Inhibition of acid secretion in gastric parietal cells by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-93

A novel Ca2+/calmodulin-dependent protein kinase II (CaM Kinase II) inhibitor, KN-93 potently inhibits gastric acid secretion from parietal cells. As previously reported (1), treatment of parietal cells with a selective inhibitor of CaM kinase II, KN-62 resulted in the inhibition of cholinergic-stimulated rabbit parietal cell secretion, whereas it failed to inhibit the histamine and forskolin response. In contrast effects of carbachol, histamine and forskolin were significantly inhibited by KN-93 with an IC50 of 0.15, 0.3 and 1 microM, respectively; these effects occurred without any changes in intracellular cyclic AMP and Ca2+ levels. In the present study we investigated the mechanism by which KN-93 acts upon the acid-secreting machinery of gastric parietal cells. Neither redistribution of the proton pump activity nor the morphological transformation were affected by KN-93. The drug only weakly inhibited the H+, K(+)-ATPase activity but strongly dissipated the proton gradient formed in the gastric membrane vesicles and reduced the volume of luminal space. Thus KN-93 acts at pH gradient formation whereas KN-62 acts only at CaM Kinase II.     

Reproducibility of functional transcranial Doppler sonography in determining hemispheric language lateralization

BACKGROUND AND PURPOSE: Since functional transcranial Doppler ultrasonography (fTCD) allows convenient and fully automated quantification of language lateralization, it seems ideal for longitudinal studies of perfusion changes during deterioration as well as recovery of language functions. However, during serial examinations, the technical, stochastic, and physiological variabilities of cerebral blood flow velocities (CBFV) have to be considered. Therefore, before fTCD is accepted as a tool for evaluation of changes in lateralization in the diseased state, its reliability in healthy subjects needs to be determined. METHODS: We performed fTCD during a word generation task based on a previously validated technique with automated calculation of the averaged CBFV differences in the middle cerebral arteries providing an index of lateralization (LI). RESULTS: (1) The accuracy of the LI as assessed by the confidence interval was better than 1% of the mean hemispheric difference. (2) On repeated examination, LIs obtained from 10 subjects showed a high test-retest reproducibility (Pearson product moment correlation coefficient r = 0.95, P < 0.0001). (3) On 10 repeated assessments of LI in the same subject, no practice effects were detected. CONCLUSIONS: Functional TCD is a suitable and very robust tool for the longitudinal quantitative measurement of cerebral language lateralization.     

Proteins and cells on PEG immobilized silicon surfaces

Functional adhesion of blood and marrow leukemic cells from 14 acute myeloid leukemia patients presenting with hyperleukocytosis was evaluated by performing cytoadhesion assays on purified (extracellular matrix proteins) and non-purified supports (MRC5 fibroblastic cell line). Results, in 30-min chromium release assay, show a mean +/- S.D. adhesion to fibronectin, collagen, and laminin respectively of 30 +/- 17%, 20 +/- 13%, 25 +/- 17% for blood leukemic cells and 18 +/- 11%, 11 +/- 10%, 11 +/- 8% for marrow leukemic cells. These differences between blood and marrow cells were statistically significant (respectively P = 0.005, P = 0.01 and P = 0.002), while no difference was noted regarding adhesion to non-purified supports. The higher adhesion of blood blast cells to purified supports was observed regardless of CD34 expression. No significant difference was observed in the expression of cell surface VLA-molecules (CD29, CD49b, CD49d, CD49e, CD49f) between blood and marrow blast cells. The addition of GM-CSF or G-CSF induced increased adhesion of marrow blasts and decreased adhesion of blood blasts leading to a loss of the difference between blood and marrow cells. In a 60-min chromium release assay, marrow blasts adhered even more than blood leukemic cells to fibronectin. In contrast, marrow blasts from 'aleukemic' acute myeloid leukemia patients did not show any modification regarding their adhesion to extracellular matrix proteins when co-cultured with growth factors.     

Unusual chromosomal organization of telomeric sequences and expeditious karyotypic differentiation in the recently evolved Mus terricolor complex

The Mus terricolor complex displays a stable homozygous arrangement of autosomal heterochromatin variations in the form of accretion of definitive autosomal short arms among three nonoverlapping populations, in concert with an expeditious evolutionary differentiation into three chromosomal species: M. terricolor I, II, and III. In contrast to the highly conservative M. musculus-like chromosomes in the coexisting sibling species, M. booduga, reshuffling and differentiation of centric heterochromatin has occurred in harmony with a revision of centric configurations, resulting in acrocentric and submetacentric autosomes. The chromosomal distribution of the prevalent vertebrate telomeric sequence (TTAGGG)n was examined by fluorescence in situ hybridization to metaphase cells of M. terricolor I, II, and III. An unusual centric organization of internal telomeric sequences was detected in all the submetacentric and acrocentric autosomes. An auxiliary role of these presumably fragile, recombinogenic telomeric sequences in the evolutionary revision of centric configurations in the terricolor complex is hypothesized.     

Prenatal corticotherapy and acceleration of fetal maturation. I. Experimental and pharmacological data

Numerous subsequent controlled trials and recent meta-analysis have confirmed the efficiency of antenatal glucocorticoid therapy in reducing both the incidence of respiratory distress syndrome (RDS) and perinatal mortality. Moreover, antenatal glucocorticoid administration reduces the odds of several severe complications relating to immaturity: intraventricular hemorrhage (IVH), ductus arteriosus patency, necrotising enterocolitis, and hemodynamic failure. Exogenous surfactant therapy has not ruled out the benefits of corticosteroids: on the contrary, a synergic effect is obtained when both antenatal and postnatal therapeutic approaches are combined. Very premature infants may also take advantage of the hormonal treatment: in this population, RDS occurrence, IVH incidence and perinatal mortality are also reduced. Unfortunately, despite convincing evidence, the incidence of antenatal steroids therapy has not yet achieved the optimal and desirable level. Obstetricians and pediatricians must be encouraged to ensure high maternal exposure to steroids when preterm delivery is likely to occur.     

Treatment of acute lateral ankle ligament ruptures. A prospective 9-13-year follow-up study of three different therapies in 79 patients

In a prospective study of 79 patients with arthrographically verified acute ruptured lateral ankle ligaments we have evaluated the long-term results of three different treatments: operation and walking-cast, walking-cast alone and elastic bandage. The average follow-up period was 11 (9-13) years, and 32 parameters concerning interview, clinical and radiographic examinations were statistically analysed. The three kinds of treatment were found to be equal, since only one parameter showed significant difference at a 5% level using Fisher's exact and the Mann-Whitney test, and no difference by using the Kruskal-Wallis test for homogeneity. Residual disabilities and late complications, such as instability, pain on activity, and the number of secondary ligament reconstructions and talocrural arthroses were low. It was concluded that nonoperative treatment provided adequate results even after a decade.     

Detection of hepatitis C virus RNA from the heart of patients with hypertrophic cardiomyopathy

We investigated hepatitis C virus (HCV) infection in 35 patients with hypertrophic cardiomyopathy and 40 patients with ischemic heart disease who were consecutively admitted to our hospital. Frequency of positive anti-HCV antibody was significantly higher in patients with hypertrophic cardiomyopathy (6 of 35 patients, 17.1%) than that in patients with ischemic heart disease (1 of 40 patients, 2.5%, p = 0.036). In three of these six patients with hypertrophic cardiomyopathy, HCV RNA was detected in myocardial tissue. In two of these three patients, HCV RNA was detected from biopsy and autopsy specimens of the ventricles, but not in the serum, suggesting that HCV may replicate in myocardial tissue and may be relevant to ventricular hypertrophy. Thus, HCV infection may play a role in the development of hypertrophic cardiomyopathy.     

History of strabismology: II--strabismology in Poland

BACKGROUND: Clinically significant allergic reactions with insulin therapy are known to occur. There have been rare reports of allergic reactions to endogenously secreted insulin manifested as insulin resistance. No reports of systemic or local allergic reactions to endogenous insulin have previously been cited, and no immunologic reactions to endogenous insulin have been reported during therapy with recombinant (rDNA) insulin. METHODS: We report a case in which the patient, a 28-year-old black woman who initially presented with gestational onset diabetes but postpartum continued to require insulin, developed generalized allergic reactions during therapy with subcutaneously injected rDNA insulin. Similar reactions occurred with sulfonylurea therapy. She was unable to tolerate any pharmacologic therapy for diabetes without concurrent use of at least 10 mg of prednisone per day. RESULTS: Skin testing with the insulin preparations were positive, while skin testing to the sulfonylurea hypoglycemic agents were negative. IgE antibodies to insulin where present in high titer. Oral challenge to sulfonylurea hypoglycemic agents produced generalized urticarial reactions coinciding with time of peak insulin secretion. Oral challenge to other medications containing sulfa produced no adverse reaction. Biphasic hypersensitivity reactions occurred during attempts at desensitization which were futile without simultaneous glucocorticoid therapy. CONCLUSIONS: This is the first report of local and systemic allergic reactions to endogenously secreted insulin in association with rDNA insulin therapy. Although immunologic complications with rDNA therapy appear less frequently than with insulin preparations, this case illustrates the need for continued awareness for potential allergic complications occurring with rDNA insulin therapy.     

The short-term effect of a smoking prevention program for the upper graders of elementary schools--the results of intervention study for two years with quasi-experimental design

The purpose of this study was to evaluate the short-term effect of a smoking prevention program for Japanese elementary school-children in the fifth and sixth grades. The program was developed with concepts found in the Know Your Body Program and the conclusions of a National Cancer Institute-convened Expert Advisory Panel, and focused on teaching about the short-term effects of smoking and on resistance to social pressures to smoke. The study was conducted with a quasi-experimental design. An intervention group (52 boys and 54 girls) received three sessions for both the fifth grade in 1992 and the sixth grade in 1993. Moreover, the intervention group received a pre-test before the first session and a post-test after the third session in each grade. A comparison group (102 boys and 91 girls) received the same tests at the same time as the intervention group, but did not receive any program on smoking prevention. The short-term effect of the program were evaluated using the results of the pre-test in the fifth grade and of the post-test in the sixth grade in both groups. The results were as follows: 1) Remarkable short-term effects of the intervention were seen in respect to awareness of the importance of not smoking in girls, and also in the knowledge of the short-term effects of smoking in both sexes. 2) The intervention was not effective with respect to intention to smoke at the age of 20 and self-efficacy of refusing to smoke in both sexes. 3) The short-term effects were not clear in the smoking behavior in both sexes because the rates of ever smokers and of monthly smokers were almost the same for two years between the intervention group and the comparison group. 4) The smoking behaviors of children, their parents and their best friends had little influence on the results of the post-test in the sixth grade.