Activation of two different but complementary biochemical pathways stimulates release of hypothalamic luteinizing hormone-releasing hormone.

Evidence exists that a norepinephrine/prostaglandin E2 (PGE2)/cAMP pathway is involved in the regulation of luteinizing hormone-releasing hormone (LHRH) secretion. The aim of the present experiments was to determine if release of LHRH from the immature rat hypothalamus could also be stimulated by activation of protein kinase C. Median eminences from 28-day-old female rats were incubated in vitro with either dioctanoylglycerol (a synthetic diacylglycerol that selectively activates protein kinase C in intact cells) or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (another protein kinase C activator). Both agents increased LHRH release, the response to dioctanoylglycerol being more pronounced than that to the phorbol ester. This direct activation of protein kinase C was not accompanied by changes in PGE2 formation. Activation of the PGE2/cAMP pathway by either norepinephrine, PGE2, or forskolin (a stimulator of adenylate cyclase) increased LHRH release. Dioctanoylglycerol or phorbol ester in conjunction with either norepinephrine, PGE2 or forskolin resulted in an additive effect on LHRH release suggesting coexistence of both pathways. Phospholipase C, which activates protein kinase C via formation of diacylglycerol, increased the release of both LHRH and PGE2. This suggests that an increase in endogenous phospholipase C activity caused by neurotransmitter inputs may lead to both activation of protein kinase C and PGE2 formation. Blockade of cyclooxygenase activity by indomethacin obliterated phospholipase C-induced PGE2 release. The same treatment reduced the LHRH response by only 50% indicating that protein kinase C activation can cause LHRH release in the absence of PGE2 synthesis. It is suggested that the median eminence of the rat possesses a protein kinase C-dependent pathway that is coupled positively to LHRH release and complements PGE2/cAMP-dependent mechanisms. Norepinephrine, however, does not appear to be the neurotransmitter responsible for activating the protein kinase C pathway. Simultaneous activation of both pathways may provide a mechanism by which a large increase in LHRH secretion occurs, such as in the afternoon of first proestrus.     

Evaluation of clinical criteria for the acute respiratory distress syndrome in pediatric patients.

OBJECTIVE: The primary goal of this study was to evaluate the validity of the North American-European Consensus Committee (NAECC) definition for acute respiratory distress syndrome (ARDS) in pediatric patients. A secondary aim was to evaluate the threshold value for the PaO2/FiO2 ratio, used to determine which pediatric patients have ARDS. DESIGN: Retrospective cohort study. SETTING: Pediatric intensive care unit. PATIENTS: Pediatric intensive care unit patients who required mechanical ventilation, died, and underwent autopsy between January 1, 1996, and December 31, 2002 (n = 34). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and chest radiograph information was collected retrospectively through chart review using a standardized data collection tool. Data included the criteria specified in the NAECC definition of ARDS and demographic information. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of clinical diagnosis of ARDS compared with a pathologic diagnosis. The threshold value of PaO2/FiO2 was identified by plotting receiver operating characteristics curves and comparing the areas under the curves. The NAECC definition yielded a sensitivity of 80.7% (95% confidence interval 60-92%), specificity of 71.4% (95% confidence interval 30-95), positive predictive value of 91.3% (95% confidence interval 70-98), negative predictive value of 50.0% (95% confidence interval 20-78), and likelihood ratio of 2.82. A PaO2/FiO2 <150 had a slightly higher (but not significantly different) specificity for ARDS than a value >200 (71% vs. 86%, p = .15) without changing sensitivity. CONCLUSIONS: Our study suggests the need for further research with larger number of children to identify an optimal Pao2/Fio2 threshold for identifying ARDS in this population.     

Papilloma virus infection. Precancer and epidermoid cancer.

We present a review of the relationship between Human Papillomavirus (HPV), Precancer and Epidermoid Cancer of the uterine cervix, Co-factors that contribute in cervical carcinogenesis and the mechanism through which Papillomaviruses transform normal cells into neoplastic cells by inducing an overproduction of the encoded proteins. We also offer final remarks and conclusions on this pathology that increases its incidence every year.     

The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes

There are several species of alternatively spliced fibronectin (FN). One of these, FN EIIIB, is primarily present in embryonic and in proliferating and migrating cells and is believed to be important for cell maturation. We have studied the synthesis, localization, and secretion of this FN isoform in isolated guinea pig megakaryocytes, nonmegakaryocytic bone marrow cells, and platelets. There was 7.5 times more general FN in megakaryocytes than in nonmegakaryocytic cells based on the analysis of equivalent amounts of protein. FN EIIIB was detected by Western blotting in megakaryocytes but not in nonmegakaryocytic cells present in bone marrow. Neither megakaryocytes nor platelets secreted FN EIIIB, while megakaryocytes secreted 25.3% +/- 4.6% general FN and platelets secreted about 61% general FN in response to thrombin. Analysis of immunostained cells by confocal microscopy revealed that FN EIIIB had been redistributed to the surface of megakaryocytes in response to thrombin. Synthesis was studied by metabolic labeling, and megakaryocytes were shown to synthesize FN and FN EIIIB. Thus, megakaryocytes and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. The expression of FN EIIIB on the megakaryocyte surface may influence migration and maturation.     

Synthesis and physico-chemical properties of poly[4-(1,1,3,3-tetramethylbutyl)phenyl methacrylate]

Poly[4-(1,1,3,3-tetramethylbutyl)phenyl methacrylate] ( 1a ) was synthesized and its physicochemical properties were determined in the condensed phase and in dilute solution. The polymerization of 4-(1,1,3,3-tetramethylbutyl)phenyl methacrylate was carried out by radical mechanism in solution with 2,2′-azoisobutyronitrile as initiator. Several samples were characterized by their intrinsic viscosity, by osmometric measurements, differential scanning calorimetry, and X-ray diffraction. The viscometric behaviour of fractions of 1a was studied in good solvents and theta solvents, and the conformational parameters were calculated. Polymer 1a presents an unusual high rigidity in the chain. X-Ray diffraction of this polymer indicates a one-dimensional ordering of a mesomorphic type.     

Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats

Gram-negative and gram-positive infections have been considered the most important causes of morbidity and mortality in patients with leukopenia following chemotherapy. However, discrimination between bacterial infections and harmless fever episodes is difficult. Because classical inflammatory signs of infection are often absent and fever is frequently the only sign of infection, the aim of this study was to assess the significance of serum interleukin-6 (IL-6), IL-10, macrophage inflammatory protein-2 (MIP-2), procalcitonin (PCT), and C-reactive protein (CRP) patterns in identifying bacterial infections during start of fever in normal and cyclophosphamide-treated (leukopenic) rats following an injection of lipopolysaccharide (LPS) or muramyl dipeptide (MDP) as a model for gram-negative and gram-positive bacterial infections. We found that, compared to normal rats, immunosuppressed animals exhibited significantly higher fevers and lesser production of all mediators, except IL-6, after toxin challenge. Moreover, compared to rats that received MDP, both groups of animals that received an equivalent dose of LPS showed significantly higher fevers and greater increase in serum cytokine levels. Furthermore, in contrast to those in immunocompetent rats, serum levels of IL-6 and MIP-2 were not significantly changed in leukopenic animals after MDP injection. Other serum markers such as PCT and CRP failed to discriminate between bacterial stimuli in both groups of animals. These results suggest that the use of the analyzed serum markers at an early stage of fever could give useful information for the clinician for excluding gram-negative from gram-positive infections.     

Glomerulocystic kidney disease in a Belgian Malinois dog: an ultrastructural, immunohistochemical, and lectin-binding study

Renal cysts in the cortex of a juvenile Belgian Malinois dog with acute renal failure were studied by means of light, scanning and transmission electron microscopy, immunohistochemistry for intermediate filaments, and binding for wheat germ agglutinin (WGA), peanut agglutinin (PNA), and Maclura pomifera agglutinin (MPA) lectins to determine the morphological and histochemical features of the epithelial cells of these cysts. The cysts were renal corpuscles with expanded urinary space. Glomerular tufts were small with poorly developed capillary loops and increased mesangial matrix. Continuity with the proximal tubule was evident in some cystic glomeruli. Two cell types lined Bowman's capsule. One was squamous with a central cilium and microvilli. The other had morphological and histochemical features of immature podocytes (parietal podocytes). These cells were round and protruded into the urinary space; they had thick cytoplasmic projections that resembled foot processes of podocytes, microvilli, and filtration slits. The parietal podocytes expressed vimentin and cytokeratins and had affinity for WGA as do normal immature podocytes. These features suggest that the parietal podocytes are derived by metaplasia of the parietal cells. The basement membrane of Bowman's capsule was irregularly thickened and showed multifocal glycosylation changes with lectin histochemistry (WGA, PNA, MPA) in areas adjacent to the parietal podocytes. Histologic and ultrastructural findings in this dog are consistent with glomerulocystic kidney disease. This is the second report of canine glomerulocystic kidney disease. Features are similar to those of the human counterpart, but it is unclear whether genetic defects cause the disease in the dog. The presence of parietal podocytes in all cysts suggests that abnormal differentiation may play an important role in the pathogenesis of this type of polycystic kidney disease.     

Palisades in primary cerebral neuroblastoma simulating so-called polar spongioblastoma. A light and electron microscopical study of an adult case

A frontal lobe neoplasm in a 25-year-old Caucasian man showed the typical histological pattern of a "polar spongioblastoma." Immunoperoxidase staining for glial fibrillary acidic protein (GFAP) was negative while silver stains in paraffin-embedded tissue, and electron microscopy displayed neoplastic cells with neuritic processes. Ultrastructurally there were microtubules, synapses and dense-core neurosecretory granules, all features of a neuroblastic neoplasm. It is suggested that this new growth with its polar spongioblastic appearance is, in fact, a moderately malignant primary cerebral neuroblastoma.     

Predictors of health-related quality of life in Parkinson’s disease: the impact of overlap between health-related quality of life and clinical measures

Quality of Life Research - This study aimed to determine predictors of health-related quality of life (HRQoL) in Parkinson's disease (PD) and to explore their predictive value before and after...