Tap water as the source of a Legionnaires' disease outbreak spread to several residential buildings and one hospital, Finland, 2020 to 2021.

In Finland, all microbiology laboratories notify findings and physicians notify Legionnaires' disease (LD) cases to the National Infectious Disease Register. All cases are interviewed, and water samples obtained from potential places of exposure. isolates from humans and water are compared by whole genome sequencing (WGS).

Aspartylglycosaminuria: a review.

Aspartylglucosaminuria (AGU), a recessively inherited lysosomal storage disease, is the most common disorder of glycoprotein degradation with a high prevalence in the Finnish population. It is a lifelong condition affecting on the patient's appearance, cognition, adaptive skills, physical growth, personality, body structure, and health. An infantile growth spurt and development of macrocephalia associated to hernias and respiratory infections are the key signs to an early identification of AGU.

Discrepancies between plasma procalcitonin and C-reactive protein levels are common in acute illness.

Aim: Procalcitonin (PCT) and C-reactive protein (CRP) are biomarkers of bacterial infection with distinct clinical qualities. This study aimed to determine the occurrence and significance of discrepancies in plasma PCT and CRP levels in hospitalised children.

Methods: This was a single centre, retrospective analysis of simultaneous PCT and CRP measurements.

Myocardial blood flow and its transit time, oxygen utilization, and efficiency of highly endurance-trained human heart.

Highly endurance-trained athlete's heart represents the most extreme form of cardiac adaptation to physical stress, but its circulatory alterations remain obscure. In the present study, myocardial blood flow (MBF), blood mean transit time (MTT), oxygen extraction fraction (OEF) and consumption (MVO2), and efficiency of cardiac work were quantified in highly trained male endurance athletes and control subjects at rest and during supine cycling exercise using [(15)O]-labeled radiotracers and positron emission tomography. Heart rate and MBF were lower in athletes both at rest and during exercise.

Maternal smoking affects lung function and airway inflammation in young children with multiple-trigger wheeze.

Background: Exposure to tobacco smoke is a well-known risk factor for childhood asthma and reduced lung function, but the effect on airway inflammation in preschool-aged children is unclear.

Objective: To examine the effect of parental smoking on lung function and fractional concentration of exhaled nitric oxide (Feno) in relation to both parental reports and children's urine cotinine concentrations in preschool-aged children with multiple-trigger wheeze.

Methods: A total of 105 3- to 7-year-old children with multiple-trigger wheeze and lung function abnormalities were recruited.

Early initiation of enzyme replacement therapy improves metabolic correction in the brain tissue of aspartylglycosaminuria mice.

Aspartylglycosaminuria (AGU) is a lysosomal storage disease caused by deficient activity of glycosylasparaginase (AGA), and characterized by motor and mental retardation. Enzyme replacement therapy (ERT) in adult AGU mice with AGA removes the accumulating substance aspartylglucosamine from and reverses pathology in many somatic tissues, but has only limited efficacy in the brain tissue of the animals. In the current work, ERT of AGU mice was initiated at the age of 1 week with three different dosage schedules of recombinant glycosylasparaginase.

Cardiopulmonary involvement in Fabry's disease.

Background: Fabry's disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipid in different tissues, including endothelial and smooth-muscle cells and cardiomyocytes.

Objectives: There is controversial data on cardiopulmonary involvement in Fabry's disease, because many reports are based on small and selected populations with Fabry's disease.

Echocardiography in Fabry disease: diagnostic value of endocardial border binary appearance.

Background And Aim: It has been reported that the endocardium in Fabry disease has a binary appearance on transthoracic echocardiography. It has been suggested that this sign could be used with good accuracy to differentiate Fabry disease from hypertrophic cardiomyopathy and even as a first filter to screen for suspected Fabry disease.

Methods: Therefore, we performed a blinded echocardiography in a non-selected population of patients with Fabry disease and matched controls.

Twenty-four-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipids in different tissues including endothelial cells and smooth-muscle cells and cardiomyocytes, and cardiovascular complications are common in the disease. Since 2001, specific enzyme replacement therapy (ERT) with alpha-galactosidase A has been available.

Vascular adhesion protein-1 in human ischaemic stroke.

Aims: Leukocyte extravasation exacerbates tissue injury after ischaemic stroke. Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule with the potential capacity to guide transmigration of inflammatory cells into ischaemic brain. Moreover, VAP-1 could worsen ischaemic brain injury due to its function as a semicarbazide-sensitive amine oxidase (SSAO) producing toxic metabolites from primary amines.

A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis.

Background: Past sun exposure and vitamin D3 supplementation have been associated with a reduced risk of multiple sclerosis (MS). There are no previous longitudinal studies of vitamin D in MS.

Objectives: To compare regulation of vitamin D and calcium homeostasis between patients with MS and healthy controls.

25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis.

Past sun exposure and vitamin D supplementation have been associated with a reduction in the risk of MS. We measured the serum concentration of 25-hydroxyvitamin D (25[OH]D) at the time of MS diagnosis in 40 MS patients and 40 controls. We found no difference in the serum levels of 25(OH)D between MS patients and controls when all samples or samples obtained during winter months were compared, but MS patients had significantly lower serum 25(OH)D concentrations in June to September than the controls.

Massive accumulation of Man2GlcNAc2-Asn in nonneuronal tissues of glycosylasparaginase-deficient mice and its removal by enzyme replacement therapy.

Aspartylglycosaminuria (AGU) is caused by deficient enzymatic activity of glycosylasparaginase (GA). The disease is characterized by accumulation of aspartylglucosamine (GlcNAc-Asn) and other glycoasparagines in tissues and body fluids of AGU patients and in an AGU mouse model. In the current study, we characterized a glycoasparagine carrying the tetrasaccharide moiety of alpha-D-Man-(1-->6)-beta-D-Man-(1-->4)-beta-D-GlcNAc-(1-->4)-beta-D-GlcNAc-(1-->N)-Asn (Man2GlcNAc2-Asn) in urine of an AGU patient and also in the tissues of the AGU mouse model.

Beta-aspartylpeptides as substrates of L-asparaginases from Escherichia coli and Erwinia chrysanthemi.

L-Asparaginase is known to catalyze the hydrolysis of L-asparagine to L-aspartic and ammonia, but little is known about its action on peptides. When we incubated L-asparaginases purified either from Escherichia coli or Erwinia chrysanthemi - commonly used as chemotherapeutic agents because of their antitumour activity - with eight small beta-aspartylpeptides such as beta-aspartylserineamide, beta-aspartylalanineamide, beta-aspartylglycineamide and beta-aspartylglycine, we found that both L-asparaginases could catalyze the hydrolysis of five of them yielding L-aspartic acid and amino acids or peptides. Our data show that L-asparaginases can hydrolyze beta-aspartylpeptides and suggest that L-asparaginase therapy may affect the metabolism of beta-aspartylpeptides present in human body.

Serious neutropenia in ALL patients treated with L-asparaginase may be avoided by therapeutic monitoring of the enzyme activity in the circulation.

The antineoplastic enzyme L-asparaginase is commonly used for the induction of remission in acute lymphoblastic leukemia (ALL). L-Asparagine is an essential amino acid for many lymphoid tumor cells and L-asparaginase catalyzes its conversion to L-aspartic acid and ammonia. The dosage of this highly toxic drug is individualized based on the body surface area of the patient, but monitoring of L-asparaginase activity during the L-asparaginase therapy is not commonly used.

Carriers of the aspartylglucosaminuria genetic mutation and chronic arthritis.

Objective: To ascertain whether being a carrier of an autosomal recessive disease, aspartylglucosaminuria (AGU), predisposes to chronic arthritis, as does AGU disease.

Methods: A group of 173 unrelated patients with rheumatoid arthritis (RA) but with no family members with AGU each gave a blood sample for AGUFin major mutation DNA analysis. A group of 131 AGU carriers who were parents of patients with AGU completed a questionnaire on joint symptoms and gave a blood sample for rheumatoid factor (RF) analysis.

Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family.

Objective: To describe an unusual kindred with adult-onset ataxia and thalamic lesions detected by brain MRI.

Methods: The authors characterized clinical, laboratory, and pathologic features of the disease and sought linkage to previously recognized ataxia loci.

Results: Two sisters and a brother developed progressive ataxia, dysarthria, mild cognitive impairment, and sensorimotor neuropathy at age 30, combined with epilepsy in one sibling.

Human leukocyte glycosylasparaginase: cell-to-cell transfer and properties in correction of aspartylglycosaminuria.

Aspartylglycosaminuria (AGU), a severe lysosomal storage disease, is caused by the deficiency of the lysosomal enzyme, glycosylasparaginase (GA), and accumulation of aspartylglucosamine (GlcNAc-Asn) in tissues. Here we show that human leukocyte glycosylasparaginase can correct the metabolic defect in Epstein-Barr virus (EBV)-transformed AGU lymphocytes rapidly and effectively by mannose-6-phosphate receptor-mediated endocytosis or by contact-mediated cell-to-cell transfer from normal EBV-transformed lymphocytes, and that 2-7% of normal activity is sufficient to correct the GlcNAc-Asn metabolism in the cells. Cell-to-cell contact is obligatory for the transfer of GA since normal transformed lymphocytes do not excrete GA into extracellular medium.

New immunochromatographic rapid test for diagnosis of acute Puumala virus infection.

A new immunochromatographic rapid test, POC PUUMALA (Erilab Ltd., Kuopio, Finland), for detection of acute-phase Puumala virus (PUUV) infection was developed based on a highly purified baculovirus-expressed PUUV nucleocapsid protein antigen and lateral immunodiffusion techniques. After addition of sample (5 microl of serum, plasma, or fingertip blood) and buffer, PUUV-specific immunoglobulin M (IgM) antibodies, if present, together with the gold-conjugated anti-human IgM, formed a specific colored line in 5 min.

Detection of the Finnish-type congenital nephrotic syndrome by restriction fragment length polymorphism and dual-color oligonucleotide ligation assays.

Background: Congenital nephrotic syndrome of Finnish type (NPHS1) is an autosomal recessive disorder characterized by severe proteinuria of intrauterine onset. Ninety-four percent of the Finnish NPHS1 chromosomes have been reported to carry either a 2-bp deletion in exon 2 (Fin(Major)) or a nonsense mutation in exon 26 (Fin(Minor)) of the NPHS1 gene. The high prevalence of only two mutations in the Finnish population enables the use of molecular techniques in the diagnosis of NPHS1 and for carrier screening.

A fluorometric assay for L-asparaginase activity and monitoring of L-asparaginase therapy.

The antineoplastic enzyme L-asparaginase is commonly used for the induction of remission in acute lymphoblastic leukemia (ALL). There is no simple method available for measuring the activity of this highly toxic drug. We incubated L-asparaginase from Erwinia chrysanthemi with L-aspartic acid beta-(7-amido-4-methylcoumarin) and measured the release of 7-amino-4-methylcoumarin fluorometrically for 30-300 min.

Enzyme replacement therapy in a mouse model of aspartylglycosaminuria.

Aspartylglycosaminuria (AGU), the most common lysosomal disorder of glycoprotein degradation, is caused by deficient activity of glycosylasparaginase (AGA). AGA-deficient mice share most of the clinical, biochemical and histopathologic characteristics of human AGU disease. In the current study, recombinant human AGA administered i.