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M Haltia

Publications and source records attributed to M Haltia.

At least 109 records · Page 6Linked to original sources
PubMed1992

Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia.

Multiple deletions of mitochondrial DNA (mtDNA) have recently been reported in familial progressive external ophthalmoplegia (PEO), in a case of progressive encephalomyopathy, and in inherited recurrent myoglobinuria. The inheritance of familial PEO has been autosomal dominant, which indicates that a mutation in an unknown nuclear gene results in several mtDNA deletions of different sizes in these patients. We report a patient with autosomal dominant PEO, whose major clinical symptom, however, was severe retarded depression. The morphological analyses of the tissue samples derived from autopsy showed various abnormalities in the mitochondria in all the tissues studied. The activities of the respiratory chain enzymes encoded by mtDNA were remarkably reduced in the skeletal muscle. The mtDNA analyses confirmed that besides myopathy, this patient had a multisystem disorder with widespread distribution of multiple deletions of mtDNA. The highest percentage of mutated mtDNA was found in the brain, skeletal muscle and the heart, the relative quantity of mutated mtDNA correlating to the severity of the clinical symptoms.

Chromosome Deletion↗
PubMed1992

[Not Available].

Explore the source record for details and available documents.

Finland↗
PubMed1991

Familial Creutzfeldt-Jakob disease in Finland: epidemiological, clinical, pathological and molecular genetic studies.

In 1974-1984 30 patients died with a diagnosis of Creutzfeldt-Jakob disease (CJD) in Finland (annual mortality rate of CJD 0.9 per million population for the years 1979-1984). Six of these patients (20%) were familial, all belonging to the same kindred. The pedigree now includes 15 affected members in four generations, and the occurrence of disease is consistent with an autosomal dominant mode of inheritance. The clinical features of CJD in this family are in most respects typical of the familial disease described elsewhere. However, the mean age at onset is 47, periodic EEG activity has not been observed, and the mean duration of illness of 27.5 months is longer than usual for either familial or sporadic CJD. Neuropathological examination of brain biopsy and autopsy specimens revealed spongiform change without amyloid plaques, and brain tissue from one patient transmitted disease to a capuchin monkey. In an analysis of the histocompatibility antigens of the family, CJD was not linked with a single haplotype, but at least 12 out of 13 CJD patients shared the HLA antigen A28. Molecular genetic studies disclosed a new G-to-A mutation in codon 178 of the PRNP gene (resulting in a substitution of asparagine for aspartic acid) in the DNA of eight family members with CJD but not in any of ten currently healthy first degree relatives of the patients, or 86 controls. The codon 178 mutation thus seems to co-segregate with CJD in this family. Linkage analysis gave a LOD score value of 3.6.

Adult↗
PubMed1991

Benign muscular dystrophy with autosomal dominant inheritance.

A slowly progressive myopathy was discovered in a family in four successive generations. Eight patients (four female, four male) from three generations were examined and they showed muscle weakness affecting predominantly proximal, but also distal, muscles. Two patients had unequivocal findings in childhood, the others showed myopathy in their twenties or thirties. Working ability was lost in physically demanding jobs in the thirties, but activities of daily living were still preserved. Elbow contractures, tight heel cords and contractures of the interphalangeal joints were frequent. Serum CK activity was usually mildly elevated and electromyographic examinations revealed myopathic changes. Histopathological changes were compatible with moderately advanced muscular dystrophy in two patients, the six others had mild myopathic changes.

Adult↗
PubMed1991

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome).

We describe 14 patients, from 11 families, who have a progressive encephalopathy with early onset. The clinical signs of the disease are severe hypotonia, convulsions with hypsarrhythmia, profound mental retardation, hyperreflexia, transient or persistent edema, and optic atrophy. These findings and the characteristic dysmorphic features allow recognition of these patients, although no basic metabolic defect has been found. Microcephaly and atrophy of the brain develop, especially in the cerebellar and brain stem areas. An autosomal recessive mode of inheritance is likely.

Brain↗
PubMed1991

Dementia associated with human immunodeficiency virus: subcortical or cortical?

Two different types of dementia and corresponding neuropathological findings of patients with human immunodeficiency virus (HIV) infection are presented. In one case, "subcortical" dementia with slow movements and mental processes as well as problems in active recall but without focal defects corresponded to diffuse leukoencephalopathy. In another case, "cortical" dementia with impaired abstraction and memory as well as several focal defects corresponded to microglial nodules in cortical and in deep grey matter, with only a mild diffuse leukoencephalopathy. Thus, in contrast to earlier interpretations, subcortical dementia does not appear to be the only form of dementia in HIV-infected patients, and cortical dysfunction may also occur.

AIDS Dementia Complex↗
PubMed1991

Lewy bodies are immunoreactive with antibodies raised to gelsolin related amyloid-Finnish type.

Lewy bodies (LB) are intraneuronal, cytoplasmic inclusion bodies. They are invariably present in Parkinson's and diffuse LB diseases. Their composition by direct biochemical methods is unknown, although LBs are immunoreactive with a number of antibodies, including anti-ubiquitin and anti-neurofilament antibodies. Familial amyloidosis, Finnish type (FAF), is an autosomal-dominant form of systemic amyloidosis. The authors have isolated and partially sequenced the amyloid. The protein has significant sequence identity with gelsolin, an actin-modulating protein. Rabbit polyclonal antibodies raised to the FAF amyloid not only immunostain the amyloid but also LBs in the cortex and substantia nigra of Parkinson's and diffuse LB disease brains. Immunoreactivity is absorbed by the purified amyloid but is unaffected by ubiquitin. This provides a link between the LB and one of the human amyloidoses, FAF.

Aged↗
PubMed1990

Gelsolin variant (Asn-187) in familial amyloidosis, Finnish type.

Familial amyloidosis, Finnish type (FAF), is an inherited form of systemic amyloidosis clinically characterized by cranial neuropathy and lattice corneal dystrophy. We have demonstrated that the protein subunit isolated from amyloid fibrils shows considerable sequence identity with gelsolin, an actin-binding protein. We have purified the amyloid subunit from a second case and further analysed different fractions from the previous one. Sequence analysis shows that, in both cases, the amyloid subunit starts at position 173 of the mature molecule; it has a heterogeneous N-terminus and contains one amino acid substitution, namely asparagine for aspartic acid, at position 15 (gelsolin residue 187), that is due to a guanine-to-adenine transversion corresponding to nucleotide-654 of human plasma gelsolin cDNA. The substitution maps in a fragment with actin-binding activity and is located in a repetitive motif highly conserved among species. Thus FAF is the first human disease known to be caused by an internal abnormal degradation of a gelsolin variant. We designate this variant of gelsolin-associated amyloidosis 'Agel Asn-187'.

Aged↗
PubMed1990

Mutation in gelsolin gene in Finnish hereditary amyloidosis.

Familial amyloidosis, Finnish type (FAF), is an autosomal dominant form of familial amyloid polyneuropathy. The novel amyloid fibril protein found in these patients is a degradation fragment of gelsolin, an actin-binding protein. We found a mutation (adenine for guanine) at nucleotide 654 of the gelsolin gene in genomic DNA isolated from five FAF patients. This site is polymorphic since the normal allele was also present in all the patients tested. This mutation was not found in two unaffected family members and 11 normal controls. The A for G transition causes an amino acid substitution (asparagine for aspartic acid) that was found at position 15 of the amyloid protein. The mutation and consequent amino acid substitution may lead to the development of FAF.

Amino Acid Sequence↗
PubMed1990

Amyloid protein in familial amyloidosis (Finnish type) is homologous to gelsolin, an actin-binding protein.

Familial amyloidosis, Finnish type, is clinically characterized by cranial neuropathy and lattice corneal dystrophy. It is an autosomal dominant form of systemic amyloidosis with small deposits of congophilic material occurring in most tissues, particularly in association with blood vessel walls and basement membranes. Amyloid fibrils were extracted from the kidney of patient VUO, and rabbit antiserum raised against the 12 kDa purified amyloid subunit displayed strong immunohistochemical reactivity with the amyloid deposits. The amino terminal sequence of this 12 kDa amyloid protein (ATEVPVSWESFNNGD) showed homology with gelsolin (or actin depolymerizing factor), a 93 kDa plasma protein. The amyloid peptide is a degradation product, starting at position 173, of the gelsolin molecule.

Actins↗
PubMed1990

Topographic heterogeneity of amyloid B-protein epitopes in brains with various forms of neuronal ceroid lipofuscinoses suggesting defective processing of amyloid precursor protein.

To verify our hypothesis of defective protease inhibitor domains that are encoded by abnormal processing of amyloid precursor protein (APP) in brains of patients with neuronal ceroid lipofuscinoses (NCL), immunohistochemical and cytochemical studies were performed with monoclonal antibodies (mAbs) directed against various domains of APP. For the studies, 22 autopsy brains were used: 12 with different forms of NCL, and 10 control brains. The staining procedure for the avidin-biotin complex (ABC) technique and the postembedding gold-labelled procedure for electron microscopy (EM) were employed. Of all mAbs used for the study, only mAbs generated against amyloid B-protein bound to neural tissue were affected with NCL. The strongest immunostaining of neurons and of some reactive glial cells was found in brains with the juvenile form of NCL. Only in the infantile form of the disease were some neurons overloaded with storage material weakly immunoreactive. In brains of patients with the adult form of NCL, immunoreactivity was found in affected neurons and in extracellularly deposited material of senile plaques. The results of EM study showed that the immunoreactivity was restricted to lysosomal cytosomes in neural tissue with any form of NCL selectively localized on the curvilinear and fingerprint proteinaceous component of ceroid lipofuscin. Studies performed on control aging brains and Alzheimer's disease (AD) brains confirmed previous observations of immunoreactivity being found diffusely in the protein component of some neurons containing lipopigment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Computed tomography and angiography do not reliably discriminate malignant meningiomas from benign ones.

Histological anaplasia, found in up to 10% of meningiomas, is an important prognostic sign as it is associated with increased recurrence rate and volume growth rate. We studied in retrospect a series of 230 primary intracranial meningiomas to discover whether histological anaplasia can be reliably foreseen in CT scans and angiograms. 205 meningiomas were histologically benign, and 25 meningiomas were classified as malignant (atypical or anaplastic), with either incipient (20) or overt (5) signs of anaplasia. Of ten CT parameters tested, three were associated significantly more often with malignant meningiomas: nodular contour (58.3% vs 26.7%), cysts (20.0% vs 4.4%) and absence of calcifications (92% vs 65.3%); none of these parameters was an absolute sign of anaplasia. 'Mushrooming', previously regarded as a definite sign of malignancy, was seen in 9% of benign meningiomas and in 21% of malignant ones. In angiography, no apparent differences between benign and malignant meningiomas were seen. The conclusion is that it is not possible to distinguish malignant meningiomas from benign ones with CT or angiography.

Anaplasia↗
PubMed1990

Isolation of human immunodeficiency virus (HIV) at autopsy one to six days postmortem.

Blood and tissue were studied for potential infectivity at autopsy of ten patients with human immunodeficiency virus (HIV) infection. Special attention was paid to the possibility of detecting HIV in bone at craniotomy. Postmortem intervals were one to six days. Specimens for HIV isolation included skull bone, brain, blood, bone marrow, spleen, and lymph node, and cerebrospinal fluid in one case. HIV grew in culture from at least one specimen from eight autopsies, one of which was performed six days postmortem. HIV was recovered from the blood of five patients and the tissue of five patients, including three with negative blood cultures. Skull bone contained HIV in two cases. HIV also grew from native spleen specimens stored for up to 14 days postmortem at 20 degrees C. Recommended precautions, including those for bone, are indicated at autopsy of HIV-infected patients even after long postmortem intervals.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Severe degeneration of rabbit vastus intermedius muscle immobilized in shortened position.

The authors have previously shown that passive daily mobilization of the rabbit hind limb immobilized with the knee in extension leads to necrosis of the deep thigh muscles and myositis ossificans-like periosteal bone formation. In this study the effect of immobilization alone on the rabbit hind limb muscles was examined similarly to that of immobilized limbs. Serum creatine kinase activities increased significantly and intravenously administered Evans blue albumin showed increased vascular permeability in the deep vastus intermedius muscle even on day 1. Necrotic fibers were clearly present in the deep part of the vastus intermedius muscle on day 5 in light and electron microscopy and in enzyme histochemistry. Fibrosis and atrophy were found later. The superficial portion of the vastus intermedius and the deep contralateral nonimmobilized vastus intermedius showed degenerative changes. Bone formation was not noted. The conclusion was that the deep vastus intermedius muscle composed almost exclusively of type I fibers is exceptionally prone to damage when immobilized in a shortened position. Contact of the necrotic muscle with the underlying periosteum is not alone sufficient to induce heterotopic ossification. The additional trauma caused by daily mobilization is needed for the myositis ossificans-like bone formation.

Animals↗