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Biomedical subjects

P Marx

Publications and source records attributed to P Marx.

At least 19 recordsLinked to original sources

Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes.

The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. H-ICSBP shares high sequence homology with its murine cognate. The derived sequence of H-ICSBP reveals restricted homology within the first 120 amino acids to three other interferon regulatory factors, IRF-1, IRF-2, and ISGF3 gamma. Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. H-ICSBP is expressed exclusively in cell lines of hematopoietic origin. The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. Furthermore, either interferon-gamma (IFN-gamma) or IFN-beta can alleviate the repression mediated by ICSBP. Therefore, ICSBP may be involved in maintaining submaximal transcriptional activity of IFN-inducible genes in hematopoietic cells. IFN treatment would then alleviate repression allowing maximal transcriptional activity of these genes.

Amino Acid Sequence

Genital secretory immune response to chronic simian immunodeficiency virus (SIV) infection: a comparison between intravenously and genitally inoculated rhesus macaques.

The humoral and genital secretory immune response to chronic SIV infection was compared between female Rhesus macaques inoculated by i.v. or intravaginal routes. Total IgG levels in serum were 10-fold higher in SIV-infected animals when compared with uninfected controls. Vaginal washes from normal macaques contained predominantly IgA and IgG, while those from SIV-infected animals contained high levels of IgG. The SIV-infected animals had high titres of SIV-specific IgG in serum, with lower but detectable IgA and IgM responses. The genital secretory immune response to SIV was similar in intravenously and intravaginally inoculated animals. The anti-SIV response in the vaginal washes consisted mainly of IgG. Within the lamina propria of the reproductive tract of animals chronically infected with SIV there were essentially no IgA or IgG plasma cells and only a small number of IgM plasma cells, while two normal animals had large numbers of IgA plasma cells. These results suggest that the mucosal immune system of the female reproductive tract is impaired in chronic SIV infection.

Administration, Intravaginal

Thoracic splenosis presenting with hemoptysis.

Thoracic splenosis (post-traumatic autotransplantation of splenic tissue) is rare and generally asymptomatic. We report a patient with thoracic splenosis presenting with repeated hemoptysis. The blood supply of the hypervascular splenic transplants originated from a bronchial and an intercostal artery. Hemoptysis improved after surgical exeresis of splenosis. Recognizing splenosis presenting with hemoptysis is important, since percutaneous embolotherapy could be hazardous because of the risk of ectopic splenic tissue infarction.

Chronic Disease

2,5-Hexanedione is a potent gliatoxin in in-vitro cell cultures of the nervous system.

Of the metabolites of hexane, 2,5-hexanedione (2,5 HD) has the strongest neurotoxic effect. There is a wealth of experimental studies in animals showing an axonotoxic mechanism consisting of an accumulation of 10 nm neurofilaments. Only few studies deal with a possible action of 2,5-HD on Schwann cells, glia cells or both. Pure neurons, pure glia and mixed cultures prepared from dorsal root ganglia (DRG) of chick embryos were studied in this model. DRG were chosen because they constitute a linkage between the peripheral and central nervous system and provide the additional advantage of containing only few defined glial and neuronal cell types. Additionally, pure neuronal cultures of sympathetic ganglia and mixed cultures of spinal cord and brain were prepared. In cultures of the different parts of the nervous system investigated, we observed at a concentration of 0.25% 2,5-HD massive toxic alterations of glial cells, whereas neurons and neurites were virtually unaffected.

Animals

Specific neurotoxic effects of different organic solvents on dissociated cultures of the nervous system.

Pure neurons were prepared from dorsal root ganglia (DRG) of 8 day old chick embryos (E8). The substances tested in this model were pure n-hexane, 2.5-hexanedione (2.5 HD) and methyl-ethyl-ketone (MEK). Differentiated cultures were exposed to these neurotoxins after two days in culture and then examined over a period of up to one week. For all three substances a specific neurotoxic effect could be demonstrated: (i) n-Hexane mainly altered the neurites, leading to focal swellings and in a second step to degenerative changes in glial cells; (ii) 2.5 HD had a minor effect on neurons and proved to be mainly gliatoxic; (iii) MEK primarily affected the neurons by swelling and disintegration of the cell body.

Animals

[Diagnosis and prognosis of carotid artery stenosis].

The diagnosis of a carotid stenosis inevitably includes a neurological examination as well as CCT or MRI of the brain. Typical neurological and neuropsychological symptoms and signs as well as syndromes are described according to the vascular supply areas of the brain. CCT as well as MRI may identify cerebral infarction or other diseases and additionally give some information with regard to the underlying etiology or pathogenesis of an infarct. Satisfactory non-invasive demonstration of the carotid and vertebral arteries including their intracranial branches can be achieved by the use of sonographic methods (Dopplersonography, B-mode imaging, Duplex and colour-coded systems). Additionally, transcranial Dopplersonography is mandatory in most instances. Cerebral angiography is only justified preoperatively or for a disease which cannot be diagnosed reliably by other means, eg. cerebral venous thrombosis. The prognosis of a carotid stenosis depends not only on the degree of luminal narrowing and the shape of the stenosis but also on the clinical status of the patient (asymptomatic or symptomatic carotid stenosis, accompanying coronary artery disease etc.). Prophylactic treatment implies therapy of risk factors as well as antiaggregation, anticoagulation and carotid endarterectomy in selected cases.

Carotid Stenosis

Neurological deterioration under isovolemic hemodilution with hydroxyethyl starch in acute cerebral ischemia.

In a prospective study, we randomly allocated 70 patients with acute ischemic stroke to two therapy groups. Up to interim analysis, 33 patients underwent bloodletting, with simultaneous infusion of an identical volume of hydroxyethyl starch (10%, 200/0.5). The target hematocrit was 35%. A control group of 37 patients did not receive hemodilution. Apart from an unequal sex distribution, the two groups were comparable with regard to age, cardiovascular risk factors, and medical history. In the hemodilution group, the mean hematocrit fell from 44.4% to 37.7%. After 14 days, improvement on the neurological score scale was 3.3 points in the hemodilution group compared with 6.5 points in the control group (p = 0.12). Subgroups with early inclusion (less than 12 hours) or pronounced lowering of hematocrit (greater than 15% of initial hematocrit) also did not profit from hemodilution. Clinical deterioration observed in eight hemodilution group patients (p less than 0.01) led to discontinuation of the study for ethical reasons.

Adolescent

[Obstruction of pulmonary arteries. Contribution of the scanner and MRI. Apropos of 10 cases].

We present a retrospective study of ten patients presenting non specific clinical manifestations in whom the diagnosis of pulmonary embolism was documented by CT scan and/or MRI. Results of CT scan and/or MRI were compared to DSA bi-selective pulmonary angiography findings. In a large number of cases, CT scan and MRI allowed the detection of the obstruction within the right and left pulmonary arteries (RPA and LPA). Although these techniques did not permit the diagnosis of peripheral clots, pulmonary infarcts were usually depicted by these two procedures. CT scan and/or MRI could be performed as first-line investigations in case of atypical clinical symptoms because of their high relevance for proximal pulmonary artery obstruction, although these two non-invasive procedures cannot indicate the aetiology of the obstruction etiology.

Evaluation Studies as Topic

Brain stem mechanism in ocular motor function.

The progress of clinical and experimental neuro-ophthalmology during the last two decades was reviewed. The ocular motor system in the brain stem was described firstly based on anatomical, neurophysiological and clinical evidences. Clinical syndromes in cerebrovascular brain stem impairments which present ocular motor dysfunction were analyzed briefly.

Animals

[Therapeutic concept in asymptomatic carotid stenosis: surgical indications from the neurologic viewpoint in comparison with spontaneous course].

The annual risk of stroke from asymptomatic carotid stenosis is about 0.5-2.5%. After successful carotid endarterectomy (CEA) the risk of suffering a stroke amounts to about 2% per year. CEA therefore seems to impose an unnecessary risk upon the patient. However, a stenosis with more than 80% luminal narrowing, a rapidly progressing stenosis, and ulcers may increase the spontaneous risk and should be evaluated in randomized studies. The same applies to prophylactic CEA of asymptomatic stenosis before major cardiac or vascular surgery.

Carotid Stenosis

[Perforation of a loop of the small intestine by a Kim-Ray Greenfield endocaval filter. Report of a case].

Kim-Ray filter complications are usually benign, such as angulation or slight migration. We report and compare with the literature one case of vena cava perforation associated with a small bowel lesion. The follow-up with regular abdominal plain X-rays allows detection of filter angulation, the first step before vena cava perforation. Cavography or CT scan depicts this perforation. Complete or partial surgical removal of the filter may be necessary.

Adult

[Carotid endarterectomy. A justifiable risk for the prevention of ischemic infarct?].

Defining the position of carotid endarteriectomy (CEA) is difficult, since the average mortality and morbidity risk of this procedure--an estimated 10% or so overall in the USA--is apparently much higher than is achievable in highly specialized centers or is indicated by uncontrolled studies. No clear indication is recognizable for asymptomatic stenoses. Possible exceptions are rapidly progressing and high-grade stenoses. Prophylactic CEA within the framework of major surgical interventions increases the risk of perioperative stroke. In the event of transient ischemic attacks (TIA), carotid endarteriectomy is justifiable when cardiac sources of embolism, severe intracranial vascular stenoses and a predominantly cerebral microangiopathy have all been excluded, as also internistic and neurological disorders that increase the risks of surgery. In the acute insult stage, CEA increases mortality severalfold, and is therefore contraindicated.

Carotid Artery Diseases

[Ulcero-mutilating acro-osteopathy in hereditary neuropathies. Differential diagnosis and pathogenesis].

Two patients, aged 51 and 70 years, had indolent ulcerations at the sole of the foot with destructive osteolysis in the bones of the feet, lesions characteristic of mutilating ulcerative acro-osteopathy. Patient 1, who had pes cavus, developed ulcerations on the balls of the feet along the second metatarsal bones, and patient 2 with pes equinovarus developed ulcers in the area of the calcaneus. Sock-like hypesthesia/hypalgesia from the toes to the ankles was present in both patients, and electrophysiological tests confirmed the presence of axonal sensory-motor neuropathy. Diabetes mellitus and alcohol abuse was excluded in both patient. Clinical findings, history and neurological disturbances in both patients identified the disease as hereditary sensory neuropathy (type I).

Aged

The value of diagnostic procedures in treating ischemic attacks and stroke.

Diagnostic procedures for cerebral ischemia make clear strategies mandatory. Careful recording of case history, internal and neurological investigation either substantiate or make unlikely TIA and stroke. CT scan not only differentiates bleedings, tumors etc from ischemia but also can give very valuable information about the underlying vascular pathology. Multiple lacunes are characteristic of cerebral microangiopathy. Territorial and branch occlusion infarcts mostly indicate embolic occlusion of pial vessels from either cardiac or arterial sources. Endzone and borderline infarctions are seen with high grade stenosis or occlusion of the internal carotid artery. The identification of embolic sources necessitates cardiological (including echocardiography) and angiological (Doppler sonography and in selected cases angiography) investigations. Therapeutic and prophylactic measures depend on the etiology of TIA and stroke and are briefly dealt with.

Carotid Arteries

Postexposure immunotherapy of simian immunodeficiency virus (SIV) infected rhesus with an SIV immunogen.

An inactivated whole simian immunodeficiency virus (SIV) immunogen given to healthy, seropositive rhesus macaques 4 months after infection had no effect on the humoral immune response to SIV, the presence of antigenemia, cell-associated viremia, or disease course. Further immunotherapeutic trials in this highly susceptible animal model should be carried out sooner after exposure, before significant loss of CD4 cells has occurred. The SIV infected macaque model will continue to serve an essential role in development and testing of anti-AIDS drugs and immunogens.

Animals

[The effect of blood glucose on the course of cerebral ischemia].

Experimental und clinical data suggest a negative influence of diabetes mellitus and hyperglycemia on the outcome of cerebral ischemia. In a retrospective analysis of 135 consecutive patients with cerebral ischemia we found more severe clinical defects in diabetics and patients with initial hyperglycemia but without previously known diabetes mellitus than in patients with initial normoglycemia. This was especially true for blood glucose above 10 mmol/l. Before drawing therapeutic conclusions, further prospective studies are necessary.

Aged