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T Salonen

Publications and source records attributed to T Salonen.

17 recordsLinked to original sources
PubMed2001

Neuronal trafficking of palmitoyl protein thioesterase provides an excellent model to study the effects of different mutations which cause infantile neuronal ceroid lipofuscinocis.

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative storage disorder in children caused by mutations in the palmitoyl protein thioesterase gene (PPT1). We have investigated here four naturally occurring previously described PPT1 mutations and show that all cause severe effects on PPT1 enzyme activity in transiently transfected COS-1 cells. Two of the mutations (delPhe84 and insCys45) cause a classical INCL phenotype and two (Thr75Pro and Leu219Gln) result in a late onset disease phenotype. All these mutated PPT1 molecules have severely altered intracellular localization in transiently transfected BHK-cells, whereas in mouse primary neuron cultures different effects were observed. In neurons the delPhe84 and insCys45 mutant polypeptides were targeted to the ER. Interestingly the Thr75Pro and Leu219Gln mutations had only minor effects on the neuronal trafficking of PPT1 and the mutated polypeptides were observed in neuronal shafts and showed colocalization with the presynaptic marker SV2. Our data indicates that neuronal cells provide an excellent model to study the genotype-phenotype correlation in INCL.

Age of Onset↗
PubMed2001

New mutations in the neuronal ceroid lipofuscinosis genes.

Thirty-eight mutations and seven polymorphisms have recently been reported in the genes underlying the neuronal ceroid lipofuscinoses (NCLs) including 11 new mutations described here. A total of 114 mutations and 28 polymorphisms have now been described in the five human genes identified which cause NCL. Thirty-eight mutations are recorded for CLN1/PPT; 40 for CLN2/TTP-1, 31 for CLN3, four for CLN5, one for CLN8. Two mutations have been described in animal genes (cln8/mnd, CTSD). All mutations in NCL genes are contained in the NCL Mutation Database (http://www.ucl.ac.uk/NCL).

Child↗
PubMed2000

CLN-1 and CLN-5, genes for infantile and variant late infantile neuronal ceroid lipofuscinoses, are expressed in the embryonic human brain.

Mutations in the CLN-1 and CLN-5 genes underlie the infantile, and Finnish variant of the late-infantile, neuronal ceroid lipofuscinoses, respectively. These disorders are characterized by a massive neuronal death early in childhood. We have studied mRNA and protein expression of CLN-1 and CLN-5 in embryonic human brains. The spatial and temporal distributions of CLN-1 and CLN-5 were similar in the embryonic human brain. Both genes are expressed at the beginning of cortical neurogenesis, and this expression increases as cortical development proceeds. In the developing cortical plate, expression is found in postmitotic migrating neuroblasts and neuroblasts that have completed migration. Expression was intense also in cells of the thalamus as well as in the future Purkinje cell layer of the cerebellum. These findings indicate that expression of CLN-1 and CLN-5 may be significant for development of a wide range of maturating neurons.

Brain↗
PubMed2000

Detection of eight novel palmitoyl protein thioesterase (PPT) mutations underlying infantile neuronal ceroid lipofuscinosis (INCL;CLN1).

The infantile form of neuronal ceroid lipofuscinosis (INCL; CLN1) is the earliest onset form of the neuronal ceroid lipofuscinoses (NCL), a group of progressive encephalopathies of children. INCL is caused by mutations in the palmitoyl protein thioesterase (PPT) gene, and we report here eight novel INCL mutations in PPT. Five of the mutations, c.456C>A, c.162-163insA, c.174-175delG, c.774-775insA, and a splice acceptor mutation IVS1-2A>G in intron 1, caused the generation of a premature STOP codon either directly or after a frameshift. One mutation was a three-bp insertion in exon 2 (c. 132-133insTGT) leading to insertion of one extra cysteine (Ser44-insCys-Cys45), and another mutation, a 3-bp deletion in exon 3 (c.249-251delCTT), led to deletion of Phe84 in PPT. A splice acceptor mutation IVS6-1G>T in intron 6 can be predicted to cause skipping of exon 7 in PPT. All of these novel mutations were associated with the classical phenotype of INCL, with the first symptoms starting around 12 months of age. The severe phenotypes could be explained by the nature of the novel mutations: five are predicted to lead to premature translational termination, thus abolishing the active site of PPT, and three will probably cause a misfolding of the nascent polypeptide. Thirty-five percent (7/20) of the disease alleles in these 11 families contained the most prevalent c.451C>T missense mutation outside Finland [Das et al., 1998]. Consequently, 31 different mutations underlying INCL have been found so far, the majority leading to classical INCL.

Amino Acid Sequence↗
PubMed2000

Reversible posterior leukoencephalopathy after combination chemotherapy.

We describe a young woman with Burkitt's lymphoma, treated with intravenous adriamycine and cyclophosphamide and intrathecal cytarabine. She developed a reversible posterior leukoencephalopathy syndrome (RPLS) with typical MRI findings. Diffusion-weighted images during the first days after the onset of symptoms predicted a small irreversible lesion in the frontal lobe, verified on T2-weighted images 1 month later. The patient showed full recovery after high-dose steroid treatment.

Adolescent↗
PubMed1999

[Blue lips].

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Adolescent↗
PubMed1998

Mouse palmitoyl protein thioesterase: gene structure and expression of cDNA.

Palmitoyl protein thioesterase (PPT) is the defective enzyme in infantile neuronal ceroid lipofuscinosis (INCL), which is a recessively inherited, progressive neurodegenerative disorder. We present here the cloning, chromosomal mapping, genomic structure, and the expression of the cDNA of mouse PPT. The mouse PPT gene spans >21 kb of genomic DNA and contains nine exons with a coding sequence of 918 bp. Fluorescence in situ hybridization to metaphase chromosomes localized the mouse PPT gene to the chromosome 4 conserved syntenic region with human chromosome 1p32 where the human PPT is located. PPT is expressed widely in a variety of mouse tissues. The mouse PPT cDNA is conserved highly with the human and rat PPT both at the nucleotide and amino acid sequence level. Transient expression of mouse PPT in COS-1 cells yielded a 38/36-kD differentially glycosylated polypeptide that was also secreted into culture media. Immunofluorescence analysis of transiently transfected HeLa cells indicated lysosomal localization of mouse PPT. Based on the high conservation of the gene and polypeptide structure as well as similar processing and intracellular localization, the function of PPT in mouse and human are likely to be very similar.

Amino Acid Sequence↗
PubMed1996

Monoamine oxidase B inhibitor selegiline protects young and aged rat peripheral sympathetic neurons against 6-hydroxydopamine-induced neurotoxicity.

Selegiline is a selective and irreversible monoamine B inhibitor with the capacity to increase the level of several antioxidative enzymes in rat brain. It can protect adrenergic neurons against injury induced by neurotoxins such as MPTP, DSP-4 and AF64A in animal studies. In addition, the protective action is not limited to catecholaminergic cells, as selegiline can also minimize the loss of developing motoneurons after axotomy. The aim of this study was to determine whether selegiline can protect peripheral catecholaminergic neurons against the neurotoxic effect of 6-OHDA. This kind of protective effect against 6-OHDA neurotoxicity has not been reported before. Wistar albino male rats aged 4 or 24 months were treated with selegiline or saline solution 1 h before 6-OHDA injection. At 2 weeks after the 6-OHDA injection, the superior cervical ganglia (SCG) and submandibular glands (SMG) were studied using catecholamine histofluorescence and immunohistochemistry for tyrosine hydroxylase (TH). The number of TH-positive cells in the SCG and the length and number of adrenergic nerve fibers in the SMG were quantified. Our findings showed that 6-OHDA caused a reduction of TH immunoreactivity and catecholamine histofluorescence in neuronal somata, as well as a decrease in the number and length of adrenergic nerve fibers in the submandibular gland. Selegiline pretreatment protected SCG neurons and their postganglionic nerve fibers in SMG against these changes in a dose-dependent manner. The mechanism through which selegiline exerts its neuroprotective effect is as yet unknown.

Aging↗
PubMed1981

Childhood cancer and parental occupation in Finland.

A case-control study was conducted of the occupations of parents of children under 15 with diagnosed malignancies. The total series contained all childhood cancers cases reported to the Finnish Cancer Registry during the period 1959-75. The parental occupations, recorded at the time of pregnancy, were collected from maternity welfare centres. The cases were analysed as a singly group or as subgroups according to the diagnoses-brain tumours, leukaemia, and all other malignancies. The maternal occupations found more frequently among cases than controls included farmers' wives (1959-68 only), pharmacists, saleswomen, bakers, and factory work of an vehicle driving, machine repair, painting, and the work of men who gave an academic degree as their occupation. Some of these occupations involve possible exposure to harmful chemicals, although chance correlations cannot be excluded.

Adolescent↗
PubMed1977

A comparison between an equimolar inhaled dose of ibuterol and terbutaline in asthmatics.

The effect of equimolar doses of ibuterol, 0.75 mg, and terbutaline, 0.50 mg, was compared in 16 asthmatics. Both drugs were given double-blind in a single dose by inhalation. The drugs did not significantly differ from each other in any of the parameters used in the trial. Both had rapid onset of action on the bronchospasm as measured with a Wright's peak flow meter. The effect was still statistically significant 300 min after the inhalation compared with the pre-treatment values. Neither drug had any effect of clinical importance on heart rate or blood pressure. No side effects were observed during the trial.

Adult↗
PubMed1976

Cancer in the offspring of fathers in hydrocarbon-related occupations.

A case-control study has been conducted to see whether a hydrocarbon-related occupation of the father at the time of conception constitutes a risk factor for malignant disease in the offspring. The series comprised 852 cancer cases from the Finnish Cancer Registry and 852 controls matched for date of birth and domicile. The father's occupation for both the cases and controls was ascertained from the records of antenatal clinics. No significant associations were found between the commonest types of childhood cancer and hydrocarbon-related occupations--that is, motor-vehicle mechanics, machinists, miners, painters, and motor-vehicle drivers. Risk ratio 2 was excluded from most of the 95% confidence intervals for children under 15 years of age. The results do not support the hypothesis that there is an excess risk of cancer in the children of fathers in hydrocarbon-related occupations.

Adolescent↗
PubMed1976

Prenatal and perinatal factors in childhood cancer.

The material consists of malignant tumours in childhood notified to the Finnish Cancer Registry in 1959-1968. The maternity health centre cards for these children were collected through the National Board of Health. The immediately preceding parturient of the same maternity health centre was selected as the control. The number of complete pairs obtained for the final analysis was 972. All data concerning the parents, the pregnancy, parturition and the child were extracted from the cards. Information on the cancer patient and the paired control was compared. The results are presented as a comparison of the total tumour series and the controls, but also in smaller sub-groups: leukaemias (373 cases), brain tumours (245 cases) and other tumours (354 cases). Other tumours are further divided into: kidney tumours (96), eye tumours (37) and bone tumours (56). No significant correlations were found between potential aetiologic factors and the cases of cancer. The risk ratio for leukaemia in the group with pelvic radiography was 1.9, and in the group given vaccination against polio 1.8. However, because of the rare occurrence of the exposure mentioned these groups were small and the increase in the risk ratio statistically insignificant. BCG vaccination of children was common (90%) and no differences were established between the tumour and the control groups in this respect.

Adolescent↗
PubMed1975

Risk indicators in childhood malignancies.

A series of 972 childhood malignancies was compared with a control series of healthy children matched for date and place of birth. Several variables were tested for possible aetiological significance. The information was obtained from the Finnish Cancer Registry and from the antenatal records of the mothers. No significant associations were found between the various types of malignancies and the variables studied. In the group consisting of all malignancies, a risk ratio of 2.0 could be significantly excluded for most variables. In the leukaemia group, both pelvic X-ray and polio vaccination were associated with slightly elevated risk ratios, but the differences between this group and the match controls were not statistically significant. BCG vaccination was performed during the perinatal period in 90% of the children, but the proportion was the same in the study and control groups, and hence the hypothesis that this vaccination confers protection was not supported. The information is considered prospective and relatively reliable, and the authors suggest that these data may be useful when more extensive series are compiled from various sources.

Adolescent↗
PubMed1975

Incidence of childhood cancer in Finland.

Between 1953 and 1970, 2,605 malignant tumors in children under 15 years of age were reported to the Finnish Cancer Registry, a population-based registry that covers the whole country (population, 4.6 million). The mean annual age-adjusted incidence rates per million were 128 in males and 108 in females. The most common neoplasms were leukemia (age-adjusted incidence rates, 43.7 in males; 34;7 in females), brain tumors (26.4 in males, 22.8 in females), renal tumors (10;0 in males, 9.1 in females), lymphomas (10.8 in males, 5.3 in females), and bone tumors (5;3 in males, 5.1 in females). This distribution is roughly the same as the observed in many other white populations. However, the incidence rates of leukemia, lymphomas, neuroblastomas, and soft-tissue tumors were somewhate lower than figures reported in the Third National Cancer Survey of the United States.

Adolescent↗
PubMedDate not supplied

Transplacental carcinogens and mutagens: childhood cancer, malformations, and abortions as risk indicators.

Childhood cancer, malformations, and spontaneous abortions in Finland were analyzed according to the parents' occupations. Children of women working in the food industry and farming and of men working in motor vehicle driving and farming appeared to have an elevated risk of cancer. Women in industrial and construction occupations had an increased risk of having malformed children and spontaneous abortions.

Abnormalities, Drug-Induced↗