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M Salo

Publications and source records attributed to M Salo.

At least 19 recordsLinked to original sources
PubMed1998

Distribution of glial cell line-derived neurotrophic factor mRNA in human colon suggests roles for muscularis mucosae in innervation.

BACKGROUND/PURPOSE: Glial cell line-derived neurotrophic factor (GDNF) is a ligand for the receptor complex of GDNF family receptor alphas (GFRalphas) and Ret receptor tyrosine kinase, the product of a known Hirschsprung's disease gene. The aim of this study was to analyze the mRNA distribution of these genes in the developing human intestine to understand their roles in enteric innervation. METHODS: Cryosections of fetal and newborn stomach, ileum, and colon were hybridized in situ with S35-labeled cRNA probes to GDNF, Ret, GFRalpha-1 or GFRalpha-2. GDNF mRNA levels in fetal ileum and colon were compared by reverse transcription-polymerase chain reaction (PCR). RESULTS: GDNF mRNA expression was abundant in the muscularis mucosae of both fetal and newborn colon but was found neither in the neural plexuses nor in other regions of the intestine. Accordingly, by reverse transcription-PCR, GDNF mRNA level was many times higher in colon than ileum. Ret, GFRalpha-1 and GFRalpha-2 mRNA were expressed in the ganglionic cells of both myenteric and submucosal plexuses throughout the intestine. CONCLUSIONS: The highly restricted distribution of GNDF mRNA suggests an important role for muscularis mucosae in the development of human enteric nervous system. Ret, GFRalpha-1, and GFRalpha-2 most likely act as GDNF receptors in colon but may have alternative ligands in other enteric segments.

Colon↗
PubMed1998

Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; OMIM *240300, also called APS 1,) is a rare autosomal recessive disorder that is more frequent in certain isolated populations. It is generally characterized by two of the three major clinical symptoms that may be present, Addison's disease and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. Patients may also have a number of other clinical symptoms including chronic gastritis, gonadal failure, and rarely, autoimmune thyroid disease and insulin-dependent diabetes mellitus. We and others have recently identified the gene for APECED, which we termed AIRE (for autoimmune regulator). AIRE is expressed in thymus, lymph nodes, and fetal liver and encodes a protein containing motifs suggestive of a transcriptional regulator, including two zinc finger motifs (PHD finger), a proline-rich region, and three LXXLL motifs. Six mutations, in cluding R257X, the predominant Finnish APECED allele, have been defined. R257X was also observed in non-Finnish APECED patients occurring on different chromosomal haplotypes suggesting different mutational origins. Here we present mutation analyses in an extended series of patients, mainly of Northern Italian origin. We have detected 12 polymorphisms, including one amino acid substitution, and two additional mutations, R203X and X546C, in addition to the previously described mutations, R257X, 1096-1097insCCTG, and a 13-bp deletion (1094-1106del). R257X was also the common mutation in the Northern Italian patients (10 of 18 alleles), and 1094-1106del accounted for 5 of 18 Northern Italian alleles. Both R257X and 1094-1106del were both observed in patients of four different geo-ethnic origins, and both were associated with multiple different haplotypes using closely flanking polymorphic markers showing likely multiple mutation events (six and four, respectively). The identification of common AIRE mutations in different APECED patient groups will facilitate its genetic diagnosis. In addition, the polymorphisms presented provide the tools for investigation of the involvement of AIRE in other autoimmune diseases, particularly those affecting the endocrine system.

Female↗
PubMed1998

Hirschsprung's disease genes and the development of the enteric nervous system.

Hirschsprung's disease or aganglionic megacolon causes chronic, congenital obstipation at an incidence of 1 per 5000 live births. Two approaches have been vital to the present understanding of the pathogenesis and genetic background of the disease: disease linkage analyses and mouse models of aganglionic megacolon. Because the increasing number of transgenic or natural mouse strains with congenital megacolon has led to mutation screening in Hirschsprung's disease patients, almost every second patient could now receive a genetic explanation for his/her disease. The known disease genes include tyrosine kinase receptor Ret, endothelin receptor B and its ligand endothelin 3. In addition, mutations have been found in the gene encoding the glial cell line-derived neurotrophic factor, the ligand for Ret, but these may only have a modifier effect. The mouse models have also provided insight into the developmental mechanisms of the normal intestinal innervation. We combine here the present clinical data on the gene mutations in Hirschsprung's disease with the experimental molecular biology data, and formulate a hypothesis on the pathogenesis of this multigenic-multifactorial disease.

Animals↗
PubMed1997

Enhanced spontaneous antibody response after coronary artery bypass surgery.

PURPOSE: Cells spontaneously secreting immunoglobulins can be seen in the blood one week after open-heart surgery. The purpose of this study was to measure the antibody specificities of activated cells. METHODS: Immune responses were studied preoperatively and on the seventh postoperative day in 18 patients undergoing elective coronary artery bypass surgery. The number of cells secreting adenovirus, measles, rubella and tetanus antigen specific antibodies spontaneously and induced by pokeweed mitogen PWM (ASCs) as well as the total number of cells secreting IgG, IgM and IgA (ISCs) were studied using an enzyme-linked immunospot (ELISPOT) assay. Spontaneous as well as phytohaemagglutinin (PHA)- and pokeweed mitogen (PWM)-induced lymphocyte proliferation was also measured. RESULTS: The number of cells spontaneously secreting IgG, IgM and IgA antibodies was increased on the seventh day after coronary bypass surgery, against adenovirus, measles, rubella and tetanus as well as the total number of cells secreting immunoglobulins IgG, IgM and IgA (P < 0.05/0.001). By contrast, only slight fluctuation was seen in the numbers of cells secreting antibodies after PWM stimulation. Spontaneous lymphocyte proliferation was also increased, PHA proliferative responses were depressed and PWM responses were not changed on the seventh postoperative day compared with preoperative values. CONCLUSION: Coronary artery bypass surgery caused marked polyclonal B cell activation demonstrated by an increase of cells producing spontaneously antibodies against virus antigens and tetanus toxoid. This activation could not be intensified by PWM stimulation.

Adult↗
PubMed1997

Neural network modeling for estimation of the aqueous solubility of structurally related drugs.

The ability of neural network models to predict aqueous solubility within series of structurally related drugs was evaluated. Three sets of compounds representing different drug classes (28 steroids, 31 barbituric acid derivatives, and 24 heterocyclic reverse transcriptase inhibitors) were studied. Topological descriptors (connectivity indices, kappa indices, and electrotopological state indices) were used to link the structures of compounds with their aqueous solubility. Separate models were built for each class of drugs using back-propagation neural networks with one hidden layer and five topological indices as input parameters. The effect of network size and training time on the prediction ability of the network was studied by the leave-one-out (LOO) procedure. In all three compound groups a neural network structure of 5-3-1 was optimal. To avoid chance effects, artificial neural network (ANN) ensembles (i.e.; averaging neural network predictions over several independent networks) were used. The cross-validated squared correlation coefficient (Q2) for 10 averaged predictions was 0.796 in the case of the steroid set. The corresponding standard error of prediction (SDEP) was 0.288 log units. For the barbiturates, Q2 and SDEP were 0.856 and 0.383, respectively, and for the RT inhibitors, these parameters were 0.721 and 0.401, respectively. The results indicate that neural networks can produce useful models of the aqueous solubility of a congeneric set of compounds, even with simple structural parameters.

Drug Design↗
PubMed1997

Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro.

We have earlier found increased percentages of T helper cells (CD4-positive lymphocytes) in the blood circulation after propofol infusion anaesthesia. Cytokines interferon-gamma (IFN gamma) and interleukin-4 (IL-4) are important in the differentiation of T helper cells into subtypes T helper type-1 (Th1) and type-2 (Th2). To study the effects of propofol emulsion, its solvent Intralipid and thiopentone on Th1/Th2 balance, measurements of IFN gamma and IL-4 production by mononuclear leucocytes were carried out in vitro. As IL-2 has a central role in immune responses to surgery, its production was also measured. Concanavalin A-stimulated mononuclear cells were cultured in the presence of propofol emulsion at 3.5 or 10 micrograms.ml-1, Intralipid 35 or 100 micrograms.ml-1, or thiopentone 3 micrograms.ml-1. Cytokine production was measured from the conditioned media of mononuclear cell cultures. Decreased IFN gamma (p < 0.001) and IL-4 concentrations (p < 0.01) were found in the presence of thiopentone, but IL-2 production was unaffected. By contrast, propofol emulsion or Intralipid had no effects on IFN gamma, IL-2 or IL-4 concentrations. Propofol 10 micrograms.ml-1 increased the IFN gamma/IL-4 ratio from the control value median 243 (162-562) (25th-75th percentile) to 363 (195-1028) (p < 0.01), but thiopentone decreased it to 145 (60-214) (p < 0.01). These findings show that propofol and thiopentone have different effects in vitro on Th1/Th2 balance and suggest that they have different modulating effects on the immune response.

Anesthetics, Intravenous↗
PubMed1997

Effects of open heart surgery on oral mucous host defence systems.

BACKGROUND: The immune response is affected by anaesthesia and surgery. This study was carried out on the effects of open heart surgery on the oral mucous host defence system, which is part of the common mucosal immune system. METHODS: Amylase, nonimmunological (lysozyme, myeloperoxidase, hypothiocyanite and thiocyanate) and immunological (IgA, IgG, and IgM) mucous host defence factors as well as oral bacterial flora were determined in the saliva of 18 patients undergoing open heart surgery preoperatively and on the 2nd, 3rd, and 7th postoperative days. To assess the specificity of the changes, the salivary flow rate and total protein content were also determined. RESULTS: Stimulated salivary flow decreased from 1.8 (1.3-2.2) ml/min (median; 25th and 75th quartiles) to 0.4 (0.3-0.5) ml/min by the 2nd postoperative day and to 0.4 (0.2-1.0) ml/min by the 3rd postoperative day (P < 0.001). Amylase, lysozyme, myeloperoxidase, total salivary peroxidase and thiocyanate levels increased, whereas hypothiocyanite levels decreased postoperatively (p < 0.01-0.001). Their total secretion rate, however, was reduced (P < 0.05-0.001) owing to the lowered salivary flow rate. IgG and IgM concentrations were raised on the 2nd, 3rd and 7th postoperative days (P < 0.05-0.001), and IgA concentrations on the 2nd postoperative day (P < 0.05). The total secretion of IgG and IgM as well as their salivary concentrations in relation to total protein concentrations also increased. The number of salivary anaerobically growing bacteria decreased postoperatively (P < 0.01), but the number of salivary streptococci remained unaffected. CONCLUSIONS: Open heart surgery decreases the salivary secretion of nonimmunological host defence factors and increases the salivary secretion of IgA, IgG and IgM.

Adult↗
PubMed1996

Structure-retention relationships of steroid hormones in reversed-phase liquid chromatography and micellar electrokinetic capillary chromatography.

Quantitative structure-retention relationship (QSRR) studies are useful in retention prediction, finding the relevant structural descriptors for analytes and estimating the relative biological activities of a series of analytes. Most of the studies have been conducted by RP-HPLC and a few by micellar electrokinetic capillary chromatography (MECC). The aim of this work was to find structural parameters and characteristics related to the RP retention and electrophoretic migration of steroids in order to predict the retention/migration of steroid hormones on the basis of their molecular structure. Retention data were obtained with an ODS column using a mobile phases aqueous methanol-acetonitrile (mobile phase A) and methanol-tetrahydrofuran (mobile phase B). MECC was conducted with a sodium dodecyl sulfate (SDS)-borate system and with a mixed micellar solution of SDS and sodium cholate. Several topological indices, such as the connectivity indices, chi, were used as structural parameters. Steric factors seem to have a great effect on the retention of steroid hormones, especially with the MeCN-containing mobile phase. Retention in mobile phase B could be predicted more accurately. Topological indices can be used in the modelling and prediction of the retention/migration of steroid hormones when the solutes form a congeneric series and stereochemical properties do not govern the separation process.

Chromatography↗
PubMed1996

Propofol infusion anaesthesia and the immune response in elderly patients undergoing ophthalmic surgery.

In our earlier studies, propofol infusion anaesthesia increased the percentage of T helper cells in middle-aged surgical patients undergoing minor or major surgery. In the present study we compared the effects of total intravenous propofol anaesthesia and combined isoflurane anaesthesia on the immune response to ophthalmic surgery in elderly patients. Twenty patients (median age 75 years, ASA 2-3) were randomly allocated to receive total intravenous propofol anaesthesia (median total dose of propofol 710 mg) or combined isoflurane anaesthesia (median end-expiratory concentration of isoflurane 0.45 vol %). The following were measured pre-operatively, at the end of operation and on the first postoperative morning: leucocyte and differential counts: percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD20, CD16) and monocytes (CD14); phytohaemagglutinin-, concanavalin A- and pokeweed mitogen-induced and unstimulated lymphocyte proliferative responses: polyclonal immunoglobulin synthesis as well as serum cortisol concentrations. The immune response to ophthalmic surgery was basically similar in both anaesthetic groups. The percentage of T helper cells in the blood circulation increased in the propofol group (p < 0.05) but not in the isoflurane group. The difference in the time-response profile for T helper cell percentages between the groups was also statistically significant (p < 0.01).

Aged↗
PubMed1995

Effects of propofol and Intralipid on immune response and prostaglandin E2 production.

The present study evaluated the effects of propofol and its solvent Intralipid on the immune response and in vivo prostaglandin E2 production in patients during induction of anaesthesia and in healthy volunteers after Intralipid injection. Fifteen female patients (median age 48 years, ASA 1-2) scheduled for uterine dilatation and curettage were randomly assigned to two groups. In group 1 propofol (median dose 3.1 mg.kg-1) and in group 2 thiopentone (median dose 6.0 mg.kg-1) were injected intravenously over 60 s. Surgery was started after collection of the last blood sample. In the second part of this study, Intralipid 10% 0.3 ml.kg-1 was injected intravenously in eight healthy volunteers (four women and four men, median age 32 years) over 60 s. Plasma bicyclo-PGE2 concentrations increased during anaesthesia induction in both anaesthetic groups (p < 0.01). By contrast, no changes were seen in plasma bicyclo-PGE2 concentrations after Intralipid injection in volunteers. Lymphocyte proliferative responses to mitogens did not change during anaesthesia induction in patients. In volunteers, Intralipid injection caused a slight increase in T-cell percentages (p < 0.01) and unstimulated lymphocyte proliferative responses (p < 0.05), but it did not affect other lymphocyte subsets and immunoglobulin production. Intralipid and propofol were not found to be immunosuppressive at clinical doses used during anaesthesia induction.

Adult↗
PubMed1995

The influence of anaesthetic technique upon the immune response to hysterectomy. A comparison of propofol infusion and isoflurane.

Earlier studies on propofol have shown increased percentages of T helper cells after minor surgery. In this study, the effects of propofol infusion anaesthesia on the immune response were compared with those of combined isoflurane anaesthesia in 30 patients (median age 47 years, ASA 1-2) undergoing major surgery. The total dose of propofol in the propofol infusion group of 15 women was 860 mg (range 540-1520 mg) and the median end-expiratory isoflurane concentration in the combined isoflurane group of 15 women was 0.6% (range 0.5-0.8). The following were measured; leucocyte and differential counts; percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16 and HLA-DR+CD3); phytohaemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated lymphocyte proliferation; plasma interleukin-6; serum group II phospholipase A2, C-reactive protein and cortisol concentrations. Measurements were made pre-operatively, at the end of the operation and on the first and fifth postoperative days. No statistically significant overall differences were observed in the immune response between the groups. The serum cortisol response was weaker in the propofol group than in the isoflurane group (p < 0.05). Time-related changes were seen within the groups.

Adult↗
PubMed1995

Leucocyte content in blood processed by autotransfusion devices during open-heart surgery.

Autologous red blood cells processed by autotransfusion devices have become increasingly common in major surgery. The finished product, however, often contains varying amounts of leucocytes. We compared leucocyte and their differential counts of blood processed by three autotransfusion devices (Haemonetics Cell Saver IV, Dideco Stat and Dideco Stat-P) during open-heart operations on 25 patients. In addition, a zymosan-induced, luminol-enhanced chemiluminescence method was used to evaluate the activity of neutrophils in prepared autologous blood. High leucocyte counts (3.6-10.9 x 10(9)l-1) were found in all saved red blood cell concentrates. The leucocyte counts of autologous blood produced by the Haemonetics device were lowest (P < 0.01) and about one third of the patients' haematocrit-corrected counts. The proportions of neutrophils were higher in salvaged blood than in the blood circulation before anaesthesia or before retransfusion (P < 0.01). However, no general activation of neutrophils was seen, but the increase in chemiluminescence activity of about 30% that was seen in four patients may suggest an increased risk of reperfusion injury in such patients after aortic declamping. In conclusion, all three autotransfusion devices left leucocytes in the processed red blood cell concentrates, although great differences occurred between the devices.

Blood Transfusion, Autologous↗
PubMed1995

Comparison of the effects of centrifugal versus roller pump on the immune response in open-heart surgery.

We compared the effects of a centrifugal pump with those of a roller pump on immune responses in 26 coronary artery bypass surgery patients during cardiopulmonary bypass (CPB). The patients were randomly allocated into a (Biomedicus) centrifugal pump group and a (Stöckert) twin roller pump group. Leucocyte and differential counts; percentages of lymphocyte subpopulations (CD3-, CD4-, CD8-, CD16-, CD20- and CD25-positive lymphocytes) and monocytes (CD14); phytohaemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated proliferation of separated lymphocytes; unstimulated and pokeweed mitogen-stimulated production of IgG, IgM, or IgA; and plasma fibronectin, C-reactive protein and serum albumin concentrations were measured preoperatively, immediately before CPB, immediately before aortic declamping and on the first postoperative morning. Significant changes were seen in these variables, but no differences occurred between the groups.

Aged↗
PubMed1994

Statistical evaluation of molecular descriptors and quantitative structure-property relationship studies of retinoids.

Various molecular descriptors, including connectivity indices, sums of the intrinsic state values, electrotopological state indices, topological equivalence indices, kappa indices, normalized Bonchev-Trinajstic and Shannon information indices, Wiener and Platt's F numbers and molecular weight, were calculated for 73 retinoids, whose structures and properties were taken from the literature. A novel methodology using statistical analyses (cluster, factor and stepwise regression) in selecting relevant molecular descriptors for quantitative structure-property relationship (QSPR) studies has been developed. The analyses were used in correlating molecular structure with affinity, pharmacokinetic properties and reversed-phase retention of retinoids.

Molecular Weight↗
PubMed1994

Effects of cardiopulmonary bypass on lymphocytes and their subset counts with or without use of autotransfusion devices.

Lymphocytes and their subset counts were determined in 30 cardiac surgery patients during cardiopulmonary bypass (CPB) with or without use of an autotransfusion device. In the autotransfusion group, centrifuged and washed autologous red blood cells (median 400 mL [range 200-770 mL]) and in the control group corresponding amounts of homologous packed red blood cells (median 500 mL [range 250-750 mL]) were transfused after declamping the aorta. The percentages of T lymphocytes (CD3) and T cytotoxic cells (CD8) increased in both groups (CD3 up to 5%, P < 0.05 and CD8 up to 35%, P < 0.01), but the percentage of T helper cells (CD4) did not change. The ratio of CD4/CD8 cells decreased (up to 34%, P < 0.01). The percentage of naive resting T cells (CD45RA) increased slightly (up to 8%, P < 0.05) whereas the percentages of memory T cells (CD45RO), T cells with IL-2 receptor (CD25), and natural killer cells (CD16) remained unaltered. The percentage of HLA-DR positive lymphocytes increased during CPB (up to 18%, P < 0.05), but it was decreased thereafter (up to 16%, P < 0.05). The percentage of monocytes (CD14) decreased first during CPB in both groups (up to 32%, P < 0.01), but it was higher in the autotransfusion device group (decreased 29% from initial value) than in the control group (decreased 65% from initial value) at the end of CPB (P < 0.05). This study shows that extracorporeal circulation has an effect on lymphocytes and their subset counts. The changes were slightly immunosuppressive. By contrast, use of autotransfusion devices had only minor effects.

Blood Transfusion↗
PubMed1994

Propofol infusion anaesthesia and immune response in minor surgery.

This study was set up to evaluate the effects of propofol infusion anaesthesia on immunological function in minor surgery. Twenty-seven patients (median age 51 years, ASA 1-2) scheduled for minor breast surgery were randomly assigned to two groups. Anaesthesia was induced in group 1 with propofol 2.5 mg.kg-1 and maintained with propofol 12 mg.kg-1 x h-1 and 30% O2 in air, whereas in group 2 anaesthesia was induced with thiopentone 4 mg.kg-1 and maintained with 70% N2O in O2. Fentanyl and vecuronium were used in both groups. The percentages of T cells (p < 0.001), B cells (p < 0.01) and memory T cells increased (p < 0.01) in both groups. T helper cell percentages increased in the propofol but not in the thiopentone group (p < 0.05). The percentages of natural killer cells decreased from pre-induction values in both groups (p < 0.001). No changes were seen in lymphocyte proliferative responses. Minor breast surgery under propofol or conventional combined anaesthesia had only minor effects on the immune response. The higher percentage of T helper cells after propofol anaesthesia compared to conventional combined anaesthesia is beneficial, but its clinical importance remains to be determined.

Adult↗