PubMed Health⌕ Search

Biomedical subjects

H Wisniewski

Publications and source records attributed to H Wisniewski.

At least 19 recordsLinked to original sources
PubMed2001

Alzheimer's disease presenilin-1 expression modulates the assembly of neurofilaments.

Mutations in presenilin-1 gene are responsible for the majority of early-onset familial Alzheimer's disease cases. The function of this protein and the mechanism underlying the pathogenicity of its mutations are still unclear. To elucidate the role of presenilin-1 in the Alzheimer's disease pathology, we tested two such mutations (P117L and M146L) for their effect in stably transfected mouse neuroblastoma cell lines. Over-expression of the wild-type presenilin-1 gene induced formation of a well-extended, orderly organized network consisting of neurofilaments assembled from the L and H subunits, while in cells with the mutant gene this network was markedly reduced to short filaments concentrated in structures resembling cups. Cells expressing the mutant gene displayed altered processing of the transgene protein and neurofilament-H, suggesting that presenilin-1 is the mediator of changes targeted at neurofilaments. The two different mutations produced similar alterations, implying that this is a common pathogenic mechanism. Presenilin-1, neurofilament-H and tau proteins showed co-localization as evidenced by confocal microscopy, suggesting a possible physiological connection between these three proteins. Presenilin-1 appears to influence assembly of the H subunit into neurofilaments and the subsequent formation of new neurites. Mutations impair this function of presenilin-1, resulting in inhibition of neurite outgrowth. That presenilin-1 influences the assembly of neurofilaments may represent a novel pathway through which presenilin-1 mutations are involved in Alzheimer's disease pathology. In this hypothesis, presenilin-1 mutations will be associated with aberrant sprouting leading to synaptic loss, a key neuropathological feature of Alzheimer's disease.

Alzheimer Disease↗
PubMed1996

In vivo structural studies of the hippocampus in normal aging and in incipient Alzheimer's disease.

Population trends indicate that in the near future the size of the elderly population will increase. This will result in a large increment in the numbers of persons suffering mild to severe levels of cognitive impairment. While considerable efforts continue to be made to explain brain changes associated with Alzheimer disease (AD), little is known of the brain changes in aging without dementia or so-called normal aging. Pathologic studies suggest that the medial temporal lobe is informative in the examination of the early brain changes related to AD. However, pathologic studies only offer a single observation and considerable uncertainty exists regarding the likelihood of progression of disease and the development of dementia. Several structural neuroimaging studies have recently investigated this anatomy and recent reports are encouraging for a medial temporal lobe based diagnosis for age-related cognitive impairments. We will present our findings on the MRI anatomy of the hippocampal formation as well as data bearing on the use of hippocampal formation imaging in the diagnosis of AD and as a predictive marker for future dementia. Our findings suggest an anatomically specific relationship between hippocampal volume and secondary memory performance. Because these observations apply to nondemented and normal elderly subjects, we are encouraged that the anatomy of age-related cognitive impairments can be reliably recognized and possibly put to use in therapeutic studies.

Aged↗
PubMed1993

Hippocampal atrophy in early Alzheimer's disease: anatomic specificity and validation.

We evaluated three groups of elderly individuals who were carefully screened to rule out clinically significant diseases that could affect cognition. They were matched for age and education. The groups included normals (N = 18), Alzheimer's Disease (AD) patients (N = 15), and minimally impaired individuals with memory complaints and impairments but who did not fulfill criteria for AD (N = 17). Volumetric measurements of different regions of the temporal lobe on the coronal scan as well as ratings of the perihippocampal cerebrospinal fluid (CSF) accumulation (HCSF) on the negative angle axial MR were carried out. Volume reductions were found in AD relative to the normals for both medial and lateral temporal lobe volumes. Only hippocampal volume reductions were found in the minimal group. The minimally impaired individuals had equivalent hippocampal volume reductions and significantly larger parahippocampal and lateral temporal lobe gyri than the AD group. The axial HCSF was validated using the coronal volumes. The combination of coronal hippocampal and perihippocampal CSF was the best predictor of the axial HCSF rating. The parahippocampal volume did not add to the predictive ability of the hippocampal-perihippocampal CSF combination. Future work should validate these findings with longitudinal designs as well as assess the issue of normal aging of these structures and their relationship to cognitive function.

Aged↗
PubMed1991

A prion protein variant in a family with the telencephalic form of Gerstmann-Sträussler-Scheinker syndrome.

We present a patient with a mutation in the open reading frame of the prion protein gene (PRNP), which results in substitution of valine for alanine at codon 117. The patient is a member of a large American kindred of German descent with the telencephalic form of Gerstmann-Sträussler-Scheinker syndrome (GSS). Two other affected members of this kindred carried this mutation, as inferred from haplotypes of their offspring and spouses. The mutation was absent in one member with a protracted neurologic illness that differed from the other affected members' illnesses. The identification of a distinct PRNP mutation in the telencephalic form of GSS supports the hypothesis that allelic forms of PRNP may correspond to distinct clinical disease entities.

Alanine↗
PubMed1987

Retinal degeneration in 3-month-old rhesus monkey infants fed a taurine-free human infant formula.

Rhesus monkey infants were raised from birth on a taurine-free soy protein-based human infant formula or on the same formula supplemented with taurine. The monkeys were killed 3 months after birth and the retinas examined by light and electron microscopy. All of the monkeys raised on formula alone showed degenerative ultrastructural changes in photoreceptor outer segments that ranged from swelling and disorientation to fragmentation and disorganization. Cones were more severely affected than rods, and changes were most pronounced in the foveal region. Changes were also noted in the fine structure of the retinal pigment epithelium. These changes were prevented in all but one monkey fed the same formula supplemented with taurine. These results provide further support for the addition of taurine to commercial human infant formulas.

Animals↗
PubMed1986

Abnormal visual cortex development in the kitten associated with maternal dietary taurine deprivation.

We have examined the visual cortex of newborn and 8-week-old kittens born to mothers consuming a taurine-supplemented or taurine-free diet using the rapid Golgi technique. Kittens from taurine-supplemented mothers exhibited normal development of the visual cortex. Kittens from taurine-depleted mothers showed striking differences. In newborn kittens, neuroblasts are aggregated both at the ventricular and pial zones, having failed to migrate and differentiate normally. Eight weeks after birth, only few pyramidal and nonpyramidal neurons are found. Those present have heavily spined dendritic processes indicative of poor arborization. Protoplasmic astrocytes are represented by undifferentiated cellular masses. The taurine concentration in the cortex of such kittens is four- to fivefold smaller than in kittens from taurine-supplemented mothers. These results suggest that normal concentrations of taurine in visual cortex, as well as cerebellum, are required for normal ontogeny of neurons. Once such deficits are established in the prenatal and immediate postnatal period, they result in permanent abnormalities. These findings have clear implications for vegetarian women who intend to have children, since virtually no taurine is present in plants and vegetables.

Aging↗
PubMed1986

Chromatin structure in scrapie and Alzheimer's disease.

Scrapie affected brains exhibit a number of pathological features in common with the human neurodegenerative condition, Alzheimer's disease. The present report describes studies on chromatin structure seen in these two disease processes. Chromatin associated proteins influence transcriptional activity of DNA through an effect upon chromatin structure. We examined chromatin structure by: measuring the capacity of the enzyme micrococcal nuclease to release mono- and dinucleosomes from isolated nuclei and measuring DNA-histone interactions by examining the effect of ambient tonicity upon the release of chromatin proteins. In two strains of mice infected with two strains of scrapie agent there was reduced accessibility to micrococcal nuclease and an increased content on dinucleosomes of the histone H1 and H1(0) types. These changes precede clinical signs of scrapie and resemble those found in the human conditions of Alzheimer's and Pick's disease. Scrapie mouse brain differs from Alzheimer brain in that scrapie does not alter histone-DNA interactions as monitored by ionically induced histone release from chromatin. Despite similarities, the scrapie agent appears to operate upon different molecular mechanisms than those found in Alzheimer's disease.

Alzheimer Disease↗
PubMed1976

Hydrocephalus: III. Reconstitution of the cerebral cortical mantle following ventricular shunting.

Adult cats with hydrocephalus were sacrificed at varying times following valveless ventricular shunting. This shunting resulted in a prompt reduction of ventricular size and rapid gross reconstitution of cortical mantle. Ultrastructurally it was evident that white matter edema persisted for many weeks, even in the presence of normal size ventricles. The areas most severely affected by the hydrocephalus such as the corpus callosum showed a paucity of myelinated fibers and their replacement by numerous reactive astrocytes. Reconstitution of the cortical mantle consists predominantly of a diminution of white matter edema and reactive astrocytosis. Clinical improvement undoubtly results from the functional improvement of remaining elements rather than from the replacement of lost elements. This scheme of hydrocephalus suggests that if hydrocephalus is relieved when only ependymal disruption and periventricular water accumulation have occurred, it may be reversible. The subsequent sequence of events consisting of axonal degeneration, myelin disruption and reactive astrocytosis may be less, if at all reversible.

Animals↗
PubMed1976

Lack of amyloidosis and renal disease in A strain mice.

Amyloid deposition in two sublines of the A strain mouse, a reputedly reliable murine model of spontaneous amyloidosis, was reevaluated using combined green polarization birefringence after Congo red staining and a fibrillar ultrastructure for amyloid identification. Both sublines were found to be devoid of amyloid at an age when the A strain mouse had been reported to have a high incidence of papillonephritis, amyloidosis, and death. This finding indicates a need for reassessment of this and other traditional models of spontaneous amyloidosis.

Adrenal Glands↗
PubMed1969

Induction in vitro of microtubular crystals by vinca alkaloids.

The addition of vinblastine or vincristine to solutions of pure microtubule protein or to supernatants from high-speed centrifugation of rabbit-brain homogenates results in the formation of a fine precipitate. Examination of this precipitate by electron microscopy reveals ordered structures with areas of ladder-like configuration.

Animals↗