Brain noradrenergic responses to training and to amnestic frontal cortex stimulation

Rats were trained in a one-trial inhibitory (passive) avoidance task prior to receiving supraseizure electrical stimulation of frontal cortex, a treatment that results in amnesia. Forebrain and brainstem norepinephrine (NE) concentrations decreased by 23% 10 min after footshock training. Posttraining frontal cortex stimulation resulted in a potentiation of the forebrain NE response (to 31–33% below control values) and in attenuation of the brainstem response (0–5% lower than control values). These results are consistent with previous findings that indicate that good retention performance is predicted by training and treatment conditions that result in approximately a 20% decrease in brain NE content as measured 10 min after training; deviations from this optimal level, presumably reflecting more or less NE release, predict poor retention in comparably trained and treated rats. Thus, memory storage processing appears to be sensitive to many manipulations that alter the endogenous posttraining brain NE response to footshock.     

The effect of pyrazole, phenobarbital, ethanol and 3-methyicholanthrene pretreatment on the in vivo and in vitro genotoxicity of N-nitrosopyrrolidine

The in vitro genotoxicity of N-nitrosopyrrolidine (NPy) hasbeen studied in Salmonella typhimuriun strain TA1535 in thepresence of untreated and pyrazole-, phenobarbital (PB)-, 4-dayethanol (EtOH)-, 10-day EtOH- and 3-methylcholanthrene (3-MC)-pretreatedmale Sprague — Dawley rat liver S-9 fractions. Unlessstated otherwise, the last pretreatment exposure was 24 h priorto sacrifice and isolation of hepatic enzymes. Pyrazole andEtOH (10-day exposure) both effectively induced the conversionof NPy into a mutagen at doses as low as 500 µM. PB andEtOH (4-day exposure) had a modest enhancing effect on the numberof revertants scored, while 3-MC and uninduced S-9 fractionsgave results not significantly different from background (noNPy). The same pretreatment protocols were used to determinethe in vivo genotoxicity of NPy in rat liver using the techniqueof alkaline elution. The inducing agents had the exact oppositeeffect in vivo with control, 3-MC- and 4-day EtOH-treated animalsshowing the highest level of DNA damage. Pyrazole and 10-dayEtOH pretreatments gave DNA elution rate constants comparableto animals not treated with NPy. However, in 10-day EtOH-pretreatedanimals which were administered NPy without a 24-h intervalbetween EtOH and NPy exposure, DNA damage was observed at thesame high levels as was seen in uninduced and 3-MC treated rats.The results are discussed in terms of a detoxification rolefor microsomal proteins and that the observed in vivo DNA damagemay be induced by enzymes associated with the nuclear compartment.     

Hormonal responses to zimelidine and desipramine in depressed patients

Plasma prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and cortisol were repeatedly measured during the morning over a 4-hour period in patients who received single or chronic doses of desipramine (DMI) or zimelidine (ZIM). Preclinical studies had suggested that DMI, an uptake inhibitor specific for norepinephrine, would have different effects than ZIM, a selective serotinin uptake inhibitor. The GH response to DMI was blunted in the depressed patients. Neither DMI nor ZIM produced changes in LH or cortisol. DMI acutely increased plasma PRL, whereas ZIM had an effect only after chronic pretreatment. Chronic DMI but not ZIM increased baseline PRL. The patterns and magnitude of responses raise questions concerning the role of serotonin and norepinephrine in PRL release in man and the applicability of current preclinical models.     

Chronic obstructive pulmonary disease and respiratory complications

Patients with chronic obstructive pulmonary disease (COPD) (N = 148) underwent general anesthesia with halothane (H) or isoflurane (I) each administered randomly to 74 patients. One hundred and ten pre-, intra-, and postoperative variables were analyzed, including outcome variables, which included intra- and postoperative respiratory complications. Univariate computer analyses demonstrated no differences between H and I groups with respect to all variables, the exception being tachycardia, which occurred significantly more frequently in patients given I. Log-linear analyses revealed that no interactions existed between H or I groups, the non-outcome variables, and the complications. We conclude that patients with COPD respond similarly to H and I and that these anesthetics are associated with similar incidences of respiratory complications.     

Isolation of human tumour-specific antigens associated with beta2 microglobulin.

In the present study the tube LAI assay was used to monitor the isolation of the TSA of 4 different types of human cancers. Each tumour antigen was found to be specific for tumours arising in the organ from which the TSA was initially derived and which were histopathologically similar. Immunochemical studies revealed that these molecules co-isolate with normal human HLA antigens and are associated with beta2m. On Sephadex G-150, the majority of the papain-solubilized tumour antigen eluted in the mol. wt range 70,000-150,000. Analysis of this material by SDS-PAGE and 6M guanidine-HC1 column chromatography indicated that the material is composed of smaller subunits with prominent peaks at approximately 40,000, 25,000 and 12,000 mol. wt. Immunoadsorbent affinity chromatography of the solubilized tumour-membrane constituents on AH-Sepharose-linked horse anti-human-beta2m indicated that the tumour antigens, like HLA molecules, contain a beta2m subunit. The specificity of binding of TSA to the immunoadsorbent columns and the immunologically specific abrogation of LAI reactivity were clearly shown. The present study, therefore, indicates that by the isolation of beta2m, human tumour antigens can also be isolated, since human tumour antigens are associated with beta2m. Whether human TSAs may perhaps be modified histocompatibility antigens remains to be answered. Although the change upon malignant transformation in the pattern of the cell-surface proteins expressing the TSA determinant remains obscure, it would appear that for tumours arising within a given organ, a consistent alteration of cell-surface proteins occurs.     

High-resolution spinal sonography in infants

High-resolution, real-time sonography of the spine revealed significant anatomic details in 29 infants, including nine with congenital malformations. Transverse sections were most useful for detecting osteochondral anomalies and for evaluating the symmetry of the spinal column and its soft-tissue contents. Longitudinal sections augmented the transverse sections and provided the most detailed anatomy of the cord and spinal arteries. A normal screening sonographic examination obviates ionizing radiation and invasive procedures, while an abnormal study implies the need for further, complementary diagnostic investigations.