Histamine H2-receptor antagonists stimulate proliferation but not migration of human gastric mucosal cellsin vitro

Gastric mucosal cell migration and proliferation are crucial events in the repair of gastric mucosal erosions. This study was designed to test the hypothesis that the H₂ blockers roxatidine and ranitidine might stimulate migration and proliferation of gastric mucous cells derived from a human well-differentiated gastric adenocarcinoma cell line (MKN 28 cells)in vitro, in conditions independent of systemic factors and of acid inhibition. Confluent monolayers of MKN 28 cells were wounded with a razor blade and were then incubated with roxatidine or ranitidine. The number of cells migrating to the damaged area was determined 24 hr later. Cell proliferation was assessed by means of [³H]thymidine uptake and cell counts after incubation with roxatidine or ranitidine. Neither H₂ antagonist significantly stimulated cell migration. On the other hand, cell proliferation was dose-dependently and significantly enhanced by incubation with roxatidine and ranitidine. Exogenous administration of TGF- significantly stimulated MKN 28 cell division. However, incubation with roxatidine or ranitidine did not increase the steady-state mRNA expression of TGF- or EGFR as assessed by northern blot analysis. Based on thesein vitro findings, we postulate that the ulcer healing effect of these H₂ antagonistsin vivo might be due in part to stimulation of gastric mucosal cell proliferation.Data from this paper have been presented in part at the 1995 meeting of the American Gastroenterological Association and published in abstract form in Gastroenterology 108:A72, 1995.     

Characterization of a family with moderate hypercholesterolemia and binding defective low density lipoprotein

Familial defective apolipoprotein B-100 (FDB) is a genetic disorder presenting with hypercholesterolemia and abnormal low density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B gene. In the present study thirteen members of a family with moderate hypercholesterolemia (250–350 mg/dl) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolemia (receptor deficiency). LDL from nine affected members displayed, in an in vitro cell binding assay, a reduced affinity (2.5 fold) for the receptor, and had normal electrophoretic mobility, size and chemical composition. Lp(a) levels in family members were comparable to those present in normolipidemics and lower than those observed in primary hypercholesterolemia. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolemic.Corresponding author.     

Untersuchung zur Kategorisierung des mandibulären Wachstumspotentials von Petrovic,Lavergne und Stutzmann

Zusammenassung In der vorliegenden Studie sollte untersucht werden, ob die vonPetrovic, Lavergne undStutzmann vorgeschlagene Kategorisierung des mandibulären Wachstumspotentials für die Behandlung mit dem Funktionsregler Geltung hat. Dazu wurden die Fernröntgenaufnahmen von 140 Patienten der Angle-Klasse II nach zirka zweijähriger Behandlung mit Funktionsreglern analysiert. Im Vergleich zu 133 unbehandelten Kindern mit Angle-Klasse II trat in fast allen Rotationsgruppen eine signifikant größere Zunahme der Unterkiefergesamtlänge ein. Zwischen der Kategorie 2 mit niedrigem Wachstumpotential und Kategorie 5 mit hohem Wachstumspotential wurden keine signifikant unterschiedlichen Zunahmen der Unterkieferlänge festgestellt.

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Summary The results of the study show whether the classification of mandibular growth potential, as proposed by Petrovic, Lavergne and Stutzmann has any influence on the treatment with a function regulator. X-rays of 140 class II patients were analysed after a treatment time of approximately 2 years. In comparison with 133 class II children without any treatment, a significant increase of the overall mandibular length was observed in almost all children treated. There was no significant difference in the increase of mandibular length between category 2 (low growth potential) and category 5 (high growth potential).

     

Comparison of fibrin glue, bioresorbable tubing and sutures in peripheral nerve repair

Regeneration of severed rat tibial nerves was functionally and morphologically compared with repair following the use of 3 anastomosis techniques: collagen guide tubes, fibrin glue and conventional microsurgical sutures. In addition, one tibial nerve was crushed in some rats. At ten weekly intervals, functional recovery, assessed by sciatic nerve stimulated evoked contraction of the flexor digitorum muscle, was quicker and more complete following nerve crush than following the anastomosis techniques which were not different from each other. Ten weeks following the surgery, the retrograde transport morphological technique indicated that the anastomosis techniques were not different from each other. The number of labeled tibial motoneurons (tube and suture groups) was significantly less than the crush group, but the glue group was intermediate. Thus, although having less extensive recovery following crush, the quicker and easier techniques of nerve repair, i.e., collagen tubes or fibrin glue, produced comparable anatomical and functional recovery as the more time-consuming, technically demanding microsurgical repair with fine sutures.     

Heterogeneity of toxicant response: sources of human variability.

While risk assessment models attempt to predict human risk to toxicant exposure, in many cases these models cannot account for the wide variety of human responses. This review addresses several primary sources of heterogeneity that may affect individual responses to drug or toxicant exposure. Consideration was given to genetic polymorphisms, age-related factors during development and senescence, gender differences associated with hormonal function, and preexisting diseases influenced by toxicant exposure. These selected examples demonstrate the need for additional steps in risk assessment that are needed to more accurately predict human responses to toxicants and drugs.     

Downregulation of neuronal cdk5/p35 in opioid addicts and opiate-treated rats: relation to neurofilament phosphorylation.

Neuronal cyclin-dependent kinase-5 (Cdk5) and its neuron-specific activator p35 play a major role in regulating the cytoskeleton dynamics. Since opioid addiction was associated with hyperphosphorylation of neurofilament (NF) in postmortem human brains, this study was undertaken to assess the status of the cdk5/p35 complex and its relation with NF-H phosphorylation in brains of chronic opioid abusers. Decreased immunodensities of cdk5 (18%) and p35 (26-44%) were found in the prefrontal cortex of opioid addicts compared with matched controls. In the same brains, the densities of p25 (a truncated neurotoxic form of p35), phosphatase PP2Ac and mu-calpain were found unaltered. Acute treatment of rats with morphine (30 mg/kg, 2 h) increased the density of cdk5 (35%), but not that of p35, in the cerebral cortex. In contrast, chronic morphine (10-100 mg/kg for 5 days) induced marked decreases in cdk5 (40%) and p35 (47%) in rat brain. In brains of opioid addicts, the density of phosphorylated NF-H was increased (43%) as well as the ratio of phosphorylated to nonphosphorylated NF-H forms (two-fold). In these brains, phosphorylated NF-H significantly correlated with p35 (r=0.58) but not with cdk5 (r=0.03). The results suggest that opiate addiction is associated with downregulation of cdk5/p35 levels in the brain. This downregulation and the aberrant hyperphosphorylation of NF-H proteins might have important consequences in the development of neural plasticity associated with opiate addiction in humans.     

Aminopenicillin allergy

Eight two children with histories of maculopapular or urticarial rashes during aminopenicillin treatment underwent skin tests, patch tests, radioallergosorbent assays and, in some cases, oral challenges. Hypersensitivity was diagnosed in eight (9.8%): immediate in four with urticarial reactions and delayed (that is cell mediated) in four with maculopapular rashes. In 49 children (38 with maculopapular eruptions, 11 with urticarial/angiooedematous reactions), negative allergologic findings were confirmed using oral challenges with the suspected drug. Maculopapular rashes may reflect delayed hypersensitivity to aminopenicillins, which can be diagnosed on the basis of late intradermal reactions and/or patch test positivity. The allergen panel must include the suspected aminopenicillin itself, as many cases are side chain specific. Most patients with urticarial reactions (more typical of immediate hypersensitivity) will also react to penicilloyl polylysine and minor determinant mixture. The time elapsed between the reaction and testing must be considered if negative results emerge, because IgE mediated sensitivity (unlike cell mediated forms) declines in the absence of antigen exposure.     

Spontaneous Splenic Rupture in a Patient with Acute Lymphoblastic Leukemia of Burkitt Type

We describe a case of spontaneous splenic rupture occurred in a patient with acute lymphoblastic leukemia of Burkitt type before starting cytotoxic chemotherapy. Left hypochondrial pain radiating to the homolateral shoulder was the only clinical symptom. Emergency computed tomography showed splenic laceration and hemoperitoneum. The patient underwent immediate laparotomy with splenectomy and experienced an uneventful postoperative recovery. Eight days after surgery, chemotherapy could be administered and complete remission was achieved. Although spontaneous rupture of the spleen is rare in leukemia and related disorders, this diagnosis should be taken in account also when clinical symptoms are mild. Following immediate operative management, patients may completely recover and receive cytotoxic chemotherapy with substantial possibilities of achieving complete remission.