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Biomedical subjects

M Möttönen

Publications and source records attributed to M Möttönen.

At least 19 recordsLinked to original sources
PubMed2006

Splitting times of doubly quantized vortices in dilute bose-einstein condensates.

Recently, the splitting of a topologically created doubly quantized vortex into two singly quantized vortices was experimentally investigated in dilute atomic cigar-shaped Bose-Einstein condensates [Y. Shin, Phys. Rev. Lett. 93, 160406 (2004)10.1103/PhysRevLett.93.160406]. In particular, the dependency of the splitting time on the peak particle density was studied. We present results of theoretical simulations which closely mimic the experimental setup. We show that the combination of gravitational sag and time dependency of the trapping potential alone suffices to split the doubly quantized vortex in time scales which are in good agreement with the experiments.

Journal Article↗
PubMed2005

CD4+ CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis.

CD4(+) CD25(+) regulatory T (T(reg)) cells play a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity. In the present study, we have explored the characteristics of CD4(+) CD25(+) T(reg) cells in patients with rheumatoid arthritis (RA). The frequency and phenotype of CD4(+) CD25(+) T cells in paired samples of synovial fluid (SF) and peripheral blood (PB) from patients with RA and PB from normal controls were analysed. An increased frequency of CD4+ cells T cells expressing CD25 was detected in SF compared to PB from patients with RA. No significant difference was observed in the numbers of CD4(+) CD25(+) T cells in PB from patients and controls. SF CD4(+) CD25(+) T cells expressed high levels of CTLA-4 (both surface and intracellular), GITR and OX40, as well as Foxp3 transcripts. Functionally, SF CD4(+) CD25(+) T cells were impaired in their proliferative responses and could suppress the proliferation of their CD4(+) CD25(-) counterparts. In conclusion, these data demonstrate that CD4(+) CD25(+) T(reg) cells, with the potential to regulate the function of effector T cells and antigen-presenting cells, accumulate in the synovium of patients with RA.

Adult↗
PubMed2004

Phenotypic characterization of regulatory T cells in the human decidua.

Pregnancy is a unique situation for the maternal immune system. We have studied and identified a CD4+CD25+ regulatory T (Treg) cell population isolated from the human decidua. This mucosal surface in the uterus is in direct contact with semiallogenic fetal cells. We observed that about 14% of the decidual CD4+ T cells have the CD4+CD25+ phenotype. The decidual CD4+CD25+ T cells expressed high frequency of intracellular CTLA-4 (CTLA-4i). The majority of CD4+CD25+CTLA-4i+ cells were also positive for GITR and OX40, typical markers for human Treg cells. The frequency of CD4+CD25+ T cells in the peripheral blood from pregnant women was found to be increased during the first and second trimester of gestation when compared to nonpregnant controls. Being an important molecule for Treg cells, the role of CTLA-4 in the regulation of indoleamine 2,3-dioxygenase (IDO) expression was also examined. The stimulation with CTLA-4Ig did not increase IDO mRNA expression in CD14+ cells from pregnant women, while IFN-gamma was observed to up-regulate IDO expression. The presence of Treg cells in the human decidua suggests that these cells are important in protecting the fetus from alloreactive immune responses at the maternal-fetal interface.

Adult↗
PubMed2003

Phenotypic characterization of human decidual macrophages.

Pregnancy is a challenge to the immune system, which not only has to protect the mother and the fetus from invading pathogens but to also maintain immunological tolerance against the fetus. However, the mechanisms inhibiting local immune responses in the maternal decidual tissue are poorly understood. We have studied decidual CD14+ macrophages, which may be important in the maintenance of a tolerance against the developing fetus. Decidual macrophages expressed HLA-DR, but lower levels of costimulatory molecule CD86 than peripheral blood CD14+ monocytes from pregnant and non-pregnant women. Decidual macrophages produced spontaneously high levels of interleukin-10. Our findings suggest that decidual macrophages could represent an inhibitory type of APCs. Supporting this conclusion indoleamine 2,3-dioxygenase (IDO), suggested to have an immunosuppressive role in pregnancy, was expressed in decidual macrophages. Furthermore, decidual macrophages were not able to differentiate into dendritic cells under the influence of IL-4 + GM-CSF. These results suggest an immunoinhibitory function of decidual macrophages at the maternal-fetal interface.

Antigen Presentation↗
PubMed2003

Chediak-Higashi syndrome: four cases from Northern Finland.

UNLABELLED: Chediak-Higashi syndrome (CHS) is a rare multiorgan disease entity with autosomal recessive inheritance characterized by oculocutaneous albinism, bleeding tendency, recurrent bacterial infections and various neurological symptoms. Intracellular vesicle formation is deficient, resulting in giant granules in many cells, e.g. giant melanosomes in the melanocytes. Diagnosis has been based on morphological examination of peripheral blood and bone marrow, with giant granules seen in cells of the myeloid lineage and in lymphocytes. The ultimate diagnostic test is to look for a mutated LYST gene. Most patients develop an accelerated phase of the disease with deposition of lymphohistiocytes in the liver, spleen, lymph nodes and bone marrow, resulting in hepatosplenomegaly, bone marrow infiltration and haemophagocytosis. Peripheral blood neutropenia becomes more profound as anaemia and thrombocytopenia develop. Most patients succumb before the age of 10 years. Four patients with CHS are described, one of whom is a long-term survivor after successful allogeneic bone marrow transplantation, two succumbed during the accelerated phase and one is living with a chronic form of the disease. CONCLUSION: Allogeneic bone marrow transplantation from an HLA-matched sibling is the therapy of choice and should be performed early. If there is no matched family donor, an unrelated donor or a placental blood graft is a good alternative. The clinical picture of CHS is heterogeneous and therapeutic decisions need to be made on an individual basis.

Bone Marrow↗
PubMed2001

MMP-2 and MMP-9 expression in adult and childhood acute lymphatic leukemia (ALL).

In the present study the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in acute lymphatic leukemia (ALL) is studied with immunocytochemical staining in bone marrow aspirate smears from 75 patients. The material included 20 adult and 55 pediatric ALL patients. In 65% of the adult ALL cases the immunoreactive protein for either MMP-2 or MMP-9 or for both the enzymes was seen. A statistically significant correlation (P 0.027) with MMP-2 positivity and appearance of extramedullary infiltrates was found in adult ALL, suggesting that the gelatinase activity could be related with increased extravasation of the leukemic cells in ALL. This has to be confirmed in a larger patient population. In pediatric patients there were only seven cases (12.7%) out of 55 with positive immunostaining for either of these metalloproteinases. MMP expression correlated with L2 FAB class, high-risk tumor group and T-cell immunophenotype, but not with extramedullary presentation in pediatric patients with ALL indicating basic biological differences between adult and childhood ALL.

Adolescent↗
PubMed2001

Cytokine levels in midtrimester amniotic fluid in normal pregnancy and in the prediction of pre-eclampsia.

Midtrimester amniotic fluid cytokines may reflect the function of the maternal immune system in the maternal-fetal interface and thus be predictive of pre-eclampsia. We determined the concentrations of interleukin (IL)-6, IL-8, IL-10, IL-11, IL-12, IL-15, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta in amniotic fluid at 14-16 weeks of gestation from women with normal pregnancies and from those who subsequently developed severe pre-eclampsia. The concentrations of the cytokines in amniotic fluid did not significantly differ between patients and normal controls. The median concentration of IL-6 was 950 pg/ml in normal pregnant women and 578 pg/ml in the patient group. The median concentration of IL-8 was 606 pg/ml in normal controls and 294 pg/ml in the patient group. The levels of IL-6, IL-8 and TGF-beta correlated positively with each other. TNF-alpha concentrations were low and similar in both groups. IL-10 and IL-12 were detected at very low levels in 37 and 7% of the samples, respectively. No difference was found in IL-15 concentrations between the groups. IL-11 was found only at low levels in both groups. Although none of the cytokines measured was predictive of pre-eclampsia, this study provides information of cytokines in amniotic fluid during the period when the spiral arteries are remodelled.

Adult↗
PubMed2001

Non-steroidal anti-oestrogens inhibit the differentiation of synovial macrophages into dendritic cells.

BACKGROUND: Dendritic cells (DC) have been suggested to play an important role in the pathogenesis of rheumatoid arthritis (RA). Agents that inhibit DC differentiation and function may have a therapeutic value in the treatment of RA. OBJECTIVE: To examine the effect of the non-steroidal anti-oestrogens toremifene and tamoxifen on the differentiation of synovial fluid (SF) macrophages into DC. METHODS: SF macrophages from patients with RA were cultured with interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) in the presence or absence of anti-oestrogens. The expression of cell surface markers on SF antigen-presenting cells (APC) was studied by flow cytometry. The capacity of SF APC to stimulate allogeneic T cells was studied using the mixed lymphocyte reaction. The production of tumour necrosis factor-alpha, IL-10 and transforming growth factor-beta1 was studied using ELISA. RESULTS: Anti-oestrogens inhibited the differentiation of SF macrophages into DC and the capacity of SF macrophage-derived DC to stimulate allogeneic T cells. CONCLUSIONS: By inhibiting the differentiation of SF macrophages into DC, non-steroidal anti-oestrogens may have beneficial effects in RA.

Aged↗
PubMed2001

Role of boron in drought resistance in Norway spruce (Picea abies) seedlings.

Norway spruce (Picea abies (L.) Karst.) seedlings fertilized with boron (B) at three rates were grown in a 3:7 mix of forest humus and quartz sand for 18 weeks. Half of the seedlings were not watered during the last 9 days of the experiment (drought treatment). The role of B in drought resistance was assessed by comparing the effects of seedling internal B concentration on the water relations, photosynthesis, growth and nutrition of well-watered and drought-treated seedlings. At the end of the drought treatment, needle B concentrations were 7.0 mg x kg(-1) at the lowest B supply rate and 17.5 and 23.5 mg x kg(-1), respectively, at the higher supply rates. Seedlings at the lowest B supply rate had fewer root tips and mycorrhizas than seedlings at the higher B supply rates. Drought treatment had a more pronounced effect on the water relations and net photosynthetic rate of seedlings than B treatment. Although seedlings at the higher B supply rates lost water more rapidly than seedlings at the low B supply rate-leading to faster stomatal closure and decreased photosynthesis-drought did not affect their final height, whereas drought reduced height growth of seedlings at the low B supply rate.

Boron↗
PubMed2000

Interleukin-15 up-regulates the expression of CD154 on synovial fluid T cells.

To investigate the role of the CD40-CD154 interaction in rheumatoid arthritis (RA), we analysed the expression of CD154 on CD3+ and CD4+ T cells in synovial fluid (SF) from patients with RA and in peripheral blood (PB) from patients and normal controls. As interleukin (IL)-15 is a potent activator of synovial T cells we wanted to study whether IL-15 also regulated the expression of CD154 on these T cells. Freshly isolated synovial T cells did not express significant levels of CD154, as evaluated using flow cytometry, whereas the expression of CD86 and human leucocyte antigen (HLA)-DR was significantly elevated on SF T cells when compared with PB T cells from patients or controls. Synovial T cells could up-regulate their CD154 expression following activation with phorbol 12-myristate 13-acetate (PMA) + ionomycin or anti-CD3 + anti-CD28 monoclonal antibodies (mAbs), but the maximal level of expression remained lower than in control T cells. IL-15 significantly increased the expression of CD154 on SF and PB T cells from patients, whereas IL-2 had minimal effects. Furthermore, IL-15 induced extensive proliferation in SF T cells. Our results show that SF T cells up-regulate the expression of CD154 in the presence of IL-15, a cytokine present in the synovium of patients with RA. These results further emphasize the role of IL-15 in the pathogenesis of RA.

Adult↗
PubMed1999

Reemphasis on lymphoblast L2 morphology as a poor prognostic factor in childhood acute lymphoblastic leukemia.

BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), the relationship between lymphoblast L1/L2 morphology and prognosis is controversial. According to some studies L2 morphology is associated with poor prognosis, whereas in others the association disappears after adjustment for other known risk factors. PROCEDURE: We investigated the prognostic importance of lymphoblast L1/L2 morphology in childhood ALL treated with current Nordic ALL protocols in Finland. From the routine bone marrow (BM) aspirate and biopsy slides of 251 children with ALL diagnosed in 1990-1995, the blast cell morphology and early treatment responses were assessed blindly in a central review, using French-American-British (FAB) criteria with the Children's Cancer Group (CCG) modification. RESULTS: L1 morphology (>90% L1) was found in 197 (80%) children and L2 (>/=10% L2) in 49 (20%). Early treatment response was poorer in L2 than in L1: >5% blasts in the marrow on day 15 were seen in 27% of L2 as opposed to 12% of L1 (P = 0.048). The 6-year event-free survival (EFS) in the study population was 75%, 76% in L1 and 70% in L2 (P = 0.34). In the group with white blood cell count (WBC) below 50 x 10(9)/liter at diagnosis, the L2 morphology was associated with inferior survival: 6-year EFS 74% in L2 and 84% in L1 (P = 0.07), with 6-year overall survival (OS) 81% vs. 91% (P = 0.035), respectively. L2 morphology was not associated with any other adverse prognostic factor analyzed. CONCLUSIONS: With the intensive Nordic ALL protocols, lymphoblast L2 morphology is an independent poor prognostic factor, influencing both the early response to treatment and, in the low-WBC group, the ultimate outcome, and should be reemphasized in risk categorization of childhood ALL.

Adolescent↗
PubMed1999

Costs arising from otitis media.

Otitis media (OM) is one of the most common diseases of childhood, and causes both direct and indirect costs to families and to society. This study calculated the costs arising from OM among 736 day care children whose infections were prospectively monitored for up to 15 mo in 10 day care centres in the city of Oulu. The children in the survey had 1.5 attacks of acute OM per person year, made 2.1 visits to a physician (cost $US55 visit(-1)) and received 1.5 courses of antimicrobials (cost $24 course(-1)). Their parents were absent from work for 1.9 d per person year (cost $85 d(-1)). Either adenoidectomy ($890 operation(-1)) or tympanostomy ($740) was performed on 6% of the children and the overall costs of surgery were $80 per person year at risk. In total, each single attack of acute OM cost $228. The average annual costs per child younger than 2 y were $1040, those for children aged 2-3 y $283 and those for children older than 3 y $141. The cumulative costs from age 6 mo to 7 y were $2549 child(-1). When the attributable risk of OM at a day care centre is taken into account, in Finland, a country with about 5 million inhabitants, OM gives rise to total annual costs of $US138 million. OM leads to considerable expenses and even expensive preventive measures would be cost-effective.

Child↗
PubMed1999

An open randomized controlled trial of infection prevention in child day-care centers.

OBJECTIVE: Child care outside the home increases children's infections substantially. We have to evaluate the possibilities for reducing the transmission of infections by an infection prevention program. DESIGN AND METHODS: A 15-month randomized controlled trial involving 20 day-care centers was conducted to evaluate the efficacy of an infection prevention program. The program was introduced in 10 centers and the other matched 10 centers served as controls. Records were made of the occurrence of infections and absences from care or work because of infections among the children, their parents and the personnel of the day-care centers. RESULTS: Both the children and the personnel in the program centers had significantly fewer infections than those in the control centers, the reduction being 9% [95% confidence interval (95% CI), 4 to 16%, P < 0.002] among 3-year-old children and 8% (95% CI 0 to 14%, P = 0.049) among the older children. The children at the program centers received 24% fewer prescriptions of antimicrobials (95% CI 22 to 27%, P < 0.001). Likewise there were 2.5 man-year fewer absences from work on the part of parents because of a child's illness during 1 year in the program centers, a 24% difference (95% CI 18 to 29%, P < 0.001). CONCLUSIONS: Effective prevention of infections is possible in child day-care centers, and this can benefit both the families and the personnel. Such a program is cost-effective even if a specialist nurse implements it.

Adult↗
PubMed1998

Interleukin-10 inhibits the capacity of synovial macrophages to function as antigen-presenting cells.

OBJECTIVE: We have investigated the effects of interleukin (IL)-10, IL-4 + granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor alpha (TNF-alpha) on the phenotype and antigen-presenting capacity of synovial fluid (SF) macrophages from patients with rheumatoid arthritis. METHODS: The effects of IL-4, IL-10, GM-CSF and TNF-alpha on the expression of surface antigens on SF macrophages were studied using flow cytometry. The effects of these cytokines on the capacity of SF macrophages to activate T cells was investigated using the allogeneic mixed lymphocyte reaction (MLR). RESULTS: IL-10 reduced the expression of CD40, CD86 and HLA-DR, and increased the expression of CD14, on SF macrophages. IL-10 had no effect on the expression of CD80. Importantly, these effects of IL-10 on the phenotype of SF macrophages appear to have functional consequences, because cells incubated with IL-10 had a significantly reduced capacity to activate T cells in MLR. The effects of IL-4, GM-CSF and TNF-alpha were generally opposite to those observed in response to IL-10. IL-4 + GM-CSF, a combination of cytokines known to induce differentiation of dendritic cells, increased the expression of CD40, CD80 and CD86, and decreased the expression of CD14 on SF macrophages. Accordingly, IL-4 + GM-CSF increased the capacity of SF macrophages to activate T cells in MLR. IL-10 inhibited the effects of IL-4 + GM-CSF on SF macrophages. CONCLUSIONS: IL-10 inhibits the antigen-presenting capacity of SF macrophages, which further emphasizes the anti-inflammatory potential of IL-10 in RA. Importantly, IL-10 is able to downregulate the APC function of SF macrophages even when they are efficiently activated.

Adult↗
PubMed1997

Use of micronutrients and alternative drugs by children with acute lymphoblastic leukemia.

The use of alternative therapies is thought to be common among cancer patients. To clarify the popularity of micronutrients among children with cancer, we performed a controlled follow-up survey. The use of micronutrients and alternative drugs by 15 families of children with acute lymphoblastic leukemia (ALL) receiving chemotherapy (62 members) and 26 control families (106 members) was monitored by means of daily diaries from November 1987 to December 1989. Forty percent of children with ALL (6 of 15) and 7.7% of their controls (2 of 26) took alternative medicines, the usage among the children with ALL being statistically significantly more common (difference, 32.3%; 95% confidence interval for difference [CI] 7.1, 57.5%; P < 0.04). All children with ALL and 50.0% of the control children (13 of 26) took vitamins (difference, 50.0%; 95% CI, 20.4-79.6%; P < 0.01). A total of 27.7% of the other members of the ALL families (13 of 47) and 11.1% of their counterparts in the control families (10 of 90) took alternative medicines, the usage in the index families being statistically significantly more common (difference, 16.6%; 95% CI, 3.4-29.7%; P < 0.03). The malignancy increased the use of alternative medicines among all members of the family and of vitamins and trace elements among the affected children.

Child↗
PubMed1997

The use of problem-based learning in dealing with cultural minority groups.

Minority peoples like the Romanies have divergent cultures. Typical cultural aspects for medical personnel to consider would include greetings and other communication, family and social support, dressing and habits of cleanliness, marriage and sexuality, honor, and other issues of importance to any human being. Some minority cultures have no geographic boundaries but they still may adopt the lifestyles of the country they live in. Physicians have to reckon with these different cultural patterns when dealing with patients. Patients must be treated equally at the same time when their personal needs require individual consideration. This consideration is reflected in both verbal and non-verbal communication with the other. Both the sender and the receiver of a message would need to know of the other. Minority groups tend to know more about the majority groups than vice versa. Most health care providers belong to the majority group and would be expected to learn more about the other. Problem-based learning can help students to understand attitudes of minority patients (like the Romanies) and handle the situation. In this instance, the students collected theory base from existing legal, cultural, and other resources and interviewed a Romany woman to verify that the information pertaining to the female case was correct. This combination of theory and experience was considered useful in preparing a case presented to a seminar with 116 medical and dental students in 1994.

Breast Neoplasms↗
PubMed1996

Granulocyte-colony-stimulating factor after allogeneic and autologous bone marrow transplantation in children.

We evaluated the use of granulocyte CSF (G-CSF) after both allogeneic BMT (allo-BMT) and autologous BMT (ABMT) in children. After allo-BMT, G-CSF was used in 15 children who were compared with 20 historical controls. The ABMT patients were two sequential groups: the G-CSF group of 13 children and 11 historical controls. The patients were conditioned with different high-dose chemotherapy regimens with or without total body irradiation. G-CSF was administered at 5 micrograms/kg/day s.c. and was continued until an absolute neutrophil count (ANC) of 1,000 x 10(6)/l was reached. Following allo-BMT, G-CSF accelerated myeloid engraftment with a difference of 5 days at the ANC level of 500 x 10(6)/l (P<0.02) and 9 days at 1,000 x 10(6)/l (P<0.001). In the ABMT patients, G-CSF also accelerated myeloid engraftment. The difference between the G-CSF group and the control group was 6 days at ANC 200 (P<0.05), 11 days at ANC 500 (P<0.02) and 17 days at ANC 1,000 (P<0.005). In the ABMT patients, benefit by G-CSF was also observed in a smaller number of days with fever and days on antibiotics. We conclude that G-CSG significantly accelerated myeloid engraftment, after both allogeneic and autologous BMT in children, and also decreased the duration of febrile illness in the ABMT patients.

Adolescent↗