Chronic parasite infection in mice induces brain granulomas and differentially alters brain nerve growth factor levels and thermal responses in paws

Schistosoma mansoni infection, both in humans and in animal models, is known to induce granulomas in the liver and intestine. It has also been reported that in humans the eggs of this parasite can reach the brain, causing psychiatric and neuropathological disorders. Whether this also occurs in rodents is unknown. To answer this question, mice were infected with this parasite and the central nervous system (CNS) examined at various time intervals. The results show that schistosomiasis induced granulomas in several regions of the CNS and increased nerve growth factor (NGF) levels in the cortex, hypothalamus and brain stem, but not in the hippocampus. The infection also caused paw hyperalgesia, as determined by the hot-plate test, and a local increase in NGF, but not in substance P. These findings indicate that the murine model of infection can be used for studying mechanisms leading to human neuroschistosomiasis and suggest that the neuropathological disorders and the sensory deficits observed in human schistosomiasis are associated with impaired levels of NGF in the peripheral and central nervous system. Received: 18 January 1996 / Revised, accepted: 16 April 1996     

Effect of 5-azacytidine on metallothionein inducibility and sensitivity to lethality of cadmium in rat osteosarcoma (ROS 17/2.8) cells.

ROS 17/2.8 cells, a cloned rat osteoblastic osteosarcoma cell line, were found to be extremely sensitive to the lethal effects of cadmium and to synthesize little, if any, metallothionein in response to cadmium exposure. Culture of cells for 24 h in the presence of 1 microM 5-azacytidine, a cytidine analog, increased the inducibility of metallothionein by cadmium and significantly reduced (P less than 0.001) cytotoxicity. Anion exchange chromatographic analysis of cadmium binding to low molecular mass cytotoxicity. Anion exchange chromatographic analysis of cadmium binding to low molecular mass cytosolic proteins showed that cells treated with cadmium and 5-azacytidine expressed at least 2 isoforms of metallothionein. One isoform of metallothionein with a low affinity for cadmium was constitutively expressed by these cells. The association of poor inducibility of metallothionein by cadmium with extreme sensitivity of cells to cadmium emphasizes the role of this protein in the cellular response to this toxic metal. The modulation of metallothionein inducibility and sensitivity to cadmium by 5-azacytidine treatment suggest that metallothionein gene structure and regulation are altered in ROS 17/2.8 cells.     

Psychotic symptoms and disorders and the risk of violent behaviour in the community

This study uses data from the Epidemiologic Catchment Area (ECA) surveys to examine the strength of the association between psychotic symptoms and violent behaviour, controlling for underlying mental disorder, substance abuse, sociodemographic characteristics and use of mental health services, in a representative sample of community residents. A replication is conducted of a study that found an increased risk of violence associated with a particular cluster of psychotic symptoms involving perceived threat and internal control-override (TCO). Respondents who reported TCO symptoms were about twice as likely to engage in assaultive behaviour as those with hallucinations or other psychotic symptoms, and about five times as likely as those with no mental disorder. The combination of substance use disorders with TCO symptoms added significantly to the risk of violent behaviour. Those with a history of using mental health services also posed a higher risk of violence, probably due to the differential selection of more severely ill and ‘dangerous’ individuals into treatment settings. Copyright © 1996 Whurr Publishers Ltd.     

Neuroendocrine and clinical effects of transdermal 17β-estradiol in postmenopausal women

The neuroendocrine and clinical effects of transdermal 17β-estradiol (rated at 50 μg/day; TTS 50) were studied in 40 postmenopausal women; ten additional postmenopausal women did not receive any drugs. The changes in LH and rectal temperature induced by the infusion of the opioid antagonist naloxone (10 mg i.v. bolus plus 10 mg/h for 4 h) were used to evaluate the central activity of endogenous opioid peptides. TTS 50 increased opioid activity, as evidenced by the restoration of the LH response (P < 0.01) and the enhancement of the hypothermic effect (P < 0.05) of naloxone. A greater reduction in hot flushes was observed in TTS 50-treated subjects than in untreated women, with the maximal effect of TTS 50 achieved after 3 months of therapy. TTS 50 did not modify the concentrations of circulating lipids, glucose or liver enzymes but reduced the biochemical parameters indicative of bone reabsorption. Bone density of the distal radius significantly increased during TTS 50 (P < 0.02), reaching its maximum value after 6 months of therapy. Thereafter bone density declined, but more slowly than in untreated women.

Our data suggest that TTS 50 has marked neuroendocrine effects, that it diminishes the incidence of hot flushes and reduces bone demineralization. By contrast, it has a very little, if any, metabolic impact on the liver or on glucose and lipid metabolism.     

IDENTIFICATION OF NEURODEVELOPMENTAL ABNORMALITY AT FOUR AND EIGHT MONTHS BY THE MOVEMENT ASSESSMENT OF INFANTS

The predictive validity of infant neuromotor evaluation by the Movement Assessment of Infants (MAI) was investigated in low-birthweight infants. Motor performance at four and eight months was examined in relation to neurodevelopmental outcome at 18 months of age. Correlations were equally strong between total MAI risk scores at four and eight months and performance on the Bayley Scales. Muscle tone observations were more discriminating at four months, and automatic reactions and volitional movement were most predictive at eight months. The MAI was highly sensitive to neurodevelopmental abnormality at four and eight months and more sensitive than the Bayley Motor Scale; both assessment tools had lower specificity at eight months. The high false-positive rate is attributed to transient neuromotor abnormalities and immaturity of motor function in low-birthweight infants with normal outcome.     

Management of status dystonicus: our experience and review of the literature.

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase-associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.     

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.

S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.     

The development of whole cell biosensors for on-line screening of herbicide pollution of surface waters

The use of mediator assisted amperometric whole-cell biosensors, monitoring microbial photosynthetic electron transfer, to screen for herbicides in intake protection by the water industry is described. Cells harvested from axenic cultures are loaded onto bacteriological filters and held against a working carbon electrode polarised against the silver chloride reference. Redox mediators are reduced by the microorganisms and then reoxidised at the working electrode resulting in a flow of current. For on-line applications the sensors are controlled by a programmable electrochemical analyser (Artek) and housed in specially designed perspex flow cells which incorporate light emitting diodes (LEDs) for photosynthetic stimulation. A range of cyanobacteria and algae have been tested, but biosensors incorporating unicellular cyanobacteria have proven the most successful. Results obtained using the cyanobacterium Synechococcus show detection levels of less than 200 ppb with response times of less than ten minutes for selected herbicides. Sensor stability in the absence of pollutant poisoning has been found to be greatly influenced by the choice of mediator. Membrane penetrating mediators such as -benzoquinone reduce sensor life to about 24 hours, while a sensor life of up to six days has been achieved with ferricyanide.     

Preclinical curriculum characteristics and institutional performance on NBME. Part I

A study was conducted that analyzed the relationship between various characteristics of the preclinical curriculum and institutional performance on the Part I examination of the National Board of Medical Examiners (NBME) at a sample of 85 U.S. medical schools. Total scheduled hours per week was the single curriculum characteristic having a positive and significant relationship with institutional NBME examination performance. However, when the data were controlled by medical school selectivity in admissions and institutional policy on the taking of the examination, total scheduled hours per week failed to make a significant contribution to the prediction of performance. The results were viewed as failing to provide support and justification for intense preclinical curriculum loads on the basis that this would enhance NBME examination performance. The authors conclude that simple comparisons of schools on the basis of mean NBME examination performance are meaningless unless the entering abilities of students and school policies on the examination are taken into account. The authors also suggest that those schools that prescribe heavy and intense preclinical curriculum loads should reexamine those policies in light of recommendations of the Project Panel on the General Professional Education of the Physician and College Preparation for Medicine.