Chromosomes and causation of human cancer and leukemia. XXI. Cytogenetically unusual cases of leukemia.

Three male patients with leukemia were found with banding techniques to have unusual cytogenetic pictures in the cells of their marrow, spleen or blood. Case No. 1 (78 yr old) was that of a Ph1-negative CML with a missing Y in the blood (cultured without PHA) and marrow cells. The patient is still alive and responding to therapy. Case No 2 (54 yr old) was considered prior to admission to have either CML or AML, but was shown, in fact, to be in the blastic phase of CML; all the cells in his marrow and spleen were Ph1-positive, but with no evidence of a translocation. Other karyotypic findings (+8, +11, +13, +21) frequently encountered in the blastic phase of CML were present in the cells of this patient. Case No. 3 (50 yr old) with AML was shown to have a Ph1 resulting from a standard translocation, i.e., [t(9;22) (q34;q11)], in a substantial number of the cells in the marrrow and blood (cultured without PHA). The implications of these unusual findings are discussed in relation to the chromosomal pictures usually encountered in these states.     

Cefadroxil once daily for three or seven days versus amoxycillin for seven days in uncomplicated urinary tract infections in women

The cure rate of acute uncomplicated urinary tract infection in general practice using 3 different treatment regimens, was studied in a randomized, multicenter trial. Patients were assigned to receive either cefadroxil 1 g once daily for 3 or 7 days or amoxycillin 375 mg t.i.d. for 7 days. 310 patients entered the study, of whom 230 could be evaluated according to the protocol. Two thirds of the cases were due to infections with Escherichia coli and about one fourth to Staphylococcus saprophyticus. No statistically significant differences in cure rates between the 3 regimens could be demonstrated neither at 1 week nor at 5 weeks of follow-up. The frequency of adverse reactions was low and similar in each treatment group.     

Personality and physiological reactions to acute psychological stress

Stable personality traits have long been presumed to have biological substrates, although the evidence relating personality to biological stress reactivity is inconclusive. The present study examined, in a large middle aged cohort (N = 352), the relationship between key personality traits and both cortisol and cardiovascular reactions to acute psychological stress. Salivary cortisol and cardiovascular activity were measured at rest and in response to a psychological stress protocol comprising 5 min each of a Stroop task, mirror tracing, and a speech task. Participants subsequently completed the Big Five Inventory to assess neuroticism, agreeableness, openness to experience, extraversion, and conscientiousness. Those with higher neuroticism scores exhibited smaller cortisol and cardiovascular stress reactions, whereas participants who were less agreeable and less open had smaller cortisol and cardiac reactions to stress. These associations remained statistically significant following adjustment for a range of potential confounding variables. Thus, a negative personality disposition would appear to be linked to diminished stress reactivity. These findings further support a growing body of evidence which suggests that blunted stress reactivity may be maladaptive.     

Molecular aspects of adrenergic modulation of cardiac L-type Ca2+ channels

L-type Ca(2+) channels are predominantly regulated by beta-adrenergic stimulation, enhancing L-type Ca(2+) current by increasing the mean channel open time and/or the opening probability of functional Ca(2+) channels. Stimulation of beta-adrenergic receptors (ARs) results in an increased cyclic adenosine monophosphate (cAMP) production by adenylate cyclase (AC) and consequently activation of protein kinase (PK) A and phosphorylation of L-type Ca(2+) channels by this enzyme. Beta(1)-Adrenergic receptors couple exclusively to the G protein Gs, producing a widespread increase in cAMP levels in the cell, whereas beta(2)-adrenergic receptors couple to both Gs and Gi, producing a more localized activation of L-type Ca(2+) channels. Other signaling intermediates (protein kinase C, protein kinase G or protein tyrosine kinase (PTK)) either have negative effects on L-type Ca(2+) current, or they interact with the stimulatory effect of the protein kinase A pathway.     

Isopeptidase: a novel eukaryotic enzyme that cleaves isopeptide bonds.

In an attempt to clarify the regulatory mechanism that accounts for the shift of protein A24 in the mitotic cycle, we demonstrated the existence of an enzyme, provisionally termed isopeptidase, that cleaves A24 stoichiometrically into histone H2A and ubiquitin. Properties of this enzyme are (i) most eukaryotes, including mammals, amphibia, chicken, and yeast, contain isopeptidase in the cytoplasm; (ii) a significant increase in enzyme binding to chromatin occurs when cells enter mitosis; (iii) Escherichia coli does not contain isopeptidase; (iv) isopeptidase has a molecular weight of 38,000; (v) at an ionic strength that induces globular conformation of H2A, isopeptidase activity is repressed; (vi) a SH group is an essential cofactor; and (vii) most divalent cations (except Mg2+ and Ca2+) are inhibitory. In view of the stoichiometric conversion of A24 into H2A and ubiquitin by isopeptidase in vitro, A24 probably contains a Gly-Gly dipeptide in isopeptide linkage but no other intervening polypeptides. Since ubiquitin in various eukaryotes binds to protein other than H2A, and is proteolytically released, isopeptidase probably acts on isopeptide bonds in general and not uniquely on those of A24. Inasmuch as isopeptidase is present throughout the cell cycle, the level of A24 in chromatin appears to be controlled by a balance between isopeptidase and an as yet unestablished H2A-ubiquitin ligase.