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Biomedical subjects

C Freed

Publications and source records attributed to C Freed.

13 recordsLinked to original sources

Blinded positron emission tomography study of dopamine cell implantation for Parkinson's disease.

We assessed nigrostriatal dopaminergic function in Parkinson's disease (PD) patients undergoing a double-blind, placebo-controlled surgical trial of embryonic dopamine cell implantation. Forty PD patients underwent positron emission tomography (PET) imaging with [18F]fluorodopa (FDOPA) prior to randomization to transplantation or placebo surgery. The 39 surviving patients were rescanned one year following surgery. Images were quantified by investigators blinded to treatment status and clinical outcome. Following unblinding, we determined the effects of treatment status and age on the interval changes in FDOPA/PET signal. Blinded observers detected a significant increase in FDOPA uptake in the putamen of the group receiving implants compared to the placebo surgery patients (40.3%). Increases in putamen FDOPA uptake were similar in both younger (age < or = 60 years) and older (age > 60 years) transplant recipients. Significant decrements in putamen uptake were evident in younger placebo-operated patients (-6.5%) but not in their older counterparts. Correlations between the PET changes and clinical outcome were significant only in the younger patient subgroup (r = 0.58). The findings suggest that patient age does not influence graft viability or development in the first postoperative year. However, host age may influence the time course of the downstream functional changes that are needed for clinical benefit to occur.

Adult↗

Rapid clinical evaluation of anosmia in children: the Alcohol Sniff Test.

Smell impairment affects 1-2% of Americans and leads to frequent physician visits. Olfactory functional testing is available in chemosensory centers, but is frequently omitted in routine cranial nerve examinations. A new smell test, using the standard 70% isopropyl alcohol pad, was developed at the UCSD Nasal Dysfunction Clinic: The Alcohol Sniff Test (AST). The current study examined the reliability of the AST in children, using test-retest measures. A standard 70% isopropyl alcohol pad was moved upward 1 cm per exhalation until the participant reported detection. Test-retest reliability of the AST in children was significant, r = 0.80. The AST predictably classified children as anosmic, hyposmic or normosmic, p < 0.0001. The AST requires only 5 minutes to administer with materials readily available in any physician's office or hospital. The AST is an effective screening tool, even in children, for the average physician who can then refer patients who show less than normal function for further comprehensive testing.

2-Propanol↗

Dopamine transporter immunoreactivity in rat brain.

The dopamine transporter (DAT) is a primary site for the action of cocaine in inducing euphoria. Its action is necessary for the selectivities of dopaminergic neurotoxins that provide the best current experimental models of Parkinson's disease. In the present report, rat dopamine transporter-like immunoreactivity (iDAT) was assessed by immunohistochemistry using newly developed polyclonal antisera raised against conjugated peptides corresponding to sequences found in the dopamine transporter's carboxy- and amino-termini. Dense iDAT was observed in patterns consistent with neural processes and terminals in the striatum, nucleus accumbens, olfactory tubercle, nigrostriatal bundle, and lateral habenula. Perikarya in the substantia nigra pars compacta were immunostained with moderate intensity using one of two immunohistochemical methods, while scattered ventral tegmental area perikarya were stained with somewhat less intensity. Immunoreactive neuronal processes with axonal and dendritic morphologies were stained in the substantia nigra and the paranigral and parabrachialis pigmentosus nuclei of the ventral tegmental area, while sparser processes were noted more medially in the ventral tegmental area. Neuronal processes were found in several laminae in the cingulate cortex, with notable fiber densities in the superficial aspects of lamina I and laminae II/III. The intensities of immunoreactivities in striatum and cerebral cortex were dramatically attenuated ipsilateral to nigrostriatal bundle 6-hydroxydopamine lesions. Specificity of immunostaining was supported by agreement of the results using sera directed against two distinct DAT segments, studies with preimmune and preadsorbed sera and studies of the extracted protein. These antisera identify and reveal details of the distribution of DAT immunoreactivity in rat brain and display variations in levels of DAT expression of likely functional significance.

Amino Acid Sequence↗

Establishment and characterization of immortalized clonal cell lines from fetal rat mesencephalic tissue.

This investigation reports for the first time the establishment of immortalized clones of dopamine-producing nerve cells in culture. Freshly prepared single-cell suspensions from fetal (12-day-old) rat mesencephalic tissue were transfected with plasmid vectors, pSV3neo and pSV5neo, using an electroporation technique. Cells were plated in tissue culture dishes which were precoated with a special substrate and contained modified MCDB-153 growth medium with 10% heat inactivated fetal bovine serum. The immortalized cells were selected by placing the transfected cells in a selection medium (modified MCDB-153 containing 400 micrograms/ml geneticin). The survivors showed the presence of T-antigens and were non-tumorigenic. Two cell lines, 1RB3 derived from cells transfected with pSV3neo, and 2RB5 derived from cells transfected with pSV5neo revealed only 1 to 2% tyrosine hydroxylase (TH)-positive cells. Repeated single-cell cloning of these cell lines by a standard technique failed to increase the number of TH-positive cells in any clones. Using three cycles of growth, alternating between hormone-supplemented, serum-free medium and serum-containing medium produced a cell line (1RB3A) that was very rich in TH-positive cells. The recloning of 1RB3A yielded clones some of which contained over 95% TH-positive cells. These cells produced homovanillic acid, a metabolite of dopamine, and may be useful not only for neural transplant but also for basic neurobiological studies.

Animals↗

Chronic salpingo-oöphoritis with hydrosalpinx formation and ureteric obstruction: A case report.

An association between gynaecological lesions and dilatation of the upper urinary tract has frequently been described. Hydronephrosis as a result of pelvic inflammatory disease has, however, rarely been reported in the literature. The case presented here illustrates the importance of investigation by means of excretory urography in patients with pelvic inflammatory disease presenting with renal symptoms and signs.

Adult↗

Echocardiographic findings in Marfan's syndrome.

Echocardiographic studies of 11 patients with Marfan's syndrome showed that in all adult patients aortic root diameters were larger than 35 mm (normal range 24 to 35, mean 30+/-2 mm). Prolapse of the mitral valve was present in seven of 11 patients. There was no relationship between the degree of aortic root enlargement and the presence of prolapse. However, in five of seven patients with prolapse there were premature ventricular contractions recorded during the echocardiogram or on a separate electrocardiogram. In four patients without prolapse, no premature atrial or ventricular contractions were seen.

Adolescent↗