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Biomedical subjects

Marjaleena Koskiniemi

Publications and source records attributed to Marjaleena Koskiniemi.

8 recordsLinked to original sources

Multiplex-PCR and oligonucleotide microarray for detection of eight different herpesviruses from clinical specimens.

BACKGROUND: Human herpesviruses cause clinically important diseases, e.g. infections of the central nervous system. New diagnostic tools are required for rapid and reliable detection of these viruses. OBJECTIVES: A microarray-based method was designed for detection of eight human herpesviruses in cerebrospinal fluid (CSF), whole blood, plasma, serum and proficiency-testing specimens. STUDY DESIGN: Herpes simplex type 1 and 2, varicella-zoster, cytomegalo-, Epstein-Barr and human herpes viruses 6A, 6B and 7 were amplified from clinical specimens by two multiplex-PCRs and transcribed to single-stranded RNAs which were hybridized to oligonucleotides on microarray. The results were compared to those from conventional PCR. In total, 227 specimens were tested including 23 CSF, 10 whole blood, 73 plasma, 10 proficiency-testing samples and 111 negative control samples. RESULTS: Concordant results were obtained in 214/227 (94%). Microarray detected 10 possible double and one triple infection. Negative control samples (70 serum, 30 CSF and 11 proficiency-testing samples) were all negative. CONCLUSIONS: Microarray is suitable for detection of multiple herpesviruses in clinical samples.

Herpesviridae↗

Plasminogen activators and their inhibitors in human saliva and salivary gland tissue.

The purpose of this study was to identify plasminogen activators (PA) and their specific inhibitors in human cell-free saliva and to investigate their expression in salivary gland tissue. Saliva samples were obtained from 34 patients visiting a neurological out-patient department. The activities of tissue and urokinase plasminogen activators (tPA and uPA, respectively), the relative inhibition of tPA, and the amounts of plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2, respectively) in cell-free saliva were studied. The activities of tPA and uPA, and tPA inhibition, were measured using in-house microtiter plate assays, and PAI-1 and PAI-2 levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry was used to evaluate the expression of PAs and PAIs in the salivary gland. Tissue plasminogen activator activity was found in most samples, with a mean activity of 0.63 IU ml(-1). uPA was observed in only a few samples. PAI-1 was not detected, but PAI-2 was present in all samples (with a mean value of 11.1 ng ml(-1)). The mean PAI-2 level in women was 12.4 and in men was 7.6 ng ml(-1). The activity of tPA and the relative inhibition of tPA seemed to be inversely associated. Tissue plasminogen activator, PAI-1, and PAI-2 were evident in salivary gland tissue, whereas the expression of uPA was low. The tPA activity in saliva suggests an active proteolysis. Plasminogen activator inhibitor 2 was found to be the main inhibitor of PAs in saliva.

Adult↗

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Journal Article↗

Co-localization of human herpes virus 6 and tissue plasminogen activator in multiple sclerosis brain tissue.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system of unknown etiology. Several viruses have been suggested as playing a role in the pathogenesis of MS. The aim of this study was to investigate the interrelationship of human herpesvirus 6 (HHV-6) and plasminogen activation at the cellular level in MS plaques. MATERIAL/METHODS: Brain tissue specimens obtained from autopsies of 15 patients with MS and 10 controls were studied immunohistochemically for HHV-6 and cytomegalovirus (CMV) antigen and tissue plasminogen activator (tPA) protein. The presence of Ebstein-Barr virus (EBV) EBER RNA was studied using RNA in situ hybridization. RESULTS: HHV-6 antigen was identified in the cells of 67% (10/15) of MS brain sections and 30% (3/10) of the control sections. All samples were negative for CMV antigen and all samples with intact RNA were negative for EBV EBER RNA as demonstrated by in situ hybridization. tPA expression was found to be increased in MS plaques compared with the control samples. Interestingly, in 5 MS samples both HHV-6 antigen and tPA stained clearly, compared with none in the controls, but HHV-6 and tPA only occasionally co-localized in the same cells. CONCLUSIONS: At the cellular level, HHV-6 and plasminogen activation seem to co-localize in MS.

Antigens, Viral↗

Varicella zoster and Borrelia burgdorferi are the main agents associated with facial paresis, especially in children.

BACKGROUND: The etiology of facial paresis (FP) often remains unresolved. Yet, a microbial association is frequently suspected. OBJECTIVE: To evaluate the infectious etiology of FP by using sensitive tests. STUDY DESIGN: We studied the serum and cerebrospinal fluid of 42 patients diagnosed with idiopathic peripheral facial paresis using sensitive serological methods and nucleic acid detection and for reference, 42 patients with other neurological disorders (OND) matched for age, sex, season and geographical area. RESULTS: Varicella zoster virus and Borrelia burgdorferi accounted for 56% of all associated agents in children with FP compared with 11% of OND (P=0.01). In adults, the respective numbers were 29 and 13%. Other treatable etiological agents, Chlamydia pneumoniae and Mycoplasma pneumoniae, accounted for 11% in children and 8% in adults and with the same prevalence between patients with FP and OND. CONCLUSIONS: Microbes, with specific therapy available accounted for 52% of all associated agents in the patients with FP when compared with 26% in controls with OND (P=0.04). Based on this, we conclude that the patients with FP may benefit from antimicrobial therapy.

Adolescent↗

CSF findings in neonates with seizures; infectious and noninfectious.

In order to evaluate parameters of cerebrospinal fluid (CSF) we studied 105 CSF samples of 50 neonates with seizures of unknown origin for cell count and chemistry (protein, albumin, glucose, IgG-index and albumin-ratio). Viral studies for 13 different microbes were performed from serum and CSF. CSF parameters of the babies with a suggested viral infection (n = 13) were compared with those without any viral findings (n = 37), and followed up to the age 45 weeks since conception. CSF mononuclear white blood cell count was < or = 20 x 10(6)/l at the age of < or = 40 weeks since conception, and thereafter i.e. at term it was < or = 10 x 10(6)/l in all neonates without viral infection, whereas mononuclear cell count was above these limits in 8 of 13 neonates with viral infection. The rate of IgG-index remained high only in the neonates with a viral infection when studied at the age of over 43 weeks since conception. We conclude that studies of CSF are a valuable diagnostic aid in CNS viral infections of neonates when evaluated in reference to the age since conception, and the limits of mononuclear white blood cells in normal CSF of neonates are in lower limits than reported before.

Age Distribution↗

Viral infections in neonates with seizures.

The aim of this study was to determine the incidence of viral infections in the central nervous system (CNS) of neonates with seizures of unknown origin. Serum and cerebrospinal fluid (CSF) samples of 50 neonates were studied for antibodies to 13 different microbes by enzyme immunoassay, and CSF samples were investigated for four specific nucleic acids by polymerase chain reaction. For viral cultures throat, stool and CSF samples were obtained. CNS viral infection was suggested in 13 of the 50 neonates (26%). Antibodies to varicella, herpes simplex 1, influenza A or B, parainfluenza 1, adeno or enteroviruses were detected in the CSF of nine children; and herpes simplex 2 specific DNA was found in one child. Cytomegalovirus was cultured from the urine of two children. In one child unspecified, but evident pleocytosis in the CSF was observed. The incidence of CNS viral infections in association with neonatal seizures may be much higher than previously reported.

Antibodies, Viral↗

Acute central nervous system complications in varicella zoster virus infections.

BACKGROUND: In a previous multicenter study on central nervous system (CNS) viral infections varicella zoster virus (VZV) appeared the most frequent etiologic agent and appeared often without rash. OBJECTIVE: To evaluate the appearance and diagnostics of VZV in CNS more thoroughly, we studied the cases systematically by using sensitive and specific methods to learn the best diagnostic approach in order to start specific therapy. STUDY DESIGN: We analyzed all serum and cerebrospinal fluid samples of 174 patients, 88 females and 86 males, with acute CNS symptoms associated with VZV infection diagnosed in the multicenter study on viral CNS infections. RESULTS: About 38 patients (22%) had chickenpox, 59 (34%) had shingles, and 77 (44%) had no cutaneous symptoms at all. The mean age of chickenpox patients was 8.6 years, of the others 46.6 and 41.4 years. VZV-specific nucleic acid was detected in the CSF in one fourth of the patients in all groups, primarily during the first week of illness. In serum specimens, specific IgM was present in two thirds of the patients with chickenpox, whereas in the others in one third of the cases. In CSF, specific IgM was present in 15-17% of patients with skin manifestations, compared with 6% of those without rash. CONCLUSIONS: The role of VZV infections in CNS complications seems remarkable, often presenting without rash. Even these cases should be promptly recognized in order to conduct proper antiviral therapy. In children, a combination of PCR and IgM tests is the best approach. In adults, PCR, together with the measurement of intrathecal antibody production yields best results.

Acute Disease↗