Familial Sneddon's syndrome

We report the familial occurrence and apparent autosomal dominant inheritance of Sneddon's syndrome with variable clinical expression. The proband, a 40-year-old woman, presented with livedo reticularis and progressive neurological deterioration following a stroke. The diagnosis was confirmed by cerebral angiogram and skin biopsy, both showing the characteristic findings. Two of the patient's sisters were reported to have been similarly affected in the past. Her mother, two additional siblings and five of her seven children exhibited various vasospastic skin phenomena. Familial aggregation of this disorder may be common and a genetic basis may be involved in its pathogenesis.     

Combined action of phthalocyanine photosensitization and gamma-radiation on mammalian cells

The response of Chinese hamster cells and human lymphocytes to the combined action of photosensitization by chloroaluminium phthalocyanine tetrasulfonate and gamma-radiation was studied using colony-forming ability and [3H]thymidine incorporation following mitogenic stimulation respectively, as endpoints. The action of both treatments was usually additive regardless of the sequence of application. However, in human lymphocytes irradiated at low temperature, the photosensitization interacted synergistically with the subsequent ionizing radiation; in this experiment the initial photosensitization reduced the yield of micronuclei produced by gamma-radiation.     

Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice.

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.     

Effects of the soluble low-molecular-mass proteins on spleen activity and cellular composition of infiltrates in rat mammary gland tumors

We showed previously that soluble low-molecular-mass tumor-associated antigens (TAA) could suppress chemically-induced tumorigenesis. In this study, we analyzed the mechanism of those findings. Studies were performed on the spleen and mammary gland tumors obtained from the following groups of rats: i) control rats treated with dimethyl-benz(alpha)antracene (DMBA), ii) vaccinated and carcinogen-treated rats with non regressed tumors, iii) vaccinated and carcinogen-treated rats with regressed tumors. Different zones of the spleen and tumors and their cellular content (Ki67+ and CD8+ cells, and macrophages) were analyzed morphometrically and immunohistochemically. Reaction of the spleen to vaccination was manifested in a significant increase in all areas of the white pulp and in a decrease in the size of the red pulp. The total number of cells in the white pulp (germinal center and PALS) and in the marginal zone was significantly higher in the spleen of rats with regressed tumors. The number of Ki67+ cells decreased significantly in both groups of vaccinated rats, but most prominently in the marginal zone and the red pulp in rats with regressed tumors. An increased number of CD8+ lymphocytes and macrophages was also seen in the red pulp. Different areas of the tumors (peripheral vs. inside at depth) showed different responses to vaccination and this difference was related to conditions of carcinogenesis, i.e. non-regressed vs. regressed tumors. In regressed tumors, all parameters studied were easily distinguishable in both areas of the tumors, while in non-regressed tumors, a marked distinction was seen only at their periphery. In regressed tumors, a negative correlation was seen at depth tumors between the number of Ki67+ cells and the number of CD8+ lymphocytes (r=-0.48). The findings indicated a strict antitumor effect of vaccination with the soluble low-molecular-mass TAA, which prevents the development of insufficiency of the immune system when an intensive immune reaction takes place.     

Subcellular morphological changes in the rat kidney after phosphorus burn.

Experimental phosphorus burns were performed on male rats, in order to evaluate the subcellular changes which had occurred as a result of their lesions. In addition to the external wound caused by the burn itself, pathological changes were observed macroscopically and microscopically in various body organs, mainly the kidneys. These were investigated under the electron microscope for subcellular alterations at their damaged sites, and for biochemical aberrations that were observed in those rats. In the phosphorus-burnt rats the glomeruli were ischemic, showed capillary collapse and exhibited proliferation of mesangial areas and basement membrane thickening. Many necrotic cells were observed in the proximal tubule, where large vacuoles containing myelin-like structures were identified. The lumen of the proximal tubules were completely occluded by cell debris and the cytoplasm was necrotic. Due to the damage caused to the glomeruli, high concentrations of serum urea, serum SGPT and PO-4 were assayed in the phosphorus-burnt rats. These changes may account for the high mortality rate after phosphorus burns and may further understanding of the damage as well as ways of approaching it.     

HSV-1 virulence for mice by the intracerebral route is encoded by the BamHI-L DNA fragment containing the cell fusion gene

Summary The phenotype of pathogenicity by direct intracerebral inoculation of herpes simplex virus type 1 (HSV-1) was mapped in the viral genome. This phenotype could be rescued by cotransfection of unit length HSV-1 DNA of an avirulent strain with the BamHI fragment L (0.70–0.738 map units) cloned from a virulent strain. The virulence function was localized in the 2.0 Kb NruI-BamHI fragment in the right-hand side of BamHI-L, the same region that encodes a virus cell-fusion gene (3). Transduction of virulence was linked with the phenotype of a larger plaque size. It is concluded that a neurovirulence function resides in the BamHI-L fragment of the HSV-1 genome, closely linked to the viral gene for cell fusion.     

Gene dosage and down's syndrome: Metabolic and enzymatic changes in PC12 cells overexpressing transfected human liver-type phosphofructokinase

Down's syndrome (DS) is a human genetic disease caused by triplication of the distal third of chromosome 21 and overexpression of an unknown number of genes residing in it. The gene for the liver-type subunit of phosphofructokinase (PFKL), a key glycolytic enzyme, maps to this region and the product is overproduced in DS erythrocytes and fibroblasts. These facts, together with abnormalities which occur in DS glycolysis, make PFKL overexpression a candidate for causing some aspects of the DS phenotype. A cellular model for examining the consequences of PFKL overexpression in DS was constructed by transfecting rat PC12 cells with the human PFKL cDNA. Phosphofructokinase (PFK) isolated from PFKL-overexpressing clones was more inhibited by ATP and citrate and less activated by fructose-6-phosphate than control PFK; similar results were obtained when PFK preparations from DS and control fibroblasts were compared. In vivo NMR measurements determined that cells overexpressing PFKL performed glycolysis 40% faster than controls. These results show that overexpression of PFKL is the cause for altered biochemical regulatory characteristics of PFK in DS fibroblasts and can result in enhancement of glycolysis rates. It is also shown that increased gene dosage can exert its influence not merely by enhancing the amounts of gene products but also by altering their biochemical nature.     

Prognostic factors in artificially ventilated stroke patients

OBJECTIVES: To evaluate the reasons for implementing artificial ventilation (AV) in patients with acute ischemic stroke (AIS), determine their outcome and characterize prognostic variables in these patients. METHODS: Consecutive patients presenting with AIS were evaluated. All patients who received AV were treated in a neurological semi-intensive care setting. RESULTS: Of the 173 patients included in the study, 27 (16%) needed AV, 16 (9%) received AV and five of these patients (31%) survived. The mean NIH stroke scale score prior to AV was 14.5+/-5.6 (vs. 9.1+/-6.2 in non-intubated patients, P=0.001). Six patients were ventilated because of neurological deterioration. Most of these patients had large hemispheric infarctions with evident herniation and midline shift on CT scans. The only one who survived the acute hospitalization did not recover and died within 3 months. In the other 10 patients, AV was instituted during cardiopulmonary decompensation (CPD). These patients generally fared better; four of them survived and were discharged after a lengthier hospital stay when compared to non-intubated patients. Variables associated with survival among intubated patients were a lower neurological disability score on admission and on day 7 after the stroke, and intubation during CPD. CONCLUSIONS: Implementing AV in semi-intensive care settings does not seem to improve survival in AIS patients with neurological deterioration. Stroke patients who need AV during CPD and those that have less severe neurological deficits may have better chances for survival.     

Susac syndrome.

OBJECTIVE: The objective of this study was to describe the clinical manifestations; radiographic, audiometric, and retinal fluorescein angiography findings; pathogenesis and treatment of Susac syndrome with review of the literature. STUDY DESIGN: We conducted a retrospective case review. SETTING: This study was conducted at a tertiary referral center. PATIENT: A 50-year-old woman presented with recurrent episodes of neurologic symptoms, bilateral sensorineural hearing loss, and silent retinal artery occlusion. INTERVENTIONS: The patient underwent complete evaluation, including magnetic resonance image studies, audiometric tests, and retinal fluorescein angiography. She was treated initially with corticosteroids and later with other immunosuppressive agents. RESULTS: The patient was initially diagnosed with left sudden sensorineural hearing loss. Despite comprehensive clinical and laboratory studies that did not reveal systemic disease, 3 weeks later, the patient developed vertigo, sensorineural hearing loss, and tinnitus in the opposite ear. The neurologic involvement and the bilateral audiologic manifestations raised the possibility of Susac syndrome. CONCLUSION: Susac syndrome is a rare disorder of unknown origin characterized by the triad of encephalopathy, fluctuating hearing loss, and visual loss resulting from microangiopathy of the brain, cochlea, and retina. The multiple organ involvement seen in Susac syndrome raises a differential diagnosis ranging from autoimmune disease, through systemic vasculitis, to multiple sclerosis. Otolaryngologists should be aware of this syndrome as a result of the vestibulocochlear manifestations and the multidisciplinary evaluation that is required.     

Successful delivery following myocardial ischemia during the second trimester of pregnancy

Acute myocardial infarction during pregnancy is considered to be associated with approximately 50% mortality of both mother and fetus. However, there are not enough data regarding the role of acute myocardial ischemia. We present a 36-year-old, pregnant, white female who was admitted twice at 18 and 20 weeks of gestation with acute myocardial ischemia. Cardiac catheterization revealed 70–80% stenosis of the mid left anterior descending artery (LAD) with normal antegrade flow and very good retrograde filling of the LAD from distal collaterals of the right coronary artery. Therefore, due to angiographic suggestion of protected LAD territory, we recommended medical therapy and scheduled a vaginal delivery that was successfully completed without cardiovascular complications. A stress thallium test performed 6 months later was normal, supporting our clinical judgment. In conclusion, every case of a pregnant woman with coronary insufficiency should be treated according to individual coronary anatomy and blood supply to the territory of the diseased artery, and should not be based on the old data in the literature. The decision for revascularization prior to delivery versus medical therapy, or Caesarean section versus natural delivery, should be made by a team of a cardiologist and an obstetrician.