Radiosynthesis of 2'-deoxy-2'-[18F]-fluoro-5-methyl-1-beta-L-arabinofuranosyluracil ([18F]-L-FMAU) for PET.

Radiosynthesis of 2'-deoxy-2'-[(18)F]-fluoro-5-methyl-1-beta-L-arabinofuranosyluracil ([(18)F]-L-FMAU) is reported. Compound 1 was synthesized and converted to 2-triflate 2. Compound 3 was prepared from 2 using tetrabutylammonium[(18)F]fluoride, converted to 4, and then coupled with 5. The crude product was hydrolyzed, and purified by HPLC to obtain 7a. The radiochemical yield of [(18)F]-L-FMAU was 26% decay corrected (d.c.) in four runs with radiochemical purity >99% and specific activity 2200 mCi/micromol. The synthesis time was 3.3-3.5h from the end of bombardment (EOB).     

Interhemispheric and ipsilateral connections in Parkinson's disease: relation to mirror movements.

Mirror movements (MM) occur in early, asymmetric Parkinson's disease (PD). To examine the pathophysiology of MM in PD, we studied 13 PD patients with MM (PD-MM), 7 PD patients without MM (PD-NM), and 14 normal subjects. Cross-correlogram did not detect common synaptic input to motoneuron pools innervating homologous hand muscles in PD-MM patients. Transcranial magnetic stimulation studies showed no significant difference in ipsilateral motor-evoked potentials between PD-MM patients and normal subjects. The MM side of PD-MM patients showed a slower increase in ipsilateral silent period area with higher level of muscle contraction than the non-MM side and normal subjects. There was less interhemispheric inhibition (IHI) at long interstimulus intervals of 20 to 50 ms in PD-MM than PD-NM. IHI reduced short interval intracortical inhibition in normal subjects and PD-NM, but not in PD-MM. IHI significantly increased intracortical facilitation in PD-MM and PD-NM patients, but not in normal subjects. Our results suggest that MM in PD is due to activation of the contralateral motor cortex. PD-MM patients had reduced transcallosal inhibitory effects on cortical output neurons and on intracortical inhibitory circuits compared to PD-NM patients and controls. These deficits in transcallosal inhibition may contribute to MM in PD patients.     

Nitroblue-tetrazolium test for the functional evaluation of phagocytic cells: A critical analysis of the methodology

The reduction of NBT to formazan has been suggested as an indicator of the reduction potential of biological systems. An increase in the amount of reduced formazan reflects the activation of the hexose monophosphate shunt of phagocytes cultivated in vitro, as a result of cellular stimulation by chemical or biological factors, or during phagocytosis. This phenomenon has been widely used for the determination of activated phagocytes by different methods. However, the technical limitations of these methods have not been evaluated carefully. In the investigations presented here threesolvents for formazan, pyridine, dioxane and dimethylformamide, have been tested for their suitability as extraction agents. For each solvent the optimal wavelength for photometric evaluation has been determined and dose relation curves between dissolved formazan and OD have been established. Several factors (time, temperature, pH, contamination with water or acid) affecting the dissolving properties and stability of formazan in different solvents have been investigated. With the solvents tested, dioxane proved to be the most suitable agent for extracting NBF. Thus, a methodology for the quantitative evaluation of NBT has been established. This method can be used for the identification of activators as well as of inhibitors of the phagocyte system.     

18F]-Dopa positron emission tomography imaging in early-stage, non-parkin juvenile parkinsonism.

There are few reports of positron emission tomography (PET) in juvenile parkinsonism (JP). We report on the results of (18)F-6-fluoro-L-dopa (FD) PET in a 14-year-old patient with JP of 5 years duration associated with atypical features. This is the youngest subject to be investigated to date. There was a severe asymmetric reduction in striatal FD uptake, with a rostrocaudal gradient in the putamen similar to that seen in adult-onset idiopathic parkinsonism. Extensive DNA analysis in this patient did not show mutations in the parkin gene.     

Type A behavior and psychological characteristics of hypertensive patients undergoing antihypertensive treatment

The aim of this study was to evaluate the presence of "type A" behaviour and possible psychological distress in 373 hypertensive patients. One-hundred and ninety-five males, 56.2 +/- 6.2 years old and one-hundred and seventy-eight females, 57.1 +/- 6.2 years old, coming from the IPPPSH and still under double-blind treatment with or without a beta-blocker (oxprenolol 160 mg SR), were studied by means of the Jenkins Activity Survey form C and several tests from the Cognitive Behavioural Assessment Battery (CBA-2.0). Seventy-four point eight percent of the patients showed a "type A" pattern, and 25.5% were in the extreme predictive interval for coronary heart disease according to WCGS. "Type A" pattern was not influenced by variables such as age, sex, education, job or previous pharmacological treatment. The patients studied did not show any particular psychological distress at the psychometric evaluation. However, special social and cultural characteristics and different therapies influenced some symptoms, such as anxiety, depression and somatic lamentation. According to this study: "type A" behaviour seems to be a steady feature of the hypertensive patient; furthermore, it seems to be due to a "biological imprinting" which can be considered a cause of hypertension; psychological distress depends on a particular set of environmental stimuli. In the first case an accurate prevention is needed while, in the second case adequate pharmacological and/or psychological therapies are needed.     

Endogenous type C RNA virus of mink (Mustela vison).

A type C RNA virus was isolated from mink lung cell line (American Type Culture Collection No. CCL 64) which had been cocultivated with 5-bromodeoxyuridine (BUDR)-treated mouse spleen cells. The virus has type C RNA virus morphology as demonstrated by electron microscopy. The complement fixation and immunofluorescent tests performed with mouse anti-p30 antisera show a distinctive difference between mink and mouse type C viruses. Complement fixation tests also indicate that mink type C virus is antigenically different from rat, feline leukemia, feline endogenous (RD-114), baboon, and woolly monkey type C viruses. The virus propagates in cells of mouse, rat, cat, sheep, dog, and human origin, but not in bovine (MDBK) or simian (BSC-1) cells. The infection of rabbit (SIRC) cells and cells of virus origin (mink lung) was followed by delayed and low-titer polymerase release in tissue culture media. The virus sediments in sucrose density gradients as a broad band of densities, 1.13–1.17 g/ml, and contains 70 and 4S RNA. The protein profile is similar to that observed in other mammalian type C viruses. The DNA complementary to the poly(A)-containing virion RNA hybridized to a high degree (72%) with the RNA from virus-producing mink lung cells but not with the RNA from mouse cell lines or uninfected mink lung cell line. The nucleotide sequences homologous to mink viral cDNA were found in mink cell DNA from both virus-producing and nonproducing cells, but not in the DNA of mouse, rat, or feline origin. The virus here described therefore represents an endogenous mink type C virus.     

A fetus with an X;1 balanced reciprocal translocation and eye disease.

A 19 week female fetus is described with a de novo X;1 reciprocal balanced translocation, with the breakpoint on the X chromosome at Xp11.4, and eye pathology consistent with the early stages of Norrie disease. The fetus seems to be an example of a female manifesting an X linked recessive disease, and it was shown that the normal X chromosome was completely inactivated in all cells examined. Norrie disease has been mapped to Xp11.3, and fluorescence in situ hybridisation studies showed that the Norrie disease gene had not obviously been disrupted. Mutation screening by SSCP analysis showed no aberrant fragments of the coding region of the gene. Several eye disease genes map to the same region of the X chromosome, but are excluded on grounds of pathology. One possibility is that this fetus has a Norrie-like eye disease caused by the mutation of another gene located at Xp11.4. If this is so, there are implications for prenatal diagnosis.     

RNA tumor virus phosphoproteins: subvirion location of the multiple phosphorylated species.

An analysis of core particles of 1.23 g/cm³ density of the endogenous feline type C virus (RD-114) showed the presence of all of the major low molecular weight structural proteins, namely p30, p12, p10, and the phosphoprotein pp15, in relative proportions similar to those detected in intact RD-114 virions. The protein kinase activity of the virus was also found to be associated with the core. A comparison of the content of multiple phosphorylated species of the pp15 derived from the core with that isolated from the whole virion demonstrated that all major phosphorylated species of RD-114 pp15 were located in the core structure.