Ultrastructural studies on the localization of IgG in the aortic endothelium and subendothelial intima of atherosclerotic and nonatherosclerotic rabbits

Immunoelectron microscopy with peroxidase-conjugated Fab fragments of anti-IgG was used for studying the localization of IgG in the aortic endothelium and subendothelial intima of atherosclerotic and nonatherosclerotic rabbits. Small amounts of IgG were found in the cell coat, in caveolae and vesicles, and also in intercellular clefts of endothelial cells from normocholesterolemic rabbits. Injured endothelial cells exhibited prominent accumulations of IgG in the cytoplasmic matrix, possibly due to leakage through plasma membrane defects. In atherosclerotic lesions from hypercholesterolemic rabbits, there was a striking increase in the amount of IgG-reactive material in the cell coat and vesicles of intact endothelial cells. Also in these animals, injured endothelial cells were characterized by a cytoplasmic IgG accumulation. There were prominent IgG depositions in the subendothelial zone of the lesions. IgG was adhering to collagen fibers, and also coating the surfaces of subendothelial foam cells. The pathophysiological significance of an interaction between such intimal IgG and phagocytes is discussed.     

Somatotopic organization along the central sulcus, for pain localization in humans, as revealed by positron emission tomography

Regional cerebral blood flow was measured with positron emission tomography (PET) in six healthy volunteers at rest and during experimentally induced, sustained cutaneous pain on the dorsum of the right hand or on the dorsum of the right foot. Pain was inflicted by intracutaneous injection of capsaicin, providing a mainly C-fibre nociceptive stimulus. Statistical analysis showed significant activations along the central sulcus (SI) area when comparing pain in the hand to pain in the foot. Separate comparison of both pain states to a baseline revealed different locations along the central sulcus for hand pain and foot pain. The encountered differences are consistent with what is previously known about the somatotopics of non-painful stimuli. When comparing painful stimuli to baseline, the contralateral anterior cingulate gyrus, the ipsilateral anterior insular cortex and the ipsilateral prefrontal cortex were implicated. The results are consistent with an involvement of SI in the spatial discrimination of acute cutaneous pain. Received: 17 October 1996 / Accepted: 12 May 1997     

Evidence from twins for acquired cellular immune hyperactivity in type 1 diabetes

Type 1 diabetes has been associated with an increased frequency of activated T cells and T-cell hyperactivity to non-specific and disease-specific stimuli including the islet autoantigen glutamic acid decarboxylase 65 (GAD). To address whether T-cell hyperactivity is genetic or acquired we measured whole blood cytokines in vitro in response to GAD or tetanus in 18 identical twin pairs, nine discordant for type 1 diabetes. In addition, the activity of 2', 5' oligoadenylate synthetase (OAS) in blood mononuclear cells was measured as a marker of viral infection. Interleukin-2 (IL-2) basally and IL-2 and interferon-gamma (IFN-gamma) in response to GAD, were detected more frequently and at higher levels in diabetic compared to non-diabetic twins. IL-10 was not different between groups. OAS activity was increased in diabetic compared to non-diabetic twins and showed a correlation with basal IL-2 and GAD-stimulated IFN-gamma and IL-10. These findings suggest that T-cell hyperactivity in type 1 diabetes is an acquired trait and could reflect persisting virus expression.     

Extended voluntary running inhibits exercise-induced adult hippocampal progenitor proliferation in the spontaneously hypertensive rat

Previous work has shown that voluntary running increases cell proliferation and neurogenesis in the dentate gyrus of the adult hippocampus. Here we report that long-term running for 24 days results in a down-regulation of hippocampal progenitor proliferation to one-half the level of nonrunning controls compared with a fivefold increase in progenitor proliferation seen after 9 days of voluntary running (short-term running). The negative effects seen on proliferation after 24 days of running were prevented by restricting daily running distances (by 30-50%) during 24 days. Long-term running for 24 days increases the response of the hypothalamic-pituitary-adrenal axis, with an increase in adrenal gland weight and increased plasma corticosterone levels, as well as decreased thymus weight, indicating a stress response as a possible mediator of decreased progenitor proliferation. Furthermore, the negative effects seen on the observed stress response after 24 days of running were prevented by restricting daily running distance. Short-term running did not alter these stress parameters compared with nonrunning controls. However, it increased phosphorylated cyclic AMP response element binding protein (pCREB) in the dentate gyrus, an increase that was not seen in nonrunning controls or after 24 days of running. Taken together, these data suggest that voluntary running does not always enhance proliferation and that the decrease in progenitor proliferation seen in long-term running is possibly mediated by mechanisms involving a stress response in the animal. However, a moderate level of long-term running was able to prevent the negative stress-related changes seen in unrestricted long-term running.     

High frequency of parvovirus B19 DNA in bone marrow samples from rheumatic patients.

BACKGROUND: Human parvovirus B19 (B19) polymerase chain reaction (PCR) is now a routine analysis and serves as a diagnostic marker as well as a complement or alternative to B19 serology. The clinical significance of a positive B19 DNA finding is however dependent on the type of tissue or body fluid analysed and of the immune status of the patient. OBJECTIVES: To analyse the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients. STUDY DESIGN: Parvovirus B19 DNA was analysed in paired bone marrow and serum samples by nested PCR technique. Serum was also analysed for B19-specific IgG and IgM antibodies and the results were compared with clinical and epidemiological data. RESULTS AND CONCLUSIONS: B19 IgG was found in 41 of 50 patients (82%) whereas none was B19 IgM positive. The serologic evaluation showed that none of the patients had acute B19 infection. However, B19 DNA was detected by PCR in 13 of 50 (26%) bone marrow samples from these patients indicating a high frequency of persistent infection compared with previous reports of patient groups and healthy controls. In the study, 22 patients had rheumatoid arthritis (RA) and 7 of these RA patients were B19 DNA positive in bone marrow. Rheumatoid factor was positive in 4 of the 7 B19 DNA positive RA patients as compared with Rheumatoid factor positivity in all of the 15 B19 DNA negative RA patients. Erosive arthritis in X-ray was less common in the B19 DNA positive group than in the B19 DNA negative group. A high frequency of parvovirus B19 DNA was thus detected in bone marrow samples in rheumatic patients. The clinical data does not support a direct association between B19 PCR positivity and rheumatic disease manifestation. Therefore, the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients must be interpreted with caution.     

Evidence for the involvement of the posterior parietal cortex in coordination of fingertip forces for grasp stability in manipulation

Grasp stability during object manipulation is achieved by the grip forces applied normal to the grasped surfaces increasing and decreasing in phase with increases and decreases of destabilizing load forces applied tangential to the grasped surfaces. This force coordination requires that the CNS anticipates the grip forces that match the requirements imposed by the self-generated load forces. Here, we use functional MRI (fMRI) to study neural correlates of the grip-load force coordination in a grip-load force task in which six healthy humans attempted to lift an immovable test object held between the tips of the right index finger and thumb. The recorded brain activity was compared with the brain activity obtained in two control tasks in which the same pair of digits generated forces with similar time courses and magnitudes; i.e., a grip force task where the subjects only pinched the object and did not apply load forces, and a load force task, in which the subjects applied vertical forces to the object without generating grip forces. Thus neither the load force task nor the grip force task involved coordinated grip-load forces, but together they involved the same grip force and load force output. We found that the grip-load force task was specifically associated with activation of a section of the right intraparietal cortex, which is the first evidence for involvement of the posterior parietal cortex in the sensorimotor control of coordinated grip and load forces in manipulation. We suggest that this area might represents a node in the network of cortical and subcortical regions that implement anticipatory control of fingertip forces for grasp stability.     

Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE

Background  

The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS) in multiple sclerosis (MS) and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE). While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions.     

Twenty-five years after Billroth II gastrectomy for duodenal ulcer

One thousand twenty-five patients underwent a Billroth II resection for duodenal ulcer between 1948 and 1956. The operative mortality rate was 2.4%. At follow-up between 22 and 30 years later, 522 had died and 423 patients were traced. Recurrent ulcer appeared in 2.6% of the cases. Postgastrectomy symptoms occurred with the following frequency: dumping 10%, diarrhea 5%, vomiting 7%, and pain 4%. Anemia developed in 18%, hypoalbuminemia and hypocalcemia in 40 and 15%, respectively. Eleven percent had lost more than 10 kg in weight. Tuberculosis was found in 3% of the cases. While 90% of the patients were satisfied with the result, 10% were failures. The overall mortality rate was significantly increased because of suicide. Gastric carcinoma was the cause of death no more often than expected.

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Resumen En años anteriores la gastrectomía Billroth II fue un procedimiento operatorio de uso común en el tratamiento de la úlcera duodenal. Los promisorios resultados de la vagotomía con drenaje, vagotomía y antrectomía y, especialmente, la vagotomía de células parietales han reducido el rol de la resección de tipo Bilroth II. El propósito del presente estudio es describir los resultados a largo plazo en un grupo de pacientes sometidos a gastrectomía Billroth II por úlcera duodenal aproximadamente 25 años antes.Entre 1948 y 1956, 1 025 pacientes consecutivos, 810 hombres y 190 mujeres, fueron sometidos a resección Billroth II por úlcera duodenal. La mortalidad operatoria fué de 2,4%. Durante el período de seguimiento entre 22 y 30 años, 522 pacientes habían muerto y 423 pacientes pudieron ser ubicados para seguimiento. Síntomas de post-gastrectomía fueron observados con la incidencia siguiente: dumping 10%, diarrea 5%, vómito 7% y dolor 4%. La anemia se presentó en el 18%, hipoalbuminemia e hipocalcemia en el 40% y en el 15% respectivamente. Se presentó tuberculosis en el 3% de los casos. El 90% de los pacientes se mostraron satisfechos con el resultado de la operación, pero el 10% restante indicó la falla del tratamiento. La mortalidad global resultó significativamente incrementada debido a una alta incidencia de suicidio. El carcinoma gástrico fue causa de muerte con una frecuencia no aumentada, o sea que no se encontró un mayor riesgo de muerte por carcinoma de esófago o del remanente gástrico.

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Résumé De 1948 à 1956, 1 025 malades atteints d'ulcère duodénal ont subi une opération de Billroth II. La mortalité a été de 2,4%. Au cours de l'évolution de 22 à 30 ans après l'intervention, 522 opérés sont décédés et 423 ont été suivis. La fréquence de la récidive a été de 2,6%. Les symptômes après gastrectomie ont atteint les taux suivants: dumping 10%, diarrhée 5%, vomissements 7%, douleur 4%. L'anémie a été constatée dans 18% des cas, l'hypoalbuminémie dans 40% des cas et l'hypocalcémie dans 15% des cas, onze pour cent des opérés ont accusé une chute pondérale supérieure à 10 kg; 3% ont présenté une tuberculose. Au total 90% des malades se sont déclarés satisfaits de l'intervention, encore que certains opérés se soient suicidés, ce nombre intervenant dans la mortalité globale. La mortalité par cancer n'a pas dépassé le taux accusé par la population en général.

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Supported by grants from the Danish Medical Research Council (No. 512-8760) and Købmand i Odense Johann & Hanne Weimann, født Seedorffs legat.