
Matti K KarvonenUniversity of Turku | UTU
Matti K Karvonen
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104
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Publications (104)
Macrophage Clever-1 contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial investigates the safety and tolerability of Clever-1 blockade with bexmarilimab in patients with treatment-refractory solid tumors and assesses preliminary anti-tumor efficacy, pharmacodynamics, and immunologic correlat...
Clever-1 expression in macrophages contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial was designed to investigate the safety and tolerability of Clever-1 blockade in patients with treatment-refractory solid tumors and to assess preliminary anti- tumor efficacy, pharmacodynamics, and immuno...
Common lymphatic endothelial and vascular endothelial receptor-1 (Clever-1) is a multifunctional type-1 transmembrane protein that plays an important role in immunosuppression against tumors. Clever-1 is highly expressed in a subset of human tumor-associated macrophages and associated with poor survival. In mice, Clever-1 supports tumor growth and...
Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73). This is a multi-center phase II double-blind, 2:1 randomized, parallel group...
Background: Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73).
Methods: This is a multi-center phase II double-blind, 2:1 random...
Background: Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73).
Methods: This is a multi-center phase II double-blind, 2:1 random...
Purpose:
Macrophages are critical in driving an immunosuppressive tumor microenvironment that counteracts the efficacy of T-cell-targeting therapies. Thus, agents able to reprogram macrophages towards a proinflammatory state hold promise as novel immunotherapies for solid cancers. Inhibition of a macrophage scavenger receptor Clever-1 has shown be...
e14530
Background: Bexmarilimab, an investigational immunotherapeutic antibody targeting Clever-1, is currently investigated in phase I/II MATINS study (NCT03733990) for advanced solid tumors. Machine learning (ML) based models combining extensive data could be generated to predict treatment responses to this first-in-class macrophage checkpoint in...
Macrophages are critical in driving an immunosuppressive tumor microenvironment that counteracts the efficacy of T-cell targeting therapies. Thus, agents that can reprogram macrophages towards a proinflammatory state hold promise as novel immunotherapies for solid cancers. Here, we report that immunotherapeutic targeting of the macrophage scavenger...
In Reply Drs Zhou and Tang comment that the survival curves crossed each other in our study,¹ and thus they questioned whether the proportionality assumption was met. Although the 1-year survival curves in the Kaplan-Meier plot overlapped at some points, the lines were generally distinct and there was no actual line crossing except at the very end,...
3097
Background: The scavenger receptor CLEVER-1 mediates the clearance of “unwanted” self-components and is highly expressed on tumor associated macrophages (TAMs). CLEVER-1 expression is associated with immunotherapy resistance and poor survival in several cancers. Pre-clinical studies demonstrate that CLEVER-1 inhibition increases TAM pro-inflam...
Purpose: Glucocorticoids are widely used to treat acute respiratory distress syndrome (ARDS) despite its use is highly controversial based on randomized controlled trials and meta-analyses.
As type I interferons (IFNs) are our first line of defense against severe viral respiratory infections, we explored whether glucocorticoids interfere with IFN s...
Importance
Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage.
Objective
To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS.
Design, Setting, and Participants
Multicenter, randomized, double-blind, p...
New antiepileptic drug (AED) options for generalised seizure types have been adopted for use as treatment for Unverricht-Lundborg disease. Whether this has led to improved seizure control or functional outcome in ULD patients remains obscure. We retrospectively identified all patients seen at Helsinki University Hospital due to Unverricht-Lundborg...
SUMMARY: The WHO MONICA Project is designed to measure the trends in mortality and morbidity from coronary heart disease (CHD) and stroke, and to assess the extent to which they are related to changes in known risk factors in different populations in 27 countries. Risk-factor data are collected from population samples examined in at least two popul...
To determine if there is a worldwide seasonal pattern in the clinical onset of Type 1 diabetes.
Analysis of the seasonality in diagnosis of Type 1 diabetes was based on the incidence data in 0- to 14-year-old children collected by the World Health Organization Diabetes Mondiale (WHO DiaMond) Project over the period 1990-1999. One hundred and five c...
The aim of this study was to examine the effects of childhood BMI growth dynamics on the risk of developing young adult-onset type 1 and type 2 diabetes.
Finnish national healthcare registers were used to identify individuals with diabetes diagnosed between 1992 and 1996 at 15-39 years of age. Non-diabetic control participants were chosen from the...
The protective role of water hardness and Mg in cardiovascular illness has been suggested in several epidemiological studies. In the present ecological study, the association of Ca, Mg, Al, Cu, F, Fe, Zn and NO3 in local ground water and spatial variation of acute myocardial infarction (AMI) incidence among men and women 35–74 years of age in rural...
The aim of this study was to examine the effects of birth order and parental age on the risk of type 1 and type 2 diabetes among Finnish individuals aged 15-39 years.
Data on all cases of type 1 diabetes (n = 1,345) and type 2 diabetes (n = 1,072), diagnosed between 1992 and 1996, were collected from four sources: standardised national reports from...
The aim of this study was to examine the incidence and trends of type 1 and type 2 diabetes in the 15-39 year-old population between 1992 and 1996 in Finland.
Data on the nationwide incidence of diabetes were obtained from four data sources: standardised reports from diabetes nurses, the Finnish National Hospital Discharge Register, the Drug Reimbu...
Neuropeptide Y (NPY) is a sympathetic neurotransmitter that plays a role in e.g. circulation, hormone release and angiogenesis. Earlier studies have shown that the Leucine 7 to Proline 7 (Leu7Pro) polymorphism of preproNPY is associated with increased risk for vascular complications in type 2 diabetes. The mechanism for this maybe altered transmitt...
Aims To examine incidence and trends of Type 1 diabetes worldwide for the period 1990–1999.
Methods The incidence of Type 1 diabetes (per 100 000/year) was analysed in children aged ≤ 14 years from 114 populations in 112 centres in 57 countries. Trends in the incidence of Type 1 diabetes were analysed by fitting Poisson regression models to the dat...
Childhood diabetes is one of the major non-communicable diseases in children under 15 years of age. It requires a life-long insulin treatment and may lead to serious complications. Along with the worldwide increase in the incidence several countries have recently reported a decreasing trend in the age of onset of the disease. The aim of this study...
In Finland, the risk of childhood Type 1 diabetes varies geographically. Therefore we investigated the association between spatial variation of Type 1 diabetes and its putative environmental risk factors, zinc and nitrates.
The association was evaluated using Bayesian modelling and the geo-referenced data on diabetes cases and population.
Neither z...
To examine the association of spatial variation in acute myocardial infarction (AMI) incidence and its putative environmental determinants in ground water such as total water hardness, the concentration of calcium, magnesium, fluoride, iron, copper, zinc, nitrate, and aluminium.
Small area study using Bayesian modelling and the geo-referenced data...
The aim of the study was to investigate the incidence of type 1 diabetes among children aged 14 years or under according to the level of urbanization of the place of residence of children at the time of diagnosis in Finland during 1987 to 1996. The analysis was carried out using a Bayesian approach and GIS. The incidence was the highest in the rura...
To provide age-gender standardized incidence rate, temporal trend and seasonal variation of Type 1 diabetes in Kuwaiti children aged < or = 14 years.
Data were prospectively collected over a period of 6 years (1992-1997) according to the DiaMond Project protocol using the capture-recapture method of ascertainment.
Data ascertainment varied between...
We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg/m(2)) and waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finni...
Alterations in monoamine oxidase A (MAOA) expression and enzyme activity may be associated with alcoholism and impulsive behavior. Therefore, functional polymorphisms in the MAOA gene would be good candidates to consider in the interindividual differences that exist in the susceptibility to alcoholism. One variant that has been considered as a cand...
The aim of the study was to examine the impact of the leucine7 to proline7 (Leu7Pro) polymorphism of the NPY gene on postprandial (PP) lipemia, post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and the response of serum lipids to a reduced fat diet.
Seven middle-aged obese subjects with Leu7Pro genotype were matched w...
Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the pr...
The leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of NPY is associated with high blood lipid concentrations and accelerated rate of atherosclerosis as well as diabetic retinopathy. Also, healthy subjects with this polymorphism have increased NPY secretion during sympathetic stimulation. Because NPY may regulate GH release and...
In Finland, the incidence of Type I (insulin-dependent) diabetes mellitus among children aged 14 years or under is the highest in the world. The increase in incidence is approximately 3% per year. A marked geographical variation in incidence was reported in Finland during the late 1980s. Our aim was to explore the most recent regional pattern in in...
Aims/hypothesis:
We aimed to study the incidence of Type I diabetes in 4 countries, Estonia, Latvia, Lithuania and Finland, during 1983–1998, focusing on the two separate periods of 1983–1990 and 1991–1998.
Methods:
Population-based incidence data from nationwide diabetes registries were used. Crude and age-standardized incidence rates using the pr...
Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular diseases.
alpha2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor subtype B mediates vasoconstriction in mice. A vari...
To investigate and monitor the patterns in incidence of childhood type 1 diabetes worldwide.
The incidence of type 1 diabetes (per 100,000 per year) from 1990 to 1994 was determined in children < or =14 years of age from 100 centers in 50 countries. A total of 19,164 cases were diagnosed in study populations totaling 75.1 million children. The annu...
A common functional polymorphism that results in a three- to four-fold difference in catechol-O-methyltransferase (COMT) enzyme activity has been related to psychiatric disorders such as ultra-ultra rapid cycling bipolar disorder, drug abuse and alcoholism (Lachman et al., 1996a; Karayiorgou et al., 1997; Vandenbergh et al., 1997; Papolos et al., 1...
Neuropeptide Y (NPY) plays an important role in the hypothalamic regulation of food intake and energy balance. According to recent findings in animals, NPY also seems to be a potent regulator of alcohol consumption. We used the recently identified Leu(7) to Pro(7) polymorphism in the signal peptide part of NPY to investigate whether the NPY system...
Addictive drugs, including ethanol, increase the brain's dopaminergic transmission, and catechol-o-methyltransferase (COMT) enzyme has a crucial role in dopamine inactivation. A common functional polymorphism in the COMT gene results in a three- to four-fold variation in enzyme activity. In a previous study, we found an association between type 1 (...
We have recently demonstrated that subjects having Pro7 in the signal peptide ofneuropeptide Y (NPY) have higher serum cholesterol and apolipoprotein B levels than individuals with wild-type (Leu7Leu7) signal peptide sequence. We investigated the association of Leu7Pro polymorphism with common carotid intima media thickness (IMT) assessed by ultras...
Both apolipoprotein E varepsilon4 allele (APOE varepsilon4) and neuropeptide Y (NPY) Pro(7)-variant have been reported to be associated with higher serum levels of total and LDL cholesterol. Since APOE varepsilon4 allele is also a major risk factor for the development of Alzheimer's disease (AD) and the genetic polymorphism of NPY has not previousl...
The Leu7Pro gene variant of the signal peptide part of neuropeptide Y (NPY), has been shown to affect cholesterol metabolism in obese adults. This study investigates whether the Leu7Pro polymorphism in the prepro-NPY has an impact on serum lipid concentrations in preschool-aged children at 5 and 7 yr of age. As birth weight may influence future lip...
To assess mortality of population-based cohorts of childhood-onset type 1 diabetic patients from the Eastern European countries of Estonia and Lithuania and compare this information with recent data from Finland.
Estonian (n = 518) and Finnish (n = 5,156) type 1 diabetic cohorts were diagnosed between 1980 and 1994, and the Lithuanian (n = 698) coh...
Background To study the epidemiology of childhood-onset type 1 insulin-dependent diabetes in Europe, the EURODIAB collaborative group established in 1988 prospective geographically-defined registers of new cases diagnosed under 15 years of age. This report is based on 16 362 cases registered during the period 1989-94 by 44 centres representing most...
In this study we tested the hypothesis that the Leu7Pro7 polymorphism in prepro neuropeptide Y (NPY) gene could be a risk marker for the development of diabetic retinopathy and analyzed a well characterized cohort of patients with Type 2 diabetes followed-up for 10 years from the time of diagnosis. The frequency of Leu7/Pro7-polymorphism was 9.3% (...
A common functional genetic polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158 Met) results in 3- to 4-fold differences in COMT enzyme activity and dopamine inactivation rate. Previous studies have shown that type I alcoholism is more common among subjects with low activity COMT genotype (LL), compared with high activity (HH) or h...
Several reports on the incidence of Type I (insulin-dependent) diabetes mellitus have suggested that the incidence is increasing. The aim of this study was to find out whether the incidence is increasing globally or restricted to a selected populations only and to estimate the magnitude of the change in incidence.
During 1960 to 1996 37 studies in...
To examine seasonal patterns of incidence of Type 1 diabetes mellitus incidence in children aged 0-14 years in Finland, Sweden, Estonia, Latvia and Lithuania during 1983-1992 (1987-1992 for Finland).
The study used a method that models incidence data using combinations of sine waves to model seasonal variation around a possible linear trend.
In Fin...
The alpha2-adrenergic receptors mediate part of the actions of the catecholamines noradrenaline and adrenaline on the regulation of energy balance. As part of an ongoing study on the genetics of obesity, the entire coding sequence of the alpha2B-adrenoceptor gene was screened in 58 obese, nondiabetic Finns by PCR-single stranded conformational anal...
To analyze the change in the age distribution at onset of type 1 diabetes in boys and girls aged 1-14 years during a 32-year period (from 1965 to 1996).
Data on the incidence of type 1 diabetes in Finland were obtained from the Central Drug Registry of the Social Insurance Institution for 1965-1986 (6,195 cases) and from the Prospective Childhood D...
In Finland, the incidence of Type I (insulin-dependent) diabetes mellitus in children aged 14 years or under is the highest in the world and the trend in incidence has been increasing. Our aim was to determine the most recent trends in incidence and the age distribution at diagnosis of Type I diabetes.
Data on the incidence of Type I diabetes in Fi...
Catechol-O-methyltransferase (COMT) is an enzyme which has a crucial role in the metabolism of dopamine. It has been suggested that a common functional genetic polymorphism in the COMT gene, which results in 3 to 4-fold difference in COMT enzyme activity, may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism. Si...
Aims/hypothesis. In Finland, the incidence of Type I (insulin-dependent) diabetes mellitus in children aged 14 years or under is the highest
in the world and the trend in incidence has been increasing. Our aim was to determine the most recent trends in incidence
and the age distribution at diagnosis of Type I diabetes. Methods. Data on the incidenc...
High serum total and low-density lipoprotein (LDL) cholesterol levels constitute the main risk factor for atherosclerotic vascular diseases. Both genetic and environmental factors are involved in the regulation of serum cholesterol levels. Neuropeptide Y (NPY), which is widely expressed in both the central and peripheral nervous systems, is known t...
High serum levels of total and LDL cholesterol are important risk factors in the development of atherosclerotic coronary artery disease. Cholesterol metabolism is affected by nutritional, environmental and genetic factors. Neuropeptide Y (NPY), which is widely expressed in both the central and peripheral nervous systems, has an important role in th...
The leptin gene (LEP) has been linked to extreme obesity. However, no common obesity-related gene variants have been found to exist in the LEP. The present study was designed to investigate the LEP for variants by screening both the putative promoter and the coding region of this gene in obese Finnish subjects (n = 200; body mass index, > 27 kg/m2)...
To examine the seasonal pattern for the clinical onset of IDDM in Finland and Sardinia, two areas where the incidence of IDDM is the highest in the world, and to determine the effect of climate and temperature on the clinical onset of IDDM.
Analysis of seasonality for the diagnosis of IDDM was based on 1,405 cases in Finland and 425 cases in Sardin...
The regional pattern of insulin-dependent diabetes mellitus (IDDM) incidence among children in Finland was analysed applying several methods attempting to describe the geographical variation in occurrence of IDDM. From 1987 to 1991 the number of newly diagnosed cases aged 14 years or less at diagnosis was 1728. The incidence, the incidence rate rat...
We present secular trends of childhood onset insulin-dependent diabetes mellitus (IDDM) in Finland, Estonia, Latvia and Lithuania during the period of 1983-1992. Incidence data were obtained from the national IDDM registries. The average age-standardized incidence per 100,000/year was 35.0 in Finland, followed by 10.2 in Estonia, 7.1 in Lithuania a...
Seasonal patterns in the incidence of insulin-dependent diabetes based on 2,062 cases diagnosed at age 14 years or under in Finland are described for the years 1987-1992. Seasonal patterns were estimated presenting the data as short Fourier series up to three harmonics together with a possible linear trend. This method allows an arbitrary shape for...
To study the relation between changes in body weight and subsequent mortality.
Prospective follow-up study.
Population study.
6441 men aged 40-59 y at baseline participating in the European cohorts of the Seven Countries Study. The men were divided into groups depending on their weight pattern ascertained from three weight measurements with interva...
Individual studies of stroke have not clearly answered two questions: on the relation, if any, between total blood cholesterol and stroke; and on how the strength of the relation between diastolic blood pressure and stroke varies with age. The associations of blood cholesterol and diastolic blood pressure with subsequent stroke rates were investiga...
In Finland, the incidence of insulin-dependent diabetes mellitus (IDDM) in children aged < 15 years is the highest in the world. The aim of this study was to determine the temporal variation in incidence and the age distribution at diagnosis of IDDM.
Data on incidence of IDDM in Finland nationwide were obtained from two sources: the Central Drug Re...
Population-based studies of the association between smoking and Chlamydia pneumoniae seropositivity do not exist. The role of smoking in the association between C. pneumoniae seropositivity and coronary artery disease (CAD) suggested by several studies has been debated. The aim of this study was to determine the relationship between smoking habits...
The relation of serum total homocysteine and lipoprotein(a) (Lp(a)) with the incidence of atherosclerotic disease was investigated among 7424 men and women aged 40-64 years free of atherosclerotic disease at baseline in 1977. During the 9-year follow-up, 134 male and 131 female cases with either myocardial infarction or stroke were identified. For...
Karvonen M (Department of Epidemiology and Health Promotion, National Public Health Institute, Elimäenkatu 25, SF-00510 Helsinki, Finland), Tuomilehto J, Pitkäniemi J, Naukkarinen A and Saikku P. Chlamydia pneumoniae IgG antibody prevalence in south-western and eastern Finland in 1982 and 1987. International Journal of Epidemiology 1994; 23: 176–18...