative stress and derangements in mitochondrial complex-I function are considered to play a prominent role in disease pathogenesis. However, the relationship of DJ-1 with other PD-linked genes and oxidative stress has not been explored. Here, we show that pathogenic mutant forms of DJ-1 specifically but differentially associate with parkin, an E3 ubiquitin ligase. Chemical cross-linking shows that pathogenic DJ-1 mutants exhibit impairments in homo-dimer formation, suggesting that parkin may bind to monomeric DJ-1. Parkin fails to specifically ubiquitinate and enhance the degradation of L166P and M26I mutant DJ-1, but instead promotes their stability in cultured cells. The interaction of parkin with L166P DJ-1 may involve a larger protein complex that contains CHIP and Hsp70, perhaps accounting for the lack of parkin-mediated ubiquitination. Oxidative stress also promotes an interaction between DJ-1 and parkin, but this does not result in the ubiquitination or degradation of DJ-1. Parkin-mediated alterations in DJ-1 protein stability may be pathogenically relevant as DJ-1 levels are dramatically increased in the detergent-insoluble fraction from sporadic PD/DLB brains, but are reduced in the insoluble fraction from parkin-linked autosomal recessive juvenile-onset PD brains. These data potentially link DJ-1 and parkin in a common molecular pathway at multiple levels that may have important implications for understanding the pathogenesis of inherited and sporadic PD.