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Biomedical subjects

K Wisniewski

Publications and source records attributed to K Wisniewski.

At least 19 recordsLinked to original sources
PubMed2001

Diagnosis of late-infantile neuronal ceroid lipofuscinosis: a new sensitive method to assay lysosomal pepstatin-insensitive proteinase activity in human and animal specimens by capillary electrophoresis.

Batten disease, or human late-infantile neuronal ceroid lipofuscinosis (LINCL) is a familiar progressive degenerative disease affecting children, caused by a deficiency of a lysosomal proteinase (tripeptidyl peptidase I, TPP-I) and characterized by the accumulation of autofluorescent storage bodies in the brain and other tissues of the body. Current methodology used to diagnose this disease needs to be improved in order to have less invasive techniques with higher resolution and shorter assay time. In this report, we discuss the potential merits of micellar electrokinetic chromatography as an excellent tool that requires minute samples but offers high resolution and a short running time for monitoring TPP-I activity in human and animal specimens.

Aminopeptidases↗
PubMed2000

Bilateral 6-OHDA lesions to the hippocampus attenuate the facilitatory effect of CCK-8 us and caerulein on memory in rats.

The involvement of dopaminergic projection to the hippocampus in the facilitatory effect of cholecystokinin-unsulphated octapeptide (CCK-8 us) and caerulein (CER) on memory motivated affectively was investigated in male rats. CCK-8 us and CER were given subcutaneously at the doses of 10 microg kg(-1)and 0.5 microg kg(-1), respectively, immediately after a single learning trial in a passive avoidance situation, after bilateral 6-OHDA lesions to the dentate gyrus of the hippocampus. In order to protect noradrenergic neurones against destruction by neurotoxin, 30 min before surgery rats were pre-treated intraperitoneally with 25 mg kg(-1)of desmethylimipramine, an inhibitor of noradrenaline uptake. Bilateral 6-OHDA lesions to the hippocampus significantly attenuate the facilitatory effect of CCK-8 us and CER on retention of passive avoidance behaviour evaluated 24 h after the learning trial. Neither, destruction of dopaminergic endings in the hippocampus, nor application of CCK-8 us and CER changed the spontaneous psychomotor activity of rats estimated in an 'open field' test. These results may indicate that the facilitatory effect of CCK-8 us and CER on memory motivated affectively is, in part, mediated by dopaminergic projection from the ventral tegmental area to the dentate gyrus of the hippocampus.

Animals↗
PubMed1999

Disruption of temporo-entorhinal connections abolishes the facilitatory effect of angiotensins on memory in rats.

It has been found in our laboratory that the positive influence of angiotensin II (AII) and its 3-7 fragment [AII(3-7)] on learning and memory processes is mediated by the excitatory amino acids, since it was abolished by NMDA receptor antagonists. The purpose of the present study was to investigate whether bilateral disruption of glutamatergic temporo- entorhinal connections may have an influence on the facilitatory effect of both angiotensin peptides on memory motivated affectively. The bilateral transections of temporo-entorhinal connections were made in 27 male rats 10 days before testing the influence of intracerebroventricular AII and AII(3-7) injection on retrieval of a passive avoidance response. Twenty-seven additional rats served as sham-operated controls. Twenty-five lesioned and 25 sham-operated animals were accepted to the final analysis. AII and its 3-7 fragment significantly improved the retrieval process in sham-operated groups of rats. Bilateral disruption of temporo-entorhinal connections totally abolished the facilitatory effect of both angiotensins on recall of information in a passive avoidance situation. Moreover, bilateral disruption of temporo-entorhinal connections markedly but not significantly attenuated crossings of squares, evaluated in an open field test, without an influence on rearings and bar approaches. These results may suggest that in the facilitatory effect of AII and AII(3-7) on memory motivated affectively involves reciprocal glutamatergic connection between lateral entorhinal cortex and temporal cortex.

Angiotensin II↗
PubMed1999

Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.

The late-infantile form of neuronal ceroid lipofuscinosis (LINCL) is a progressive and ultimately fatal neurodegenerative disease of childhood. The defective gene in this hereditary disorder, CLN2, encodes a recently identified lysosomal pepstatin-insensitive acid protease. To better understand the molecular pathology of LINCL, we conducted a genetic survey of CLN2 in 74 LINCL families. In 14 patients, CLN2 protease activities were normal and no mutations were identified, suggesting other forms of NCL. Both pathogenic alleles were identified in 57 of the other 60 LINCL families studied. In total, 24 mutations were associated with LINCL, comprising six splice-junction mutations, 11 missense mutations, 3 nonsense mutations, 3 small deletions, and 1 single-nucleotide insertion. Two mutations were particularly common: an intronic G-->C transversion in the invariant AG of a 3' splice junction, found in 38 of 115 alleles, and a C-->T transition in 32 of 115 alleles, which prematurely terminates translation at amino acid 208 of 563. An Arg-->His substitution was identified, which was associated with a late age at onset and protracted clinical phenotype, in a number of other patients originally diagnosed with juvenile NCL.

Amino Acid Sequence↗
PubMed1999

Synthesis and characterization of new chiral peptide nucleic acid (PNA) monomers.

PNAs are DNA analogues in which the nucleic acid's backbone is replaced by a chiral or achiral pseudopeptide backbone and nucleobases are attached to the backbone by methylene carbonyl linkers. The easy to modify PNA structure gives the possibility to obtain monomers, and subsequently oligomers, with improved properties. We have synthesised several new PNA monomers, starting from a series of 2'-substituted methyl N-(2-Boc-aminoethyl)glycinates. The pseudodipeptides were obtained using modified Kosynkina's method, based on the reductive amination of N-Boc-protected alpha-amino aldehydes [glycinal, isoleucinal, valinal, tryptophanal, serinal(Bzl), prolinal] with methyl glycinate. The compounds were then acylated with nucleic acid base derivatives by simplified procedure, and the purification was limited to the last step of the synthesis. The applied procedure is useful in synthesis of various chiral PNA monomers.

Aldehydes↗
PubMed1999

New procedure of the Mitsunobu reaction as the key step in peptide nucleic acid (PNA) monomers synthesis.

PNAs are relatively novel DNA analogues, intensively studied due to their potential as gene-targeted drugs with antigene and antisense properties. In 1996 we elaborated a new method of synthesis of PNA monomer backbones based on the Mitsunobu reaction with N-tosyl-protected (Tos) amino acid esters as acidic components of the reaction. Since the method used for the Tos group removal requires conditions incompatible with various functional groups, here we modified the procedure by replacing the tosyl group with o-nitrobenzenesulfonyl (o-NBS) group. Using the new procedure we obtained protected PNA monomer backbones with various amino acid side chains. The pseudodipeptide secondary amine groups were then deprotected by thiolysis, and after standard work-up acylated with thymin-1-ylacetic acid, to give the protected monomers. Since the deprotection of the secondary amine group occurs under mild conditions, the procedure is of general applicability and allows various modifications of PNA structure by using diverse beta-amino alcohols and alpha-amino acid esters.

Amino Acids↗
PubMed1996

Migration disorders leading to a wide spectrum of brain malformations in a case with multiorganic dysgeneses: A new syndrome?

A case of a preterm infant who died with multiorgan, mainly cerebro-oculo-cutaneous malformations is presented. The brain dysgenesias consist of early disturbances of neuronal migration. They result on appearance of nodular subcortical heterotopias, cortical anomalies including pachy- and polymicrogyria and focal intrusion of numerous abnormally migrating nerve cells into leptomeninges. A various degree of nerve and glial cell maturity was observed within heterotopic tissue. The other malformations include eye, skin and internal organs anomalies. Similarities and differences between our case and another previously described cases were discussed but it seems difficult to include the analysed case into one of the known syndromes.

Brain↗
PubMed1996

Solcoseryl improves learning and memory in rats.

Our previous experiments have shown that Solcoseryl (S), a protein-free extract of calves' blood stimulates locomotor activity and decreases haloperidol catalepsy in rats. In this study the influence of S on acquisition, consolidation, and recall of both, conditioned avoidance responses (CARs) and passive avoidance behaviour was tested. S at the intraperitoneal (i.p.) dose of 1.25 ml/kg significantly improved acquisition and at the dose of 1.0 ml/kg recall of CARs. In the passive avoidance situation the significant effect on acquisition and recall of information was observed after i.p. injection of 1.0 ml/kg of S, and on consolidation after 0.75 ml/kg. These data indicate that S may positively affect the CNS processes responsible for learning and memory.

Actihaemyl↗
PubMed1995

Classification of the neuronal ceroid-lipofuscinoses: expansion of the atypical forms.

The neuronal ceroid-lipofuscinoses (NCL) are a group of different genetic diseases. The major types of NCL are expressed by six forms which represent different clinicopathologic and genetic forms. These are CLN-1, Infantile; CLN-2, Late Infantile; CLN-3, Juvenile; CLN-4, Adult-Recessive; CLN-5, Adult-Dominant; and CLN-6, Early Juvenile. The distinction between CLN-4 and CLN-5 is still disputatious. CLN-6 has been called CLN-5. A seventh classification of NCL represents from 12 to 20% of those afflicted. This group consists of an extensive array of atypical types of ceroid-lipofuscin accumulation in the secondary lysosomes of neurons and cells of other tissues (e.g., skin, conjunctiva, and lymphocytes) or by presumed clinical and genetic relationships. The authors have identified 15 atypical subtypes of NCL. These as a group are here described as a seventh form. Further biochemical, molecular, and genetic studies will identify more precisely the phenotypic and genotypic expression of these "minor" forms of NCL.

Adolescent↗
PubMed1994

New X-linked mental retardation (XLMR) syndrome with distinct facial appearance and growth retardation.

We report on 2 brothers and their nephew with an apparently new X-linked mental retardation (XLMR) syndrome characterized by a distinct facial appearance, growth retardation, and severe mental retardation. The facial traits included triangular shape; bifrontal narrowness; malar flatness; blepharophimosis; very deeply set eyes; epicanthus inversus; bulbous nose; low hairline; low-set, deeply cupped, and protruding ears; short ill-defined philtrum; and thin tented upper lip. These facial anomalies are particularly striking and recognizable even at birth. The boys were small for gestational age and remained below -2 SD in growth parameters. With age, large joint contractures developed. Pectus excavatum was apparent at birth but became more obvious with age. Global developmental delay was evident in infancy. The brothers were nonverbal while their nephew spoke simple words. Optic atrophy, esotropia, nystagmus, and spastic diplegia were evident. They were self-abusive, hyperactive, and poorly coordinated. CT scans demonstrated atrophic hydrocephalus. No EEG abnormalities were detected. Karyotypes were 46,XY and fragile X negative. Routine chemistries; amino, organic, and uronic acids; oligosaccharides; lysosomal enzymes; and very long chain fatty acids were normal. Remarkable phenotypic similarity between these brothers and their nephew and lack of manifestations in their mothers makes X-linked recessive inheritance likely. This syndrome, which does not appear to have been reported previously, adds to the delineation of XLMR.

Abnormalities, Multiple↗
PubMed1991

Analysis of neocortex in three males with the fragile X syndrome.

Fragile X [fraX] syndrome is a common hereditary disorder associated with a fragile site marker at Xq27.3 which clinically presents as a form of mental retardation (MR). Postmortem investigation of 3 fraX positive males with mild to moderate MR did not document any gross neuropathological changes. Golgi analysis of neocortical dendritic spine morphology extended our previous observations of immature, long, tortuous spines in one adult case of fraX (Rudelli, et al., Acta Neuropathologica 67:289-295, 1985) to 2 new cases. Evidence for similar dendritic spine abnormalities was found, although Golgi analysis was less than optimal because of incomplete dendritic stain impregnation. Neocortical intra-layer cell density was also investigated in all 3 cases. Cresyl violet stained neurons were counted in 10 randomly selected fields in neocortical layers II-VI of cingulate and temporal association areas (Brodmann's areas 23 and 38). Neuron counts in fraX and control neocortex showed no significant differences. Thus, abnormal dendritic spine morphology with preservation of neuronal density appears to characterize the neocortex in individuals with this common form of mental retardation.

Adolescent↗
PubMed1989

Detection of blood group A antigen expression in human colon cancer using monoclonal antibodies with different specificities.

Blood group antigen expression in human colon cancer was studied by means of two monoclonal antibodies of broad anti-A (HE-14) and anti-type 3 and type 4 chain-based A and H (HE-10) specificity. These antigens were proved to reappear in tumors of the distal colon, the HE-10 antibody reacting more frequently (9 out of 12 samples) than HE-14 (5 out of 12 samples) and frequently with supranuclear staining of the cytoplasm probably in those places of the Golgi apparatus where carbohydrate antigens are synthesized. This staining pattern is characteristic of HE-10 in normal colonic mucosa as well. With HE-14, staining was often absent in less differentiated tumors, while HE-10 did react in such tumors. In this connection, the possible expression of type 3 and type 4 chain H antigens in the tumor tissue is discussed. In some cases, these two antibodies gave different staining patterns in parallel sections from the same tissue sample, primarily at the cellular level. Three out of 12 cases showed blood group antigen expression in the mucosa of the distal colon adjacent to the tumor only when HE-10 antibody was used.

ABO Blood-Group System↗
PubMed1988

Behavioral effects of angiotensin II and angiotensin II-(4-8)-pentapeptide in rats.

One nM of angiotensin II (AII) or angiotensin II-(4-8)-pentapeptide [AII(4-8)] given intracerebroventricularly did not affect locomotor and exploratory behavior of rats in open field. AII significantly increased and AII(4-8) did not affect vertical activity of animals in electromagnetic motimeter. Neither of the peptides influenced horizontal activity in the motimeter. Both peptides intensified stereotypy produced by apomorphine and amphetamine. AII significantly improved, while AII(4-8) did not affect, consolidation of memory of the correct way to food in T-maze. Similarly, AII increased and AII(4-8) did not change the rate of acquisition of conditioned avoidance responses in a shuttle-box. Of the two examined peptides only AII significantly improved retrieval of memory of the passive avoidance behavior. The results show that AII(4-8) influences central dopaminergic system but, unlike its parent peptide AII, has no apparent effect on memory.

Angiotensins↗
PubMed1988

Agenesis of the corpus callosum: clinical, neuroradiological and cytogenetic studies.

This study examined 35 patients with developmental disabilities who were referred for diagnostic evaluation that later revealed agenesis of the corpus callosum (ACC) by computerized tomography (CT). Sixteen had partial ACC, six had complete ACC, and one had a hypoplastic corpus callosum. In the other twelve cases, ACC existed, but the degree of callosal defect was not specified. Other intracranial defects were frequently present. Clinically, 15 patients (43%) had a history of seizures, 28 (82%) were mentally retarded or developmentally delayed and an additional five patients (15%) possessed borderline intelligence, and 10 (29%) had cerebral palsy. Ocular, spinal, and orofacial abnormalities were often present. Detailed summaries of these findings are given in Table I. Although several genetic causes of ACC have been identified, in the vast majority, the etiology is assumed to be multifactorial. In our study, two patients had trisomy 8 mosaicism and 11 (35%) had a family history of developmental disability. A review of the literature on chromosomal abnormalities in acalossal patients revealed 81 additional cases, which are discussed and outlined in Table II.

Adolescent↗
PubMed1987

Genetics and expression of the fragile X syndrome.

The discovery of the Fragile X (fra(X] syndrome represents a major advance in our understanding of mild mental retardation. This X-linked syndrome is the most common hereditary form of mental retardation. Recent estimates find that approximately 1/981 males and 1/677 females carry the fra(X) chromosome. The majority of affected males are moderate to severely retarded, but about 20% are mildly retarded and about 5% are borderline. Approximately 20% of males who inherit the fra(X) chromosome are termed non-penetrant; they do not express it cytogenetically and are of normal intellect. About 1/3 of carrier females show mental impairment and about 10% are mildly retarded. We have found evidence for genetic heterogeneity based on linkage analysis to flanking DNA probes. Some large families show tight linkage between fra(X) and the flanking probe F9, while others show loose linkage. Preliminary findings indicate the linkage heterogeneity may also be related to cognition: affected males in tightly linked families tended to be mildly retarded.

Cognition Disorders↗