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O Jensson

Publications and source records attributed to O Jensson.

At least 19 recordsLinked to original sources
PubMed1995

Mapping the locus of atrophia areata, a helicoid peripapillary chorioretinal degeneration with autosomal dominant inheritance, to chromosome 11p15.

Atrophia areata (AA) is an early onset autosomal dominant helicoid peripapillary chorioretinal degeneration, which was first demonstrated to be hereditary in an Icelandic family. It is characterized by bilateral wing-shaped atrophic areas of the retina, radiating from the optic disk. Primary complaints of affected individuals are due to refractive errors and scotomata associated with myopia which increases with age. A genome linkage search with 112 microsatellite DNA markers resulted in the highest probability of location for AA on chromosome 11. We genotyped 18 polymorphic markers on chromosome 11 and seven showed significant linkage to AA. The markers D11S1323 and D11S902 on 11p15 flank the region encompassing the gene for AA.

Choroiditis↗
PubMed1995

Wilson disease in Iceland: a clinical and genetic study.

A survey of Wilson disease in Iceland has revealed two large kindreds with affected individuals. We have carried out studies of haplotypes of dinucleotide repeat polymorphisms (CA repeats) flanking the Wilson disease gene. The same mutation, a 7-bp deletion, is present in both families, and the clinical features are similar. The haplotype data and nature of the mutation support the existence of a founder chromosome carrying the mutation. This Icelandic mutation was not found in patients of Irish or Scottish origins, who could share some of the Icelandic ancestral genes. Although the protein function is predicted to be completely abolished by the deletion, predicting early-onset liver disease, we find that the patients present with later-onset neurological and psychiatric symptoms. We show that alternative splicing of the transcript in the region of the deletion could contribute to later onset, suggesting that alternative isoforms of the protein might have some functional significance.

Adolescent↗
PubMed1992

Hereditary cystatin C amyloid angiopathy: identification of the disease-causing mutation and specific diagnosis by polymerase chain reaction based analysis.

Hereditary cystatin C amyloid angiopathy (HCCAA) is a dominantly inherited disease characterized by amyloidosis, dementia and fatal cerebral hemorrhage of young adults. A method for rapid and simple diagnosis of HCCAA is described. It is based upon oligonucleotide-directed enzymatic amplification of a 275-bp genomic DNA segment containing exon 2 of the cystatin C gene from a blood sample, followed by digestion of the amplification product with AluI. Loss of an AluI recognition site in the amplified DNA segment from HCCAA patients results in a deviating band-pattern at agarose gel electrophoresis, compared with that obtained from normal subjects or unaffected HCCAA family members. In a population of 9 patients with manifest HCCAA, 14 patients with other causes of brain hemorrhage and 16 healthy individuals, the diagnostic procedure displayed a sensitivity and specificity for HCCAA of 100%. Amplified DNA segments from 4 HCCAA patients of four different families were analyzed by nucleotide sequencing; the HCCAA-causing mutation in all families was found to be a single T----A substitution in the codon for amino acid residue 68 of cystatin C.

Amino Acid Sequence↗
PubMed1992

On the role of monocytes/macrophages in the pathogenesis of central nervous system lesions in hereditary cystatin C amyloid angiopathy.

The pathogenesis of the deposition of a variant cystatin C as amyloid in hereditary cystatin C amyloid angiopathy (HCCAA) is not known. To address this question the synthesis and secretion of cystatin C in cultured monocytes from 9 carriers of the mutated cystatin C gene (5 symptomatic and 4 asymptomatic) was examined. The quantity of cystatin C in cells and supernatants was determined by the ELISA method, Western blots were done and selected samples immunostained for cystatin C. Monocytes from individuals carrying the gene defect synthesized cystatin C that was apparently not truncated, a form found in the cerebral amyloid deposits in HCCAA, but showed a distinctly lower rate of cystatin C synthesis than monocytes from healthy controls. The main difference was that the quantity of cystatin C was significantly lower in the supernatants in monocyte cultures from carriers of the gene defect than from healthy controls, possibly due to a partial block in its secretion. This abnormal processing of the cystatin C could explain the low cerebrospinal fluid levels of cystatin C in HCCAA and might be a part of the pathogenetic pathway of amyloid deposition. Furthermore it could, through a lower extracellular concentration of this inhibitor of cysteine proteinases, contribute to destruction of the amyloidotic blood vessels, leading to the most serious clinical manifestation in HCCAA, intracerebral hemorrhage.

Adolescent↗
PubMed1992

Natural killer cell function and malignant cell phenotype in hairy cell leukaemia.

We have followed for 33 months the changes that occurred in natural killer (NK) cell numbers and activity in a patient (A) with hairy cell leukaemia (HCL), using a single cell assay and a microcytotoxicity assay. The composition of the peripheral blood mononuclear cell population and malignant cell phenotype were also analysed. During this period he received treatment with interferon and his grossly enlarged spleen was removed. Four further patients were also studied, two were splenectomized and all had received treatment with interferon. In four of the five patients studied there was an apparent link between low NK activity and presence of a tumour-infiltrated spleen, and in the fifth patient, who was aleukemic and had no splenomegaly, NK function was related to disease activity. There was no correlation between NK activity and the number of target binding (TB) cells in these five patients. IFN had little direct effect on overall NK activity, but the proportion of killing cells among TB cells was increased. Three patients showed binding of several cells to a single target. Further analysis revealed that in the patients most of the TB cells were not CD56-positive NK cells, in contrast to TB cells from normal subjects. In patient A a large proportion (84%) of TB cells were identified as malignant cells and in patient E 15% of TB cells were malignant cells. The phenotype of the malignant cells was: CD19+, HLA-DR+ and CD25(Tac)+, except for patient A. In this patient the hairy cells were positive for the NK marker CD56 as well as the monocyte marker CD14. Furthermore, a change occurred in phenotype as only later samples carried CD25. It is concluded that the level of NK function correlates closely with disease activity in HCL and that competitive target cell binding by malignant cells may be one cause of depressed NK-cell function in hairy cell leukaemia.

Antigens, CD↗
PubMed1991

[Scandinavian recommendations for transfusion medicine].

A central issue at the 13th Scandinavian Congress on Blood Transfusion Medicine was national self-sufficiency in plasma and plasma products, as outlined in the resolution adopted by the Council of Europe in 1990. Delegates also discussed the serological screening of donors to prevent the transmission of infection, new developments in the production of blood components, leukocyte filtration and serological technology.

Blood Banks↗
PubMed1990

Structure and expression of the human cystatin C gene.

The structural organization of the gene for the human cysteine-proteinase inhibitor cystatin C was studied. Restriction-endonuclease digests of human genomic DNA hybridized with human cystatin C cDNA and genomic probes produced patterns consistent with a single cystatin C gene and, also, the presence of six closely related sequences in the human genome. A 30 kb restriction map covering the genomic region of the cystatin C gene was constructed. The positions of three polymorphic restriction sites, found at examination of digests of genomic DNA from 79 subjects, were localized in the flanking regions of the gene. The gene was cloned and the nucleotide sequence of a 7.3 kb genomic segment was determined, containing the three exons of the cystatin C structural gene as well as 1.0 kb of 5'-flanking and 2.0 kb of 3'-flanking sequences. Northern-blot experiments revealed that the cystatin C gene is expressed in every human tissue examined, including kidney, liver, pancreas, intestine, stomach, antrum, lung and placenta. The highest cystatin C expression was seen in seminal vesicles. The apparently non-tissue-specific expression of this cysteine-proteinase inhibitor gene is discussed with respect to the structure of its 5'-flanking region, which shares several features with those of housekeeping genes.

Amino Acid Sequence↗
PubMed1990

The amino terminal portion of cerebrospinal fluid cystatin C in hereditary cystatin C amyloid angiopathy is not truncated: direct sequence analysis from agarose gel electropherograms.

The isolated amyloid substance in hereditary cystatin C amyloid angiopathy (HCCAA) is mainly composed of a cystatin C variant devoid of the 10 amino terminal amino acid residues of extracellular cystatin C from healthy individuals. We have developed a procedure for protein sequencing directly from agarose gel electropherograms and used this in conjunction with isoelectric focusing to investigate the amino terminal sequence of cerebrospinal fluid (CSF) cystatin C in HCCAA patients. The amino-terminal sequence determined for cystatin C from a HCCAA patient CSF sample, Xaa-Ser-Pro-Gly-Lys-Pro-Pro-Xaa-Leu-Val-Gly-Gly-Pro-Met-Xaa-Ala-Xaa-Val, showed that the protein was not amino-terminally truncated. CSF cystatin C from all nine HCCAA patients investigated was found to have an isoelectric point identical to that of native cystatin C, and the truncated form of cystatin C isolated from amyloid deposits was shown to contribute to less than 1% of the total amount of cystatin C in CSF. The total cysteine proteinase inhibitory capacity of CSF from HCCAA patients was lower than that of CSF from other patients. This decreased CSF inhibitory capacity in HCCAA patients was caused by decreased levels of cystatin C, since the levels of the other two cysteine proteinase inhibitors found in CSF, alpha 2-macroglobulin and kininogen, were significantly higher than in CSF from non-HCCAA patients.

Amino Acid Sequence↗
PubMed1990

The first Icelandic family with X-linked agammaglobulinaemia: studies of genetic markers and immune function.

This paper describes studies of genetic markers and immune functions in the first Icelandic family identified with X-linked agammaglobulinaemia (X-LA), including three affected brothers. The eldest brother was diagnosed at the age of 9 in 1963. He suffered repeated infections and died at the age of 23. The other two affected brothers, diagnosed at 6 years and 1 year of age, are alive and well on immunoglobulin replacement therapy at the ages of 32 and 24. All were typed for HLA, complement, and various other markers. Pedigree analysis suggests an X-linked segregation of the disease. Their serum IgG is maintained at normal levels on therapy. Several parameters of immune function were studied. The following results were obtained for the X-LA brothers: B cells are absent in their peripheral blood samples. T-cell numbers are normal, but monocytes are increased in numbers and activity. No immunoglobulin production could be elicited in vitro with PWM and no cells containing cytoplasmic Ig were detectable among PWM-stimulated blasts. Nevertheless the proliferative response was particularly vigorous, but the responding cells were shown to be exclusively T cells. No blast transformation could be achieved with EB virus. NK-cell activity was normal/high normal. Other cell-mediated immune functions were normal. In conclusion our data indicate that the differentiation of B cells is blocked in the two surviving X-LA brothers. They have survived for a longer time and in better health than is generally reported. Early diagnosis and adequate replacement treatment with Ig is clearly crucial. Vigorous non-specific immune mechanisms may help to compensate for the defective specific immunity.

Agammaglobulinemia↗
PubMed1990

X chromosome genes involved in the regulation of facial clefting and spina bifida.

Congenital malformations such as cleft palate and spina bifida may be multifactorial in etiology. They occur as a result of both environmental agents and defective genes. Consequently it is both practically and intellectually difficult to study their effects experimentally. The advent of molecular biology technology has enabled many genes on the human chromosome to be mapped and some to be cloned. Using these techniques and families that display common congenital malformations inherited in a purely genetic manner, the genetic defects can be separated from the environmental components. This report documents our studies of several families that have cleft palate or spina bifida as X-linked disorders. Their phenotype is similar to the more common multifactorial cases but segregates as a single gene in an X-linked fashion. Localization of these genes using different X chromosome DNA probes and linkage analysis is the first step towards our understanding of the genetic contribution to the etiology of congenital malformations.

Anencephaly↗
PubMed1989

The saga of cystatin C gene mutation causing amyloid angiopathy and brain hemorrhage--clinical genetics in Iceland.

Firstly, we review investigations of hereditary cystatin C amyloid angiopathy, which is caused by a mutation in the cystatin C gene. Symptoms of brain haemorrhages, which lead to death in young adults, are the hallmark of this disorder. The mutation can now be detected by the RFLP method using Alu I restriction enzyme and cystatin C cDNA probe. Secondly, we give an overview of other clinical genetic studies in Iceland with emphasis on activities initiated or sponsored by the Genetical Committee of the University of Iceland. The list of references covers most publications on genetic studies of Icelanders.

Amyloidosis↗
PubMed1989

Absence of the cystatin C amyloid in the cerebral amyloid angiopathy, senile plaque, and extra-CNS amyloid deposits of aged Japanese.

Amyloid protein in Icelandic patients with hereditary cerebral amyloid angiopathy (CAA) is a variant of cystatin C. Immunoreactivities of the cystatin C and other amyloid proteins were investigated in CAA and other senile amyloid deposits in the Japanese sporadic aged cases including patients with dementia of Alzheimer type, and compared with those in Icelandic hereditary CAA. Compared with positive reaction of cystatin C in Icelandic hereditary CAA, no immunoreactivity of cystatin C was found in senile amyloid deposits of the Japanese aged including CAA. Immunoreactivity of the amyloid beta protein was negative in Icelandic hereditary CAA, for which CAA and senile plaque amyloid in the Japanese senile brains were positive. Our data suggest that the cystatin C amyloid would be present only in hereditary CAA, but not in the CAA and other senile amyloid deposits of the sporadic aged cases.

Aged↗
PubMed1989

Mutation in the cystatin C gene causes hereditary brain hemorrhage.

Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder leading to massive brain hemorrhage and death in young adults (Jensson et al., 1987). A variant of a potent inhibitor of cysteine proteinases, cystatin C (Barrett et al., 1984), is deposited as amyloid fibrils in the cerebral arteries of the patients (Ghiso et al., 1986). We have used the full length cystatin C cDNA probe (Abrahamson et al., 1987) to demonstrate a mutation in the codon for leucine at position 68, which abolishes an Alu I restriction site in cystatin C gene of the HCCAA patients. The Alu I marker has been used to show that this mutation is transmitted only in the affected members in all eight families investigated, proving that the mutated cystatin C gene causes HCCAA. This DNA marker will be useful for the diagnosis of HCCAA in patients, asymptomatic affected individuals and also for pre-natal diagnosis. HCCAA is the first human disorder known to be caused by an abnormal gene for a cysteine proteinase inhibitor.

Amyloidosis↗