Petteri Multimäki

In situ localization of collagen production by chondrocytes and osteoblasts in fracture callus.

An experimental model of fracture-healing was used to study the production of types-I and II collagen by in situ hybridization. The distribution of cartilage matrix in callus was determined by histochemical staining. Messenger RNA (mRNA) for cartilage-specific type-II collagen was detectable as early as the fifth day in a small number of cells that had acquired a chondrocyte phenotype but that also contained type-I collagen mRNA, suggesting an ongoing change in the expression of collagen genes. The location of the first chondrocytes, which were adjacent to cortical bone, suggested that they originated from cells that had derived from the periosteum by differentiation. On the seventh day of callus formation, the presence of both type-I and type-II collagen mRNA in chondrocytes of expanding cartilage suggested that most growth occurred by differentiation of mesenchymal cells and less by proliferation of differentiated chondrocytes. Expansion continued until the tenth to fourteenth day, after which the cartilage was replaced by woven bone. This was characterized by the presence of osteoblasts that were active in the synthesis of type-I collagen.

Elevated proα2(I) collagen mRNA levels in cultured scleroderma fibroblasts result from an increased transcription rate of the corresponding gene

Fibroblasts cultured from affected and unattected skin sites of three scleroderma patients were studied for the activation of type I collagen gene expression. Dot blot hybridizations with proα2(I) collagen specific cDNA probe revealed 2.9–4.8‐fold increases in proα2(I) mRNA levels in the affected fibroblasts over the unaffected control cells. Transcription rate of the proα2(I) gene in the nuclei isolated from the same cells was 2.0–3.7‐fold higher in the scleroderma fibroblasts than in the controls. The results show that scleroderma fibroblasts have undergone activation of collagen gene expression at the transcriptional level, which subsequently results in elevated procollagen mRNA levels, overproduction of collagen, and development of dermal fibrosis.

Do mental health problems in childhood predict chronic physical conditions among males in early adulthood? Evidence from a community-based prospective study.

BACKGROUND Previous studies have documented associations between mental and physical health problems in cross-sectional studies, yet little is known about these relationships over time or the specificity of these associations. The aim of the current study was to examine the relationship between mental health problems in childhood at age 8 years and physical disorders in adulthood at ages 18-23 years. METHOD Multiple logistic regression analyses were used to examine the relationship between childhood mental health problems, reported by child, parent and teacher, and physical disorders diagnosed by a physician in early adulthood. RESULTS Significant linkages emerged between childhood mental health problems and obesity, atopic eczema, epilepsy and asthma in early adulthood. Specifically, conduct problems in childhood were associated with a significantly increased likelihood of obesity and atopic eczema; emotional problems were associated with an increased likelihood of epilepsy and asthma; and depression symptoms at age 8 were associated with an increased risk of asthma in early adulthood. CONCLUSIONS Our findings provide the first evidence of an association between mental health problems during childhood and increased risk of specific physical health problems, mainly asthma and obesity, during early adulthood, in a representative sample of males over time. These data suggest that behavioral and emotional problems in childhood may signal vulnerability to chronic physical health problems during early adulthood.

Construction of a Human Proα1(III) Collagen cDNA Clone and Localization of Type III Collagen Expression in Human Fetal Tissues

A cDNA clone for human pro alpha 1(III) collagen mRNA was isolated from a cDNA library constructed for human fetal skin RNA. The clone, pHFS3, was identified by restriction mapping and sequencing. Comparison with previously published human type III collagen sequences revealed some differences which may reflect individual variation. The clone was used to study the expression of type III collagen mRNA in various fetal tissues in comparison to the expression of type I collagen mRNAs. In 15-18-week fetal skin the ratio of alpha 1(I) to alpha 1(III) collagen mRNAs was 0.8. Diaphyseal and calvarial bone contained high amounts of type I collagen mRNA and low levels of type III collagen mRNA, resulting in high type I/type III ratios. In situ hybridization of sections of skeletal tissues was employed to identify the cells containing the mRNAs for types I, II and III procollagens. The results revealed differential expression patterns for these three collagen types in various human fetal tissues. Lack of coordinate expression suggests that production of type I and type III collagens is under different regulatory mechanisms in developing skeletal tissues.

Differential expression of fibrillar collagen genes during callus formation

An experimental fracture healing model in the rat tibio-fibular bone was employed to study the appearance of messenger RNAs for types I, II and III collagens during endochondral fracture repair. Total RNA was extracted from normal bone and from callus tissue at various time points. The total RNAs were analyzed in Northern hybridization for their contents of procollagen mRNAs using specific cDNA clones. The results show that during the first week of fracture repair type III collagen mRNA is increased to the greatest extent, followed by type II collagen mRNA during the second week. The 28-day callus resembles bone by containing mainly type I collagen mRNAs and very little type II or III collagen mRNA.

Separate and interactive contributions of weak inhibitory control and threat sensitivity to prediction of suicide risk

Biobehavioral dispositions can serve as valuable referents for biologically oriented research on core processes with relevance to many psychiatric conditions. The present study examined two such dispositional variables-weak response inhibition (or disinhibition; INH-) and threat sensitivity (or fearfulness; THT+)-as predictors of the serious transdiagnostic problem of suicide risk in two samples: male and female outpatients from a U.S. clinic (N=1078), and a population-based male military cohort from Finland (N=3855). INH- and THT+ were operationalized through scores on scale measures of disinhibition and fear/fearlessness, known to be related to DSM-defined clinical conditions and brain biomarkers. Suicide risk was assessed by clinician ratings (clinic sample) and questionnaires (both samples). Across samples and alternative suicide indices, INH- and THT+ each contributed uniquely to prediction of suicide risk-beyond internalizing and externalizing problems in the case of the clinic sample where diagnostic data were available. Further, in both samples, INH- and THT+ interactively predicted suicide risk, with individuals scoring concurrently high on both dispositions exhibiting markedly augmented risk. Findings demonstrate that dispositional constructs of INH- and THT+ are predictive of suicide risk, and hold potential as referents for biological research on suicidal behavior.

Military fitness class of Finnish 18-year-old men--prediction of military fitness class at call-up with the YASR and sociodemographic factors.

ObjectiveThe aim of this study was to examine psychosocial factors associated with military fitness class, classified as capability of service, vs. temporary or permanent exemption from service.MethodParticipants were 2,340 (80% of the original sample) Finnish 18-year-old men at call-up for obligatory military service who filled in the Young Adult Self-Report (YASR) questionnaire.ResultsTemporary exemption from military service was independently associated with the YASR total problem score, externalizing and internalizing problems, excessive alcohol use, drug use, problems with peers and family, and mental health service use.Permanent exemption was independently associated with problems with peers and family.ConclusionThe YASR is a potential selection tool to be used at call-up. Temporary exemption was more strongly associated with psychosocial problems than permanent exemption. Because of the high level of psychological problems among those temporarily exempted, the call-up situation offers a unique opportunity to identify those with problem behaviour and risk of marginalization.

Childhood Predictors of Military Fitness: A Prospective, Community-Based, Follow-up Study from Age 8 to Age 18

Knowledge of the impact of childhood psychosocial problems on success in military service is scarce. The purpose of the study was to assess whether childhood psychosocial problems are associated with suitability for military service. The subjects were 2,622 Finnish boys born in 1981. They were first assessed with the Rutter parent and teacher questionnaires and self-reports (Childrens Depression Inventory) at age 8. Their suitability for military service was assessed at age 18. A wide range of childhood problems, especially internalizing disorders, predicted release from military service. All informants had predictive association with later suitability for military service. The majority of children with psychiatric problems were later estimated to be fit for military service. The results show a predictive association between childhood psychiatric problems and early adult psychosocial impairment, as estimated by the ability to serve in the military forces.