Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo: effects of median forebrain bundle stimulation frequency, stimulation pattern, and dopamine autoreceptors

In vivo microdialysis coupled with HPLC and radioimmuno-assay techniques were used to analyze dopamine (DA) and neurotensin (NT) in prefrontal cortical extracellular fluid following electrical stimulation of mesocortical axons. The release (overflow into the extracellular fluid) of both DA and NT increased with increasing number of impulses and with frequency. At the lowest frequency tested (2.5 Hz), DA release was significantly increased, while there was no significant increase in the release of NT. As the frequency of stimulation was increased from 2.5 to 20 Hz, the ratio of extracellular DA:NT decreased exponentially. Stimulation in a burst pattern produced greater release of both DA and NT than tonic stimulation when the number of impulses per second and the total number of impulses were held constant. Furthermore, blockade of DA autoreceptors with sulpiride stereoselectively increased the release of DA while decreasing the release of NT. These data suggest that the release of coexistent molecules (DA and NT) from mesocortical neurons can be influenced by physiological and pharmacological factors such that under certain conditions simultaneous or differential release may occur.     

Effects of dextromethorphan on regional cerebral blood flow in focal cerebral ischemia

Dextromethorphan (DM), a noncompetitive NMDA antagonist, has been demonstrated to reduce ischemic neuronal damage and edema, but DM's influence on cerebral blood flow has not been extensively studied. In this investigation, it is shown that DM has significant effects on regional cerebral blood flow (rCBF) patterns in a rabbit model of focal cerebral ischemia. rCBF was measured using radioactive microspheres following a 1 h permanent occlusion of the left internal carotid, anterior cerebral, and middle cerebral arteries in rabbits. Somatosensory evoked potentials (SEPs) were used to assess the degree of ischemia; only animals where SEPs were completely abolished were used for a frequency distribution analysis of rCBF. It was found that there were significantly more regions with lower flows in animals treated with normal saline (NS) (n = 7) compared to animals treated with DM (n = 7) (p less than 0.05, ipsilateral left side; p less than 0.001, contralateral right side). The frequency distribution medians were 27.5 ml 100 g-1 min-1 (left) and 70.0 ml 100 g-1 min-1 (right) in the NS group vs. 34.5 ml 100 g-1 min-1 (left) and 80.5 ml 100 g-1 min-1 (right) in the DM group. The left and right hemispheric regional means were 29.4 +/- 20 and 74.3 +/- 23 ml 100 g-1 min-1, respectively, in the NS group vs. 34.4 +/- 16 and 91.0 +/- 28 ml 100 g-1 min-1, respectively, in the DM group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Outcome and clinical course in inpatient bulimic women: a 2- to 9-year follow-up study

BACKGROUND: One previous follow-up study suggested that inpatient bulimic women do quite poorly; after an interval of 2 to 5 years, only 13% were recovered. To examine the course and outcome of a sample of patients with bulimia nervosa that was severe enough to require inpatient hospitalization, the authors conducted the following study. METHOD: Women (N = 52) with DSM-III-R bulimia nervosa were sought 2 to 9 years after hospitalization. Prior to contact, a retrospective chart review was conducted to determine global functioning and admission diagnoses. At follow-up, patients participated in a 4 to 6 hour interview that assessed current and lifetime Axis I disorders (SCID-I), current Axis II disorders (PDE), eating behaviors (EAT, BSQ, EDI, PSR), global functioning (GAF), social adjustment (SAS-SR), and treatment and medical problems experienced since discharge. To assess the significance of differences between the recovered and the currently bulimic women, Yates-corrected chi-square tests and two-tailed t tests were used. RESULTS: Of the 52 women, 46 were interviewed, 1 had died, and 5 could not be located. Of the 46 interviewed women, 39% had fully recovered, 20% had partially recovered, and 41% were currently bulimic. The likelihood of recovery increased with length of time since discharge. While medical problems related to the bulimia were few, treatment with phenelzine was associated with three reports of serious hypertensive episodes, one of which led to death. Global functioning before hospitalization, lifetime DSM-III-R Axis I diagnoses, and current Axis II diagnoses were not associated with outcome. CONCLUSIONS: These findings suggest that even severely ill bulimic patients have a significant chance of achieving full recovery.     

Treatment of HTLV-I-associated myelopathy with high-dose intravenous gammaglobulin

Summary Fourteen patients with HTLV-1-associated myelopathy were treated with high-dose intravenous gammaglobulin (IVGG). Ten received 10 g/day of IVGG and 4 received 400 mg/kg of body-weight/day of IVGG for 5 consecutive days. Improvement of spastic paraparesis was observed in 10 within 7 days of the commencement of IVGG. The therapeutic effects were sustained for more than 3 weeks in some patients. There were no side effects. Analysis of factors of relevance to the clinical improvement with IVGG showed that the beneficial response was preferentially found in patients having a high CSF titre of anti-HTLV-I antibodies, a high CSF IgG level and a marked brain MRI abnormality.     

Familial association of intracranial aneurysms and cervical artery dissections.

BACKGROUND AND PURPOSE: The familial occurrence of intracranial aneurysms and cervical artery dissections has been described in different families and supports the hypothesis that a primary arteriopathy may play a role in the pathogenesis of these disorders. Although the basis for this arteriopathy is generally not believed to be similar among cases of intracranial aneurysms and cervical artery dissections, several similarities exist in the epidemiology of these disorders and a common underlying arterial abnormality may be suspected. SUMMARY OF REPORTS: The medical records of all 175 patients with spontaneous dissections of the cervical arteries who were seen at the Mayo Clinic between 1970 and 1989 were reviewed to identify families in which intracranial aneurysms and cervical dissections coexisted. Three families were identified in which intracranial aneurysms and cervical artery dissections were observed among siblings. These families are described in detail. CONCLUSIONS: The familial occurrence of intracranial aneurysms and cervical artery dissections within the same families provides support to the importance of a common underlying arteriopathy in the pathogenesis of both these disorders. The underlying vascular defect may, at least in some cases, be inherited.     

Folding and function of the myelin proteins from primary sequence data.

To explain how the myelin proteins are involved in the organization and function of the myelin sheath requires knowing their molecular structures. Except for P2 basic protein of PNS myelin, however, their structures are not yet known. As an aid to predicting their molecular folding and possible functions, we have developed a FORTRAN program to analyze the primary sequence data for proteins, and have applied this to the myelin proteins in particular. In this program, propensities for the secondary structure conformations as well as physical-chemical parameters are assigned to the amino acids and the pattern of these parameters is examined by calculating their average values, autocorrelation functions and Fourier transforms. To compare two proteins, their sequences are aligned using a unitary scoring matrix, and homologies are searched by plotting a two-dimensional map of the correlation coefficients. Comparison of the corresponding myelin basic proteins (MBP) and P0 glycoproteins (P0) for rodent and shark showed that the conserved residues included most of the amino acids which were predicted to form the alpha or beta conformations, while the altered residues were mainly in the hydrophilic and turn or coil regions. In both rodent and shark the putative extracellular domain of P0 glycoprotein displayed consecutive peaks of beta propensity similar to that for the immunoglobulins, while the cytoplasmic domain showed alpha-beta-alpha folding. To trace the immunoglobulin fold along the P0 sequence, we compared the beta propensity curve of P0 with that of the immunoglobulin M603, whose three-dimensional structure has been determined. We propose that the flat beta-sheets of P0 are orientated parallel to the membrane surface to facilitate their homotypic interaction in the extracellular space. An extra beta-fold in the extracellular domain of shark P0 compared with rodent P0 was found, and this may result in a greater attraction between the apposed extracellular surfaces and may account for a smaller extracellular space as measured by x-ray diffraction. A computer search of the myelin protein sequences for functional motifs revealed sites for N-glycosylation, phosphorylation, nucleotide binding, and certain enzyme activities. We note especially that there are potential nucleotide binding sites in proteolipid protein (PLP), MBP and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). This is consistent with the experimental observations that PLP acts like an ionophore or proton channel when reconstituted into planar lipid bilayers, MBP binds GTP, and CNP catalyzes in vitro the hydrolysis of 2',3'-nucleotides into corresponding 2'-nucleotides.     

Methods for repeated recording in visual cortex of anesthetized and awake behaving infant monkeys.

This report describes methods for making repeated recordings from visual cortex in infant macaque monkeys (age range 5 weeks to 7 months) both under nitrous oxide anesthesia and in an alert behaving state. These methods permitted successful collection of single-unit data from inferior temporal cortex and other areas in a longitudinal fashion from individual infants. For the anesthetized experiments, modifications of our standard techniques for surgical preparation and maintenance of the animal in an anesthetized, artificially ventilated state permitted repeated recording sessions while assuring the animal's continued health and normal growth. Following implantation with an eye coil, monkeys as young as 5 weeks could be trained to perform a fixation task during alert recording sessions which were likewise performed on a repeated basis with maintained health and development. Further, comparison of results from anesthetized and awake recording sessions indicates that alert recording is preferable for collecting certain types of data from visual cortex in infant monkeys.     

Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock

Patients treated with high doses of interleukin-2 (IL-2) because of cancer, develop hemodynamic and vasopermeability changes, that resemble those observed in sepsis. These patients thus provide a unique opportunity to study the early events in the development of septic shock. We analysed the changes that occurred in the contact system of coagulation in plasma from 4 patients, who together received seven 12-day cycles of high doses of IL-2. Levels of factor XII and prekallikrein during the cycles progressively fell to 50 and 30% of their initial levels, respectively, whereas significant increases in plasma factor XIIa- and kallikrein-C1-inhibitor complexes were not observed (in 3 out of 211 samples slightly increased levels of both complexes were found). The reductions in factor XII and prekallikrein were only in part due to protein leakage, since levels were still significantly lower, i.e., 80 and 50%, respectively, when corrected for albumin decreases. Levels of high molecular weight kininogen (HMWK) also decreased during IL-2 therapy, however, this decrease paralleled that of albumin. SDS-PAGE analysis of plasma HMWK did not reveal increased cleavage of this protein. The reduction of factor XII and prekallikrein, corrected for protein leakage, significantly correlated with albumin levels and inversely with daily cumulative weight gain in the patients. Thus, we demonstrate that factor XII and prekallikrein decrease during IL-2 therapy. As these decreases, already observed after 1 day treatment, were disproportional to that of albumin, a negative acute phase reactant, and correlated with signs of the vascular leak syndrome, we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.(ABSTRACT TRUNCATED AT 250 WORDS)