Herpes simplex virus type 1 infections: the fate of CNS cells.
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Encephalitis↗
Biomedical subjects
A C Peters
Publications and source records attributed to A C Peters.
Interphase cytogenetic analysis of gliomas.
Interphase cytogenetics is the application of nonradioactive in situ hybridization with chromosome-specific DNA probes to interphase nuclei. The possibilities and limitations of this new technique for the study of chromosomal aberrations in gliomas are discussed.
Brain Neoplasms↗
Follow-up magnetic resonance imaging in Hallervorden-Spatz disease.
Bilateral high signal emitting areas in the globus pallidus surrounded by low signal emitting areas have been described as a typical MRI finding in Hallervorden-Spatz disease (HSD). We made a diagnosis of HSD in an 11-year-old girl with progressive dystonia of 4 years duration who showed these typical MRI abnormalities. An initial MRI at the age of 9 was normal. Pathological confirmation of these typical MRI findings has not yet been described, but earlier reports as well as our case suggest that MRI may be helpful in making a clinical diagnosis of HSD. This case further shows that MRI may be normal in an early stage of the disease.
Child↗
Increased neurotoxicity of arsenic in methylenetetrahydrofolate reductase deficiency.
A 16-year-old girl from Surinam presented with mental deterioration and severe paraparesis with areflexia and bilateral Babinski signs. Laboratory examination showed a hyperhomocysteinemia that was caused by 5,10-methylene-tetrahydrofolate reductase (MTHFR) deficiency. In addition, urine samples contained large amounts of arsenic. An open bag with the pesticide copper acetate arsenite was found to be the source of exposure. In remethylation defects such as MTHFR deficiency, the concentration of methyldonors is severely reduced. As arsenic is detoxified by methylation, we suggest that the MTHFR deficiency in this girl might explain the fact that of all family members exposed to arsenic, only she developed severe clinical signs and symptoms of arsenic poisoning.
Adolescent↗
Conventional and controlled release valproate in children with epilepsy: a cross-over study comparing plasma levels and cognitive performances.
We studied plasma levels and behavioural effects of a newly developed controlled release formulation of valproate (VPA-CR) in children with epilepsy. Valproate plasma levels and performances in attention and vigilance tasks were monitored during a 12-h period (daytime), both during monotherapy of conventional valproate (VPA) and 4 weeks after switching to a similar dosage of VPA-CR taken once daily. There was no significant difference between the two formulations with respect to mean diurnal trough and peak valproate plasma levels, and to mean fluctuation. The significantly higher Cmax/Cmin ratio during VPA-CR seems mainly due to low valproate plasma levels early in the morning. Neuropsychological assessment showed no significant differences, either between patients and controls, or within patients and controls when comparing the results obtained on the VPA and VPA-CR day. During both VPA and VPA-CR treatment, no correlation was found between cognitive performance and valproate plasma levels. The advantage of VPA-CR is that the once daily regimen may increase compliance and is more convenient for schoolchildren.
Adolescent↗
Interphase cytogenetics: a new tool for the study of genetic changes in brain tumors.
Interphase cytogenetics is the application of nonradioactive in situ hybridization with chromosome-specific DNA probes to interphase nuclei. In this study, interphase cytogenetics was used to investigate 66 primary brain tumors (33 gliomas, 30 meningiomas, and three medulloblastomas) for numerical chromosomal aberrations of chromosomes 1, 6, 7, 10, 11, 17, 18, X, and Y. Of the 33 gliomas (17 astrocytomas grades II, III, and IV, five oligoastrocytomas, seven oligodendrogliomas, and four ependymal tumors), 22 were near diploid, while the remaining 11 showed a significant triploid or tetraploid component. The predominant specific aberrations in gliomas were an over-representation of chromosome 7 (13 cases) and an under-representation of chromosome 10 (16 cases). These changes were observed in grade III and grade IV astrocytomas, as well as in oligodendrogliomas. Other frequent numerical changes were a gain of chromosome 17 (six cases) and a loss of chromosome 18 (seven cases). This loss of chromosome 18 seemed relatively specific for gliomas with an oligodendroglial component (six cases). Only two of 33 gliomas displayed no genetic abnormality with the probes used. Seven patients with astrocytomas died of their brain tumor during the clinical follow-up period. Their astrocytomas did not show a different chromosomal constitution compared to the other gliomas. For the meningiomas, the probe panel was extended with a probe specific for chromosome 22. Loss of chromosome 22 was obvious in 21 of the 30 meningiomas, and was the sole abnormality in 11 meningiomas; in the other 10, this loss was associated with other chromosomal changes. Five of these tumors with additional aberrations were recurrent or atypical meningiomas. It is suggested that interphase cytogenetics can contribute to a better understanding of the biological behavior of these tumors and possibly result in better insights into prognosis and strategies for therapy.
Adult↗
Effects of salt concentration on bacterial growth on plates with gradients of pH and temperature.
A temperature gradient device has been used to produce pH-temperature gradient plates. The response of Salmonella typhimurium and Bacillus cereus to continuous gradients of pH and temperature has been mapped. A third variable, sodium chloride, was investigated by incorporating it at different concentrations in a series of gradient plates. Both organisms exhibited an optimum temperature and pH range for maximum salt tolerance.
Bacillus cereus↗
Follow-up of intractable seizures in childhood.
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Anticonvulsants↗
Interphase cytogenetics of brain tumors.
The development and application of a procedure for interphase cytogenetics on brain tumor material is described. Nuclei isolated from freshly removed brain tumor tissue were investigated for chromosomal aberrations by nonradioactive in situ hybridization with a panel of chromosome-specific probes. The panel consisted of nine satellite DNA probes specific for the centromeric regions of chromosomes 1, 6, 7, 10, 11, 17, 18, X, and Y. For each probe, the number of hybridization signals per cell was determined in 200 nuclei. It was inferred from the hybridization results that in 11 gliomas (seven astrocytomas grade II-IV, three oligodendrogliomas, and one ependymoma) the numerical aberrations were gains of chromosomes 1 (once), 7 (twice), 10 (once), 11 (twice), and X (twice); losses of chromosomes 1 (once), 10 (twice), 17 (twice), and Y (once); and complete tetraploidy (once). Among the 18 investigated meningiomas monosomy 18 and trisomy 17 were observed once and twice, respectively. An additional hybridization with a cosmid probe for the BCR gene on 22q11 indicated monosomy 22q in 11 meningiomas. These results show the value of interphase cytogenetics for the analysis of solid tumors for which it is relatively difficult to obtain sufficient metaphases of good quality for conventional cytogenetics.
Adult↗
Polymerase chain reaction for early detection of HSV-DNA in cerebrospinal fluid: an experimental mouse encephalitis study.
A series of experiments was carried out using a mouse HSV-1 encephalitis model for detecting HSV-DNA in CSF by the polymerase chain reaction (PCR). The results were correlated with the time period after corneal inoculation, clinical signs and symptoms, and progression of infection in brain tissue (antigen detection and histopathology), and were compared with virus isolation by spin-amplified culture (SAC/IF). The PCR proved to be superior to SAC/IF, both with respect to early detection and the percentage of positive samples. The results of PCR did not correlate with signs of disease, nor with the interval post-inoculation. A correlation with the spread of HSV within the brain tissue was found. The possible pathways for virus spread from brain parenchyma to the CSF as well as a possible explanation for the low amounts of virus and viral-DNA within the CSF are discussed.
Animals↗
An investigation of the effects of four variables on the growth of Salmonella typhimurium using two types of gradient gel plates.
The effect of four variables (pH, temperature, sodium chloride concentration and sodium nitrite concentration) on the growth of Salmonella typhimurium CRA663 was investigated using a two-dimensional gradient gel technique. Two methods were used. In the first method the gradients comprised NaCl and pH and in the second method a temperature gradient incubator was used to produce a temperature-pH gradient. Using image analysis, the growth on the plates was depicted as three-dimensional wire frame graphs. At neutral pH and in conditions of low salt, growth was observed over the temperature gradient range of 14-41 degrees C. The optimum growth range was reduced to 21-29 degrees C in conditions of acid pH and/or increased NaCl concentration. The growth on the temperature-pH gradient plates had an irregular surface appearance suggesting that changes in growth rate were occurring at different points of temperature and pH. The effects of increased salt concentration together with acidic pH increased the inhibitory effect of the sodium nitrite. The gradient gel plate technique may be a means of rapidly screening the effect of multiple variables on the growth on microorganisms that may be found in food.
Culture Media↗
Toxicology and carcinogenesis studies of two grades of pentachlorophenol in B6C3F1 mice.
Toxicology and carcinogenesis studies of pentachlorophenol (penta), a biocide used primarily as a wood preservative, were conducted by feeding diets containing a technical-grade composite or Dowicide EC-7 (a commercial grade with lower levels of contaminants) to groups of B6C3F1 mice. Based primarily on liver lesions (hepatocellular necrosis, degeneration, and cytomegaly) observed in 6-month studies, diets containing 100 or 200 ppm technical-grade pentachlorophenol or 100, 200, or 600 ppm EC-7 were fed to groups of 50 male and 50 female mice for 2 years. Control groups consisted of 35 animals. For the most part, mean body weights of mice exposed to technical-grade penta were comparable to those of controls. During the second year, the 600-ppm EC-7 female mice averaged 85% of the control body weights. Feed consumption by exposed mice was similar to that by controls. The average daily doses of penta were approximately 0, 17-18, 35, or 114-118 (EC-7) mg/kg. Survival of mice did not appear to be significantly affected by exposure to either technical penta or EC-7 at the doses used in these studies; survival of the control male mice (technical-grade) was comparatively low. Compound-related neoplasms were observed in three organs/systems: liver, adrenal gland medulla, and vascular endothelium. Dose-related increases of hepatocellular adenomas and of carcinomas were observed in male and female mice exposed to both technical penta and EC-7, although the increase was less marked in females exposed to technical penta. Pheochromocytomas of the adrenal gland in exposed male mice were significantly greater than those in controls for both technical penta and EC-7. These neoplasms were also increased in female mice exposed to EC-7 but not to technical penta. Hemangiosarcomas in the spleen and/or liver were increased in female mice that received technical penta and EC-7. The results of these studies show that both technical penta and Dowicide EC-7 are carcinogenic for mice, causing neoplasms in multiple organs/systems. In addition, the results suggest that the carcinogenic responses were due almost exclusively to penta itself, with possibly a minimal potentiating influence by the contaminants in the induction of liver neoplasms in male mice.
Animals↗
Carcinogenicity of p-chloroaniline in rats and mice.
p-Chloroaniline (PCA), a dye intermediate, was evaluated for potential long-term toxicity and carcinogenicity. Groups of 50 F344/N rats of each sex were given by gavage PCA hydrochloride in deionized water at doses of 0, 2, 6 or 18 mg/kg body weight, 5 days/wk for 103 wk. Groups of 50 male and female B6C3F1 mice of each sex were given 0, 3, 10 or 30 mg/kg on the same schedule. In general, body weights and survival were unaffected by PCA administration. In rats the group given 18 mg/kg had mild haemolytic anaemia and slight increases in methaemoglobin at various times during the study. Fibrosis of the spleen was significantly increased in all PCA-treated groups of male rats and in the 18-mg/kg group of female rats. Sarcomas of the spleen occurred in male rats, their incidence being 0/49, 1/50, 3/50 and 38/50 in control low-, mid- and high-dose groups, respectively. There was a slightly increased incidence of pheochromocytomas of the adrenal gland in both male and female rats. Dosed groups of male mice had increased incidences of hepatocellular adenomas or carcinomas (11/50, 21/49, 20/50 and 21/50 in controls, low- mid- and high-dose groups, respectively). Haemangiosarcomas of the liver or spleen were also increased in the high-dose group (incidences of 4/50, 4/49, 1/50 and 10/50 in controls, low-, mid- and high-dose groups, respectively). In conclusion, PCA was carcinogenic in male rats and male mice.
Adenoma↗
Comparative toxicity and tissue distribution of antimony potassium tartrate in rats and mice dosed by drinking water or intraperitoneal injection.
Antimony potassium tartrate (APT) is a complex salt that until recently was used worldwide as an antischistosomal drug. Treatment was efficacious only if APT was administered intravenously to humans at a near lethal total dose of 36 mg/kg. Because unconfirmed epidemiologic studies suggested there might be an association between APT treatment and bladder cancer, we initiated prechronic toxicity studies with the drug to select a route of administration and doses in the event that chronic studies of APT were needed. The toxicity and concentration of tissue antimony levels were compared in 14-d studies with F344 rats and B6C3F1 mice administered APT in the drinking water or by ip injection to determine the most appropriate route for longer term studies. Drinking water doses estimated by water consumption were 0, 16, 28, 59, 94 and 168 mg/kg in rats and 0, 59, 98, 174, 273, and 407 mg/kg in mice. APT was poorly absorbed and relatively nontoxic orally, whereas ip administration of the drug caused mortality, body weight decrements, and lesions in the liver and kidney at doses about one order of magnitude below those in drinking water. Because of these data and the dose-related accumulation of antimony in the target organs, an ip dose regimen was selected for subsequent studies. Both sexes of F344 rats and B6C3F1 mice were given 0, 1.5, 3, 6, 12, and 24 mg/kg doses of APT every other day for 90 d by ip injection. There were no clinical signs of toxicity nor gross or microscopic lesions in mice that could be attributed to toxicity of APT, although elevated concentrations of antimony were detected in the liver and spleen of mice. Rats were more sensitive than mice to the toxic effects of APT, exhibiting dose-related mortality, body weight decrements, and hepatotoxicity. The concentrations of antimony measured in liver, blood, kidney, spleen, and heart of rats were proportional to dose, but there were no biochemical changes indicative of toxicity except in the liver. Hepatocellular degeneration and necrosis occurred in association with dose-related elevations in activities of the liver-specific serum enzymes sorbitol dehydrogenase and alanine aminotransferase. By alternating the site of abdominal injection and the days of treatment, mesenteric inflammation at the site of administration was minimized in the rats and mice, indicating that the ip route would be suitable for chronic studies.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration, Oral↗
Feasibility of in situ hybridisation with chromosome specific DNA probes on paraffin wax embedded tissue.
The feasibility was studied of in situ hybridisation using chromosome specific DNA probes on paraffin wax embedded normal and malignant tissues from different organs. Both isolated nuclei and 5 microns sections were used in in situ hybridisation experiments with biotinylated repetitive DNA probes specific for the centromeric regions of chromosomes 1 and 17. The hybridisation results were visualised with peroxidase-diaminobenzidine. The optimal pretreatments with sodium thiocyanate and pepsin were experimentally defined for the different tissues. Although interphase cytogenetics on paraffin wax embedded tissue is possible, the results indicate that it has its limitations, compared with investigations on fresh tumour tissue.
Chromosomes, Human, Pair 1↗
Interphase cytogenetics reveals somatic pairing of chromosome 17 centromeres in normal human brain tissue, but no trisomy 7 or sex-chromosome loss.
Nuclei isolated from normal human brain tissue, collected from six autopsies, were hybridized with a panel of nine satellite DNA probes specific for the centromeric regions of chromosomes 1, 6, 7, 10, 11, 17, 18, and the X and Y chromosomes. The results did not confirm the recently reported trisomy 7 and loss of sex chromosomes observed in metaphases obtained from normal brain tissue after short-term cultures; however, cells of all six brains displayed somatic pairing of the chromosome 17 centromeres in approximately 50% of the nuclei.
Brain↗
Detection of herpes simplex virus in the ependyma of experimentally infected mice.
Forty-five Swiss albino mice were inoculated with HSV-1 (strain McKrae) by the corneal route. The spread of HSV to the brain stem and the ventricular ependyma was investigated. The polymerase chain reaction (PCR) was used to detect HSV-DNA in the CSF during the course of infection. The ependyma of the third and fourth ventricle and the central canal contained viral antigen at a late stage of infection in up to 60% of mice. At this stage we found that many animals gave a positive PCR in the CSF although no antigen could be detected in the ependymal cells. The presence or absence of antigen containing cells could not be related to detection of HSV-DNA in the CSF. The results show that infection of the ventricular wall is not important for the spread of HSV to the CSF.
Animals↗
Cerebral vasculopathy associated with primary varicella infection.
A previously healthy 5-year-old boy developed cerebral vasculopathy, presenting as two episodes of acute hemiparesis 3 and 9 months, respectively, after a primary varicella infection (chickenpox). This association has not been reported before, to our knowledge, although cerebral vasculopathy is a well-known complication of herpes zoster ophthalmicus. The diagnosis was based on the presence of oligoclonal varicella-specific IgG in the cerebrospinal fluid and angiographic findings. Clinical and angiographic follow-up, and serial thymidine kinase activity levels in the cerebrospinal fluid suggested a self-limiting course of the virus-induced vasculopathy. Varicella zoster virus seems to be another potential causative agent to be considered in acute childhood hemiplegia.
Brain↗