Biomedical subjects

S Fritz

Publications and source records attributed to S Fritz.

At least 19 recordsLinked to original sources

PubMed2006

Estimation of genetic parameters for quantitative trait loci for dairy traits in the French Holstein population.

A marker-assisted selection program (MAS) has been implemented in dairy cattle in France. The efficiency of such a selection program depends on the use of correct genetic parameters for the marked quantitative trait loci (QTL). Therefore, the objective of this study was to estimate the proportion of genetic variance explained by 4 QTL described in previous studies (these QTL are segregating on chromosomes 6, 14, 20, and 26). Genotypes for 11 markers were available for 3,974 bulls grouped within 54 sire families of the French Holstein population undergoing MAS. The parameters were estimated for 4 QTL and 5 dairy traits: milk, fat and protein yields, and fat and protein percentages. The proportion of genetic variance explained by the QTL ranged from as low as 0.03 to 0.36%. Both lack of marker informativity and poor monitoring of QTL transmission might limit the accuracy of estimation. The QTL explained a larger proportion of genetic variance for milk composition traits. The QTL on chromosome 14 and chromosomes 6 and 20 have their largest influence on fat and protein percentages, respectively. The overall proportions of genetic variance explained by the QTL were 27.0, 30.7, 24.1, 48.2, and 33.6% for milk, fat and protein yields, and fat and protein percentages, respectively. These results clearly indicated that a large part of the genetic variance is explained by a small number of QTL and that their use in MAS might be beneficial for dairy cattle breeding programs.

Animals↗

PubMed2005

Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma -- CapRI: study protocol [ISRCTN62866759].

UNLABELLED: After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. DESIGN: The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrollment. DISCUSSION: The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

Adenocarcinoma↗

PubMed2004

Ovarian function and morphology after deletion of the DARPP-32 gene in mice.

A plethora of systemic and local signaling molecules regulate ovarian function, but how different signaling molecules interact within an ovarian target cell is not known. Here we report that endocrine cells of the ovary express a phosphoprotein, DARPP-32 (dopamine and cyclic AMP-regulated phosphoprotein of Mr 32,000), which integrates signaling molecules in neurons. We thus hypothesized that DARPP-32 might act in a similar way in ovarian endocrine cells and therefore studied whether DARPP-32 gene deletion has consequences for ovarian functions in mice. Reproductive performance of adult mutants did not differ from wild-type females, as judged from numbers of litters and pups delivered. Similar steroid levels in mutant and wild-type mice ruled out gross abnormalities in the hypothalamic-pituitary-ovarian axis. However, an analysis of ovarian morphology, using serially sectioned ovaries, revealed several differences. Ovaries of young adult mutant mice at 2 - 3 months contained luteinized follicles, but fewer corpora lutea. At 5 - 6 months, large cysts were found in mutant mice, as well as reduced numbers of preantral follicles and antral follicles. Interstitial cell hypertrophy and degeneration was marked in all mutant ovaries at this age. Thus, while the lack of DARPP-32 does not overtly alter reproductive performance in adult mice, it is associated with progressive alterations and derangements of growth and development of ovarian follicles, suggesting premature ovarian ageing. This implies that ovarian DARPP-32 is involved in follicular development, presumably by integrating effects of signaling molecules, which act together to ensure efficient follicular development.

Animals↗

PubMed2002

Development of an experimental ovarian tumor: immunocytochemical analysis.

OBJECTIVE: The aim of the present work was to study whether immunocytochemical parameters present in the normal ovary were altered after tumor development under high gonadotropin levels. METHODS: Ovarian tumors (luteoma): castrated female rats had an ovary grafted into the spleen; tumors were left to develop for 1, 2, 3 or 7 months. The presence of apoptotic cells (TUNEL method) and the expression of proliferating cell nuclear antigen (PCNA), gap junction protein (Cx43), steroidogenic acute regulatory protein (StAR), aromatase and synaptosome-associated protein of 25 kDa (SNAP-25) were determined by immunocytochemistry. Some of these findings were confirmed by RT-PCR (Cx43, StAR, SNAP-25). Inhibin subunit mRNAs were investigated by Northern blot. RESULTS: PCNA staining of tumors was mainly found in granulosa cells of transforming follicles and was absent from luteinized follicles. A nearly complete absence of apoptosis was observed. Cx43 was mainly found in follicles, while it was very weakly expressed or absent in luteinized follicles. StAR protein expression, indicating active steroidogenesis, was demonstrated only in luteinized follicles and in thecal cells, but was absent from granulosa cells. Aromatase immunoreactivity was very intense in granulosa and also present in luteal cells. Membrane-associated and cytoplasmic SNAP-25 immunostaining was determined in patches of endocrine cells in the follicles, as well as in the luteinized follicles. The expression of mRNAs for Cx43, StAR and SNAP-25 (RT-PCR) and inhibin subunits (Northern blots) were confirmed in 1-, 3- and 7-month-old tumors. CONCLUSIONS: These results indicated that luteoma most likely develop from unruptured follicles by hypertrophy and proliferation of follicular cells. Circulating gonadotropins seem to play a fundamental role in maintaining the expression of proteins typically expressed in normal ovary, while avoiding apoptosis in this tissue.

Animals↗

PubMed2001

Increases in circulating and lymphoid tissue interleukin-10 in autoimmune lymphoproliferative syndrome are associated with disease expression.

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which genetic defects in proteins that mediate lymphocyte apoptosis, most often Fas, are associated with enlargement of lymph nodes and the spleen and a variety of autoimmune manifestations. Some patients with ALPS have relatives with these same apoptotic defects, however, who are clinically well. This study showed that the circulating levels of interleukin 10 (IL-10) were significantly higher (P <.001) in 21 patients with ALPS than in healthy controls. Moreover, the peripheral blood mononuclear cells (PBMCs) and lymphoid tissues of these patients with ALPS contained significantly higher levels of IL-10 messenger RNA (mRNA; P <.001 and P <.01, respectively). By fractionating PBMC populations, disproportionately high concentrations of IL-10 mRNA were found in the CD4(-)CD8(-) T-cell population, expansion of which is virtually pathognomonic for ALPS. Immunohistochemical staining showed intense IL-10 protein signals in lymph node regions known to contain CD4(-)CD8(-) T cells. Nonetheless, in vitro studies showed no influence of IL-10 on the survival of CD4(-)CD8(-) T cells. Overexpression of IL-10 in patients with inherited apoptotic defects is strongly associated with the overt manifestations of ALPS.

Apoptosis↗

PubMed2001

Connection of the mitochondrial outer and inner membranes by Fzo1 is critical for organellar fusion.

Mitochondrial membrane fusion is a process essential for the maintenance of the structural integrity of the organelle. Since mitochondria are bounded by a double membrane, they face the challenge of fusing four membranes in a coordinated manner. We provide evidence that this is achieved by coupling of the mitochondrial outer and inner membranes by the mitochondrial fusion machinery. Fzo1, the first known mediator of mitochondrial fusion, spans the outer membrane twice, exposing a short loop to the intermembrane space. The presence of the intermembrane space segment is required for the localization of Fzo1 in sites of tight contact between the mitochondrial outer and inner membranes. Mutations in the intermembrane space domain of yeast Fzo1 relieve the association with the inner membrane. This results in a loss of function of the protein in vivo. We propose that the mitochondrial fusion machinery forms membrane contact sites that mediate mitochondrial fusion. A fusion machinery that is in contact with both mitochondrial membranes appears to be functionally important for coordinated fusion of four mitochondrial membranes.

Cell Polarity↗

PubMed2001

StAR protein is increased by muscarinic receptor activation in human luteinized granulosa cells.

Cultured human luteinized granulosa cells (GC) are a unique model to study regulation of the human corpus luteum, e.g. by local factors, including acetylcholine (ACh). GC express functional ACh-receptors of the M1-type (M1R). Priming with the cholinergic agonist carbachol for 24 h, followed by a 24 h stimulation with human chorionic gonadotrophin (hCG), significantly increased progesterone levels (up to 2-fold), compared with hCG stimulation alone. This is likely due to the effect of carbachol, observed after 24 h, to increase the levels of steroid acute regulatory (StAR) protein, as found in Western blots. StAR protein was increased (2-10-fold), while P450 side chain cleavage (SCC) enzyme was unaffected. Thus, one role of muscarinic receptor activation in human GC is regulation of StAR protein and, subsequently, progesterone production.

Carbachol↗

PubMed2001

Transposition and gene disruption in the male germline of the mouse.

We have tested a synthetic, functional, transposon called Sleeping Beauty for use in mice as a germline insertional mutagen. We describe experiments in which mutagenic, polyadenylation-site trapping, transposon vectors were introduced into the germline of mice. When doubly transgenic males, expressing the Sleeping Beauty transposase gene (SB10) and harboring poly(A)-trap transposon vectors, were outcrossed to wild-type females, offspring were generated with new transposon insertions. The frequency of new transposon insertion is roughly two per male gamete. These new insertions can be passed through the germline to the next generation and can insert into or near genes. We have generated a preliminary library of 24 mice harboring 56 novel insertion sites, including one insertion into a gene represented in the EST database and one in the promoter of the galactokinase (Gck) gene. This technique has promise as a new strategy for forward genetic screens in the mouse or functional genomics.

Animals↗

PubMed2001

Expression of muscarinic receptor types in the primate ovary and evidence for nonneuronal acetylcholine synthesis.

The presence of muscarinic receptors (MR) in the ovary of different species has been recognized, but the identity of these receptors as well as ovarian sources of their natural ligand, acetylcholine (ACh), have not been determined. Because luteinized human granulosa cells (GC) in culture express functional MR, we have determined whether the group of the related MR subtypes, M1R, M3R, and M5R, are present in vivo in human and rhesus monkey ovaries. To this end, ribonucleic acids (RNAs) of different human and monkey ovaries as well as RNAs from human GC and monkey oocytes were reverse transcribed and subjected to PCR amplification, followed by sequencing of the amplified complementary DNAs. Results obtained showed that M1R, M3R, and M5R messenger RNAs are present in adult human and monkey ovaries; oocytes express exclusively the M3R subtype, whereas GC express M1R and M5R. To determine the ovarian source(s) of the natural ligand of these ACh receptors, we attempted to localize the enzyme responsible for its synthesis with the help of a monoclonal antibody recognizing choline acetyltransferase for immunohistochemistry. In neither human nor monkey sections did we detect immunoreactive choline acetyltransferase-positive fibers or nerve cells, but, surprisingly, GC of antral follicles showed prominent staining. To determine whether GC can produce ACh, human cultured GC derived from preovulatory follicles were analyzed using a high pressure liquid chromatography technique. The results showed that these cells contained ACh in concentrations ranging from 4.2-11.5 pmol/10(6) cells. Samples of a rat granulosa cell line likewise contained ACh. Thus, the ovary contains multiple MR, and GC of antral follicles are able to synthesize ACh, the ligand of MR. We propose that ACh may serve as an as yet unrecognized factor involved in the complex regulation of ovarian function in the primate, e.g. regulation of cell proliferation or progesterone production.

Acetylcholine↗

PubMed2000

DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites.

STAT transcription factors are expressed in many cell types and bind to similar sequences. However, different STAT gene knock-outs show very distinct phenotypes. To determine whether differences between the binding specificities of STAT proteins account for these effects, we compared the sequences bound by STAT1, STAT5A, STAT5B, and STAT6. One sequence set was selected from random oligonucleotides by recombinant STAT1, STAT5A, or STAT6. For another set including many weak binding sites, we quantified the relative affinities to STAT1, STAT5A, STAT5B, and STAT6. We compared the results to the binding sites in natural STAT target genes identified by others. The experiments confirmed the similar specificity of different STAT proteins. Detailed analysis indicated that STAT5A specificity is more similar to that of STAT6 than that of STAT1, as expected from the evolutionary relationships. The preference of STAT6 for sites in which the half-palindromes (TTC) are separated by four nucleotides (N(4)) was confirmed, but analysis of weak binding sites showed that STAT6 binds fairly well to N(3) sites. As previously reported, STAT1 and STAT5 prefer N(3) sites; however, STAT5A, but not STAT1, weakly binds N(4) sites. None of the STATs bound to half-palindromes. There were no specificity differences between STAT5A and STAT5B.

Base Sequence↗

PubMed2000

Fragment kinetic energies and modes of fragment formation

Kinetic energies of light fragments ( A</=10) from the decay of target spectators in 197Au+197Au collisions at 1000 MeV per nucleon have been measured with high-resolution telescopes at backward angles. Except for protons and apart from the observed evaporation components, the kinetic-energy spectra exhibit slope temperatures of about 17 MeV, independent of the particle species, but not corresponding to the thermal or chemical degrees of freedom at breakup. It is suggested that these slope temperatures may reflect the intrinsic Fermi motion and thus the bulk density of the spectator system at the instant of becoming unstable.

Journal Article↗

PubMed2000

Probing the conformation of the sugar transport inhibitor phlorizin by 2D-NMR, molecular dynamics studies, and pharmacophore analysis.

Sodium/D-glucose cotransport, one of the prototypes for sodium gradient-driven symport systems in kidney and intestine, is known to be inhibited by aromatic and aliphatic glucosides (Diedrich, D. F. Biochim. Biophys. Acta 1963, 71, 688-700; Diedrich, D. F. Arch. Biochem. Biophys. 1966, 117, 248-256; Kipp, H.; et al. Biochim. Biophys. Acta 1996, 1282, 124-130; Ramaswamy, K.; et al. Biochim. Biophys. Acta 1976, 433, 32-38). The conformation in which the most potent inhibitor, phlorizin, interacts with the transport protein was investigated with different approaches. Phlorizin consists of the glucose moiety and two aromatic rings (A and B) joined by an alkyl spacer. First the interaction of these various parts of the molecule was determined by two-dimensional (2D) solution NMR. From the 2D-NOESY (nuclear Overhauser effect) measurements spatial distances (up to 5 A) between various interacting H atoms could be detected. Using these values as distance constraints, conformations of phlorizin were calculated and analyzed by the valence force-field method. As a result, a set of conformations could be obtained. The most probable phlorizin conformation shows a nearly perpendicular arrangement of the two aromatic rings (A and B) with the ring B situated above the sugar ring. A very similar conformation could be found by using molecular dynamics simulations when water was chosen as the solvent. This phlorizin conformation in aqueous solution then served as a template for conformational analysis of various phlorizin derivatives. The resulting conformations of derivatives were taken as input to establish a pharmacophore model using the DISCO calculation. As a result, the essential elements of phlorizin for interaction with its binding pocket could be deduced: namely hydrogen bonding via hydroxyl groups of the pyranoside at C(2), C(3), C(4), and C(6) and at C(4) and C(6) of aromatic ring A and hydrophobic interactions via the pyranoside ring and aromatic ring A. Finally, from these conformational features of the pharmacophore the dimension of the phlorizin binding site on the sodium/D-glucose cotransporter was estimated to be 17 x 10 x 7 A(3).

Computer-Aided Design↗

PubMed2000

D1-Receptor, DARPP-32, and PP-1 in the primate corpus luteum and luteinized granulosa cells: evidence for phosphorylation of DARPP-32 by dopamine and human chorionic gonadotropin.

The multifunctional phosphoprotein "dopamine and cAMP-related phosphoprotein, M(r) 32,000" (DARPP-32), which is able to act as an intracellular third messenger, was previously found to be present in human luteinized granulosa cells (GCs) and human ovary. DARPP-32 phosphorylation in GCs was increased by dopamine (DA) acting via a DA-1 receptors (D1-R). In the present study, we examined whether the major endocrine signaling molecule for GCs, LH/human CG (hCG), could also affect DARPP-32 phosphorylation. Immunoprecipitation studies showed that hCG, as well as DA, increased phosphorylation of DARPP-32 at threonine residues within 10 min, indicating that the signal transduction pathways of a hormone and a neurotransmitter involve DARPP-32 in GCs. Phosphorylated DARPP-32 is known to inhibit a cellular phosphatase (PP-1), which was also found to be expressed by GCs. Using RT-PCR and sequence analyses we showed that DARPP-32, PP-1, and D1-R genes were not restricted to cultured luteinized GCs, but were expressed in vivo, in the corpus luteum (CL) of the rhesus monkey throughout its entire life span. Whereas hCG increased steroid production in monkey luteinized GCs and in isolated luteal cells, DA failed to affect basal or hCG-stimulated progesterone production. This indicates that, unlike the LH/hCG receptor, the D1-R is not directly linked to steroid production. Although the precise role of D1-R in the CL remains to be shown, the presence of D1-R, DARPP-32, and its target PP-1 in this endocrine tissue, as well as the phosphorylation of DARPP-32 by a gonadotropin and by DA in luteinized GCs, indicate that the signal transduction pathways of the neurotransmitter DA and the gonadotropin hCG/LH involve DARPP-32. The PP-1 inhibitor DARPP-32 may, thus, be a third messenger used by both DA and hCG/LH to exert common regulatory influences on the cells of the CL.

Amino Acid Sequence↗

PubMed1999

Determination of cDNA, gene structure and chromosomal localization of the novel human 17beta-hydroxysteroid dehydrogenase type 7(1).

We have identified human 17beta-hydroxysteroid dehydrogenase type 7 (17beta-HSD 7). The novel human cDNA encodes a 37 kDa protein that shows 78 and 74% amino acid identity with rat and mouse 17beta-HSD 7, respectively. These enzymes are responsible for estradiol production in the corpus luteum during pregnancy, but are also present in placenta and several steroid target tissues (breast, testis and prostate) as revealed by RT-PCR. The human 17beta-HSD 7 gene (HSD17B7) consists of nine exons and eight introns, spanning 21. 8 kb and maps to chromosome 10p11.2 close to susceptibility loci for tumor progression, obesity and diabetes. The HSD17B7 promoter (1.2 kb) reveals binding sites for brain-specific and lymphoid transcription factors corresponding to additional expression domains in hematopoietic tissues and the developing brain as identified by in silico Northern blot.

17-Hydroxysteroid Dehydrogenases↗

PubMed1999

Bias due to incomplete follow up in a cohort study.

AIM: To investigate the bias introduced by incomplete follow up in a cohort study of ocular outcome after premature birth. METHODS: A geographically defined cohort of children born before 32 weeks' gestation was prospectively recruited at birth to study the ocular outcome at 2 years. On the basis of attendance at 2 years, the children's families were allocated to one of three groups: group 1 attended for follow up, group 2 were difficult to trace, and group 3 were very reluctant for assessment. All children were examined by a single ophthalmologist, masked to these groupings. RESULTS: 558 children (98.8% of study group) were examined, of whom 505 were in group 1, 20 in group 2, and 33 in group 3. The groups which were more difficult to study (groups 2 and 3) showed a significantly higher prevalence of ocular abnormalities, including strabismus (p=0. 02) and cicatricial retinopathy of prematurity (p=0.002) compared with those attending for follow up. Further, not all of these cases could have been identified by review of the children's previous records. Ocular abnormalities would be underestimated by 16% (11.3% in group 1 compared with 13.4% in the total cohort, p=0.77). CONCLUSIONS: This study suggests that the prevalence of abnormalities would be underestimated by incomplete follow up, as those subjects who were most difficult to obtain for study had a significantly higher prevalence of abnormalities.

Bias↗

PubMed1999

Functional and molecular characterization of a muscarinic receptor type and evidence for expression of choline-acetyltransferase and vesicular acetylcholine transporter in human granulosa-luteal cells.

Previously, we provided evidence for the presence of a class of muscarinic receptors on human luteinized granulosa cells (human GC) that is linked to transient increases in intracellular free calcium levels, but not to steroid production. The precise nature of the receptor is not known, and neither its function nor the source of its natural ligand acetylcholine (ACh) is clear. To address these issues we used RT-PCR approaches and isolated complementary DNAs corresponding to the M1 receptor subtype from reverse transcribed human GC messenger ribonucleic acids. M1 receptors were further shown by immunocytochemistry, using a M1 receptor antiserum. Single cell calcium measurements showed that the M1 receptor was functionally active and linked to acute increases in intracellular free calcium, as the M1 receptor specific antagonist pirenzepine blocked the Ca2+-mobilizing effect of oxotremorine M (a muscarinic agonist). An unexpected consequence of M1 receptor activation was evidenced by the ability of muscarinic agonists to stimulate the proliferation of human GC within 24 h. In vivo, ACh, the natural ligand of these receptors is thought to be contained in cholinergic nerve fibers innervating the ovary. Surprisingly, the prerequisite for the synthesis of ACh, the enzyme choline-acetyltransferase (ChAT), is also expressed by human GC, as shown by Western blotting and immunocytochemistry. In addition, these cells express another marker for ACh synthesis, namely the gene for the vesicular acetylcholine transporter, as evidenced by RT-PCR cloning, Western blotting, and immunocytochemistry. In conclusion, our data identify the M1 receptor in human GC and point to a novel, trophic role of the neurotransmitter ACh. Furthermore, the presence of the prerequisites of ACh synthesis in human GC indicate that an autocrine/paracrine regulatory loop also exists in the in vivo counterparts of these cells in the ovary, i.e. in the cells of the preovulatory follicle and/or of the young corpus luteum.

Acetylcholine↗

PubMed1999

Sources and function of neuronal signalling molecules in the gonads.

While the hypothalamic-pituitary-gonadal axis is crucial for the function of the gonads, non-endocrine regulatory influences are exerted by other factors within the gonads. Among these factors are neurotransmitters, such as catecholamines. Several types of receptors for catecholamines exist in the gonads on vascular or endocrine cells. Their activation can alter blood flow, steroidogenesis and gene expression, depending on the target cells. Recently a neuronal-like cell type expressing catecholamine-biosynthetic enzymes and neuronal proteins was identified in testis and ovary of human and non-human primates. Together with the well-known sympathetic innervation, this gonadal nervous system may serve as a source of catecholamines. Dopamine is present in the follicular fluid. Oocytes, while not able to perform de novo synthesis of catecholamines, were shown to utilize dopamine to produce norepinephrine. This catecholamine then acts on beta-adrenoreceptors of follicular cells to increase cAMP. Oocytes may thus indirectly via dopamine and cAMP be able to control their own meiotic arrest. In addition, neurotransmitters may also be synthesized in other, non-neuronal ovarian cells. Thus, cultured human granulosa-luteal cells possess the acetylcholine synthesizing enzyme and the acetylcholine-specific vesicular transporter protein. These cells also express muscarinic-receptors (M1), which are linked to the mobilization of intracellular calcium and cell proliferation. This suggests involvement of the acetylcholine system in follicular growth and in the periovulatory events. In neurons, neurotransmitters alter the properties of the neuronal cell membrane. If this is the case in endocrine cells of the gonads is not yet clear, but the recent identification of voltage-activated potassium and sodium channels in human luteinized granulosa-luteal cells raises this question and opens a door to a new area of investigation.

Acetylcholine↗

PubMed1999

A comparison of phonemic, semantic, and alternating word fluency in Parkinson's disease.

Word fluency in 45 medicated non-demented Parkinson's disease (PD) patients and 45 normal control subjects was studied with a Phonemic Word Fluency (PWF) task using the letters F, A, and S, a Semantic Word Fluency (SWF) task using the categories animals, boys' names, and states, and an Alternating Word Fluency (AWF) task requiring the person to alternate between colors and occupations, animals and states, and words beginning with C and P. The number of words generated did not differ for trials with F, A, S, or states, but PD patients generated significantly fewer animal names and boys' names. PD patients also generated significantly fewer words on each of the three AWF trials. The PD patients scored 21% lower than the normal control group on the total AWF score, but only 10% lower for the PWF and SWF scores. The greater impairment on the AWF task which requires the use of internal attentional control to rapidly shift mental set can be considered a type of executive functioning deficit. This is consistent with the growing literature suggesting frontal systems dysfunction in PD and with the view that dopaminergic treatment only incompletely restores functioning in the frontostriatal system.

Journal Article↗