Increased immune response in the acute phase of systemic lupus erythematosus and psoriatic arthritis caused by serum factors.

In the acute phase of systemic lupus erythematosus the serum contains factors, with molecular weights ranging from 780,000 daltons to 1.5 million daltons, which induce blast transformation of autologous lymphocytes. In addition to the high-molecular weight components, low-molecular weight factors (75,000 and 160,000 daltons) which also induce an increase in lymphocytic transformation have also been demonstrated. In contrast to the high-molecular weight components the low-molecular factors stimulate the transformation of autologous and homologous lymphocytes. During transformation, lysis of autologous target fibroblasts occurs. The low-molecular weight mitogenic components remain stable after 30 min at 56 degrees C. The significance of such mediators for the pathogenesis of systemic lupus erythematosus is discussed.

Predominant sensorimotor area left hemisphere dysfunction in schizophrenia measured by brain electrical activity mapping.

Using a newly developed system of brain electrical activity mapping (Alvar Electronics, Paris), we studied 10 right-handed, schizophrenic subjects who had been treated with neuroleptics (5 of the disordered and 5 of the paranoid type) and compared them with 10 controls by applying a cortical activation schedule involving a multisensorimotor coordination task. All tasks were referenced to resting states after a specially designed relaxation program. In schizophrenics, we found high, predominantly bifrontal, delta and theta power values, which is in agreement with the literature, and low beta power values, which are possibly due to the neuroleptic treatment. The major result, however, was a widespread left hemisphere dysfunction during multisensorimotor activation, with a predominance over the primary sensory and motor cortical areas. The area of the supplementary motor regions was not affected. Combined with the evidence of genetic and psychometric studies, our results lend further support to the hypothesis that left hemisphere functioning in schizophrenia is impaired. They also suggest that there is a special and independent sensory and motor processing system impairment in schizophrenia.

EEG mapping of left hemisphere dysfunction during motor performance in schizophrenia.

With a newly developed system of brain electrical activity mapping we studied 10 right-handed, neuroleptic-treated schizophrenics (five of the disorganized, five of the paranoid type, corresponding to 295.1 and .3 in DSM-III), compared with 10 normal controls. Increasingly complex motor tasks were used for cortical activation, all functional states being referenced to resting states recorded after a special relaxation program. We found higher delta and theta amplitudes during rest, as noted in previous studies, and lower beta power values. As a major result, however, we found a widespread left hemisphere dysfunction in schizophrenics, predominantly in the left primary sensory and motor areas. Additionally, we found signs of a "compensatory" overactivation in patients in motor tasks, when this hemisphere is not "used" by normal persons. The results support our findings obtained with this method during multisensory motor coordination in schizophrenia. The results in these patients suggest that these are not merely vigilance, attention, or motivation dysfunctions, but rather specific cortical correlates of impaired motor performance.

Pathological cerebral blood flow during motor function in schizophrenic and endogenous depressed patients.

In this investigation we examined eight Type I (positive symptoms without marked negative symptomatology), eight Type II (marked negative symptoms) schizophrenic patients of the disordered and paranoid diagnostic subgroups (DSM-III 295.1 and 295.3), eight severely (HAMD above 35) and eight less severely (HAMD below 20) endogenous depressed patients, and eight control persons using the 133Xe inhalation method in resting condition and during motor activity of the dominant right hand. In all patient groups we found flow activation patterns that were different from those observed in normal control persons. During motor activation in Type I schizophrenics and in less severely endogenous depressed patients, we found a bilateral hyperflow and a diffuse cortical flow increase, also involving deeper cerebral structures. In Type II schizophrenics and severely endogenous depressed patients, however, we found a widespread nonreactivity of the regional cerebral blood flow (rCBF) to motor activation, with no flow increase in the contralateral primary motor area. In normal control individuals, we reproduced a 25% flow increase that was strictly limited to the contralateral primary motor area, as already reported by other authors. As only the schizophrenic patients were not under antipsychotic medication (4 with a washout of at least 1 week prior to the investigation, 12 never treated with drugs before), contaminating effects of the medication cannot be ruled out for the endogenous depressed patient groups. However, in schizophrenic patients, these results suggest a diffuse disorganization and lack of laterality of motor functional systems. In addition, the change from hyperactivity to hyporeactivity might indicate cerebral functional correlates of the change from Type I to Type II symptomatology in schizophrenic patients, which could possible prove to be of clinical importance.

Bilateral brain dysfunction during motor activation in type II schizophrenia measured by EEG mapping.

In this final electroencephalographic (EEG) mapping study of our series on motor dysfunction in neuroleptic-treated schizophrenic patients, we studied 10 right-handed patients with marked negative symptomatology [type II; raw score on the SANS (Munich version) 31.4 +/- 5.1]. Simple and multisensorimotor tasks involving both the dominant and nondominant hand were used for cortical activation. All tasks were referred to resting states obtained after specially designed relaxation procedures. In contrast to predominantly type I patients (SANS-MV score 12.3 +/- 4.9) of our previous EEG mapping studies, we found for resting states minor evidence (only) of increased power values in the frequency bands delta and theta. Furthermore, in contrast to signs of "left hemisphere dysfunction" and possible "compensatory right hemisphere overactivation" during motor tasks, which we discussed previously for our type I patients, we found for the type II schizophrenics a bilateral brain dysfunction. This consisted of "nonreactivity" in all frequency bands except alpha, in which, on the contrary, a "hyperreactivity" seemed to be present. In combination with evidence of bilateral hemispheric dysfunction in type II patients reported by other authors using EEG, evoked potentials, regional cerebral blood flow (rCBF) and magnetic resonance imaging (MRI) methods, this suggests that marked bilateral brain dysfunction may be correlated in schizophrenia with a clinical syndrome corresponding rather to the "negative pole" of the positive-negative dimension. In contrast, "left hemisphere dysfunction" and "signs of compensatory overactivation" seem to be linked more to a "positive" symptomatology. Finally, discrepancies of our EEG mapping and rCBF findings during motor activity suggest, speculatively, "uncoupling" between electrical and circulatory parameters in schizophrenia involving both hemispheres in type II, and predominantly the left hemisphere in type I, patients.

Auditory perception of music measured by brain electrical activity mapping.

The brain electrical activity of right-handed normal subjects was studied while they were exposed to auditory stimulation of the music type. The material presented was a note, a scale and a melody, recorded on magnetic tape. Each stimulus condition lasted 45 sec. The first 30 sec were analysed using brain electrical activity mapping in the delta (1-4 Hz), alpha (8-12 Hz) and beta 2 (18-24 Hz) frequency bands. The results showed significant bilateral reaction differences for all conditions, showing a left midtemporal activation predominance for the note and scale conditions, but a right midtemporal and frontal predominance for the melody. The results are discussed in terms of functional specialization for different levels of processing.

Cancer after bone marrow transplantation. IBMTR and EBMT/EULEP Study Group on Late Effects.

Cancer may be serious late effect of marrow transplantation. Radiation, chemotherapy, immunosuppression and the original disease for which transplantation was performed may predispose to the development of cancer. 116 of 9732 patients reported to the IBMTR (International Bone Marrow Transplant Registry) have developed a new malignancy. Late effects were evaluated by the EBMT-EULEP (European Bone Marrow Transplant-European Late Effect Project) Late Effect Study Group in 147 patients surviving 6 years and 79 patients surviving more than 10 years. New malignancies developed in 11 of these patients. Lymphomas and leukemia comprised 73 cases reported to the IBMTR and one case reported to the EBMT-EULEP study. Tumors of the skin, oropharynx, vulva vagina and cervix prevailed in 41 patients with solid tumors. The distribution of malignancies is similar to that observed in organ transplant patients not given radiation or chemotherapy and suggests immunosuppression as a major contributory factor. In dogs the incidence of malignancies was studied after either chemotherapy or total body radiation in various regimens and marrow transplantation. Both chemotherapy and radiation shortened tumor-free survival in comparison to untreated dogs. Higher doses, larger fractions and shorter treatment schedules enhanced earlier tumor development. Soft tissue sarcomas and thyroid carcinoma were most frequent in treated, mammary carcinoma in untreated dogs. In treated dogs deaths from cancer were observed starting at the age of 5 years as compared to untreated dogs at the age of 9 years. The data from animal experiments indicate that the incidence of solid tumors in marrow transplant patients may still rise in the coming decades.

Motor responses measured by brain electrical activity mapping.

The brain electrical activity of right-handed normal subjects was studied while they were exposed to motor performance tasks that were of increasing difficulty. Each task lasted 45-60 s, and a 30-s period of each task was analyzed by a spectrum analyzer. Data are presented in topographic maps showing the electrical activity for each task, in delta (1-4 cycles [c]/s), alpha (8-12 c/s), and beta 2 (18-24 c/s). The results showed a bilateral decrease in amplitude in sensorimotor areas relative to baseline, for a single hand movement. Tasks that required the programming of movement showed baseline/task differences in amplitude in additional areas; the right frontal area, the prefrontal area, the posterior parietal area, and the left temporal area. The results obtained suggest that different topographical areas are involved in motor tasks that require increased level of programming.

Studies on canine bone marrow long-term culture: effect of stem cell factor.

Long-term culture of canine marrow cells allows in vitro studies of the hematopoietic system of the dog and characterization of early progenitor cells. Colonies of fresh marrow cells grew equally good in both agar or methylcellulose supplemented with fetal calf serum, while colonies of long-term cultures required agar-based medium containing human serum. Optimum colony growth was obtained when stem cell factor (SCF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) were used as growth stimuli of colony forming units (CFU). Similar results were achieved with several cell culture media. Addition of hydrocortisone to long-term cultures improved clonogenic growth of cultured cells. Addition of 2-mercaptoethanol had no effect. Strong differences were observed in long-term culture with different horse serum lots and the addition of fetal calf serum to long-term culture suppressed CFU growth of cultured cells. Recharging of cultures with fresh marrow cells on day 7 of culture improved CFU growth only in the following week but had little effect on the outcome. Adding SCF to long-term cultures led to differentiation of more primitive cells and destruction of the stromal layer. Investigation of purified and cultured cell populations was possible when preestablished long-term cultures as stromal layers were used. Loss of long-term culture-initiating ability could be demonstrated in this system with lineage negative marrow cells expanded ex vivo with SCF and GM-CSF.

[Complications following talus trauma]. / Komplikationen nach Talustrauma.

The injuries of the talus are rare. In this retrospective study, complications of 359 talar lesions are studied. Secondary displacement occurred in 8%. Bone infection remained low in spite of frequent primary skin injury (20%). Bone fusion was slow but no case of non-union could be found. Avascular necrosis of the body or of the trochlea occurred in 33% but could be partially prevented by accurate reduction of the fractured bone. Osteoarthritis occurred in 33%.

Investigation of the blood-brain barrier for IgG in inflammatory syndromes of the central nervous system.

To investigate whether an intravenously administered compound of the IgG class is able to penetrate the CSF barrier despite its high molecular weight, 12 hepatitis B surface antibody (anti-HBs)-negative patients received 20 ml each of a beta-propiolactone-treated IgG compound with a high anti-HBs titer (1:115,000) as a marker. 8 had an inflammatory CSF syndrome. In cases of inflammatory CSF syndromes, significantly more marked IgG crossed the blood-brain barrier, this could be of considerable clinical importance.

Immune phenotype of canine hematopoietic progenitor cells.

The immune phenotype of canine hematopoietic progenitor cells was studied by immunoseparation and culturing of separated cells. Two separation methods were used, the magnetic cell sorting system (MACS) and the fluorescence activated cell sorter (FACS). For separation rat anti dog antibodies Dog 13 and Dog 14 directed against Thy-1, and Dog 26 as well as cross-reactive mouse anti human antibodies IOT2a and 7.2 directed against MHC class II were used. Separated cell populations were cultured in semisolid agar before and after long-term culture on a pre-established irradiated stromal cell layer. After 28 days, adherent and nonadherent cells were harvested from long-term culture. The MACS system allowed separation of cells into positive and negative fractions. Long-term culture-initiating cells (LTC-IC) were found in both the Thy-1+ and the Thy-1- fraction, but the content of LTC-IC was higher in the Thy-1+ fraction. The MACS system did not allow separation of progenitor cells according to the expression of MHC class II antigen detected by Dog 26 and the cross-reactive antibodies IOT2a and 7.2. In contrast to the MACS system the FACS allowed separation of negative, low-positive and high-positive cell populations. Low-positive fractions were well defined for Thy-1 and less well defined for MHC class II. CFU before and after long-term culture were exclusively observed in the low positive fraction (Thy-1(lo+)). Using MHC class II antibody Dog 26 LTC-IC were found mainly in the negative and low positive fraction, and CFU were observed mainly in the low and high positive fraction. In conclusion pluripotent canine hematopoietic precursor cells are low positive for Thy-1 and for MHC class II. In this respect canine hematopoietic progenitor cells are comparable to those of mouse and man.

Diminished cerebral metabolic response to motor stimulation in schizophrenics: a PET study.

Positron emission tomography (PET) and the deoxyglucose method were used to measure cerebral metabolism in 14 normals and 13 schizophrenics at rest and during performance of simple and complex finger-movement sequences. The normals, but not the schizophrenics, showed significant metabolic activation in mesial frontal and contralateral sensorimotor and premotor regions during the complex movement. The relative metabolism of schizophrenics was significantly lower than normal in frontal regions and higher than normal in thalamus and basal ganglia under all scanning conditions. The results suggest that schizophrenics may have a brain dysfunction which limits their capacity to produce a focal metabolic response to stimulation in several functionally distinct brain regions.

MeV ion jets from short-pulse-laser interaction with thin foils.

Collimated jets of carbon and fluorine ions up to 5 MeV/nucleon ( approximately 100 MeV) are observed from the rear surface of thin foils irradiated with laser intensities of up to 5 x 10 (19)W/cm(2). The normally dominant proton acceleration could be surpressed by removing the hydrocarbon contaminants by resistive heating. This inhibits screening effects and permits effective energy transfer and acceleration of other ion species. The acceleration dynamics and the spatiotemporal distributions of the accelerating E fields at the rear surface of the target are inferred from the detailed spectra.