School success in childhood and subsequent prodromal symptoms and psychoses in the Northern Finland Birth Cohort 1986.

BACKGROUND: Low IQ is a risk factor for psychosis, but the effect of high IQ is more controversial. The aim was to explore the association of childhood school success with prodromal symptoms in adolescence and psychoses in adulthood. METHODS: In the general population-based Northern Finland Birth Cohort 1986 (n = 8 229), we studied the relationship between teacher-assessed learning deficits, special talents and general school success at age 8 years and both prodromal symptoms (PROD-screen) at age 15-16 years and the occurrence of psychoses by age 30 years. RESULTS: More prodromal symptoms were experienced by those talented in oral presentation [boys: adjusted odds ratio (OR) 1.49; 95% confidence interval 1.14-1.96; girls: 1.23; 1.00-1.52] or drawing (boys: 1.44; 1.10-1.87). Conversely, being talented in athletics decreased the probability of psychotic-like symptoms (boys: OR 0.72; 0.58-0.90). School success below average predicted less prodromal symptoms with boys (OR 0.68; 0.48-0.97), whereas above-average success predicted more prodromal symptoms with girls (OR 1.22; 1.03-1.44). The occurrence of psychoses was not affected. Learning deficits did not associate with prodromal symptoms or psychoses. CONCLUSIONS: Learning deficits in childhood did not increase the risk of prodromal symptoms in adolescence or later psychosis in this large birth cohort. Learning deficits are not always associated with increased risk of psychosis, which might be due to, e.g. special support given in schools. The higher prevalence of prodromal symptoms in talented children may reflect a different kind of relationship of school success with prodromal symptoms compared to full psychoses.

Vitamin D status and correlates of low vitamin D in schizophrenia, other psychoses and non-psychotic depression - The Northern Finland Birth Cohort 1966 study.

There is limited knowledge available on the association of vitamin D with psychiatric disorders in young adults. We aimed to investigate vitamin D levels and associating factors in schizophrenia, other psychoses and non-psychotic depression. We studied 4,987 participants from the Northern Finland Birth Cohort 1966 (31 years) with available serum 25-hydroxyvitamin D [25(OH)D] measurements. The final sample was divided into four groups: schizophrenia (n = 40), other psychoses (n = 24), non-psychotic depression (n = 264) and control (n = 4659). To account for the influence of environmental and technical covariates, we generated a vitamin D score variable with correction for season, sex, batch effect and latitude. We further examined how vitamin D levels correlate with anthropometric, lifestyle, socioeconomic and psychiatric measures. Neither serum 25(OH)D concentration nor vitamin D score differed between schizophrenia, other psychoses, non-psychotic depression and control group. The prevalence of vitamin D deficiency was 3.2%, insufficiency 25.5%, and sufficiency 71.3%. Low vitamin D score correlated with regular smoking in the group with schizophrenia. No difference was observed in other psychiatric conditions. We did not find any difference in vitamin D status between schizophrenia, psychoses, non-psychotic depression and control groups, but future studies are warranted to elucidate the role of vitamin D in psychiatric conditions.

Association between family history of mental disorders and outcome in psychotic disorders.

We investigated the association of family history of mental disorders, especially psychosis, with occupational and clinical outcome in psychotic disorders in a longitudinal population-based cohort. The Northern Finland Birth Cohort 1986 (n = 9432) was used to gather the data. In total 189 individuals with psychosis were identified by age of 28. The outcome was assessed by using register information regarding occupational activity, disability pension and hospital treatments due to psychiatric cause. Parental psychosis and any psychiatric disorder were used as predictors of outcome. The results showed that presence of any parental psychiatric disorder was associated with higher number of days spent at hospital and higher number of hospitalizations in psychotic disorders, but was not associated with occupational outcome or disability pension. The presence of parental psychosis was not associated with outcome. These findings suggest that the presence of any psychiatric disorder among parents may increase the risk of poorer outcome in psychoses in terms of need of hospitalisations. Based on this study the presence of parental psychosis is not associated with outcome, but the result should be interpreted with caution due to the small sample size and conflict with the results of earlier studies.

Smokin' hot: adolescent smoking and the risk of psychosis.

OBJECTIVE: Daily smoking has been associated with a greater risk of psychosis. However, we are still lacking studies to adjust for baseline psychotic experiences and other substance use. We examined associations between daily smoking and psychosis risk in a 15-year follow-up while accounting for these covariates in a prospective sample (N = 6081) from the Northern Finland Birth Cohort 1986. METHODS: Self-report questionnaires on psychotic experiences (PROD-screen), tobacco smoking and other substance use were completed when the cohort members were 15-16 years old. Tobacco smoking was categorized into three groups (non-smokers, 1-9 cigarettes and ≥10 cigarettes/day). Psychosis diagnoses were obtained from national registers until the age of 30 years. RESULTS: Subjects in heaviest smoking category were at increased risk of subsequent psychosis (unadjusted HR = 3.15; 95% CI 1.94-5.13). When adjusted for baseline psychotic experiences the association persisted (HR = 2.87; 1.76-4.68) and remained significant even after adjustments for multiple known risk factors such as cannabis use, frequent alcohol use, other illicit substance use, parental substance abuse, and psychosis. Furthermore, number of smoked cigarettes increased psychosis risk in a dose-response manner (adjusted OR = 1.05; 1.01-1.08). CONCLUSION: Heavy tobacco smoking in adolescence was associated with a greater risk for psychosis even after adjustment for confounders.

Structural properties of the human corpus callosum: Multimodal assessment and sex differences.

A number of structural properties of white matter can be assessed in vivo using multimodal magnetic resonance imaging (MRI). We measured profiles of R1 and R2 relaxation rates, myelin water fraction (MWF) and diffusion tensor measures (fractional anisotropy [FA], mean diffusivity [MD]) across the mid-sagittal section of the corpus callosum in two samples of young individuals. In Part 1, we compared histology-derived axon diameter (Aboitiz et al., 1992) to MRI measures obtained in 402 young men (19.55 ± 0.84 years) recruited from the Avon Longitudinal Study on Parents and Children. In Part 2, we examined sex differences in FA, MD and magnetization transfer ratio (MTR) across the corpus callosum in 433 young (26.50 ± 0.51 years) men and women recruited from the Northern Finland Birth Cohort 1986. We found that R1, R2, and MWF follow the anterior-to-posterior profile of small-axon density. Sex differences in mean MTR were similar across the corpus callosum (males > females) while these in FA differed by the callosal segment (Body: M>F; Splenium: F>M). We suggest that the values of R1, R2 and MWF are driven by high surface area of myelin in regions with high density of "small axons".

Prostate cancer screening in men aged 50 to 69 years (STHLM3): A prospective population-based diagnostic study. Grönberg H, Adolfsson J, Aly M, Nordström T, Wiklund P, Brandberg Y, Thompson J, Wiklund F, Lindberg J, Clements M, Egevad L, Eklund M.Lancet Oncol. 2015 Dec;16(16):1667-76. [Epub 2015 Nov 10]. doi: 10.1016/S1470-2045(15)00361-7.

BACKGROUND: The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone. METHODS: The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50 to 69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms [232 SNPs], and clinical variables [age, family, history, previous prostate biopsy, prostate exam]), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com, number ISRCTN84445406. FINDINGS: The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (P<0.0001), the area under the curve was 0·56 (95% CI: 0·55-0·60) with PSA alone and 0·74 (95% CI: 0·72-0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (P<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of≥3ng/ml to diagnose high-risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI: 24-39) and could avoid 44% (35-54) of benign biopsies. INTERPRETATION: The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes. FUNDING: Stockholm County Council (Stockholms Läns Landsting).

A comparison of the cumulative incidence and early risk factors for psychotic disorder in young adults in the Northern Finland Birth Cohorts 1966 and 1986.

AIMS: Few studies have compared time trends for the incidence of psychosis. To date, the results have been inconsistent, showing a decline, an increase or no significant change. As far as we know, no studies explored changes in prevalence of early risk factors. The aim of this study was to investigate differences in early risk factors and cumulative incidences of psychosis by type of psychosis in two comparable birth cohorts. METHODS: The Northern Finland Birth cohorts (NFBCs) 1966 (N = 12 058) and 1986 (N = 9432) are prospective general population-based cohorts with the children followed since mother's mid-pregnancy. The data for psychoses, i.e. schizophrenia (narrow, spectrum), bipolar disorder with psychotic features, major depressive episode with psychotic features, brief psychosis and other psychoses (ICD 8-10) were collected from nationwide registers including both inpatients and outpatients. The data on early risk factors including sex and place of birth of the offspring, parental age and psychosis, maternal education at birth were prospectively collected from the population registers. The follow-up reached until the age of 27 years. RESULTS: An increase in the cumulative incidence of all psychoses was seen (1.01% in NFBC 1966 v. 1.90% in NFBC 1986; p < 0.001), which was due to an increase in diagnosed affective and other psychoses. Earlier onset of cases and relatively more psychoses in women were observed in the NFBC 1986. Changes in prevalence of potential early risk factors were identified, but only parental psychosis was a significant predictor in both cohorts (hazard ratios ≥3.0; 95% CI 1.86-4.88). The difference in psychosis incidence was not dependent on changes in prevalence of studied early risk factors. CONCLUSIONS: Surprisingly, increase in the cumulative incidence of psychosis and also changes in the types of psychoses were found between two birth cohorts 20 years apart. The observed differences could be due to real changes in incidence or they can be attributable to changes in diagnostic practices, or to early psychosis detection and treatment.

Latent variable mixture modeling in psychiatric research--a review and application.

Latent variable mixture modeling represents a flexible approach to investigating population heterogeneity by sorting cases into latent but non-arbitrary subgroups that are more homogeneous. The purpose of this selective review is to provide a non-technical introduction to mixture modeling in a cross-sectional context. Latent class analysis is used to classify individuals into homogeneous subgroups (latent classes). Factor mixture modeling represents a newer approach that represents a fusion of latent class analysis and factor analysis. Factor mixture models are adaptable to representing categorical and dimensional states of affairs. This article provides an overview of latent variable mixture models and illustrates the application of these methods by applying them to the study of the latent structure of psychotic experiences. The flexibility of latent variable mixture models makes them adaptable to the study of heterogeneity in complex psychiatric and psychological phenomena. They also allow researchers to address research questions that directly compare the viability of dimensional, categorical and hybrid conceptions of constructs.

Difficulty in making contact with others and social withdrawal as early signs of psychosis in adolescents--the Northern Finland Birth Cohort 1986.

AIM: Social withdrawal is among the first signs of the prodromal state of psychosis seen in clinical samples. The aim of this prospective study was to find out whether difficulty in making contact with others and social withdrawal precede first episode psychosis in the young general population. METHODS: The members of the Northern Finland Birth Cohort 1986 (n=6274) completed the PROD-screen questionnaire in 2001-2002. The Finnish Hospital Discharge Register was used to detect both new psychotic and non-psychotic disorders requiring hospitalisation during 2003-2008. RESULTS: Twenty-three subjects developed psychosis and 89 developed a non-psychotic mental disorder requiring hospitalisation during the follow-up. Of those who developed psychosis, 35% had reported difficulty or uncertainty in making contact with others and 30% social withdrawal in adolescence. In hospitalised non-psychotic disorder, the corresponding precentages were 10 and 13% and in the control group without hospital-treated mental disorder 9 and 11%. The differences between psychotic and non-psychotic hospitalised subjects (P<0.01) as well as controls (P<0.001) were statistically significant regarding difficulty or uncertainty in making contact with others. CONCLUSIONS: In this general population-based sample self-reported difficulty or uncertainty in making contact with others in adolescence preceded psychosis specifically compared to hospitalised non-psychotic mental disorders and controls.

Response initiation in young adults at risk for psychosis in the Northern Finland 1986 Birth Cohort.

INTRODUCTION: This is one of the very few studies to investigate the specific executive function/processing speed component of response initiation in subjects at familial risk (FR) for psychosis, and the first such study in subjects at clinical risk (CR) for psychosis. METHODS: Participants (N = 177) were members of the general population-based Northern Finland 1986 Birth Cohort in the following four groups: FR for psychosis (n = 62), CR for psychosis (n = 21), psychosis (n = 25) and control subjects (n = 69). The response initiation of these groups was compared in three different tests: Semantic fluency, Stockings of Cambridge and Spatial working memory. RESULTS: The two risk groups did not differ significantly from control group, but differed from, and outperformed the psychosis group in semantic fluency response initiation. CONCLUSIONS: Response initiation deficits were not evident in a non-help seeking psychosis high-risk sample.

Disruptive behaviour disorder with and without attention deficit hyperactivity disorder is a risk of psychiatric hospitalization.

AIM: To evaluate the psychiatric hospitalization among adolescents diagnosed with disruptive behaviour disorders (DBD) and/or attention deficit hyperactivity disorder (ADHD). METHODS: The sample (N = 457) was drawn from the Northern Finland Birth Cohort 1986. Four groups were formed, based on the K-SADS-PL diagnostic interview procedure: adolescents with DBD (n = 44), ADHD (n = 91), comorbid DBD and ADHD (n = 72) and without either DBD or ADHD (n = 250). Information from the Finnish Hospital Discharge Register (FHDR) was used to evaluate the psychiatric hospitalization among the study subjects. RESULTS: When compared with no diagnosis group, the adolescents with behavioural disorders had an increased risk (adjusted odds ratios: DBD = 4.4, ADHD = 2.2, comorbid DBD & ADHD = 5.6) of having also psychiatric disorder in the FHDR. The onset age of the psychiatric disorders in the FHDR (medians: DBD = 14.9, ADHD = 7.5 and DBD & ADHD = 15.3 years) and the combined length of hospitalization (medians: 25, 50 and 26 days, respectively) differed among adolescents with behavioural disorders compared with those with no diagnosis (median age 12.1 years and length of hospitalization 4 days). CONCLUSION: Adolescents diagnosed with DBD (with and without ADHD) are at high risk of undergoing psychiatric hospitalization during their life.

Brain-derived neurotrophic factor increases the motility of a particular N-methyl-D-aspartate /GABA-responsive subset of neural progenitor cells.

Neurotrophins like brain-derived neurotrophic factor (BDNF) promote the migration of subsets of neural progenitor cells. The mechanism by which motility is increased and the functional properties of BDNF-responsive cells are not very well known. We have used the neurosphere model, combining time-lapse microscopy, immunocytochemistry, and Ca(2+) imaging, to study the effect of BDNF on parameters such as motility and neurotransmitter responsiveness of migrating neural progenitors. At the initiation of differentiation thick glial glutamate-aspartate transporter (GLAST)-positive radial processes emerged from the neurosphere, followed by the exit of neuron-like cells. The neuron-like cells moved outside the radial processes in a phasic manner with intermittent surges of motility and stationary periods. BDNF increased the number and promoted the progress of the neuron-like cells by prolonging surges and decreasing the length of stationary phases. The average rate of cellular movement during surges was unaffected by BDNF. BDNF also caused a several fold increase in positive staining for tropomyosin-related kinase B (TrkB) receptors and neuronal markers such as Calbindin, microtubule-associated protein-2 (MAP-2), and neuron-specific nuclear protein (NeuN) in cells outside the radial network. Calcium imaging allowed for further characterization of the BDNF-responsive cell population. Kainate-responsive cells, denoting the expression of AMPA/kainate receptors, dominated in the outer migration layers while cells responding to (S)-3,5-dihydroxyphenylglycine (DHPG) via metabotropic glutamate receptor 5 (mGluR5) dominated in the inner migration layers. BDNF did not appreciably affect the distribution of these cells but promoted the redistribution of a small subpopulation (about 20%) of N-methyl-D-aspartate (NMDA)- and GABA-responsive cells to the outermost layers of migration. The results demonstrate that BDNF does not affect cell motility per se but alters the phasic behavior of cell movement by promoting periods of high motility in a defined subpopulation of cells which give a robust Ca(2+) response to NMDA and GABA.

Development of a time-resolved fluorescence resonance energy transfer assay (cell TR-FRET) for protein detection on intact cells.

An assay named Cell TR-FRET based on time-resolved fluorescence resonance energy transfer, here utilized for detection of receptor proteins on intact cells, is described. In this assay, intact membrane-biotinylated Sf9 cells expressing human interleukin-2Ralpha due to infection with a recombinant baculovirus were prelabeled with a streptavidin-europium (Eu(3+)) chelate, the donor. These prelabeled cells were used in a homogeneous assay by addition of a fluorochrome-labeled anti-hIL-2Ralpha-specific antibody, 7G7B6-Cy5, the acceptor. Binding of 7G7B6-Cy5 to hIL-2Ralpha expressed on the cell surface and europium-labeled streptavidin to surface biotin esters brings the donor and the acceptor in close proximity, allowing transfer of energy from the excited state donor to the acceptor. This energy transfer was specifically inhibited by unlabeled antibody and by free biotin. The described assay constitutes a general method since no specific component of the cell membrane is labeled, thereby allowing a number of binding studies on the cell membrane, including receptor density determinations, to be performed. In addition, due to the rapid fashion in which the Cell TR-FRET assay is accomplished, it can be a valuable method not only for identifying novel membrane-associated proteins, but also for drug screening of large samples in high-throughput format.

Generation of hydroxyl radicals by the antiviral compound phosphonoformic acid (foscarnet).

Phosphonoformic acid (foscarnet) is an antiviral agent that is used to treat severe cytomegalovirus infections in AIDS patients. We demonstrate by using the ferrous iron indicator Ferrozine and ascorbic acid (vitamin C) that foscarnet can chelate ferric iron and form a redox-active iron complex. By using the hydroxyl radical indicator coumarin-3-carboxylic acid we found that the foscarnet-Fe3 complex formed can readily catalyze hydroxyl radical (.OH) generation by the Fenton reaction: (Fe2+ + H2O2-4Fe3+ + .OH + -OH) if hydrogen peroxide and ascorbic acid are present. Hydroxylation of coumarin-3-carboxylic acid could be blocked by addition of known hydroxyl radical scavengers such as mannitol, sucrose, glucose and dimethyl sulfoxide. Moreover, by using a DNA nicking assay, we found that foscarnet catalyzed hydroxyl radicals can induce single strand brakes in DNA. The potency of the hydroxyl radicals formed to induce damage could also be demonstrated in a phosphate-free buffer where the hydroxyl radicals formed attacked and liberated phosphate from the foscarnet molecule. Our results indicate that foscarnet catalyzed hydroxyl radical formation might take place during conditions where a peroxide generating system(s), vitamin C and transitions metals are present.

Method enabling fast partial sequencing of cDNA clones.

Pyrosequencing is a nonelectrophoretic single-tube DNA sequencing method that takes advantage of cooperativity between four enzymes to monitor DNA synthesis. To investigate the feasibility of the recently developed technique for tag sequencing, 64 colonies of a selected cDNA library from human were sequenced by both pyrosequencing and Sanger DNA sequencing. To determine the needed length for finding a unique DNA sequence, 100 sequence tags from human were retrieved from the database and different lengths from each sequence were randomly analyzed. An homology search based on 20 and 30 nucleotides produced 97 and 98% unique hits, respectively. An homology search based on 100 nucleotides could identify all searched genes. Pyrosequencing was employed to produce sequence data for 30 nucleotides. A similar search using BLAST revealed 16 different genes. Forty-six percent of the sequences shared homology with one gene at different positions. Two of the 64 clones had unique sequences. The search results from pyrosequencing were in 100% agreement with conventional DNA sequencing methods. The possibility of using a fully automated pyrosequencer machine for future high-throughput tag sequencing is discussed.

Production and partial characterization of mouse monoclonal antibodies recognizing common cytokine receptor gamma chain (gammac) of human, mouse and primate origin.

Monoclonal antibodies specific for the common cytokine receptor gamma chain, gammac, were produced using traditional hybridoma technology. Fusion of P3X63-Ag8.653 myeloma cells with splenocytes from Balb/c mice immunized with Spodoptera frugiperda insect cells infected with the recombinant baculovirus VL1392-hIL-2Rgamma resulted in several hybridoma cell clones producing monoclonal gammac-specific antibodies. Four of these antibody-producing clones, IIIC3, IIIE8, IG3 and IF10C5, were further characterized by immunoblotting, flow cytometry and ELISA. Data are presented demonstrating that the generated monoclonal antibodies can identify the extracellular domain of the common cytokine receptor gamma chain of human and mouse origin, and two of the antibodies recognize gammac of primate origin as well.

Fetal and adult human CNS stem cells have similar molecular characteristics and developmental potential.

The mammalian central nervous system (CNS) contains multipotent stem cells that develop into neurons, astrocytes and oligodendrocytes. Our current data show that fetal and adult human CNS stem cell isolates display similar proliferation kinetics, differentiate into three major cell types of the nervous system and express similar sets of regulatory genes. However, each individual CNS stem cell isolate could be distinguished by its specific gene expression and developmental potential.

Method enabling pyrosequencing on double-stranded DNA.

Pyrosequencing is a new nonelectrophoretic, single-tube DNA sequencing method that takes advantage of co-operativity between four enzymes to monitor DNA synthesis (M. Ronaghi, M. Uhlén, and P. Nyrén, Science 281, 363-365). Pyrosequencing has so far only been performed on single-stranded DNA. In this paper different enzymatic strategies for template preparation enabling pyrosequencing on double-stranded DNA were studied. High quality data were obtained with several different enzyme combinations: (i) shrimp alkaline phosphatase and exonuclease I, (ii) calf intestine alkaline phosphatase and exonuclease I, (iii) apyrase and inorganic pyrophosphatase together with exonuclease I, and (iv) apyrase and ATP sulfurylase together with exonuclease I. In many cases, when the polymerase chain reaction was efficient exonuclease I could be omitted. In certain cases, additives such as dimethyl sulfoxide, single-stranded DNA-binding protein, and Klenow DNA polymerase improved the sequence quality. Apyrase was the fastest and most efficient of the three different nucleotide degrading enzymes tested. The data quality obtained on double-stranded DNA was comparable with that on single-stranded DNA. Pyrosequencing data for more than 30 bases could be generated on both long and short templates, as well as on templates with high GC content.

Direct analysis of single-nucleotide polymorphism on double-stranded DNA by pyrosequencing.

Pyrosequencing, a new method for DNA sequencing, is gaining widespread use for many different types of DNA analysis. The method takes advantage of four coupled enzymes in a single tube assay to monitor DNA synthesis in real time using a luminometric detection system. Here, we demonstrate the use of pyrosequencing for direct analysis of single-nucleotide polymorphism on double-stranded PCR product. Pyrosequencing data on the human glutathione peroxidase gene (GPX1) from several individuals were analysed and three different allelic variants were determined and confirmed. The possibility of further simplifying the sequencing and template-preparation steps is discussed.

Detection of baculovirus-infected insect cells by flow cytometric side-scatter analyses.

BACKGROUND: The baculovirus expression vector system (BEVS), utilizing the Autographa californica nuclear polyhedrosis virus (AcNPV), has turned out to be an attractive alternative for high-level expression (<600 mg/l) of recombinant proteins. However, there is a shortage of reliable methods for monitoring the infection process in situations where marker proteins cannot be used. METHODS: Three recombinant baculoviruses, FastBac1-wtGFP, VTBac-GFP, and VL1392-hIL-2Ralpha, all having the genes inserted under the transcriptional control of the polyhedrin gene promoter of the Autographa californica nuclear polyhedrosis virus (AcNPV), were used to infect Spodoptera frugiperda (Sf9) and Mamestra brassicae (IZD-MB-0503) insect cells. The infection process of the recombinant baculoviruses was monitored by flow cytometric side-scatter and fluorescence intensity analyses over a period of 6-96 h. RESULTS: A clear correlation between the side-scatter (SSC) signal and the relative fluorescence was observed for both of the infected cell lines, compared to noninfected cells. Comparison of SSC histograms from noninfected insect cells with cells infected with the nonfluorescent recombinant baculovirus VL1392-hIL-2Ralpha showed a clear increase of SSC for the infected cells. CONCLUSIONS: The SSC parameter can therefore be utilized for flow cytometric monitoring of a baculovirus infection process in situations where suitable markers are not available.