[Clinicopathologic characteristics of low grade primary gastric non-Hodgkin's lymphomas: experience from a single center]. / Caractéristiques clinico-pathologiques des lymphomes gastriques primitifs de bas grade de malignité.

AIM: To report the clinicopathological data and the treatment outcomes in patients with primary gastric low grade non-Hodgkin's lymphoma. METHODS: We carried out a retrospective analysis of 16 consecutive patients (median age 46 and range 28-75 years) who presented to our department with histopathological diagnosis of primary gastric low grade non-Hodgkin's lymphoma. We analyzed clinical manifestations, endoscopic features, pathological features,Helicobacter pylori infection and treatment. RESULTS: Common symptoms included abdominal pain (87.5%),vomiting (62.5%), and gastrointestinal bleeding (25%). Endoscopic appearances were mainly ulcers and ulcerations (93.75%).Endoscopic biopsy confirmation rate reached 87.5% when biopsies were repeated. Helicobacter pylori detection rate was 75%. A total of 9 patients received surgeries. Three patients had chemotherapy and 8 patients had Helicobacter pylori eradication therapy. The range of follow-up was 2-74 months with a median of 27 months. A complete remission was obtained in 12 cases, whereas 1 patient died and 3 were lost of view. CONCLUSION: Eradication therapy may be offered as an initial treatment option in patients with low-grade gastric lymphoma.

[Monoclonal gammopathy and primary colonic mantle cell lymphoma]. / Une gammapathie monoclonale associée à un lymphome colique primitif à cellules du manteau.

The association of a monoclonal gammopathy (MG) with a B cell non-Hodgkin's lymphoma (NHL) is a well-known phenomenon. It has been recognized in many subtypes of primary gastrointestinal lymphoma but its association with primary colonic mantle cell lymphoma has never been yet described. We report a 65-year-old man who presented with an exudative ascites and constipation. Serum electrophoresis showed a monoclonal peak in the gamma region of 45g/L and immunoelectrophoresis confirmed the presence of monoclonal gammopathy of IgM kappa type. Bone marrow aspirate was normal. Radiologic and endoscopic investigations evidenced a primary colonic mantle cell lymphoma. Although the association of an MG with an NHL and, in particular, to a primitive digestive location appears a rare phenomenon, endoscopic investigations in patients with MG appears legitimate in the presence of any digestive sign.

Effective inhibition of herpes simplex virus 1 gene expression and growth by engineered RNase P ribozyme.

Using an in vitro selection procedure, we have previously isolated ribonuclease P (RNase P) ribozyme variants that efficiently cleave an mRNA sequence in vitro. In this study, an M1GS RNA variant was used to target the mRNA encoding human herpes simplex virus 1 (HSV-1) major transcription activator ICP4. The variant is about 15 times more efficient in cleaving the ICP4 mRNA sequence in vitro than the ribozyme derived from the wild type RNase P ribozyme. Moreover, the variant is also more effective in inhibiting viral ICP4 expression and growth in HSV-1-infected cells than the wild type ribozyme. A reduction of approximately 90% in the expression level of ICP4 and a reduction of 4000-fold in viral growth were observed in cells that expressed the variant. In contrast, a reduction of <10% in the ICP4 expression and viral growth was observed in cells that either did not express the ribozyme or produced a catalytically inactive ribozyme mutant. These results provide direct evidence that RNase P ribozyme variants can be highly effective in inhibiting HSV-1 gene expression and growth and furthermore, demonstrate the feasibility of developing highly effective RNase P ribozyme variants for anti-HSV applications by using in vitro selection procedures.

Differential effects of the protein cofactor on the interactions between an RNase P ribozyme and its target mRNA substrate.

RNase P from Escherichia coli is a tRNA-processing enzyme and consists of a catalytic RNA subunit (M1 RNA) and a protein component (C5 protein). M1GS, a gene-targeting ribozyme derived from M1, can cleave a herpes simplex virus 1 mRNA efficiently in vitro and inhibit its expression effectively in viral-infected cells. In this study, the effects of C5 on the interactions between a M1GS ribozyme and a model mRNA substrate were investigated by site-specific UV crosslink mapping. In the presence of the protein cofactor, the ribozyme regions crosslinked to the substrate sequence 3' immediately to the cleavage site were similar to those found in the absence of C5. Meanwhile, some of the ribozyme regions (e.g. P12 and J11/12) that were crosslinked to the leader sequence 5' immediately to the cleavage site in the presence of C5 were different from those regions (e.g. P3 and P4) found in the absence of the protein cofactor and were not among those that are believed to interact with a tRNA. Understanding how C5 affects the specific interactions between the ribozyme and its target mRNA may facilitate the development of gene-targeting ribozymes that function effectively in vivo, in the presence of cellular proteins.

A ribozyme derived from the catalytic subunit of RNase P from Escherichia coli is highly effective in inhibiting replication of herpes simplex virus 1.

A sequence-specific ribozyme (M1GS RNA) derived from the catalytic RNA subunit of RNase P from Escherichia coli was used to target the mRNA encoding human herpes simplex virus 1 (HSV-1) major transcription activator, ICP4. A reduction of more than 80% in the expression level of ICP4 and a reduction of about 1000-fold in viral growth were observed in cells that stably expressed the ribozyme. In contrast, a reduction of less than 10 % in ICP4 expression and viral growth was observed in cells that either did not express the ribozyme or produced a catalytically inactive ribozyme mutant. Thus, M1GS ribozyme is highly effective in inhibiting HSV-1 growth and can be used as a general gene-targeting agent for anti-HSV applications.

Effects of weight cycling on urinary catecholamines: sympathoadrenal role in refeeding hypertension.

OBJECTIVES: We sought to determine whether the sympathetic nervous system plays a role in the hypertensive response to refeeding from a very low-calorie diet (VLCD). DESIGN: Cycles of weight loss and regain were induced in the obese spontaneously hypertensive rat (SHROB) model of genetic obese hypertension. METHODS: A 12-day VLCD (1/6 of baseline calories) was alternated with 4-6 weeks of ad libitum chow refeeding for three cycles. Control SHROB ate chow ad libitum. Urine was collected for 24 h before and after each period of VLCD, and catecholamines were measured radioenzymatically. Tail cuff blood pressures and body weight were measured in parallel with urine collections. Kidneys were collected for assay of alpha2-adrenergic receptor density. RESULTS: VLCD induced rapid weight loss, but all the lost weight was regained during refeeding. Blood pressure fell during caloric restriction, but rose above baseline during refeeding. Urinary excretion of norepinephrine, epinephrine and dopamine changed several fold during weight cycling. Urinary catecholamines paralleled the changes in blood pressure, falling during caloric restriction and rebounding during refeeding. Dopamine showed the greatest decreases during weight loss and rises during weight regain, whereas epinephrine changed the least and norepinephrine was intermediate. Weight cycling elevated blood pressure above the initial baseline throughout the rapid weight gain phase of refeeding. The density of alpha2-adrenergic receptors was decreased in both the renal medulla and cortex of weight cycled SHROB, consistent with receptor down-regulation owing to overstimulation. CONCLUSIONS: The exacerbations of hypertension during weight regain in SHROB coincide with sustained activation of sympathoadrenal activity, as reflected in urinary catecholamine excretion and adrenergic receptor down regulation.

Helicobacter pylori in dyspeptic Jordanian patients.

UNLABELLED: To study the prevalence of Helicobacter pylori infection in dyspeptic Jordanian patients. PATIENTS AND METHODS: Two hundred and twenty seven consecutive dyspeptic Jordanian patients were studied with endoscopy, endoscopic biopsies, culture, and CLO urease testing for the detection of H. pylori. RESULTS: Helicobacter pylori positivity in both culture and CLO urease testing was 86%, being 78% in culture and 80% in CLO test separately. The majority of our patients were in the age range 21-60 years and H. pylori positivity was more than 90% in them. CONCLUSION: Helicobacter pylori is a common infection in dyspeptic Jordanian patients regardless of the underlying cause. Males were affected more than females.

[Esophageal cancer with esophagotracheal fistula. Treatment by esophageal prosthesis. Report of two cases]. / Cancer de l'oesophage avec fistules oesotracheales. Traitement par protheses oesophagiennes. A propos de deux observations.

Esophageal cancer has a bad prognosis because of late diagnosis. The rate of Survival is very low. Palliative treatment is frequently made. The aim of the treatment is to allow feeding, and treat some complications likes breathing troubles. We report two cases of esotracheal fistulae secondary to esophageal cancer. The esophageal fistula was successfully treated by esotracheal prosthesis.

[Systemic manifestations of chronic hepatitis C]. / Les manifestations systemiques des hépatites virales C chroniques.

It's well known that hepatitis C virus (HCV) related chronic liver disease may be associated with various extra hepatic disorders. These manifestations can revealed the hepatic disease. We review the available data on the conditions and asses their clinical implications: vascular, cutaneous, articular, neurological or renal disorders. There is no correlation between these extra hepatic manifestations and the severity of liver disease. Several recent studies have established a strong link between HCV infection and essential mixed cryoglobulinemia but some other extra hepatic associations are just fortuitous. Others datas are necessary to better analyze these extra hepatic disorders and to offer the beneficial treatment of patients with chronic hepatitis C.

[Association of Sjögren's syndrome and Plummer Vinson syndrome]. / Association d'un syndrome de Gougerot Sjögren et d'un syndrome de Plummer Vinson.

Dysphagia is a common complaint of patients with Sjogren's syndrome, but its mechanism remains a subject of controversy. The association of Sjogren's syndrome with Plummer-Vinson syndrome remains uncommon. We report a 56-year-old women who presented both disorders. The diagnosis of the Plummer-Vinson syndrome was based on the classic triad of dysphagia, iron-deficiency anaemia and oesophageal webs. The diagnosis of Sjogren's syndrome was based on the presence of three Fox criteria. This association should incite us to search for common immuno-genetic pathogenic factors between these two syndromes.

UV cross-link mapping of the substrate-binding site of an RNase P ribozyme to a target mRNA sequence.

RNase P ribozyme cleaves an RNA helix that resembles the acceptor stem and T-stem structure of its natural ptRNA substrate. When covalently linked with a guide sequence, the ribozyme can function as a sequence-specific endonuclease and cleave any target RNA sequences that base pair with the guide sequence. Using a site-directed ultraviolet (UV) cross-linking approach, we have mapped the regions of the ribozyme that are in close proximity to a substrate that contains the mRNA sequence encoding thymidine kinase of human herpes simplex virus 1. Our data suggest that the cleavage site of the mRNA substrate is positioned at the same regions of the ribozyme that bind to the cleavage site of a ptRNA. The mRNA-binding domains include regions that interact with the acceptor stem and T-stem and in addition, regions that are unique and not in close contact with a ptRNA. Identification of the mRNA-binding site provides a foundation to study how RNase P ribozymes achieve their sequence specificity and facilitates the development of gene-targeting ribozymes.

The protein cofactor allows the sequence of an RNase P ribozyme to diversify by maintaining the catalytically active structure of the enzyme.

To study the effect proteins have on the catalysis and evolution of RNA enzymes, we simulated evolution of RNase P catalytic M1 RNA in vitro, in the presence and absence of its C5 protein cofactor. In the presence of C5, functional M1 sequence variants (not catalytically active in the absence of C5) were selected in addition to those identical to M1. C5 maintains the catalytically active structure of the variants and allows for an enhanced spectrum of M1 molecules to function in the context of a ribonucleoprotein (RNP) complex. The generation of an RNP enzyme, requiring both RNA and protein components, from a catalytically active RNA molecule has implications for how modern RNP complexes evolved from ancestral RNAs.

Muscarinic receptor binding sites of the M4 subtype in porcine lung parenchyma.

Muscarinic acetylcholine receptors regulate distal airway resistance and secretion. The subtype expressed in the lung in different species remains uncertain. It has recently become possible to identify the M4 subtype by careful comparison of antagonist affinities. We characterized the binding of [3H]quinuclidinyl benzilate ([3H]QNB) to muscarinic receptors in cell membranes from lung parenchyma of 2-8 week old pigs in comparison to cloned human M3 and M4 receptors expressed in COS cells, to M2 in rat atria and to M4 in bovine adrenal medulla. In porcine lung, [3H]QNB bound with high affinity (Kd = 95 +/- 9 pM) to a single homogeneous population of muscarinic receptor sites (Bmax = 340 +/- 10 fmol/mg protein). Competition studies showed that the affinity (expressed as pKi) of 3 selective blockers was in close agreement between pig lung and cloned human m4 (r = 0.996). A series of 10 blockers showed affinities closely matching reported values for M4 receptors of the adrenal medulla (r = 0.965). Conversely, affinity values in porcine lung differed significantly (P < 0.05, t-test) from those determined in parallel with either human cloned M3 or with rat atria expressing the M2 subtype. We conclude that pig lung muscarinic receptor binding sites most closely resemble the M4 subtype, in contrast to the M3 subtype typical of large airways in this species.

Further evaluation of the effects of 7.5% sodium chloride/6% Dextran-70 (HSD) administration on coagulation and platelet aggregation in hemorrhaged and euvolemic swine.

In previous studies, we determined that incubation of high concentrations of the 7.5% saline (HS) component of HSD with human blood, in vitro, significantly prolonged prothrombin time (PT), and reduced platelet aggregation. Considering the rapid plasma volume expansion following HSD infusion, the present study tested the hypothesis that any HS-induced effects on coagulation would have no clinical significance when HSD was infused for the treatment of hemorrhagic hypotension. Conscious, splenectomized pigs, either euvolemic (n = 11) or bled 27 ml/kg over 60 min (n = 9), were treated with the proposed therapeutic dose of 4 ml/kg HSD. Blood samples were withdrawn prior to and at the end of the hemorrhage and 0.5, 1, 2, 3, 4, 24, 48, 72, and 168 hr following HSD infusion, and PT, activated partial thromboplastin time (APTT), and platelet aggregation were determined. HSD did not significantly affect PT, APTT, or platelet aggregation in either group of swine at any time measured. In other studies, HSD did not prolong bleeding times after 1 or 2 hr in euvolemic pigs. These data further support the premise that a single dose of HSD for the prehospital treatment of hemorrhagic hypotension will not adversely affect blood coagulation.

Acute and subacute toxicity of 7.5% hypertonic saline/6% dextran-70 (HSD) in dogs. 1. Serum immunoglobulin and complement responses.

Clinical use of modern dextran solutions has been limited by concerns of anaphylactoid reactions. To assess the short-term antigenic response to 7.5% hypertonic saline in 6% Dextran-70 (HSD), sera were obtained from dogs involved in the acute and subacute toxicology testing of HSD and its individual components, and analyzed for IgG, IgM and C3 complement. In separate studies, beagles were infused i.v. with a single dose of HSD or its components at 20 ml kg-1 (the maximum tolerated dose; MTD), or the MTD daily for 14 days, and serum was obtained prior to and at various times after infusion up to 14 days. In both studies, despite serum dextran concentrations exceeding 2000 mg dl-1, no induction of IgG, IgM or C3 complement concentrations were observed. In addition, serum IgG immunoelectrophoretic patterns were of normal curvature, position and intensity; the immunoprecipitin bands were not displaced, bowed, inhibited or thicker than the normal preinfusion immunoelectrophoretograms. The data suggest that single or multiple HSD i.v. injections, as much as five times the proposed therapeutic level for the treatment of hypovolemia, evoked no increase in antibody titers in dogs. Therefore, therapeutic use of HSD in the treatment of hemorrhagic shock should not be associated with widespread concomitant allergic complications.