Natural killer cell activity and CSF monoamine metabolites in suicide attempters

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.     

Early pathological changes in progressive multifocal leukoencephalopathy: a report of two asymptomatic cases occurring prior to the AIDS epidemic

Serial sections of formalin-fixed, paraffinembedded blocks from two asymptomatic, non-AIDS cases of progressive multifocal leukoencephalopathy (PML) were stained with a double-label immunocytochemical method for detection of glial fibrillary acidic protein and JC virus (JCV) capsid proteins and with luxol fast blue/hematoxylin-eosin. In case 1 small, rounded lesions of about 1-mm diameter were seen within a restricted area in the posterior part of the superior frontal gyrus of both cerebral hemispheres, suggesting an early manifestation of the disease. Fully developed demyelinated lesions of the classical type with JCV-infected oligodendrocytes appeared in the white matter and along its border with the cortex. Lesswell-developed lesions, believed to be precursors to the fully developed ones, were seen in the gray and white matter. Of special interest were areas which contained small collections of enlarged, glial fibrillary acidic protein (GFAP)-positive astrocytes without capsid antigen and which seemed to lack destruction of myelin as judged from the appearance of matching serial sections stained for myelin. Large lesions in the brain of case 2 showed the well-known features of advanced PML. The close relation between some astrocytes and oligodendrocytes with viral antigen raises the possibility of early intercellular passage of virus. Vacuolation, seen within or near lesions in both cases, has previously been noted in the CNS infected by HIV, but not in PML. It is suggested that PML, a disease of both oligodendrocytes and astrocytes, may actually begin in astroglial cells which, under the influence of a restricted JCV infection, become reactive, express GFAP and pass on virus to the more highly susceptible oligodendrocytes with which they are in contact.Supported in part by a grant N.S.07596 from the National Institute of Neurological Disorders and Stroke. The work was carried out in the Laboratory of Experimental Neurophathology, NINDS, and in the Department of Pathology II, Karolinska Institute, Stockholm     

Manganese induced brain lesions inMacaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging

A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [¹¹C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [¹¹C]-raclopride, demonstrating D₂ dopamine receptors, and [¹¹C]-l-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [¹¹C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [¹¹C]-l-dopa decarboxylation was not significantly altered indicating a sparing of [¹¹C]-l-dopa decarboxylation during manganese poisoning. A transient decrease of [¹¹C]-raclopride binding occurred but at the end of the study D₂-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i. e. before a reversal of the manganese accumulation.     

The meaning of good sleep: a longitudinal study of polysomnography and subjective sleep quality

SUMMARY  The present study sought to investigate the meaning of subjectively good sleep, using a longitudinal and intraindividual design. Eight subjects slept in an isolation unit according to an irregular schedule of 6h sleeps and 1h naps, designed to give normal amounts of time in bed (1/3 of total), but variable sleep quality. Eight sleeps and eight naps were used for longitudinal simple and multiple regression analyses with standard polysomnographical sleep variables as predictors and subjective sleep quality as dependent variables. The results showed that subjective sleep quality (and related variables) was closely related to sleep efficiency, but not sleep stages. At least 87% efficiency was required for ratings of 'rather good' sleep. In addition, sleep quality ratings improved with closeness (of the awakening) to the circadian acrophase (17.00–21.00 hours) of the rectal temperature rhythm. The subjective ease of awakening differed from most other other variables in that it was related to low sleep efficiency. Objective and subjective homologues of sleep length and sleep latency showed high mean intraindividual correlations ( r = 0.55 and 0.64, respectively). It was concluded that objective measures of sleep continuity were closely reflected in perceived sleep quality and that sleep quality essentially means sleep continuity.     

Improvement in histological diagnosis of primary hyperparathyroidism with a monoclonal antiparathyroid antibody

The monoclonal antiparathyroid antibody E11 reacts with a glycoprotein of high molecular weight, which acts as a calcium receptor on the surface of parathyroid cells and mediates calcium regulation of parathyroid hormone (PTH) release. Reduced expression of the calcium receptor has been implicated as a cause of the defect in PTH regulation in the pathological parathyroid parenchyma of patients with hyperparathyroidism (HPT). The present study evaluated the efficacy of immunostainings with the E11 antibody in comparison with routine histopathological methods including staining by the oil red O technique for histological discrimination between normal and pathological parathyroid glands. Parathyroid tissue from euparathyroid individuals invariably presented intense and homogeneous surface staining, with the antibody on virtually all chief cells, while the pathological glands from patients with HPT consistently showed heterogeneous and reduced immunostaining. Even minimally enlarged pathological glands from individuals with mild hypercalcemia and the normal-sized glands associated with adenomas displayed parathyroid chief cells with reduced antibody reactivity. The monoclonal antiparathyroid antibody should constitute a useful tool in parathyroid histopathology not only by its ability to identify the parathyroid tissue, but also by directly demonstrating the functionally normal and abnormal cells within the parathyroid tissue.     

Microcirculation in the upper trapezius muscle during varying levels of static contraction,fatigue and recovery in healthy women —a study using percutaneous laser-Doppler flowmetry and surface electromyography

Summary Microcirculation in the upper portion of the trapezius muscle was measured percutaneously by continuous laser-Doppler flowmetry (LDF) during two 10-min series of alternating 1-min periods of static contraction and rest determined electromyographically (EMG). Stepwise increased contraction was induced by keeping the arms straight and elevated at 30, 60, 90 and 135°, which was repeated with a 1-kg load carried in each hand. Thereafter, fatigue and recovery were recorded while the subject kept her arms straight and elevated at 45° carrying the 1-kg hand load as long as possible, followed by rest with arms hanging and no load. A group of 16 healthy women of different ages was studied. Signal processing was done on line using a 386 SX computer. The LDF- and root-mean-square (rms) EMG signals were normalized. Spectrum analyses of EMG mean power frequency (MPF) and median spectrum frequency were performed. The rms-EMG increased significantly with an increase in the calculated shoulder torque (r=0.75). Accumulated local fatigue was indicated by a decrease in MPF with increased shoulder angle and added load (r = –0.54). Blood flow increased with increased shoulder angle (r=0.82, with hand loadr=0.62) and with increased shoulder torque (r=0.72), and also showed a significant increase with increased EMG activity (r=0.74). The LDF showed a negative correlation to MPF (r= –0.67), with increased values when MPF was lowered. During the endurance test, a moderate increase of LDF occurred which reached its maximum during the 1st min of recovery. Then, a slow return to the base level was recorded. The ability to increase the flow in the microcirculation with increasing muscle load was not diminished with age.     

Identification of an N-linked glycan in the V1-loop of HIV-1 gp120 influencing neutralization by anti-V3 antibodies and soluble CD4

Summary Glycosylation is necessary for HIV-1 gp120 to attain a functional conformation, and individual N-linked glycans of gp120 are important, but not essential, for replication of HIV-1 in cell culture. We have constructed a mutant HIV-1 infectious clone lacking a signal for N-linked glycosylation in the V1-loop of HIV-1 gp120. Lack of an N-linked glycan was verified by a mobility enhancement of mutant gp120 in SDS-gel electrophoresis. The mutated virus showed no differences in either gp120 content per infectious unit or infectivity, indicating that the N-linked glycan was neither essential nor affecting viral infectivity in cell culture. We found that the mutated virus lacking an N-linked glycan in the V1-loop of gp120 was more resistant to neutralization by monoclonal antibodies to the V3-loop and neutralization by soluble recombinant CD4 (sCD4). Both viruses were equally well neutralized by ConA and a conformation dependent human antibody IAM-2G12. This suggests that the N-linked glycan in the V1-loop modulates the three-dimensional conformation of gp120, without changing the overall functional integrity of the molecule.     

Comparison of flagellum and sonicate antigens for serological diagnosis of Lyme borreliosis

A sonicate antigen and two concentrations of a purified flagellum antigen ofBorrelia burgdorferi were compared for serological diagnosis of Lyme borreliosis by an enzyme immunoassay (EIA). Generally, the higher concentration of flagellum antigen was found to be superior to the lower concentration, which was diluted eight times compared to the higher concentration. The diagnostic sensitivity for IgG antibody detection increased from 13 % in the sonicate EIA to 31 % in the best flagellum EIA assay (p=0.01) in sera from patients with erythema migrans (n=70), and from 34 % to 55 % (p=0.01) in sera from patients with neuroborreliosis (n=77). However, the sensitivity for IgG in sera from patients with acrodermatitis chronica atrophicans (n=20) was high in both assays: 90 % in the sonicate EIA compared to 95 % in the flagellum EIA. Regarding IgM, there was no significant difference between the sensitivity of the assays in sera from any of the patient groups. The sensitivity values for IgM and IgG in cerebrospinal fluid (CSF) from patients with neuroborreliosis were also without significant differences. Sera and CSF from patients with meningitis/encephalitis of non-Borrelia etiology (n=35), multiple sclerosis (n=9) or syphilis (n=24), served as controls. The flagellum EIA showed a significantly improved specificity for IgG in CSF from controls with syphilis (p<0.01). It is concluded that purifiedBorrelia burgdorferi flagellum antigen is superior to a sonicate antigen, especially for serodiagnosis of the early stages of Lyme borreliosis.