Predictive value of prior Rose angina for myocardial infarction confirmation after emergency admissions.

The Rose Questionnaire, developed to facilitate screening for the presence of coronary artery disease, has shown good utility for white men and more variable utility among Latino, African-American, and female subjects. This study investigated its utility for prediction of outcome in patients with suspected myocardial infarction. A total of 1428 white, Latino, and African-American subjects completed questionnaires after emergency admission, which were correlated with diagnoses at the time of discharge from a public hospital and private hospital. Results indicated that subjects with positive questionnaires were less likely to have infarction confirmed at discharge, except for those with a prior history of myocardial infarction, than those with a negative response. These data are important in evaluating the overall utility of the Rose Questionnaire and the significance of angina.     

Interleukin-6 production by astrocytes: Induction by the neurotransmitter norepinephrine

Astrocytes contribute to the immunocompetence of the central nervous system (CNS) via their expression of class II major histocompatibility complex (MHC) antigens and the production of inflammatory cytokines such as interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Of these cytokines, IL-6 is of particular interest because one of its many immune and inflammatory actions is the promotion of immunoglobulin synthesis, and it is thought that IL-6 expression within the brain exacerbates autoimmune diseases of the CNS, which are marked by local immunoglobulin production. Several stimuli induce astrocyte IL-6 expression, including such inducible endogenous factors as IL-1β and TNF-α. We have investigated the possibility that a constitutively present endogenous factor, the neurotransmitter norepinephrine (NE), can induce astrocyte IL-6 production. We report that NE induces both IL-6 mRNA and protein in primary neonatal rat astrocytes, with optimal induction at 10 μM. IL-6 protein induction by NE is comparable to that seen with IL-1β or TNF-α, and NE synergizes with these cytokines for a ten-fold enhanced effect. In contrast to astrocytes, microglia are relatively unresponsive to NE, IL-1β and TNF-α for IL-6 production. Experiments with the β-adrenergic receptor agonist isoproterenol, and α and β-adrenergic receptor antagonists (propranolol, phentolamine, atenolol, and yohimbine) indicate that β₂ and α₁-adrenergic receptors are involved in NE induction of astrocyte IL-6 expression. These results help to further the understanding of neuron-glial interactions, and the role of astrocytes and adrenergic activity in immune responses within the CNS.     

Long-term incorporation of tritiated adenine into deoxyribonucleic acid and ribonucleic acid by Treponema pallidum (Nichols strain)

Treponema pallidum (Nichols strain), extracted in medium containing Eagle minimal essential medium 50% fresh, heat-inactivated normal rabbit serum, and 1.0 mM dithiothreitol, was incubated under 3% oxygen in the presence of tritiated nucleic acid precursors. [8-3H]adenine was incorporated with high efficiency into trichloroacetic acid-insoluble material; 2'-deoxyadenosine and uridine were incorporated in lower quantities, and thymine and thymidine were not incorporated. Incorporation of [3H]adenine was inhibited by penicillin G, mitomycin C, actinomycin D, and erythromycin, but was not affected by cycloheximide. Partial purification of nucleic acids from T. pallidum incubated with [8-3H]adenine for 36 to 72 h and subsequent treatment with ribonuclease and deoxyribonuclease revealed that 15 to 20% of the trichloroacetic acid-precipitable counts were resistant to ribonuclease but susceptible to deoxyribonuclease. A simple assay was developed in which NaOH treatment was used to distinguish incorporation into ribonucleic acid and deoxyribonucleic acid. Both ribonucleic acid and deoxyribonucleic acid synthesis continued for 6 days of incubation under 3% O2, whereas incorporation was limited to the first day of incubation in samples incubated under aerobic or anaerobic conditions. T. pallidum thus appears to be capable of significant de novo deoxyribonucleic acid and ribonucleic acid synthesis under microaerobic conditions.     

Changes in transmitter release patterns in vitro induced by tremorgenic mycotoxins

The neurochemical effects of the tremorgenic mycotoxins Verruculogen and Penitrem A, which produce a neurotoxic syndrome characterized by sustained tremors, were studied using sheep and rat synaptosomes. The toxins were administered in vivo, either by chronic feeding (sheep) or ip injection 45 min prior to sacrifice (rat). Synaptosomes were subsequently prepared from cerebrocortical and spinal cord/medullary regions of rat, and corpus striatum of sheep. Penitrem A (400 mg mycelium/kg) increased the spontaneous release of endogenous glutamate, GABA, and aspartate by 213%, 455%, and 227%, respectively, from cerebrocortical synaptosomes. Verruculogen (400 mg mycelium/kg) increased the spontaneous release of glutamate and aspartate by 1,300% and 1,200% respectively, but not that of GABA, from cerebrocortical synaptosomes. The spontaneous release of the transmitter amino acids or other amino acids was not increased by the tremorgens in spinal cord/medullary synaptosomes. Penitrem A pretreatment reduced the Veratrine (75 microM) stimulated release of glutamate, aspartate and GABA from cerebrocortical synaptosomes by 33%, 46%, and 11% respectively, and the stimulated release of glycine and GABA from spinal cord/medulla synaptosomes by 67% and 32%, respectively. Verruculogen pretreatment did not alter the Veratrine-induced release of transmitter amino acids from cerebrocortex and spinal cord/medulla synaptosomes. Penitrem A pretreatment increased the spontaneous release of aspartate, glutamate and GABA by 68%, 62%, and 100%, respectively, from sheep corpus striatum synaptosomes but did not alter the synthesis and release of dopamine in this tissue. Verruculogen was shown to cause a substantial increase (300-400%) in the miniature-end-plate potential frequency at the locust neuromuscular junction. The response was detectable within 1 min, rose to a maximum within 5-7 min, and declined to the control rate over a similar period. No change in the amplitude of the m.e.p.p.s was observed. These effects of the tremorgens on transmitter release are interpreted in terms of their mode of action.     

Births of normal daughters after MicroSort sperm separation and intrauterine insemination, in-vitro fertilization, or intracytoplasmic sperm injection

The world's first deliveries of normal babies after use of flow cytometric separated human sperm cells (MicroSort) for preconception gender selection are reported. Offspring were of the desired female gender in 92.9% of the pregnancies. Most of these pregnancies and births were achieved after simple intrauterine insemination.      

Inhibition of cysteine proteinases by autolytic digestion is mediated by CBP2/Hsp47

CBP2/Hsp47 is a glycoprotein normally limited to the ER-Golgi where it is first associated with procollagen chains at a very early point during translation of nascent chains and later with properly folded procollagen. Although CBP2/Hsp47 is regarded as a molecular chaperone belonging to the serpin superfamily, this protein does not appear to inhibit serine proteinases. Here we demonstrate that CBP2/Hsp47 functions in a manner similar to other serpin superfamily members by cross class inhibiting cysteine proteinases. A CBP2/Hsp47 to cathepsin L inactivation stoichiometery of approximately 1.5 revealed concurrent cleavage of CBP2/Hsp47 with proteinase inactivation. Cleavage of the CBP2/Hsp47 was shown to occur outside the P1-P1' at the P16-P15 and P2'-P3' bonds. In addition, the proteinase bands in SDS/PAGE diminished on reaction of the enzyme with CBP2/Hsp47. These results sustain a mechanism advocated by Bjork et al. (1998), in which cysteine proteinases assault a peptide bond in the reactive site loop of serpins, (CBP2/Hsp47) adjacent to the P1-P1' bonds involved in serine proteinase inhibition. The reaction proceeds with the substrate pathway dominating in the cysteine proteinase reaction. In these complexes the cysteine proteinases, papain and cathepsin L, are rendered more susceptible to proteolysis and are degraded by active enzyme. These properties help explain the mechanism by which CBP2/Hsp47 increases the fidelity of collagen production. Moreover, if CBP2/Hsp47 is shown to involve the multiplexin subclass of collagens, it may further provide a mechanism by which the motogen and angiogenic properties during development and/or neoplasia are regulated.     

Effect of intravenous streptokinase as compared with that of tissue plasminogen activator on left ventricular function after first myocardial infarction

In a double-blind trial comparing two thrombolytic agents as treatment for acute myocardial infarction, we randomized 270 consecutive patients an average (+/- SD) of 2.5 +/- 0.6 hours after the onset of chest pain from a first myocardial infarction--135 to receive intravenous streptokinase (1.5 million units over 30 minutes) and 135 to receive intravenous recombinant tissue plasminogen activator (rt-PA) (100 mg over three hours). The primary end point was left ventricular function as assessed by cineangiography performed three weeks after infarction. The effects of the two agents on left ventricular function were similar. The ejection fraction was identical (58 +/- 12 percent) in both groups. The end-systolic volume was 61 +/- 29 ml in the streptokinase group and 66 +/- 31 ml in the rt-PA group (P not significant). Patency rates at three weeks for the infarct-related artery were also similar (75 percent in the streptokinase group and 76 percent in the rt-PA group). Reinfarction rates at 30 days were the same (5 percent) in both groups. One patient had a fatal intracerebral hemorrhage 13 hours after receiving rt-PA, and another had a fatal cerebellar hemorrhage 21 hours after receiving rt-PA for reinfarction nine days after treatment with streptokinase. An intention-to-treat analysis revealed that mortality at 30 days was 3.7 percent in the rt-PA group as compared with 7.4 percent in the streptokinase group (P greater than 0.2). Follow-up for a mean of 9.0 months revealed no significant difference in survival; we observed 12 deaths (8.9 percent) in the streptokinase group and 8 deaths (5.9 percent) in the rt-PA group (P = 0.34). We conclude that rt-PA and streptokinase, in the doses given, have similar effects on left ventricular function after a first myocardial infarction. Because of the small number of deaths, it is not possible to determine whether their effects on mortality are similar.