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Biomedical subjects

P Nowacki

Publications and source records attributed to P Nowacki.

At least 19 recordsLinked to original sources
PubMed2003

Different presentations of late-detected phenylketonuria in two brothers with the same R408W/R111X genotype in the PAH gene.

Although the clinical heterogeneity of phenylketonuria (PKU) is well established, some questions about this condition remain. Subjects from the same family who share the same mutations in the phenylalanine hydroxylase (PAH) gene are expected to display similar disease courses, and therefore, when blood phenylalanine (Phe) levels, genotype and dietary treatment are all similar, differences in patient outcomes require additional explanations. The present authors describe two entirely different courses of late-detected PKU in two brothers with the same R408W/R111X genotype in the PAH gene. The older sibling was diagnosed with PKU at the age of 4 years and given treatment. His IQ was 97 at 26 years of age and moderate involvement of periventricular white matter was detected. The younger brother was diagnosed with PKU at the age of 11 months and given treatment. His IQ was < 25 at 22 years of age and severe dysmyelination changes were found by magnetic resonance imaging. The differences in the courses of the disease between these two brothers appear to be related to variations in their blood-brain barriers.

Adult↗
PubMed2001

Peritumoral angiogenesis around primary and metastatic brain neoplasms. Morphometric analysis.

In an interface between brain tumour and surrounding tissue there occur simultaneously two very important phenomena. On the one hand there is a proliferation of peritumoral vessels penetrating into the neoplasm in which they make alike tumoral vessels. On the other hand, neoplastic cells penetrate from the tumour into the vicinity along peritumoral vessels. To determine the influence of the histological type of different brain tumours, their malignancy degree as well as location in the central nervous system on peritumoral vessels morphological appearance, the detailed morphometric analysis was carried out. The morphological examination and computerised morphometric analysis were conducted on 166 primary and metastatic CNS neoplasms taken during routine neurosurgical procedure. It turned out that the peritumoral angiogenesis depends predominantly on the malignancy of brain tumours. This angiogenesis may be modified by local environmental factors--it is more evident within the white matter than in the cerebral cortex. One of the important factors may be reactive peritumoral astrogliosis. There is no specific CNS region predisposed to the development of peritumoral angiogenesis.

Adolescent↗
PubMed2001

Guillain-Barre syndrome in patient with Burkitt's lymphoma and type 2 diabetes mellitus.

Although peripheral neuropathies are commonly observed in patients with non-Hodgkin's malignant lymphomas (NHML), Guillain-Barre syndrome (GBS) belongs to the occasional complications of lymphoproliferative disorders. It appears in less than 0.3 per cent of NHML. It is worthy of note that in the reported case there occurred three independent risk factors of peripheral neuropathy: Burkitt's lymphoma, chemotherapy and type 2 diabetes mellitus. Based on clinical course, EMG finding and neuropathological examination, in spite of normal cerebrospinal fluid protein content, GBS as a paraneoplastic disorder was diagnosed. It was assumed that chemotherapy and diabetes mellitus conduced to severe neuropathy.

Burkitt Lymphoma↗
PubMed2000

Morphometric analysis of axons in the minute multiple sclerosis lesions and shadow plaques in patients with multiple sclerosis.

The objective of the present study was to quantitatively detect axons in the minute multiple sclerosis (MS) lesions and in shadow plaques, taking into consideration the relapsing-remitting(R-R) and secondary progressive(SP) stages of MS. The brain tissue of 12 patients deceased due to MS was investigated. An image-computerized analysis was made for measurements of axons. Based on the findings we concluded that damage to axons appears in both the minute MS lesions and in shadow plaques. Demyelination and ineffective (too late or too slow) remyelination seemed to be very important factors in axonal damage. Irreversible damage to axons may appear in both the secondary progressive and relapsing-remitting stages of MS, causing permanent neurological deficits, irrespective of the duration of the disease.

Adult↗
PubMed2000

Amyotrophic form of Creutzfeldt-Jakob disease with rapid course in 82-year-old man.

The authors present a case of Creutzfeldt-Jakob disease in 82-year-old man. Besides the onset of the disease in the elderly and short survival time (8 weeks), other uncommon clinical and morphological features also characterized our case. An evident amyotrophic syndrome, confirmed in morphological findings, developed soon after the CJD onset. The spongiform change also observed within the white matter of cerebral hemispheres allowed us to diagnose the 'panencephalopathic' form of CJD.

Aged↗
PubMed1999

Computerized morphometric analysis of the cerebellum in patients with lymphoblastic lymphomas of various survival time.

Post-mortem neuropathological investigations of the cerebellum were carried out in 15 patients deceased due to lymphoblastic lymphoma (LBL). In patients with survival time of LBL longer than 20 months, neuronal structures of the cerebellum appeared to be significantly rarefied. It was especially observed within granular layer, less frequently in Purkinje and dentate nuclei cells. In cases with longer survival time shrinkage and deformation of neurons, especially Purkinje and dentate nuclei cells were observed. The morphometric analysis suggests that the cerebellar neuronal changes might be a consequence of remote effects of LBL on nervous tissue. The longer survival time contribute to the nervous system exposure on remote effects of neoplasm. The dentate nuclei cells are damaged due to remote effect of lymphoma, irrespective of Purkinje cells destruction.

Adult↗
PubMed1999

Computerized morphometric analysis of human leukemic and lymphomatous cells in various histological environments of central nervous system.

The leukemic and lymphomatous cells appear within the central nervous system (CNS) in 5 different environments: in CNS vessels, perivascular spaces, meninges, nervous tissue and in CNS hemorrhages. A computerized analysis of geometric and densitometric parameters of neoplastic cells in these compartments were done for better recognition of penetration and spreading of leukemia and lymphoma within the CNS. A post-mortem neuropathological investigations were carried out on 16 patients deceased due to acute myeloblastic leukemias (M1, M2), blastic phase of chronic myelogenous leukemia, lymphoblastic lymphoma and acute lymphoblastic leukemia. Following nuclear parameters of neoplastic cells were analyzed: area, "form factor", mean, minimal and maximal density. An evident differentiation of nuclear parameters within the CNS environments was found. The nuclei within the perivascular spaces and especially in CNS hemorrhages were significantly shrunken and dense (p < 0.01), but not evidently deformed. The intracerebral infiltrates appeared to be most differentiated group (p < 0.01). Morphometric values of leukemic and lymphomatous cells show regressive changes of neoplastic cells within the CNS perivascular spaces, nervous tissue and in CNS hemorrhages. These changes depend on unfavorable factors in the mentioned CNS environments, and also on time of cell persistence in these regions. Meninges were found to be the only CNS structure facilitating the survival and proliferation of leukemic and lymphomatous cells.

Central Nervous System Neoplasms↗
PubMed1999

Neuropathological changes within the brain of rabbits with experimental model of antiphospholipid syndrome in different time after immunization.

The post-mortem neuropathological investigations were carried out on 20 female New Zealand rabbits. Two main types of changes were found: inflammatory, including meningeal and perivascular infiltrates, and thrombotic within the nervous tissue. The findings revealed that active process within the CNS persists at least 3 months after APS was evoked, however its intensity, especially necrotic changes and vessel wall thickening evidently diminish. The active APS after experiment had been finished was also confirmed in blood samples.

Animals↗
PubMed1998

In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function.

Mutations in the human phenylalanine hydroxylase gene (PAH) altering the expressed cDNA nucleotide sequence (GenBank U49897) can impair activity of the corresponding enzyme product (hepatic phenylalanine hydroxylase, PAH) and cause hyperphenylalaninemia (HPA), a metabolic phenotype for which the major disease form is phenylketonuria (PKU; OMIM 261600). In vitro expression analysis of inherited human mutations in eukaryotic, prokaryotic, and cell-free systems is informative about the mechanisms of mutation effects on enzymatic activity and their predicted effect on the metabolic phenotype. Corresponding analysis of site-directed mutations in rat Pah cDNA has assigned critical functional roles to individual amino acid residues within the best understood species of phenylalanine hydroxylase. Data on in vitro expression of 35 inherited human mutations and 22 created rat mutations are reviewed here. The core data are accessible at the PAH Mutation Analysis Consortium Web site (http://www.mcgill.ca/pahdb).

Animals↗
PubMed1998

Central nervous system involvement in pregnant rabbits with experimental model of antiphospholipid syndrome.

A postmortem neuropathological investigations were carried out on 23 female rabbits divided into 3 groups; pregnant animals with experimental antiphospholipid syndrome (APS), nonpregnant rabbits with antiphospholipid syndrome and nonpregnant animals without antiphospholipid syndrome. The aim of study was to analyze the CNS changes related to experimental model of APS in rabbits and to answer, whether pregnancy influences the intensity of CNS changes related to APS. The findings suggest that the experimental model of APS used in our study appeared to be effective in the development of the CNS involvement in rabbits. The extent thickening of CNS vessel wall is the most common feature of vasculopathy related to APS. In rabbits, pregnancy seems to be a factor facilitating the CNS damage related to APS.

Animals↗
PubMed1997

The PAH mutation analysis consortium database: update 1996.

A website (http://www.mcgill.ca/pahdb ) is maintained by the curators for a Consortium (88 investigators, 28 countries) and all other users; it serves a relational database for human locus-specific genetic variation in a defined DNA sequence (GenBank U49897); (100 kb on human chromosome 12q24.1, gene symbol PAH). The intragenic nucleotide variation is both rare (Q< 0.01), extensive (>320 different mutations) and phenotype modifying, causing hyperphenylalaninemia by impairing phenylalanine hydroxylase function (see OMIM 261600), as well as polymorphic and neutral, the latter providing informative locus-specific haplotypes (>1200 different mutation/haplotype associations). The PAH database contains both offline core components (mutations, population associations and data source information) and several accessory online components: (i) relative frequencies of mutations by populations/regions (expanding file); (ii) data on genotype- phenotype correlations both in vitro and in vivo (new file); (iii) polymorphic haplotype structures (new file); (iv) intron sequence data (new file for design of primers); (v) description of mouse homologues (new file for mutations and phenotypes); (vi) the predicted PAH gene mutability profile (improved graphic); (vii) a clinical field for patient use (new interface with database). The website home page has been revised and a counter is recording >15 visits per day. Linkages to other mutation databases and an alliance of mutation database curators (new) are expanding. The primary 'electronic publication' reports now vastly exceed print reports. PAHdb serves as a prototype for obtaining, storing and distributing records of human genetic variation.

Animals↗
PubMed1997

Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations.

We analyzed correlations between mutant genotypes at the human phenylalanine hydroxylase locus (gene symbol PAH) and the corresponding hyperphenylalaninemia (HPA) phenotypes (notably, phenylketonuria [OMIM 261600]). We used reports, both published and in the PAH Mutation Analysis Consortium Database, on 365 patients harboring 73 different PAH mutations in 161 different genotypes. HPA phenotypes were classified as phenylketonuria (PKU), variant PKU, and non-PKU HPA. By analysis both of homoallelic mutant genotypes and of "functionally hemizygous" heteroallelic genotypes, we characterized the phenotypic effect of 48 of the 73 different, largely missense mutations. Among those with consistent in vivo expression, 24 caused PKU, 3 caused variant PKU, and 10 caused non-PKU HPA. However, 11 mutations were inconsistent in their effect: 9 appeared in two different phenotype classes, and 2 (I65T and Y414C) appeared in all three classes. Seven mutations were inconsistent in phenotypic effect when in vitro (unit-protein) expression was compared with the corresponding in vivo phenotype (an emergent property). We conclude that the majority of PAH mutations confer a consistent phenotype and that this is concordant with their effects, when known, predicted from in vitro expression analysis. However, significant inconsistencies, both between in vitro and in vivo phenotypes and between different individuals with similar PAH genotypes, reveal that the HPA-phenotype is more complex than that predicted by Mendelian inheritance of alleles at the PAH locus.

Alleles↗
PubMed1997

Subacute cerebellar degeneration as a remote effect of breast cancer.

Clinical investigations on the case of a 61-year-old woman with a few year history of neurological symptoms, who underwent mastectomy caused by ductal carcinoma, 12 years prior to the appearance of the clinical syndrome did not reveal the cause of the disease. On the post-mortem examination solitary metastasis of adenocarcinoma to the retroperitoneal lymph node was present. Histologically, in the cerebellum the degeneration of the Purkinje cells with extensive Bergmann glia reaction was diagnosed. The authors discuss the connection between lesions of CNS and neoplastic disease.

Breast Neoplasms↗
PubMed1996

F wave studies after intrathecal methotrexate administration.

Electrophysiological examinations were done on 20 patients aged 40-71 years with recently diagnosed high grade non-Hodgkin's lymphomas. General chemotherapy and intrathecal chemotherapy in order to prevent central nervous system (CNS) involvement were begun. On the first day of chemotherapeutic cycle patients received intrathecally methotrexate (ITMTX) and prednisolone. Electrophysiological study was carried out twice in each subject: before ITMTX injection and a day after injection. The study procedure included: a conventional nerve conduction examination (peripheral conduction velocity and compound muscle action potential amplitude), the F wave latency and amplitude measurement and F ratio (F-M-1/2M) calculation for peroneal and tibial nerve bilaterally. Results of the first and the second examinations were statistically compared by t-Student's test. No significant differences between values of estimated parameters were found. The study revealed no recent alterations in proximal, paraspinal motor conduction and motor neuron excitability due to antidromical activation after single ITMTX administration.

Adult↗
PubMed1996

Leukemic cells growth fraction in the central nervous system in blastic phase of chronic myelogenous leukemia.

Clinical and neuropathological investigations were carried out in 6 patients, deceased due to blastic phase of chronic myelogenous leukemia (BPCML). Growth fraction of leukemic cells in peripheral blood, cerebrospinal fluid and in the central nervous system (CNS) was studied, using mitotic index and immunohistochemical staining technique with the monoclonal antibody antiproliferating cell nuclear antigen (anti-PCNA). The results suggest that in BPCML the proliferative activity of leukemic cells is low both in peripheral blood, cerebrospinal fluid, cerebral leukostasis and within the leptomeningeal and intracerebral infiltrates, even in cases with a very high white blood cells count. It can confirm the opinion that in BPCML, accumulation rather than proliferation of leukemic cells plays an important role in the development of the CNS leukemia.

Adult↗
PubMed1996

[Transthyretin and albumin in cerebrospinal fluid in patients with acute leukemias or lymphomas of high grade malignancy].

Transthyretin and albumin in lumbar cerebrospinal fluid (CSF) and in serum were repeatedly assessed in 40 patients with acute leukemias or high grade non-Hodgkin's lymphomas. The patients were divided into 3 groups. Group I-5 individuals with clinical manifestations of leukemic or lymphomatous meningosis; Group II-33 cases with no clinical data of central nervous system involvement by neoplasm (leukemia/lymphoma); Group III-2 patients in whom extramedullary solid leukemic or lymphomatous infiltrations were diagnosed. It was revealed that blood-brain-barrier dysfunction due to neoplastic infiltration of leptomeninges went with an increase of albumin blood-CSF barrier dependent- and with decrease of blood-CSF barrier-independent transthyretin concentrations. In patients with extramedullary tumors an evident increase of albumin and total-CSF transthyretin and no blood-CSF barrier-independent transthyretin concentrations below the tumor location were observed. It can betray a complete block of the vertebral canal subarachnoid space below the neoplastic compression of the spinal cord. Cytostatics application, either general or intrathecal, did not influence the CSF albumin and transthyretin levels.

Adolescent↗
PubMed1996

Lymphomatous infiltrates within leptomeninges and spinal roots in adult patients with non-Hodgkin's lymphomas after intrathecal methotrexate administration.

Based on post-mortem neuropathological evaluation the authors analyzed the incidence and distribution of the lymphomatous infiltrates within the leptomeninges and spinal roots in 21 patients with high grade non-Hodgkin's lymphomas (HGNHL) treated with intrathecal methotrexate (ITMTX) prophylaxis. The investigations revealed that lymphomatous infiltrates were most frequent within cerebellar leptomeninges and around spinal roots. In spinal leptomeninges and roots the infiltrates occurred significantly rare after more than 3 ITMTX injections, but further ITMTX applications did not diminish infiltrates incidence in the mentioned regions. In the remaining regions infiltrates incidence was similar, irrespective of the number of ITMTX injections. From the neuropathological point of view ITMTX prophylaxis isn't able to prevent the development of the infiltrates in the mentioned regions. In an attempt to determine the clinical usefulness of the ITMTX prophylaxis in adult patients with HGNHL and to elaborate optimal prophylactic management, the more detailed clinical and pathological evaluations are required.

Adolescent↗