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Biomedical subjects

H Mustonen

Publications and source records attributed to H Mustonen.

At least 19 recordsLinked to original sources
PubMed2005

Improved early risk stratification and diagnosis of myocardial infarction, using a novel troponin I assay concept.

BACKGROUND: We evaluated the clinical performance of a novel cardiac troponin I (cTnI) assay specifically designed to improve the very early risk stratification in acute coronary syndromes. SUBJECTS AND METHODS: Serum and plasma samples (taken 0, 6-12 h and 24 h after admission) from 531 patients with suspected acute coronary syndrome were studied using a novel investigational cTnI assay, reference cTnI assay and myoglobin. The lowest cTnI concentration giving a total assay imprecision of 10% was used as the positive myocardial infarction (MI) cut-off value. RESULTS: At the time of admission, the investigational assay was positive in 27.9% of the patients, the reference cTnI assay was positive in only 17.5% (P < 0.001) and myoglobin in 24.1% (P = 0.067). Receiver operating characteristic (ROC) curve analysis for the detection of myocardial injury on admission gave area-under-curve (AUC) values of 0.937, 0.775 and 0.762, respectively (P < 0.001). Of those MI patients who presented within 3 h of symptom onset, 50.0% were identified by the investigational assay at the time of presentation, compared with 44.2% by myoglobin (P = 0.791) but only 11.5% by the reference assay (P < 0.001). CONCLUSIONS: The novel cTnI assay considerably improves the performance of cTnI as an early rule-in biomarker for MI.

Aged↗
PubMed2004

Ethanol induces volume changes and gap junction closure via intracellular Ca2+ signalling pathway in cultured rabbit gastric epithelial cells.

BACKGROUND: Ethanol is a well-established 'barrier breaker' in gastric mucosa, but its effects at cellular level remain to be detailed. METHODS: Gastric epithelial cells were isolated from rabbits and cultured to monolayers. Intracellular calcium was measured spectrofluorometrically with fura-2. The patency of gap junctions was assessed by photobleaching a small area of 5-carboxyfluorescein loaded monolayer and measuring recovery of fluorescence. For cell volume measurements the change in fluorescence intensity was followed in calcein-loaded monolayers with a confocal microscope. RESULTS: Intracellular calcium concentration was increased from 65 +/- 9 to 140 +/- 17 nM; recovery of fluorescence signal after photobleaching was diminished from 53% +/- 11% to 9% +/- 3%; and cell volume was decreased significantly after 10 min exposure to 5% (vol/vol) ethanol. This volume decrease was prevented with serosal application of the potassium channel blocker, quinine, or by blocking the intracellular calcium signalling pathway with the intracellular calcium-chelating agent BAPTA. This suggests that luminal ethanol opens the basolateral calcium-dependent potassium selective channels via calcium signalling pathway, with resultant shrinkage of the cell. CONCLUSION: Intracellular calcium concentration is increased, gap junctions are closed and cell volume is decreased after exposure to 5% ethanol. Since gap junctions are known to be calcium gated, it is likely that their closure is secondary to the elevated cytosolic calcium in ethanol injured cells. This may have a protective function by limiting intercellular spread of impending cell injury. The opening of the basolateral potassium channel probably underlies the ethanol-induced cell shrinkage and might contribute to the ethanol-provoked epithelial damage.

Animals↗
PubMed2002

Roles of cytoskeleton and tyrosine receptor mediated signal transduction in the restitution of isolated guinea pig gastric mucosa.

BACKGROUND: The immediate response of the GI-epithelium to a superficial injury is primarily directed to restore the disturbed epithelial continuity in a process called restitution. The involvement of both structural (cytoskeleton) and humoral (growth factors and cytokines) signal transduction systems in the process has been documented. Previously, in experimental circumstances the role of the two systems has been examined as two distinct units. Nevertheless, in normal conditions in vivo, the two systems are presumably acting simultaneously. This study investigates the functional roles of cytoskeleton and tyrosine receptor mediated signalling in the regulation of restitution. METHODS: Guinea pig gastric mucosa was mounted in Ussing-chamber, injured with 1.25 M NaCl and subsequently perfused for 4 h. Simultaneously, the electrophysiological resistance of the tissue (R) was recorded. During the recovery, the tissue was exposed bilaterally either to modulators of cytoskeleton (cytochalasin B/lysophosphatidic acid) or of tyrosine receptor mediated signalling (genistein/epidermal growth factor + transforming growth factor-alpha). After the experiment, the tissue was analysed morphologically and the proliferative index (PI) was determined morphometrically. RESULTS: Exposure of the tissue to cytochalasin caused a significant decrease of both restitution (tissue resistance) and proliferation (PI), whereas simultaneous treatment with EGF+ TGFalpha restored both restitution and proliferation. Correspondingly, exposure of the tissue to genistein during restitution impaired the process as well as induction of proliferation, while simultaneous exposure to lysophosphatidic acid restored the processes. Exposure of the tissue to EGF+ TGFalpha and lysophosphatidic acid simultaneously resulted in a mild, but insignificant additive inductions of both restitution and proliferation. CONCLUSIONS: Restitution is controlled by both structural and humoral signalling systems. If one of the regulating systems fails, stimulation of the other restores the process. Simultaneous stimulation of both systems has a minor additive effect on both restitution and proliferation.

Animals↗
PubMed2001

Regular-dose versus high-dose omeprazole in peptic ulcer bleeding: a prospective randomized double-blind study.

BACKGROUND: It has been suggested that profound acid inhibition along with endoscopic therapy might prevent rebleeding and reduce mortality in patients with peptic ulcer bleeding. The aim of the study was to test the possible equivalence of a high dose and the regular dose of omeprazole in peptic ulcer bleeding. METHODS: We performed a prospective randomized double-blind study involving 142 patients with acute peptic ulcer bleeding (Forrest classification I-II: spurting or oozing bleeding, non-bleeding visible vessel, clot and black base). One-hundred-and-two (71.8%) patients received endoscopic treatment (adrenaline injection and/or heater probe) in pre-entry. Patients were randomly assigned to receive the regular dose of omeprazole intravenously (20 mg once a day for 3 days, i.e. 60 mg/72 h) or a high dose of omeprazole (80 mg bolus + 8 mg/h for 3 days, i.e. 652 mg/72 h). Rebleeding, surgery and death were the outcome measures. RESULTS: Six (8.2%) of the 73 patients receiving the regular dose of omeprazole and 8 (11.6%) of the 69 patients receiving the high dose of omeprazole rebled (P = 0.002 for equivalence, equivalence limit 0.15). Three (4.1%) of the former patients and 5 (7.2%) of the latter group underwent surgery. Four (5.5%) patients in the regular-dose and 2 (2.9%) in the high-dose group died within 30 days. CONCLUSION: Under the defined tolerance limits, the regular dose of omeprazole is as successful as a high dose in preventing peptic ulcer rebleeding.

Aged↗
PubMed2001

HCl causes less intracellular acidification in Necturus gastric mucosa surface epithelial cells than other acids.

Luminal acid causes intracellular acidification in the gastric epithelium, but the mechanism by which H(+) enters surface cells remains obscure. This study addressed the problem by assessing how different acids affect intracellular pH in gastric surface cells. Isolated Necturus maculosus antral mucosa was exposed to HCl, HNO(3), H(2)SO(4), and H(3)PO(4) at pH 2.30. Intracellular pH was measured with microelectrodes. The physicochemical interaction of a synthetic model of gastric phospholipids with the different acids was studied using Langmuir film balance. Exposure to luminal HNO(3), H(2)SO(4), or H(3)PO(4) caused significantly larger intracellular acidification than exposure to HCl. The degree of acidification was not dependent on the valence or nature of the anionic counterion of the acid but significantly correlated with the amount of molecular acid. By Langmuir film balance, subphases acidified with HNO(3), H(2)SO(4), or H(3)PO(4) caused more close packing of phospholipid molecules than those acidified with HCl, possibly allowing hydrogen bonding between head groups to facilitate H(+) movement across the phospholipid membrane. HCl causes significantly less intracellular acidification in gastric epithelium than HNO(3), H(2)SO(4), or H(3)PO(4). This may be caused by the lower amount of molecular HCl in solution and possible hydrogen bonding between the head groups of phospholipid molecules and the other acids.

Acids↗
PubMed2001

Nitric oxide donors retard wound healing in cultured rabbit gastric epithelial cell monolayers.

Effects of nitric oxide (NO) on gastric wound healing were investigated in primary rabbit gastric epithelial cell cultures. We analyzed the speed of cell migration, proliferation, and apoptosis after creating a round wound on the cell cultures. The monolayers were incubated with or without the NO donor sodium nitroprusside, oxatriazolimine 1,2,3,4-oxatriazolium, 5amino-3-(3,4-dichlorophenylchloride), or the peroxynitrite generator 3-morpholinosydnomine-N-ethylcarbamide. The possible role of cGMP as a second messenger of NO was investigated with 8-bromo-cGMP. The role of O2(-*) was evaluated using diethyldithiocarbamate and pyrogallol. The effects of superoxide dismutase and allopurinol were also investigated. NO inhibited the speed of cell migration and proliferation and induced cell apoptosis in a dose- and time-dependent manner. The effects were augmented with O2(-*) generators and ameliorated by O2-(8) scavengers, whereas cGMP had no significant effect on wound healing. NO donors retard gastric wound healing by inhibiting migration and proliferation and inducing cell apoptosis. These effects do not seem to be mediated via cGMP, but O2(-*). or peroxynitrites may be involved.

Animals↗
PubMed2000

Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer.

BACKGROUND & AIMS: Identification of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome enables prevention of colorectal cancer (CRC) by means of colonoscopy and polypectomies. We evaluated the efficacy of screening in a controlled trial over 15 years. METHODS: Incidence of CRC and survival were compared in 2 cohorts of at-risk members of 22 families with HNPCC. Colonic screening at 3-year intervals was arranged for 133 subjects; 119 control subjects had no screening. Genetic testing was offered to subjects in whose families the causative mutation was known. RESULTS: CRC developed in 8 screened subjects (6%) compared with 19 control subjects (16 %; P = 0.014). The CRC rate was reduced by 62%. In mutation-positive subjects alone, the CRC rates were 18% in screened subjects and 41% in controls (P = 0.02). The decrease resulted from the removal of adenomas in 13 mutation-positive individuals (30%) and in 6 subjects with unknown mutation status (40%). All CRCs in the study group were local, causing no deaths, compared with 9 deaths caused by CRC in the controls. The overall death rates were 10 vs. 26 subjects in the study and control groups (P = 0.003), 4 vs. 12 in mutation-positive subjects (P = 0.05). CONCLUSIONS: Colonoscopic screening at 3-year intervals more than halves the risk of CRC, prevents CRC deaths, and decreases overall mortality by about 65% in HNPCC families.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Topical prostaglandin E2 protects isolated gastric mucosa against acidified taurocholate-, but not ethanol- or aspirin-induced injury.

This study investigates whether topical prostaglandins protect isolated gastric mucosa against injury provoked by acidified "barrier-breaking" agents. Intracellular pH (pHi), apical cell membrane potential (Vcm) and intraepithelial resistances in isolated Necturus antral mucosa were measured using double-barreled liquid sensor microelectrodes. Topical PGE, treatment protected the antral mucosa against acidified taurocholate-induced injury, reducing significantly (P<0.05) intracellular acidification (pHi from 7.39+/-0.05 to 7.08+/-0.08 vs. from 7.30+/-0.02 to 6.62+/-0.15), and opposing significantly the changes in Vcm (hyperpolarization followed by depolarization), and completely abolishing the decrease in transmembrane resistance (Rt from 702+/-37 to 723+/-39 Ohms x cm2 vs. from 721+/-34 to 270+/-105 Ohms x cm2). Also the ratio of apical and basolateral membrane resistances (Ra/Rb) remained at a significantly higher level in PGE2-treated tissues. In contrast, PGE2 treatment had no protective influence on the changes of the respective parameters in acidified ethanol or acetylsalicylic acid injured mucosas. Topical prostaglandin E2 protects isolated gastric mucosa against acidified taurocholate, but not against ethanol- or acetylsalicylic acid-induced injury.

16,16-Dimethylprostaglandin E2↗
PubMed2000

Gender differences in alcohol consumption and adverse drinking consequences: cross-cultural patterns.

AIMS: To examine the consistency and/or variability of gender differences in drinking behavior cross-culturally. DESIGN, SETTING, PARTICIPANTS: Women's and men's responses in 16 general population surveys from 10 countries, analyzed by members of the International Research Group on Gender and Alcohol. MEASUREMENTS: Comparable measures of drinking, versus abstention, typical drinking frequencies and quantities, heavy episodic drinking, intoxication, morning drinking, and alcohol-related family and occupational problems. FINDINGS: Women and men differed little in the probability of currently drinking versus abstaining, but men consistently exceeded women in typical drinking frequencies and quantities and in rates of heavy drinking episodes and adverse drinking consequences, while women were consistently more likely than men to be life-time abstainers. In older age groups, both men and women drank smaller quantities of alcohol and were more likely to stop drinking altogether, but drinking frequencies did not change consistently with age. CONCLUSIONS: A theoretical synthesis proposes that gender roles may amplify biological differences in reactions to alcohol, and that gender differences in drinking behavior may be modified by macrosocial factors that modify gender role contrasts.

Adult↗
PubMed2000

Relationships of drinking behaviour, gender and age with reported negative and positive experiences related to drinking.

AIMS: To assess associations between drinking behaviour, gender and age with reported experiences related to drinking. DESIGN: Cross-sectional survey. SETTING AND PARTICIPANTS: Interviews were performed in 1992 with a representative sample of the Finnish population between 15 and 69 years of age (N = 3446). MEASUREMENTS: Annual intake of alcohol, frequency of drunkenness, and 14 negative and eight positive reported experiences related to drinking. FINDINGS: Logistic regression models showed that overall intake and frequency of drunkenness were independently associated with almost all reported positive and negative consequences of drinking. Women more commonly reported that drinking had helped them to sort out interpersonal problems at home or in the work-place, to feel more optimistic about life, and to express their feelings. Men more commonly reported that drinking had helped them to be funnier and wittier and to get closer to the opposite sex. Drunken driving was markedly male behaviour, but women more commonly reported other types of reckless behaviour and adverse consequences of drinking. However, men more commonly said they were criticized by family for their drinking. With the exception of health problems, both positive and negative consequences of alcohol were more common among younger drinkers. CONCLUSIONS: Once overall intake and frequency of drunkenness were controlled for, significant differences between men's and women's perceptions of the costs and benefits of alcohol consumption emerged. Men tended to perceive more hedonic benefits while women perceived more functional benefits. Women reported behaving more recklessly in drinking situations. In light of the results, women were not under selective social control.

Adolescent↗
PubMed1999

Relationships between characteristics of drinking occasions and negative and positive experiences related to drinking.

The relationships between characteristics of drinking occasions and experiences related to drinking were studied. Interviews were conducted in 1992 with a representative sample of the Finnish population between 15 and 69 years of age. The analyses were based on 10,039 drinking occasions of 1,483 male and 1,373 female drinkers. Intake of alcohol and the frequency of drunkenness were the most important predictors of both negative and positive experiences related to drinking. Characteristics of the drinking situations contributed significantly to the explanatory models, but their predictive power was small. Public and large-group drinking situations tended to increase and private and intimate situations tended to decrease the number of both negative and positive experiences related to single drinking occasions. The same situations that lead to increased positive experiences with drinking also increase the risk for negative experiences.

Adolescent↗
PubMed1998

Improved intraepithelial two-dimensional cable analysis with application to necturus gastric antral mucosa.

Previously 2D cable analysis has been performed with two microelectrodes, one for passing intraepithelial current and the other for measuring the voltage response in multiple cells along the distance scale. This requires that the epithelium must be in a stable state for a considerably long period because of the multiple impalements. To follow changes of intraepithelial resistances in chambered Necturus antral mucosa with good temporal resolution, four/five electrodes were used to impale cells in the same preparation and the intraepithelial current (6.5-20 nA) was conducted sequentially to three/four of the electrodes, one at a time, to obtain six/ten independent voltage response measurements along the distance scale. The solution to the 2D cable equations was fitted to results and apical, basolateral and shunt resistances were calculated. It was found that an incorrect distance configuration can ruin the precision of the measurement. The distance configuration can, however, be optimized. The resistance values calculated with the 2D cable analysis were very close to those obtained by the amiloride exposure technique in the same tissues. The improvement gained with this work is better temporal resolution (even <10 s) when measuring epithelial resistances.

Amiloride↗
PubMed1998

Prognosis of colorectal cancer varies in different high-risk conditions.

Variation in prognosis between different colorectal cancer (CRC) patient groups was studied by comparing the survival rates of patients belonging to three cancer predisposition groups with those with sporadic CRC. The high-risk groups included 43 members of hereditary nonpolyposis colorectal cancer (HNPCC) families, 25 patients with familial adenomatous polyposis (FAP) and 33 patients with underlying ulcerative colitis (UC). The control group included 122 consecutive sporadic CRC patients. Cumulative 5-year survival was highest in HNPCC (86%), which is significantly better than in sporadic colorectal cancer (59%, hazard ratio 0.41, P = 0.02). Cancer associated with UC had a 5-year survival rate of 39%, which is significantly less than in sporadic cancer (hazard ratio 1.83, P = 0.03). There was no significant difference in the survival between patients with FAP and patients with sporadic CRC (hazard ratio 1.27, P = 0.5). Exclusion of cases detected by screening examinations slightly reduced the survival rates; 85% for HNPCC, 53% for FAP and 28% for UC. However, the differences between the groups remained significant. The survival of patients with HNPCC was found to be better than that among other groups in this study, which probably relates to the specific tumourigenesis involving DNA mismatch repair dysfunction.

Adenomatous Polyposis Coli↗
PubMed1997

Luminal acid increases apical cell membrane resistance in isolated Necturus antral mucosa.

BACKGROUND & AIMS: The gastric mucosa must have efficient protective mechanisms to maintain physiological intracellular pH. The aim of this study was to investigate the effect of low luminal pH on apical membrane permeability. METHODS: Chambered Necturus antral mucosa was perfused with Ringer's/95% O2-5% CO2 at pH 7.25. The mucosal side was exposed to pH 4.0-2.0 with four microelectrodes placed in surface cells. Two-dimensional cable analysis was used to measure apical, basolateral, and shunt resistances. In some experiments, liquid sensor pH or Na(+)-selective microelectrodes were used. RESULTS: Luminal acidification hyperpolarized apical cell membrane potential and increased apical cell membrane resistance from 21.3 +/- 2.6 (pH 7.25) to 38.0 +/- 2.3 k omega.cm2 (pH 3.0; n = 8). The increase in apical cell membrane resistance was preceded by transient intracellular acidosis from 7.32 +/- 0.07 (pH 4.0) to 7.23 +/- 0.06 (pH 3.0; n = 6). Similar intracellular acidosis (provoked by NH4+ prepulse) failed to cause the effects observed with luminal acid. The increase in apical cell membrane resistance caused by luminal acid was eliminated when N-methyl-D-glucamine+, but not Na+, was substituted for all cations in the luminal solution. CONCLUSIONS: Luminal acidification (pH 3.0-2.0) closes apical amiloride-blockable Na+ channels. Protons are probably able to pass and even block these channels, but their effect in closing the channels does not occur intracellularly.

Acids↗
PubMed1996

High systemic HCO3(-) and topical 16,16-dimethyl-PGE2 protect gastric mucosa against luminal acid by enhancing its preepithelial buffer capacity.

Systemic metabolic alkalosis and topical prostaglandins protect the gastric mucosa against luminal acid. This study investigates whether this protection is mediated by increased epithelial HCO3(-) secretion with resultant alkalization of the pre-epithelial mucus-HCO3(-) buffer layer. surface pH of chambered ex vivo rat gastric epithelium was measured with liquid sensor pH microelectrodes during luminal perfusion of increasing acidities (0, 10, 30, 50, 100 mM HCL). The experimental groups were: (1) control, (2) topical 16,16-dimethyl-PGE2 treatment, (3) high-HCO3(-) metabolic alkalosis, and (4) low HCO3(-) respiratory alkalosis. The gastric mucosa of PGE2-treated and high-HCO3(-) alkalotic rats tolerated significantly better luminal acid than that of controls, but the tolerance of low-HCO3(-) alkalotic rats was significantly impaired. There was a significant correlation between arterial HCO3(-) concentration (but not arterial pH) and surface pH (r = 0.81, P < 0.01). This suggests that the gastric mucosa against luminal acid are, at least in part, mediated by enhanced buffer capacity of the pre-epithelial mucus-HCO3(-)layer.

16,16-Dimethylprostaglandin E2↗
PubMed1995

Regulation of intracellular pH in isolated Necturus gastric mucosa during short-term exposure to luminal acid.

BACKGROUND/AIMS: Continuous exposure to gastric acid implies efficient control mechanisms of intracellular pH (pHi) in the gastric epithelium. This study assessed the roles of Na+, H+, and HCO3- transport mechanisms in controlling pHi during short-term exposure of the gastric epithelium to luminal acid. METHODS: pHi and Na+ activity (aiNa) were measured with liquid sensor microelectrodes in isolated Necturus antral mucosa, modulating ion transport mechanisms by ion removal and pharmacological inhibition. RESULTS: Short-term exposure to luminal acid (pH 2.3) acidified pHi by 0.3 pH units, whereafter pHi stabilized. This was associated with transient increase in aiNa. Blocking of Na+/H+ exchange (in the presence of HCO3-/CO2) by removal of Na+ or addition of amiloride eliminated the increase in aiNa and resulted in uncontrolled acidification of pHi. Similarly, blocking of HCO3- transport (in the presence of Na+) by removal of HCO3-/CO2 or addition of 4-acetamido-4-isothiocyanatostilbene-2,2-disulfonic acid resulted in uncontrolled acidification of pHi despite increase in aiNa. Blocking of Na+/K+ exchange with ouabain eliminated the recovery of aiNa and also resulted in uncontrolled acidification of pHi. CONCLUSIONS: The data indicate that during short-term exposure of the gastric mucosa to luminal acid, both Na+/H+ antiport and HCO3- transport are needed to control pHi and maintain it within physiological ranges.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1995

New beverages, new drinking contexts? Signs of modernization in Finnish drinking habits from 1984 to 1992, compared with trends in the European Community.

The dynamics of change in drinking patterns is discussed using the data from the drinking habits surveys conducted in Finland in 1984 and 1992. The results are compared with a respective analysis on the EU countries from 1988 by Hupkens, Knibbe & Drop (1993). The analysis is based on changes in beverage preferences. In the Finnish case, both wine and mild beer appear as new beverages, gaining popularity in the late 1980s. For beer, both the elites and the population at large were involved in that process. For wine, the interest in the new beverage was stronger among the elites. There were notable gender differences in adopting the new beverage. Some of the differences were related to the older cultural patterns of wine as a woman's drink and beer as a male beverage. The results also point to difficulties in analysing the dynamics of change on the basis of cross-sectional data, as was done in the earlier analysis on the EC countries. The Finnish data shows that even the inter-group dynamics of drinking patterns may change over a relatively short period of time.

Adolescent↗