Protoplasmic astrocytoma with multifocal involvement: case report and radiological findings.

Protoplasmic astrocytomas are a poorly characterized and extremely rare subtype of astrocytoma. We describe the CT, MR and 18F-fludeoxyglucose positron emission tomography (FDG-PET) findings of a multifocal protoplasmic astrocytoma in a 29-year-old male with neurological deficits. He was initially diagnosed with neurosarcoidosis based on imaging. MRI demonstrated intraparenchymal lesions involving the right temporal lobe and cerebellum. These appeared as extremely hyperintense signals on T 2 weighted imaging and as homogeneous enhancements with a small non-enhancing cystic component on contrast-enhanced MR. Diffuse post-contrast enhancement of the craniospinal meninges was also noted. Post-radiation therapy PET-CT demonstrated a highly FDG-avid tumour in the right temporal lobe and left cerebellum. To our knowledge, a multifocal form of protoplasmic astrocytoma in an adult patient has not been previously described.

A nonradioactive method for sizing most D11S533 alleles discretely.

A method is described which allows accurate nonradioactive sizing of most DllS533 alleles, which are characterized by a highly variable number of 6 bp units. In a small population sample of German origin the heterozygosity of the locus was estimated to be 0.933.

Transsynaptic effect of an intrastriatal fetal nigral graft on the sensitivity of the substantia nigra pars reticulata to muscimol in the rat.

In the present study, we have investigated the effect of a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway and of a fetal nigral graft in the striatum on circling induced by unilateral microinjection of muscimol in a target structure of the striatum, the substantia nigra pars reticulata. A group of ovariectomized female rats received a unilateral nigral lesion with 6-hydroxydopamine. The lesioned animals were then tested for apomorphine circling (0.25 mg/kg sc). The animals which displayed circling with this drug were divided into two groups with equivalent circling rate. One group received a graft of 1.5 x 10(6) cells taken from the ventral mesencephalon of 14- to 15-day-old rat embryos and the other was kept as control. Six months after the graft, all animals received one microinjection on each side of the GABAergic agonist muscimol (25 ng/0.5 microliters) in site A (rostral part) or in site B (caudal part) of the substantia nigra pars reticulata using indwelling guide cannulae. Circling was monitored during 90 min after the injection. Our results show that: (1) Unilateral degeneration of the nigrostriatal pathway was associated with a decrease of contralateral rotation when muscimol was injected in site A (rostral part) and an increase when administrated in site B (caudal part) of the substantia nigra pars reticulata on the lesioned side compared to the intact side. (2) A fetal nigral graft implanted into the striatum can normalize the changes in GABAergic sensitivity in site A but not in site B of the substantia nigra pars reticulata.

A fetal nigral graft prevents behavioral supersensitivity associated with repeated injections of L-dopa in 6-OHDA rats. Correlation with D1 and D2 receptors.

The effect of repeated administration of L-3,4-dihydroxyphenylalanine was studied behaviorally and biochemically in grafted versus non-grafted rats with a 6-hydroxydopamine unilateral lesion of the dopaminergic nigro-striatal pathway. Non-grafted rats receiving 14 injections of L-3,4-dihydroxyphenylalanine increased their contraversive circling while grafted rats did not, even after fourteen injections. The density of striatal dopamine receptors was examined by autoradiography using the ligands [3H]-SCH 23390 for dopamine D1 receptors and [3H]-spiperone for D2 receptors. In rats with a lesion of the nigro-striatal dopaminergic pathway, an increase of [3H]-SCH 23390 and [3H]-spiperone binding in the lesioned striatum was observed when compared with the striatum on the intact side. Chronic treatment with L-3,4-dihydroxyphenylalanine led to a further increase in D1 receptor density in the lesioned as well as the intact side. A similar pattern was observed for D2 receptors although the change did not reach significance. A graft of fetal nigral neurons brought the density of both D1 and D2 receptors on the lesioned side back to the level of the intact side. This is observed both in acutely or chronically L-3,4-dihydroxyphenylalanine treated rats. This study suggests that nigral grafts protect the striatum against L-3,4-dihydroxyphenylalanine-induced supersensitivity. It appears that the graft preserves the symmetry of the striatum even though there is an increase of D1 dopamine receptors. These results suggest that a fetal nigral graft could prevent the induction of 3-4-dihydroxyphenylalanine- induced dyskinesia in parkinsonian patients.

Emphasis on high-density lipoprotein cholesterol in patients with coronary artery disease.

Although numerous epidemiologic and lipid intervention studies clearly demonstrate the pivotal role of high-density lipoprotein cholesterol (HDL-C) on risk of coronary artery disease (CAD), the National Cholesterol Education Program (NCEP) has emphasized only total cholesterol and low-density lipoprotein cholesterol (LDL-C), and has underemphasized the role of HDL-C in their lipid assessment and treatment recommendations. In a review of 113 consecutive patients in our cardiac rehabilitation program, lipid levels improved modestly with cardiac rehabilitation. "Ideal" lipids (LDL-C < 130 mg/dL according to the NCEP) were present in 49% before the rehabilitation program and in 46% afterward. In fact, 60 (53%) of our patients had total cholesterol levels < 200 mg/dL and would require no further lipid assessment or treatment according to the NCEP. Of these 60 patients, 40 (67%) had low HDL-C (< or = 35 mg/dL). In our total study group, 56% (63/113) had HDL-C < or = 35 mg/dL and 33% (37/113) had HDL-C < or = 30 mg/dL before rehabilitation (compared to 42% and 21%, respectively, after rehabilitation. On the other hand, a "high-risk" LDL-C value (> or = 160 mg/dL) was found in only 17% of patients at baseline and in only 13% after the cardiac rehabilitation program. Using an approach that incorporates the pivotal role of both LDL-C and HDL-C (LDL-C > or = 160 mg/dL or HDL-C < or = 35 mg/dL) for our patients with known CAD, 65% would require drug treatment before rehabilitation and 53% after rehabilitation. We conclude that: (1) lipids improve only modestly (though the change is significant statistically) with cardiac rehabilitation; (2) low levels of HDL-C are prevalent in cardiac rehabilitation patients and are much more prevalent than elevated LDL-C, both before and after rehabilitation; and (3) the NCEP should reevaluate the pivotal role of HDL-C in its assessment and treatment guidelines, particularly in patients with known CAD, since emphasis on both LDL-C and HDL-C is needed for optimal primary and secondary prevention of CAD.

Regional changes of striatal dopamine receptors following denervation by 6-hydroxydopamine and fetal mesencephalic grafts in the rat.

Young adult female rats received a 6-hydroxydopamine lesion in the left substantia nigra and, 3 weeks later, some of them were grafted with a cell suspension from the ventral mesencephalon of rat embryos (14-15 days old). Six months after transplantation, some grafted rats, following injection of amphetamine, had switched to turning only toward the intact side (type 1), whereas others turned toward the intact side only during the first half of the test (type 2). Levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid were, respectively, 2%, 15% and 35% of the intact side in the denervated striatum of 6-hydroxydopamine rats. Dopamine concentrations were restored to 13% and 10% of the intact side in the grafted striatum of type 1 and type 2 animals, respectively. Levels of homovanillic acid were unchanged following grafts whereas those of dihydroxyphenylacetic acid increased by 209% and 247% in the grafted striatum of type 1 and type 2 animals, respectively. The ratios of dihydroxyphenylacetic acid/dopamine as well as homovanillic acid/dopamine were low in the intact striatum whereas they increased in the denervated striatum with or without graft. The tyrosine hydroxylase immunoreactivity decreased by about 80% in the denervated striatum of 6-hydroxydopamine rats. In type 1 rats, tyrosine hydroxylase immunoreactivity revealed that the graft was localized in the dorsomedial part of the denervated striatum, whereas in type 2 animals, it was also in the medial striatum but it overlapped the dorsal and ventral parts of it equally. D1 as well as D2 dopamine receptors were measured throughout the striatum (9.0-7.6 rostral-caudal coordinates), by autoradiography, using [3H]SCH 23390 (D1 antagonist) and [3H]spiperone (D2 antagonist) binding. Supersensitive D2 receptors were normalized in the dorso- and ventromedial parts of the grafted striatum. D2 receptor density was higher in type 2 than in type 1 rats, more specifically at 8.6-8.2 rostral-caudal coordinates, where the graft was. D1 receptor supersensitivity was modest compared to D2 receptors in the striatum of 6-hydroxydopamine rats and decreased following grafts. DA receptors changes in the striatum, following fetal mesencephalic grafts, may explain the behavioral recovery seen in grafted rats.

Neurobehavioral profile of neuropeptide Y.

In order to better delineate the profile of central actions of neuropeptide Y (NPY), the effects of intracerebroventricular administration of several doses (2.5-20 micrograms) of the peptide on spontaneous activity, muscular tone, body temperature, food intake, nociception and cataleptic manifestations were examined in rats. Results indicate that, starting at 5 micrograms. NPY significantly decreased motor activity of animals in a dose-related fashion. NPY also significantly lowered body temperature of animals. The hypothermic effect was obtained following injections of 10.0 and 20.0 micrograms of the peptide. Administration of the same two doses of NPY resulted in significant increases in food intake, muscular tone and induced a significant catalepsy in animals. On the other hand, nociceptive response times of animals in the hot plate test were not affected by any of the NPY doses tested. Together, these results indicate that the profile of NPY's neurobehavioral actions is more complex than previously reported and suggest that the peptide might be implicated functionally in a variety of neurophysiological processes.

Correlation of functional recovery after a 6-hydroxydopamine lesion with survival of grafted fetal neurons and release of dopamine in the striatum of the rat.

Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least two weeks later they were tested with amphetamine (5 mg/kg, s.c.) and apomorphine (0.25 mg/kg, s.c.). A cell suspension from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. The amphetamine test was then repeated every month for six months. The pattern of circling to amphetamine before the graft was strictly ipsiversive in all animals. From the first month we observed a progressive change and three patterns of rotation could be observed. In 21% of animals, the total number of ipsiversive turns in 90 min actually increased but during the first 20 min the animals turned contralaterally to the lesion (and to the graft). In 38% of animals, the total number of turns switched from ipsiversive to contraversive with the animals turning initially toward the intact side and during the second half of the test toward the lesion. Finally 41% of rats progressively switched to turning only toward the intact side. In all cases, maximal contraversive turning occurred during the initial 20 min. In these rats, tyrosine hydroxylase-positive cells were detected mainly in the dorsal striatum with a few in the central portion. Moreover there was a strong correlation between the number of surviving grafted neurons and the growth of their fiber into the host striatum and the extent of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Decrease of behavioral and biochemical denervation supersensitivity of rat striatum by nigral transplants.

The effect of fetal mesencephalic transplants on dopamine receptor supersensitivity has been studied behaviorally and biochemically in rats with a unilateral lesion of the nigrostriatal pathway. Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least one month later they were tested with apomorphine (0.25 mg/kg, s.c.), amphetamine (5 mg/kg, s.c.), LY 171555 (D2 agonist) (0.5 mg/kg, i.p.) and CY 208243 (D1 agonist) (0.5 mg/kg, s.c.). A suspension containing approximately 1.5 x 10(6) cells from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. Six months later, grafted dopamine neurons reinnervated the medial part of the dorsal striatum, increased the dopamine level and reversed the rotational asymmetry evoked by amphetamine. Apomorphine given four months post-transplant still elicited contraversive circling but the number of turns was reduced. Circling evoked six months post-transplant by CY 208243 or LY 171555 was significantly less in grafted rats than in lesioned non-grafted rats. The density of dopaminergic receptors in the striatum of grafted and lesioned rats was examined by autoradiography by means of in vitro binding with [3H]SCH 23390 for D1 receptors and [3H] spiperone for D2 receptors. The results show that intrastriatal nigral transplants decrease the supersensitivity of the D2 receptors and to a lesser extent of the D1 receptors. Normalization of D2 receptors may explain the decrease of behavioral supersensitivity following administration of apomorphine and D2 agonist in grafted rats. D1 receptors were less affected by the lesion and also less normalized than D2 receptors by the transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal dopamine neuron transplants prevent behavioral supersensitivity induced by repeated administration of L-dopa in the rat.

We have studied in adult rats bearing a unilateral nigral lesion the effect of nigral grafts into the striatum on behavioral supersensitivity induced by chronic treatment of L-DOPA (100 mg/kg i.p.) plus benserazide (50 mg/kg i.p.). Repeated administration of L-DOPA increases contraversive circling. In rats without graft the contraversive circling was significantly increased after 8 and 14 daily injections of L-DOPA. On the other hand, the animals with transplants showed no such increase. Behavioral supersensitivity induced by repeated treatment of L-DOPA is often correlated with dyskinesia observed in the Parkinsonian patients. This suggests that the graft might be able to prevent this secondary effect.

Chemical ionization pyrolytical spectra of DNA.

The chemical ionization-pyrolytical (CI-Py) spectra of DNA and deuterated DNA (Herring Sperm) are recorded. The 200-800 a.m.u. region is examined for CH4, NH3, ND3, electron-capture and OH- CI spectra. The origin of major ion species is discussed.

Metabolism of 14C-thymoxamine in rat and man.

1. After oral administration of 14C-thymoxamine to rat and man the total 14C excreted in urine and faeces was determined. 2. Six metabolites were isolated from the excret of man and rat by chemical extraction and identified by g.l.c.-mass spectral analyses. 3. Two other metabolites, highly polar and resistant to enzymic hydrolysis, were isolated by extraction on XAD2 resin and h.p.l.c. analysis. These two metabolites were identified by n.m.r. and by mass spectrometry in the fast atomic bombardment mode. 4. These two major metabolites of thymoxamine in man and rat have been identified and characterized as the sulphate conjugates of desacetyl-thymoxamine and N-monodesmethyl-desacetyl-thymoxamine.

Evidence for the dark repair of ultraviolet damage in Saccharomyces cerevisiae mitochondrial DNA.

Evidence for the dark repair of ultraviolet damage to yeast mitochondrial DNA has been observed. The ultraviolet dose necessary to inflict significant damage to both nuclear and mitochondrial DNA was determined. Cell survival at large doses of ultraviolet light was observed after immediate and delayed plating of yeast onto 1% pyruvate and 1% glucose media. In the highly lethal dose ranges of irradiation an increase in the number of normal colonies appeared after a period of liquid holding and delayed plating. This increase, demonstrated separately on 1% glucose and 1% pyruvate media suggested that the repair of both mitochondrial and nuclear DNA had occurred. After low doses of ultraviolet light an actual decrease in the number of petite survivors was seen after delayed plating, even though the total number of survivors increased. When a known repair inhibitor, caffeine, was added to the liquid holding buffer prior to the delayed plating of yeast, a marked decrease in the number of petites did not occur after delayed plating. Therefore, the decrease in the number of petite survivors after delayed plating following low doses of ultraviolet light is attributed to the repair of yeast mitochondrial DNA.