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H Potter

Publications and source records attributed to H Potter.

At least 19 recordsLinked to original sources
PubMed2004

Environmental enrichment improves cognition in aged Alzheimer's transgenic mice despite stable beta-amyloid deposition.

Environmental enrichment (EE) has been shown to improve cognitive performance and brain indices of cognition in normal mice and rats. Because the therapeutic potential of intensive, long-term EE to benefit patients with Alzheimer's disease (AD) has yet to be explored, the present study evaluated the effect of long-term EE on cognition in an animal model of AD, the APPsw transgenic mouse. Beginning at 16 months of age, APPsw mice were put into EE or standard housing for 4 months and then tested in four cognitive-based tasks (Morris maze, circular platform, platform recognition, and radial arm water maze) between 20 and 22 months of age. Our results indicate that long-term EE of aged APPsw mice results in global, overall improvement in cognitive function across these tasks without decreasing brain beta-amyloid (A beta) deposition. The results suggest that long-term EE/cognitive stimulation could provide cognitive stabilization or improvement to AD patients through mechanisms independent of A beta deposition and clearance.

Aging↗
PubMed2001

Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer's disease.

Alpha(1)-antichymotrypsin (ACT), an acute-phase inflammatory protein, is an integral component of the amyloid deposits in Alzheimer's disease (AD) and has been shown to catalyze amyloid beta-peptide polymerization in vitro. We have investigated the impact of ACT on amyloid deposition in vivo by generating transgenic GFAP-ACT-expressing mice and crossing them with the PDGF-hAPP/V717F mice, which deposit amyloid in an age-dependent manner. The number of amyloid deposits measured by Congo Red birefringence was increased in the double ACT/amyloid precursor protein (APP) transgenic mice compared with transgenic mice that only expressed APP, particularly in the hippocampus where ACT expression was highest, and the increase was preceded by elevated total amyloid beta-peptide levels at an early age. Our data demonstrate that ACT promotes amyloid deposition and provide a specific mechanism by which inflammation and the subsequent upregulation of astrocytic ACT expression in AD brain contributes to AD pathogenesis.

Alzheimer Disease↗
PubMed2001

The anatomy and histology of the rotator interval capsule of the shoulder.

Forty-seven rotator interval regions from fetuses and 10 fresh-frozen rotator interval regions from adult cadavers were evaluated by gross dissection and light microscopy. Specimens from adults also were evaluated with ultrasound and magnetic resonance imaging. An analysis of 37 fetal specimens (> 14 weeks gestation) revealed two rotator interval types: Type I (9 of 37) was defined by a contiguous bridge of capsule consisting of poorly organized collagen fibers. A Type II rotator interval (28 of 37) had a complete defect covered by only a thin layer of synovium. Similar to the Type II rotator interval in the fetus, a rotator interval defect was present in six of eight specimens from adults. Histologically, the capsular tissue within the rotator interval consisted of poorly organized collagen fibers in specimens from the fetus and adult. Maximal opening of the rotator interval was seen by ultrasound with internal rotation and downward traction of the hyperextended arm in the coronal, oblique, and sagittal planes. Magnetic resonance imaging of the rotator interval region permitted anatomic evaluation. The complete absence of tissue in 28 of 37 fetuses suggests that the rotator interval defect is congenital. The authors recommend that surgeons carefully evaluate the integrity of the tissue within the rotator interval. When rotator interval closure is desired such as in patients with a persistent sulcus sign after arthroscopic stabilization, suturing the edges of more substantial tissue immediately adjacent to the boundaries of the rotator interval region would seem prudent.

Adult↗
PubMed2000

Ultrastructural observations on sperm storage in the ovary of the platyfish, Xiphophorus maculatus (Teleostei: poeciliidae): the role of the duct epithelium.

Sperm storage is an important phenomenon occurring in viviparous and oviparous teleosts and contributes to the reproductive life history of these forms. There is a paucity of morphological studies on sperm storage in fishes. The majority of these have been confined to the light level of investigation. In this report, we describe, at the ultrastructural level, sperm storage in the viviparous platyfish, Xiphophorus maculatus. Female platyfish, as is typical of the poeciliids, are capable of storing viable sperm for up to several months within the ovary and gonoduct. We observed that sperm stored within inseminated platyfish became associated with specific epithelial cells (SACs) lining the oviduct. Two forms of association were seen: 1) sperm were found within deep surface pits and pockets, and 2) the spermatozoa were taken up and incorporated within the cytoplasm of the SACs. Junctional complexes in the form of tight junctions (zona occludens) and desmosomes at the apico-lateral surfaces of the SACs were prevalent. The junctions could have contributed to allograft survival of the haploid heterogenetic sperm cells within the female's reproductive tract. Our results shed light on the mechanism of sperm storage in the platyfish and could serve as a model for other poeciliid species and teleosts that are capable of storing sperm.

Animals↗
PubMed2000

Immune response to an 18-kilodalton outer membrane antigen identifies lipoprotein 20 as a Helicobacter pylori vaccine candidate.

Experiments were performed using the standardized murine model of Helicobacter pylori infection to determine the immunogenicity of H. pylori outer membrane vesicles in immune protection. These vesicles, which are naturally shed from the surface of the bacterium, induce a protective response when administered intragastrically to mice in the presence of cholera holotoxin, despite the absence of the urease enzyme and associated Hsp54 chaperonin. Immunoblotting identified a specific serum immunoglobulin G (IgG) response to an 18-kDa outer membrane protein in a significant number of immunized animals. This commonly expressed, immunodominant protein was subsequently identified as lipoprotein 20 (Lpp20). Hybridoma backpacks secreting an IgG1 subclass monoclonal antibody to Lpp20 were generated in H. pylori-infected mice and were found to significantly reduce bacterial numbers, providing evidence that this surface-exposed antigen is a true vaccine candidate and not merely an antigenic marker for successful, protective immunization.

Animals↗
PubMed1999

Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5'-untranslated region sequences.

The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both base-line and IL-1-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD.

Alzheimer Disease↗
PubMed1999

Chromosome missegregation and trisomy 21 mosaicism in Alzheimer's disease.

A connection between Alzheimer's disease (AD) and Down syndrome (trisomy 21) is indicated by the fact that all Down syndrome individuals develop Alzheimer's disease neuropathology by the 4th decade of life. Previous studies have examined the frequency of aneuploidy and other chromosomal defects in cells from familial Alzheimer's disease (FAD) patients, with varying results. To investigate the possibility that a specific type of aneuploidy--trisomy 21 mosaicism--may contribute to Alzheimer's disease, we used quantitative fluorescence in situ hybridization to measure the number of trisomy 21 cells in primary fibroblast cultures from AD and unaffected subjects. The 27 AD cultures, including 15 that were derived from individuals carrying FAD mutations in presenilin 1 or 2, exhibited a significant approximately twofold increase in the number of trisomy 21 cells compared to 13 control cultures. A small double-hybridization experiment suggested that the aneuploidy in AD cells was not limited to chromosome 21 but extended at least to chromosome 18 as well. In a parallel study, the endogenous presenilin proteins in fibroblasts were localized to the centrosomes, the nuclear envelope, and its associated interphase kinetochores. Together these results indicate that the presenilin proteins may be involved in mitosis and that FAD mutations in the presenilin genes may predispose to chromosome missegregation (nondisjunction). The data reported here also suggest that trisomy 21 mosaicism may contribute to other forms of AD that are not caused by a presenilin mutation.

Alleles↗
PubMed1999

Idiopathic pseudoaneurysm of the dorsalis pedis artery mimicking pigmented villonodular synovitis.

Pseudoaneurysm of the dorsalis pedis artery is uncommon and is usually associated with a history of trauma to the vessel. Without such a history, the diagnosis may be challenging, because the mass may be confused with other common soft tissue masses in the foot. This case report describes a 67-year-old man with an idiopathic pseudoaneurysm of the dorsalis pedis artery that mimicked pigmented villonodular synovitis.

Aged↗
PubMed1998

The essential role of inflammation and induced gene expression in the pathogenic pathway of Alzheimer's disease.

Alzheimer's disease is among the most common diseases of advanced age affecting almost one out of ten individuals who survive beyond the age of 65 years, and an another 10% for each additional decade of the life-span. The prognosis of the disease is an inexorable decline of mental functions leading to complete dependence on caretakers in the late stages of the disease. Alzheimer's disease will become a steadily increasing financial health-care problem in the industrialized world with the increasing longevity and ageing of the population. To-date there are no effective therapeutics. However, during the last years promising findings suggest that anti-inflammatory treatment strategies might be efficient. Here, we will review the experimental and epidemiological findings which support the idea that inflammatory mechanisms play an important role in Alzheimer's disease pathogenesis. The review of the experimental findings will be focussed on the amyloid-associated proteins, alpha1-antichymotrypsin and apolipoprotein E, as well as the major cytokines. In addition, the epidemiological studies on non-steroidal anti-inflammatory drugs and traumatic head injury will be summarized. We hypothesize a pathogenic model for Alzheimer's disease in which the expression of amyloid-associated proteins/pathological chaperones, induced by inflammatory cytokines, plays an essential role in accelerating the disease progress, and suggest potential targets for drug discovery based on such a model.

Aged↗
PubMed1998

A general RNA-binding protein complex that includes the cytoskeleton-associated protein MAP 1A.

Association of mRNA with the cytoskeleton represents a fundamental aspect of RNA physiology likely involved in mRNA transport, anchoring, translation, and turnover. We report the initial characterization of a protein complex that binds RNA in a sequence-independent but size-dependent manner in vitro. The complex includes a approximately 160-kDa protein that is bound directly to mRNA and that appears to be either identical or highly related to a approximately 1600-kDa protein that binds directly to mRNA in vivo. In addition, the microtubule-associated protein, MAP 1A, a cytoskeletal associated protein is a component of this complex. We suggest that the general attachment of mRNA to the cytoskeleton may be mediated, in part, through the formation of this ribonucleoprotein complex.

Animals↗
PubMed1997

Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation.

Mutations in two related genes, presenilin 1 and 2, account for most early-onset familial Alzheimer's disease. Although structural features indicate that the presenilins are membrane proteins, their function(s) is unknown. We have localized the presenilins to the nuclear membrane, its associated interphase kinetochores, and the centrosomes-all subcellular structures involved in cell cycle regulation and mitosis. The colocalization of the presenilins with kinetochores on the nucleoplasmic surface of the inner nuclear membrane, together with other results, suggests that they may play a role in chromosome organization and segregation, perhaps as kinetochore binding proteins/receptors. We discuss a pathogenic pathway for familial Alzheimer's disease in which defective presenilin function causes chromosome missegregation during mitosis, resulting in apoptosis and/or trisomy 21 mosaicism.

Alzheimer Disease↗
PubMed1997

Cytoskeletal changes in the brains of mice lacking calcineurin A alpha.

Hyperphosphorylated tau, the major component of the paired helical filaments of Alzheimer's disease, was found to accumulate in the brains of mice in which the calcineurin A alpha gene was disrupted [calcineurin A alpha knockout (CNA alpha -/-)]. The hyperphosphorylation involved several sites on tau, especially the Ser396 and/or Ser404 recognized by the PHF-1 monoclonal antibody. The increase in phosphorylated tau content occurred primarily in the mossy fibers of the CNA alpha -/- hippocampus, which contained the highest level of calcineurin in brains of wild-type mice. The CNA alpha -/- mossy fibers also contained less neurofilament protein than normal, although the overall level of neurofilament phosphorylation was unchanged. In the electron microscope, the mossy fibers of CNA alpha -/- mice exhibited abnormalities in their cytoskeleton and a lower neurofilament/microtubule ratio than those of wild-type animals. These findings indicate that hyperphosphorylated tau can accumulate in vivo as a result of reduced calcineurin activity and is accompanied by cytoskeletal changes that are likely to have functional consequences on the affected neurons. The CNA alpha -/- mice were found in a separate study to have deficits in learning and memory that may result in part from the cytoskeletal changes in the hippocampus.

Animals↗
PubMed1996

Structure and alternative splicing of the presenilin-2 gene.

Missense mutations in the presenilin-1 (PS-1) and presenilin-2 (PS-2) genes have been shown to be causes of autosomal dominant Alzheimer's disease (the AD3 and AD4 loci, respectively). Alternative splicing has previously been reported in the PS-1 gene. In this study, elucidation of intron/exon boundary sequences revealed that PS-2 is encoded by 10 coding exons. In addition, PS-2 cDNA cloning and RT-PCR using RNA from a variety of normal tissues revealed the presence of alternatively spliced products. These products included species with in frame omissions of exon 8 and simultaneous omissions of exons 3 and 4.

Alternative Splicing↗