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Immunoglobulin A enteropathy: a possible variant of Henoch-Schönlein purpura.

This study calls attention to a new syndrome presenting with gastrointestinal symptoms including abdominal pain, vomiting, and/or hematemesis and endoscopic multiple lesions predominantly in the descending duodenum, without the skin rash observed in Henoch-Schonlein purpura. We examined the gastrointestinal mucosa for IgA deposits in nine children and compared the results with those for three patients with Henoch-Schönlein purpura. In addition, gastroduodenal biopsy specimens of 11 patients with various diseases were studied as controls for IgA staining. Intestinal histology showed nonspecific mucosal inflammation without vasculitis. In six patients without rash (67%), IgA deposition was observed in the capillary wall with the same staining pattern as seen in two patients with Henoch-Schonlein purpura. Compared with the controls (9%), the positive rate of IgA deposition was significantly higher in nonrash patients (P < 0.01). Deposited IgA showed immunoreactivities of polymeric IgAl containing J chain. IgA deposits were ultrastructually seen along the plasma membranes of the endothelial cells. Overall, the data suggest that IgA deposition played a pathogenetic role in the gastrointestinal damage in this group of patients presenting primarily with gastrointestinal complaints. Further studies are needed to clarify whether this patient population has a variant of Henoch-Schönlein purpura or a distinct "IgA enteropathy."

Adolescent↗

Sickle hemoglobin (HbS) allele and sickle cell disease: a HuGE review.

Sickle cell disease is caused by a variant of the beta-globin gene called sickle hemoglobin (Hb S). Inherited autosomal recessively, either two copies of Hb S or one copy of Hb S plus another beta-globin variant (such as Hb C) are required for disease expression. Hb S carriers are protected from malaria infection, and this protection probably led to the high frequency of Hb S in individuals of African and Mediterranean ancestry. Despite this advantage, individuals with sickle cell disease exhibit significant morbidity and mortality. Symptoms include chronic anemia, acute chest syndrome, stroke, splenic and renal dysfunction, pain crises, and susceptibility to bacterial infections. Pediatric mortality is primarily due to bacterial infection and stroke. In adults, specific causes of mortality are more varied, but individuals with more symptomatic disease may exhibit early mortality. Disease expression is variable and is modified by several factors, the most influential being genotype. Other factors include beta-globin cluster haplotypes, alpha-globin gene number, and fetal hemoglobin expression. In recent years, newborn screening, better medical care, parent education, and penicillin prophylaxis have successfully reduced morbidity and mortality due to Hb S.

Adolescent↗

The complete amino acid sequence of a hirudin variant from the leech Hirudinaria manillensis.

Unlike the European leech Hirudo medicinalis, the Asian jawed leech Hirudinaria manillensis is specialized for feeding on mammalian blood. In the salivary glands of both these leeches, there is a potent inhibitor of thrombin, called hirudin, which acts as an anticoagulant. We have reported previously the isolation and purification of a variant of hirudin, called bufrudin, from the head portions of Hirudinaria. In the present study, the complete amino acid sequence of bufrudin was determined by automated Edman degradation of peptide fragments generated after cleavage of protein with trypsin or thermolysin. Comparison of the primary structure of bufrudin, with hirudin HV1, show about 70% sequence identity with deletion of two amino acids, but the key amino acids at the C-terminus, involved in the inhibition of thrombin, are conserved. However, similar sequence comparison of bufrudin with hirullin P18, a hirudin variant isolated from the same leech species but from whole leech, instead of heads, reveals even less sequence identity of about 60%. From the amino acid sequence, it is suggested that the conformation of the C-terminal portion of bufrudin may be significantly different from hirullin P18, but similar to hirudin HV1, upon its interaction with thrombin. These results indicate that, as with Hirudo leech, various isoforms of hirudin also exist in Hirudinaria leech, with a significant change occurring in the structure of the molecule during the evolution of leeches.

Amino Acid Sequence↗

United snakes.

Since their debut in 1987, snakes (active contour models) have become a standard image analysis technique with several variants now in common use. We present a framework called "United Snakes", which has two key features. First, it unifies the most popular snake variants, including finite difference, B-spline, and Hermite polynomial snakes in a consistent finite element formulation, thus expanding the range of object modeling capabilities within a uniform snake construction process. Second, it embodies the idea that the heretofore presumed competing technique known as "live wire" or "intelligent scissors" is in fact complementary to snakes and that the two techniques can advantageously be combined by introducing an effective hard constraint mechanism. The United Snakes framework amplifies the efficiency and reproducibility of the component techniques, and it offers more flexible interactive control while further minimizing user interactions. We apply United Snakes to several different medical image analysis tasks, including the segmentation of neuronal dendrites in EM images, dynamic chest image analysis, the quantification of growth plates in MR images and the isolation of the breast region in mammograms, demonstrating the generality, accuracy and robustness of the tool.

Algorithms↗

Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes.

Hepatocyte nuclear factor 4 (HNF4) was first identified as a DNA binding activity in rat liver nuclear extracts. Protein purification had then led to the cDNA cloning of rat HNF4, which was found to be an orphan member of the nuclear receptor superfamily. Binding sites for this factor were identified in many tissue-specifically expressed genes, and the protein was found to be essential for early embryonic development in the mouse. We have now isolated cDNAs encoding the human homolog of the rat and mouse HNF4 splice variant HNF4 alpha 2, as well as a previously unknown splice variant of this protein, which we called HNF alpha 4. More importantly, we also cloned a novel HNF4 subtype (HNF4 gamma) derived from a different gene and showed that the genes encoding HNF 4 alpha and HNF4 gamma are located on human chromosomes 20 and 8, respectively. Northern (RNA) blot analysis revealed that HNF4 GAMMA is expressed in the kidney, pancreas, small intestine, testis, and colon but not in the liver, while HNF4 alpha RNA was found in all of these tissues. By cotransfection experiments in C2 and HeLa cells, we showed that HNF4 gamma is significantly less active than HNF4 alpha 2 and that the novel HNF4 alpha splice variant HNF4 alpha 4 has no detectable transactivation potential. Therefore, the differential expression of distinct HNF4 proteins may play a key role in the differential transcriptional regulation of HNF4-dependent genes.

Alternative Splicing↗

Expression and distribution of cortical type aromatase mRNA variant in the adult rat brain.

Our previous study showed that a relatively high level of the aromatase mRNA existed in the cerebral cortex (CC) of the rat, where the aromatase activity was reported to be little or absent. To elucidate the identity of the aromatase mRNA in the CC of the rat, we investigated the 5'-region of the aromatase mRNA in the rat CC. When the sequence of the 5'-region of the cortical message was analysed by the 5'-rapid amplification of cDNA ends (5'-RACE) with the antisense primer for exon II using the RNA extracted from the CC, no clone could be isolated. However, the upstream sequence from the 5'-end of exon IV of the aromatase clones, isolated from the CC by RACE with the antisense primers for exon V, was different from that on the aromatase mRNA encoding the full translated region. The new sequence of the cortical type message, called the cortical type aromatase mRNA variant, was located on the intron upstream of exon IV in the genomic cDNA. Distribution of the brain aromatase message with exons III-V and the cortical type aromatase mRNA variant were analysed by the reverse transcription-polymerase chain reaction (RT-PCR) using total RNAs extracted from the hypothalamus-preoptic area (HPOA), amygdala (AMY) and CC. The PCR products with primers for exons III-V were generated from the HPOA and AMY, but not from the CC. On the other hand, the PCR products with primers for exon IIIv (cortical type aromatase mRNA variant specific)-V were detected in significant amounts in the CC as well as the HPOA and AMY. These results indicate the existence of the aromatase mRNA variant lacking exons I-III in the adult rat brain. This cortical type mRNA variant seemed to be widely distributed in the tissues.

Animals↗

[Cor triatriatum dextrum resulting from the persistence of embryonic remnants of the right valve of the sinus venosus: prevalence and echocardiographic aspects in a large consecutive non-selected patient population].

BACKGROUND: Cor triatriatum destrum is a rare congenital malformation, usually associated with complex right heart abnormalities, characterized by a membrane that divides the right atrium into two chambers. It is considered the result of the incomplete and abnormal regression of the embryonic right valve of the sinus venosus. When the valve regresses the cephalic portion forms the crista terminalis and the caudal portion develops into the Eustachian and Thebesian valve. With an incomplete regression, a fenestrated or an unfenestrated membrane may persist in the right atrium. We describe the clinical and echocardiographic characteristics of this type of remnants in the right atrium. METHODS: In a 4-month period, 1728 transthoracic two-dimensional and Doppler echocardiographic studies were consecutively performed. RESULTS: Twenty-seven patients (16 males, 11 females, mean age 55 +/- 21 years, range 1-87 years) were occasionally recognized to be affected by a membrane inside the right atrial cavity. On the basis of its echocardiographic appearance (a membranous structure connecting the orifice of the inferior vena cava to the atrial septum with evident fenestration in 74% of cases), absence of associated congenital abnormalities (92.5% of cases), interatrial shunt or abnormal flow pattern of venous systemic return, a diagnosis of a normal benign anatomic variant of sinus venous remnants (similar to the so-called "Chiari's network") could be made in every case. CONCLUSIONS: The incomplete regression of the embryonic right valve of the sinus venosus may leave a fenestrated or an unfenestrated membrane in the right atrium that should be considered a normal benign variant of the so-called "Chiari's network".

Adolescent↗

[Peroral preparations of cephalosporin antibiotics].

Three successful generations of cephalosporin antibiotics can be divided into parenteral and peroral substances. Both have similar antibacterial and hence therapeutical properties. It is usual to include into the first generation of peroral cephalosporins the so-called phenylglycine, or hydroxyphenylglycine derivatives. The carbacephem variant of Cefaclor (Panoral Lilly), Loracarbef, however, has improved properties and although it is a phenylglycine drug, it could be classified as a second generation cephalosporin. Here we include also the so-called ester-prodrugs: 2nd generation parenteral cephalosporins esterified in the position of C4 (cefuroxime-axetil, Zinnat, cefpodoxime-proxetil, Oralox, etc.). They are broad-spectrum antibiotics, not hydrolysed by resistant bacteria, and, hence, they are effective also against cephalosporin-(1. generation) resistant strains. New structures of cephalosporins, e.g. cefixime and ceftibuten (Cedax) could be classified as cephs of the 3rd generation. They, are stable even against destruction by strains resistant to Cefotaxime or Ceftazidime, and, thus, effective against such bacteria, whose number is expected to increase in the near future. It is concluded that the possibility to administer cephalosporins having different properties, spectrum and stability by both parenteral and peroral way is highly welcomed mainly in pediatric practice and that there are several new and promising drugs in this still developing group of antibacterials.

Administration, Oral↗

Fusion of COL1A1 exon 29 with PDGFB exon 2 in a der(22)t(17;22) in a pediatric giant cell fibroblastoma with a pigmented Bednar tumor component. Evidence for age-related chromosomal pattern in dermatofibrosarcoma protuberans and related tumors.

In contrast with classic dermatofibrosarcoma protuberans (DP), genetic information about the juvenile or pigmented variant forms of DP, so-called giant cell fibroblastoma (GCF) and Bednar tumor (BT), is limited. In the sole karyotyped case of BT a supernumerary ring containing chromosomes 17 and 22 sequences, similar to DP rings, was reported, whereas in three GCF cases, t(17;22) or der(22)t(17;22) with COL1A1-PDGFB fusion involving exons 11, 40, and 47, respectively, have been described. Here, we report the first cytogenetic and molecular analysis of a tumor from a 5-year-old child that contained both GCF and BT components. The karyotype and molecular analyses confirmed the common histogenetic origin between DP, GCF, and BT in showing the presence of a der(22)t(17;22) fusing the COL1A1 exon 29 to PDGFB exon 2. Because COL1A1 exon 29 has been involved previously in gene fusion with PDGFB exon 2 in several cases of adult or infantile DP presenting either t(17;22) or ring chromosomes, our results support the concept that DP, GCF, and BT are morphologic variants of a same entity, rather than distinct tumors. Of interest, our findings give prominence to the relation between patient age and the chromosomal rearrangement pattern in DP and related tumors. Whereas only a few adult DP cases presented with translocations, all the infantile cases, either DP, GCF, or mixed BT-GCF, as shown here, contained translocation derivatives but not ring chromosomes. All the ring chromosomes were observed in adult cases. With respect to cytogenetic studies, DP, GCF, and BT appear to be a unique model for age-related chromosomal rearrangement progression.

Adolescent↗

Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical, and ultrastructural study of a case and review of the literature.

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.

Diagnosis, Differential↗

Massive programmed cell death in intestinal epithelial cells induced by three-dimensional growth conditions: suppression by mutant c-H-ras oncogene expression.

Deregulation of molecular pathways controlling cell survival and death, including programmed cell death, are thought to be important factors in tumor formation, disease progression, and response to therapy. Studies devoted to analyzing the role of programmed cell death in cancer have been carried out primarily using conventional monolayer cell culture systems. However the majority of cancers grow as three-dimensional solid tumors. Because gene expression, and possibly function, can be significantly altered under such conditions, we decided to analyze the control and characteristics of cell death using a compatible three-dimensional tissue culture system (multicellular spheroids) and compare the results obtained to those using two-dimensional monolayer cell culture. To do so we selected for study an immortalized, but nontumorigenic line of rat intestinal epithelial cells, called IEC-18, and several tumorigenic variants of IEC-18 obtained by transfection with a mutant (activated) c-H-ras oncogene. The rationale for choosing these cell lines was based in part on the fact that intestinal epithelial cells grow in vivo in a monolayer-like manner and form solid tumors only after sustaining certain genetic mutations, including those involving the ras gene family. We found that the IEC-18 cells, which grow readily and survive in monolayer cell culture, undergo massive cell death within 48-72 h when cultured as multicellular spheroids on a nonadhesive surface. This process was accompanied by a number of features associated with programmed cell death including chromatin condensation (Hoechst 33258 staining) apoptotic morphology, DNA degradation, and a virtual complete loss of colony forming (clonogenic) ability in the absence of apparent membrane damage as well as accumulation of lipid containing vacuoles in the cytoplasm. Moreover, enforced over-expression of a transfected bcl-2 gene could prevent this cell death process from taking place. In marked contrast, three different stably transfected ras clones of IEC-18 survived when grown as multicellular spheroids. In addition, an IEC cell line (called clone 25) carrying its mutant transfected ras under a glucocorticoid inducible promoter survived in three-dimensional culture only when the cells were exposed to dexamethasone. If exposure to dexamethasone was delayed for as long as 48 h the cells nevertheless survived, whereas the cells became irreversibly committed to programmed cell death (PCD) if exposed to dexamethasone after 72 h. These results suggest that intestinal epithelial cells may be programmed to activate a PCD pathway upon detachment from a physiologic two-dimensional monolayer configuration, and that this process of adhesion regulated programmed cell death (ARPCD) can be substantially suppressed by expression of a mutant ras oncogene.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A spindle cell variant of diffuse large B-cell lymphoma possesses genotypic and phenotypic markers characteristic of a germinal center B-cell origin.

Lymphoma with prominent spindle cell features, the so-called spindle cell lymphoma, is an unusual morphological variant of diffuse large B-cell lymphoma. Five new cases of spindle cell lymphoma have been analyzed by a multiparameter approach in order to clarify its clinical and biological features. All patients presented advanced stage disease with extranodal involvement. Vagina was the most common extranodal site. All patients received chemotherapy and are alive in complete remission. Morphologically, all five cases exhibited proliferation of spindle cells with a vaguely storiform pattern highly suggestive of spindle cell neoplasms of nonlymphoid origin. In contrast, the results of immunohistochemical analysis indicated that all five cases were hematolymphoid neoplasms of the B-cell lineage. These lymphomas consisted of a B-cell clonal population which exhibited somatic immunoglobulin and BCL-6 mutations as well as BCL-6 protein expression. The neoplastic spindle cells therefore closely resemble B cells residing in the germinal center. The absence of MUM1 expression in neoplastic spindle cells suggested that neoplastic spindle cells may be related to the early phases of intragerminal center maturation of B cells. The germinal center phenotype, with restricted expression of BCL-6, was associated with the presence of a primary extranodal origin, normal lactate dehydrogenase levels, and good response to treatment.

Adult↗

Multiple mechanisms of immune evasion by African trypanosomes.

During infection of a mammalian host, African trypanosomes are in constant contact with the host's immune system. These protozoan parasites are infamous for their ability to evade the immune responses by periodically switching their major variant surface glycoprotein (VSG), a phenomenon called antigenic variation. Antigenic variation, however, is likely to be only one of several mechanisms enabling these organisms to thrive in the face of the immune defenses. The ability to grow in high levels of interferon-gamma (IFN-gamma) and to avoid complement-mediated destruction may also facilitate the parasite's survival. In this review we summarize (i) the activation of trypanosome genes for three different VSGs during antigenic variation, (ii) the secretion of a trypanosome protein that induces host CD8 T cells to produce IFN-gamma, and (iii) the evidence for trypanosome protein similar to a surface protease of Leishmania that plays a role in resistance to complement-mediated lysis.

Amino Acid Sequence↗

A variant of fibrous dysplasia (osteofibrous dysplasia).

We are reporting the cases of five patients with a tumor-like lesion that has recently been called osteofibrous dysplasia but has also been called osteogenic fibroma, monostotic cortical fibrous dysplasia, and a variant of fibrous dysplasia. The lesions in our patients developed in childhood and were located in the diaphysis of the tibia, which was bowed anteriorly. The structural stability of the limb was not affected. In four patients the lesion recurred after a biopsy and curettage was performed in childhood. No further surgical procedure was done until the patients reached skeletal maturity. The lesion in one patient was biopsied at the age of twenty-one years. No subsequent treatment was recommended.

Adult↗

Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants: comparison with mGluR1.

The main excitatory neurotransmitter in the brain, glutamate (Glu), activates not only receptor-channels, but also receptors coupled to G-protein called metabotropic Glu receptors (mGluRs). Eight genes coding for mGluRs have been characterized to date giving rise to even more proteins due to alternative splicing phenomena. Here we characterized a splice variant of mGluR5, called mGluR5b which contains a 32 amino acid fragment inserted in the cytoplasmic tail, 50 residues after the 7th transmembrane domain. mGluR5b mRNAs are present in different regions of the adult rat brain and are expressed at a higher level than mGluR5a mRNA. Functional analysis of mGluR5a and mGluR5b revealed that they share all the properties of mGluR1a, but not those of mGluR1b or 1c. Like mGluR1a, both mGluR5a and mGluR5b activate a rapid and transient current in Xenopus oocytes. When expressed in LLC-PK1 cells, they show the same subcellular distribution as mGluR1a, and stimulate both inositol phosphate (IP) and cAMP production. Moreover, cells expressing mGluR5a or mGluR5b, like those expressing mGluR1a have a higher basal PLC activity that is not inhibited by glutamate-pyruvate transaminase (GPT), suggesting that these receptors have an intrinsic activity. Interestingly, the pharmacological profiles of mGluR5a and b are identical, but different from that of mGluR1a. Most agonists, except glutamate, are more potent on mGluR5a/b than on mGluR1a. Interestingly, the mGluR1a antagonists MCPG and 4CPG have no effect on mGluR5a/b; 4C3HPG which is a full antagonist at mGluR1a is a partial agonist at mGluR5a/b. These results indicate that the long C-terminal intracellular domain present only in mGluR1a and mGluR5a/b, although not well conserved, is likely to be involved in the specific functional properties of these receptors. Although the ligand recognition sites of mGluR5a/b and mGluR1a are highly conserved, these receptors have different pharmacology.

Alternative Splicing↗

Cyclin D1/PRAD1/BCL-1 alternative transcript [B] protein product in B-lymphoid malignancies with t(11;14)(q13;q32) translocation.

The cyclin-D1/PRAD1 oncogene, a key regulator of the G1-phase progression of the cell cycle, has been identified as the long-sought BCL-1 oncogene in B-cell malignancies with t(11;14)(q13;q32) translocation. A novel alternative spliced cyclin-D1 transcript, called transcript[b], has been identified. The level of the variant transcript[b] was lower than that of the originally reported cyclin-D1 transcript, called transcript[a], in several human non-lymphoid cancer cell lines but the endogenous cellular expression of transcript[b] products has not yet been determined. Northern-blot analysis and reverse-transcription-polymerase-chain-reaction (RT-PCR) analysis revealed that transcript[b] mRNA is well expressed in B-lymphoid cell lines with t(11;14)(q13;q32) translocation and at much lower or undetectable levels in other cells. Western-blot analysis using a human cyclin-D1-specific monoclonal antibody, which can recognize and distinguish the products of transcripts [a] and [b], strongly suggested that the transcript [b] protein is indeed expressed in these B-cell lines. The present study provides identification of the endogenous cellular expression of the cyclin-D1-transcript[b] protein and strongly suggests that this alternative form of cyclin D1 may play a significant role in the molecular pathogenesis of B-lymphoid malignancies with t(11;14)(q13;q32) translocation.

Alternative Splicing↗

Sternocleidomastoid myofascial flap for head and neck reconstruction.

BACKGROUND: The use of the sternocleidomastoid (SCM) muscle in the repair of soft tissue defects arising after surgery for neoplasms of the head and neck has been a subject of controversy. We describe a variant of the SCM muscle flap called the "SCM myofascial flap" and report our experience with this flap in head and neck reconstruction. METHODS: Six patients underwent head and neck reconstruction with the SCM myofascial flap. The head and neck defects included partial laryngeal, pharyngeal defects, and concave soft tissue neck defects after resection. RESULTS: Follow-up of the patients ranged from 6 to 91 months. In the case of laryngeal and pharyngeal reconstruction, all had a good voice and were able to eat by mouth without aspiration. Two of the four patients were decannulated. The only complication was a laryngo-cutaneous fistula. CONCLUSION: We have used this flap with success, in soft tissue augmentation and in laryngeal and pharyngeal reconstruction following tumor resection. The technique and the results of our experience are discussed. We believe that in selected cases, the SCM myofascial flap is ideal for reconstruction of head and neck defects.

Aged↗

6-hydroxydopamine lesions in anuran amphibians: a new model system for Parkinson's disease?

We investigated the effects of dopamine depletion on acoustically guided behavior of anurans by conducting phonotaxis experiments with female gray treefrogs (Hyla versicolor) before and 90 min after bilateral injections of 3, 6, or 12 microg 6-hydroxydopamine (6-OHDA) into the telencephalic ventricles. In experiments with one loudspeaker playing back a standard artificial mating call, we analyzed the effects of 6-OHDA on phonotactic response time. In choice tests we measured the degree of distraction from the standard call (20 pulses/s) by three different variants with altered pulse-rate (30/s, 40/s, 60/s). Five days after experiments, brains were immunostained for tyrosine hydroxylase. Labeled neurons were counted in the suprachiasmatic nucleus, posterior tuberculum, interpeduncular nucleus, and locus coeruleus, and correlation between neuronal numbers and behavioral scores was tested. Response times increased together with 6-OHDA concentrations, which was mainly due to longer immobile periods before the animals started movement. In choice tests the most irrelevant stimulus (60/s) distracted 6-OHDA injected females from the standard stimulus, while sham injected controls were undistracted. The number of catecholaminergic neurons decreased with increasing 6-OHDA concentration in the suprachiasmatic nucleus, posterior tuberculum, and interpeduncular nucleus. The normalized number of immunoreactive neurons in the posterior tuberculum was positively correlated with phonotaxis scores in the one-speaker test, demonstrating that motor deficits are a function of tubercular cell loss. We conclude that bilateral 6-OHDA lesions in anuran amphibians cause motor (difficulty to start movements) as well as cognitive symptoms (higher distraction by irrelevant stimuli) that have also been described for human Parkinson patients.

Acoustic Stimulation↗