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Biomedical subjects

M Mäkinen

Publications and source records attributed to M Mäkinen.

At least 19 recordsLinked to original sources

Teaching basic life support to nurses.

BACKGROUND AND OBJECTIVE: Every member of healthcare personnel should be able to perform basic life support including defibrillation (CPR-D). The biggest cost of implementation is training and these costs need to be reduced. The purpose of this randomized study was to evaluate the applicability of distance learning as a method to teach CPR-D. METHODS: Nurses (n = 56) working in a geriatric hospital were randomized into three groups. The first group was given the Internet-based CPR-D course and the second was given a traditional, small-group CPR-D course. A third group without specific training in CPR-D served as a control group. An objective structured clinical examination (OSCE) was performed 2 weeks after the courses with a manikin patient having a cardiac arrest. RESULTS: The median score of all participants was 31/49 (range 21-38). The reliability of the checklist was adequate (Cronbach alpha 0.77). Nurses receiving traditional CPR-D performed better than those receiving the Internet-based course (median score 34 vs. 28, P < 0.05) and the control group (median score 34 vs. 26, P < 0.0001). Nurses receiving Internet-based course performed similarly as the control group (median score 28 vs. 26, ns). CONCLUSIONS: Distance learning cannot substitute for traditional small-group learning.

Education, Distance↗

An electrospray ionization Fourier transform ion cyclotron resonance mass spectrometric study of the gas-phase stabilities and fragmentation of N-alkylammonium resorcarenes.

Five N-alkylated ammonium resorcarene derivatives, differing either in the nitrogen atom or in the lower rim alkyl chain, were studied using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The main purpose was to clarify the fragmentation and the relative stabilities of the protonated molecules by collision-induced dissociation (CID) experiments. The results indicate that fragmentation of the upper rim alkyl amino substituents at the 2-position occurs readily. Variation in the gas-phase stabilities of these molecules was also observed. In addition, the proposed fragmentation pathways are depicted.

Alkylation↗

Patterns of dermal exposure to hazardous substances in European union workplaces.

Workplace dermal exposure assessment is a complex task that aims to understand the dynamic interaction between the skin and the hazardous substances present in the surrounding environment. A European project known as RISKOFDERM gathered dermal exposure data in 85 workplaces (industrial and other types) in five countries in Europe. In order to optimize data collection and to develop a representative picture of dermal exposure, scenarios (tasks made up of a series of activities) were grouped together into dermal exposure operation units (DEOs). The allocation of scenarios to relevant DEOs was achieved on the basis of similarities of exposure routes, tasks and professional judgement. Sampling and quantification procedures were based on the approaches recommended by the OECD protocol. The laboratories involved in the analysis of the samples participated in quality assurance programmes. This exercise resulted in 419 body measurements and 437 measurements on hands expressed in terms of formulation (product) in use. Exposures for a given scenario varied by several orders of magnitude. The extent and patterns of exposure were found to be dependent on various exposure determinants, including inter- and intra-scenario variations. Hands were found to be the most contaminated parts of the body. Exposure patterns for liquid and solid contaminants were different. On the basis of the analysis of the data presented here, the averaged results (median and 95th percentile) for a given DEO unit should not be used as a representative measure of dermal exposure for all scenarios within that DEO without taking the exposure determinants into account. However, the data could be used to develop an exposure matrix (indicative exposure distributions) for different types of scenario and workplace, using determinants of exposure and a Bayesian approach to integrating expert opinion.

European Union↗

Expression of cyclooxygenase-2 in intestinal goblet cells of pre-diabetic NOD mice.

Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, is expressed in constitutive (COX-1) and inducible (COX-2) isoforms. The COX-2 has been proposed to be involved in development of autoimmune type 1 diabetes (T1D). We examined COX-2 expression in the gut-associated lymphoid tissue (GALT), and found COX-2 was strongly expressed in goblet cells of non-obese diabetic (NOD) mice at the apical villi at the age of 2.5 weeks, clearly before the onset of insulitis, while the expression in the control BALB/c mice was weak or absent at all ages (P < 0.001). Lipopolysaccharide (LPS) given intraperitoneally slightly increased COX-2 expression in the goblet cells and epithelium of both NOD and BALB/c mice. High-resolution confocal microscopy showed that the surroundings of the goblet cells contained no COX-2, implying that the enzyme is synthesized by the goblet cells. The COX-2 is secreted from goblet cells into the intestinal lumen along with mucins. The COX-2 concentration in the goblet cell of BALB/c and especially of NOD mice was markedly higher than that in the intraepithelial lymphocytes or lamina propria macrophages. High mucin COX-2 from goblet cells may increase luminal prostaglandin synthesis, alter epithelial permeability, modulate intestinal immune responses and modify functional properties of the lymphocytes in the GALT, which all may be important for the initiation of the autoimmune phenomenon in the NOD mice.

Animals↗

Applicability of homogeneous exposure groups for exposure assessment in the chemical industry.

The purpose of the study was to assess occupational exposure to chemicals, by taking the aspects presented in European standard EN 689 into account, especially with respect to homogeneous exposure groups and their suitability as the basis for exposure assessment. In addition, dermal exposure to chemicals was assessed when appropriate. The industries studied included a plywood factory, a paint factory and a sewage treatment plant of an oil refinery. The workers were classified into homogeneous exposure groups by the persons in charge of occupational health issues in the respective workplaces. The concentrations of the contaminants were measured in workplace air by breathing-zone and stationary sampling, and these approaches were compared. Dermal exposure was measured when applicable. The homogeneity of the grouping was tested with analysis of variance whenever possible. The tasks studied in plywood manufacturing fulfilled the criteria of homogeneous exposure groups for both respiratory and dermal exposure. The group of operators in the sewage treatment plant was highly homogeneous. The complicated organization of the tasks made the use of homogeneous exposure groups (HEG) unsuitable at the paint factory. These findings show that reliable exposure assessment cannot be achieved with a formal standard; instead, comprehensive occupational hygiene evaluation is needed. It should also have a great importance when exposure models are developed.

Chemical Industry↗

Expression of insulin-receptor substrate-1 and -2 in ovaries from women with insulin resistance and from controls.

OBJECTIVE: To evaluate the role of insulin-receptor substrate (IRS)-1 and -2 in ovary dysfunction in women with insulin resistance. DESIGN: Immunoblotting and immunohistochemical analyses of the localization and staining intensity of IRS-1 and IRS-2 in the ovaries of women with the polycystic ovary syndrome (PCOS) and gestational diabetes mellitus. SETTING: Department of Obstetrics and Gynecology, Turku University Central Hospital. PATIENT(S): Sections of ovary were obtained at the time of cesarean section from five volunteers without medical complications and three patients with gestational diabetes mellitus. Paraffin-embedded ovary sections were selected from those on file from the department of pathology; four were from women with a histologic diagnosis of PCOS and seven were from women with endometriosis (controls). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Protein expression of IRS in human ovary samples. RESULT(S): Immunoblotting with specific monoclonal and polyclonal antibodies showed the presence of 165-kDa and 183-kDa proteins that corresponded to the size of IRS-1 and IRS-2, respectively, in normal pregnant ovaries and human cultured follicles. Immunohistochemical staining showed that positive IRS-2 expression in antral follicles was restricted to theca internal cells in ovulatory ovaries but was distributed widely in all compartments of follicles in different stages in polycystic ovaries. Compared with follicles at a similar stage of development in ovulatory ovaries, follicles in polycystic ovaries showed decreased staining for IRS-1 in granulosa cells but increased staining for IRS-2 in theca internal cells. These features of IRS-1 and -2 expression were also noted in preantral and atretic follicles from patients with gestational diabetes mellitus compared with those who had uncomplicated pregnancy. CONCLUSION(S): This study highlights a shift of the follicular insulin signal protein from IRS-1 to IRS-2 in insulin-resistant states and suggests an association between this change and ovarian abnormality in PCOS and gestational diabetes mellitus.

Adult↗

Separation of linoleic acid oxidation products by micellar electrokinetic capillary chromatography and nonaqueous capillary electrophoresis.

In this work the suitability of micellar electrokinetic capillary chromatography (MEKC) and nonaqueous capillary electrophoresis (CE) to the analysis of the primary oxidation products of linoleic acid was studied with uncoated fused-silica capillaries. The primary autoxidation products of linoleic acid are the four hydroperoxide isomers 13-hydroperoxy-cis-9, trans-11-octadecadienoic acid, 13-hydroperoxy-trans-9, trans-11-octadecadienoic acid, 9-hydroperoxy-trans-10,cis-12-octadecadienoic acid, 9-hydroperoxy-trans-10, trans-12-octadecadienoic acid. Addition of a surfactant such as sodium dodecyl sulfate (SDS) or sodium cholate (SC) into the running buffer (20-30 mM 3-(cyclohexylamino)-1-propanesulfonic acid (CAPS) or ammonium acetate, pH 9.5-11) was required to enhance the water solubility of the sample and selectivity of the separation. MEKC proved to be a promising new technique for the separation of the primary oxidation products of lipids giving results comparable to high performance liquid chromatography (HPLC). Partial separation of hydroperoxide isomers was also achieved using nonaqueous CE with methanol-acetonitrile-sodium cholate as running buffer.

Chromatography, Micellar Electrokinetic Capillary↗

Assessment of total exposure to phenol-formaldehyde resin glue in plywood manufacturing.

OBJECTIVE: Respiratory and dermal exposure to phenol-formaldehyde resin-glue components used in plywood manufacturing were assessed. METHODS: Formaldehyde and phenol were monitored in the workplace air. Formaldehyde was measured both in the breathing zones of the workers and at stationary sampling sites. Phenol was used as a marker agent for dermal exposure due to its near-nonvolatility at the temperatures occurring during the present study and to its ready absorption through the skin, causing systemic exposure in addition to local skin rashes. Sampling and analytical methods were developed to measure the dermal exposure to phenol. Sampling was accomplished with whole-body dosimetry using Tyvek coveralls and cotton gloves. In addition, a liquid chromatography method was developed for the analysis of phenol from dermal exposure samples. RESULTS: As expected, formaldehyde was noted to be the major compound causing respiratory exposure. When exposure assessment was done on the basis of air samples collected both at stationary sampling sites and in the breathing zones of the workers the agreement between the results obtained was good. The dermal sampling revealed that the workers were exposed to phenol, but the risk for toxic effects was slight due to the low concentrations of urinary phenol. CONCLUSIONS: We conclude that it is possible to use the stationary sampling method for the assessment of respiratory exposure in a plywood factory instead of the usually more complicated breathing-zone sampling. This study also demonstrates the importance of taking dermal exposure into account, at least due to the ability of the resins to cause skin rashes, in assessment of the exposure to chemicals in plywood manufacturing.

Administration, Cutaneous↗

New world, but not Old World, monkeys carry several genes encoding beta-microseminoprotein.

It was shown by Southern hybridization that cotton-top tamarin and common marmoset, New World monkeys, carry three or more genes encoding beta-microseminoprotein, also known as PSP94. In contrast, the genomes of Old World monkeys, as represented by rhesus macaque and sacred baboon, contain a single gene. Clones containing three different genes encoding beta-microseminoprotein were isolated from a cotton-top tamarin genomic library. They carry two complete genes of four exons and a third gene lacking the first exon. The structure suggests that the three genes are functionally active and give rise to transcripts that are approximately 86% similar in sequence. By sequencing one gene in full, it was shown that the introns carry an excess of interspersed repeats, on average 29% of the introns consist of Alu repeats. A phylogenetic analysis demonstrated that the genes probably arose in New World monkeys after the separation from Old World primates.

Alu Elements↗

Coronary pressure as a determinant of B-type natriuretic peptide gene expression in isolated perfused adult rat heart.

The role of coronary flow in the regulation of ventricular B-type natriuretic peptide (BNP) gene expression was studied in isolated perfused rat heart preparation. The increase of coronary flow from 5 ml/min to 20 ml/min for 2 h resulted in a 132+/-6 mm Hg increase in aortic perfusion pressure. The changes in BNP mRNA and immunoreactive BNP (IR-BNP) levels in response to hemodynamic stress were compared to those of c-fos and adrenomedullin (ADM) gene expression. The increase of coronary flow resulted in 1.5-fold increases in the left ventricular BNP mRNA (P < 0.001) and IR-BNP (P < 0.05) levels in 2-month old rats. There was also a 1.5-fold (P < 0.05) increase in ventricular c-fos mRNA levels, whereas ADM mRNA levels decreased by 74% (P < 0.001) in the left ventricle. In 18-month old rats, the increase in coronary flow decreased left and right ventricular BNP mRNA levels by 18% (P < 0.05) and 39% (P < 0.001), respectively. There were no changes in IR-BNP peptide and c-fos mRNA levels, whereas ADM mRNA levels decreased by 46% (P < 0.001) in the left ventricles. The results show that increased aortic perfusion pressure results in differential expression of cardiac genes including up-regulation of ventricular BNP and c-fos gene expression and down-regulation of ADM gene expression. Furthermore, aging seems to elevate the threshold at which hemodynamic stress of the heart results in a response at BNP gene level.

Adrenomedullin↗

Skin tumor development and keratin expression in different experimental models. Relation to inducing agent and target tissue structure.

The applicability of the experimental skin carcinogenesis model for studies of tumor development was examined by exposing the skin of various mouse strains to different chemical carcinogens and UV radiation regimens, in order to analyze the development and progression of the neoplastic process and the role of differentiation markers such as keratins. In tumor-sensitive hairy NMRI mouse skin, the chemical carcinogen, 7,12-dimethylbenz(a)-anthracene (DMBA) induced an abnormal epidermal cell differentiation and structural irregularities associated with an altered keratin expression, as well as numerous papillomas and squamous cell carcinomas. A suboptimal dose of UVB irradiation increased the number of DMBA-induced benign squamous neoplasms. Low doses of benzo(a)pyrene resulted in mild epidermal alterations, but only in one tumor. High doses of UVB induced a large number of undifferentiated spindle cell tumors with few keratinpositive cells in NMRI mice, similar though fewer tumors in hairy, heavily pigmented C57BL/6 mice, numerous papillomas and squamous cell carcinomas in hairless hr/hr mice but only two papillomas in hairy, moderately pigmented DBA/2 mice while UVA exposure produced only two papillomas in hairless SKH-1 mice. In conclusion, the extent and type of skin tumor development depended upon the induction regimen: physical, chemical, dose and duration, as well as on the skin structure: pigmentation and adnexal development, all of which have to be taken into account when relating experimental results to human conditions.

9,10-Dimethyl-1,2-benzanthracene↗

p53 expression in skin carcinogenesis and its relationship to cell proliferation and tumour growth.

The immunoreactivity of p53 protein was studied in relation to tumour development, histopathological characteristics, cell proliferation, and basement membrane organisation following the induction of skin carcinogenesis in tumour-sensitive and -resistant mouse strains by ultraviolet (UV) irradiation or 7,12-dimethylbenz(a)anthracene (DMBA). In non-neoplastic skin exposed to UV irradiation or DMBA, p53 immunoreactivity was observed in nearly 50% of the basal layer cells. These cells were morphologically and histochemically indistinguishable from the p53-negative cells, occurring similarly in the tumour-producing and the tumour-negative mouse strains and regardless of subsequent tumour formation. In induced epidermal hyperplasia and in benign tumours, p53-positive and proliferating cells constituted 40-50% of all cells in the basal layer, while superficial cells were p53 negative. In dysplastic epidermis, p53-positive cells and proliferating cells were seen in all cell layers. In the case of squamous cell carcinomas, p53-positive proliferating cells in differentiated neoplasms were localised close to the basement membrane and, more frequently, in border areas showing invasion and basement membrane destruction. In horn cysts, centrally located cells were non-proliferating and p53 negative. In moderately differentiated neoplasms, proliferating cells were located closer to the basement membrane, while p53-positive cells were distributed diffusely in the neoplasm. In poorly differentiated neoplasms, p53-positive cells were more common than proliferating cells and were arranged in a diffuse pattern. The results showed that the number and location of p53-positive cells depended upon histology, with a close relationship to tumour type and degree of malignancy, but not on the mode of induction, nor on the animal strain or the relationship to subsequent tumour formation.

9,10-Dimethyl-1,2-benzanthracene↗

Collagenous colitis and Yersinia enterocolitica infection.

Collagenous colitis is a rare clinical and pathological entity characterized by watery diarrhea and deposition of collagen beneath the surface epithelium of the colon. Its etiology is unknown. We present a careful retrospective clinicopathological analysis of six patients with collagenous colitis diagnosed at our hospital during a three-year period. Three of the patients had had a Yersinia enterocolitica infection, detected by stool culture and elevated serum antibody titers, preceding the diagnosis of collagenous colitis. Four patients had duodenal villous atrophy, which in two patients was refractory to a gluten-free diet. We propose that Yersinia enterocolitica infection may be a triggering factor for the development of collagenous colitis in some cases. Duodenal villous atrophy not responding to gluten withdrawal is common in association with collagenous colitis.

Adult↗

Conserved region mutations of the p53 gene are concentrated in distal colorectal cancers.

Distal colorectal cancers, especially those in the rectum, are more aggressive and more commonly recurrent than proximal cancers. We studied the possible relationship between p53-gene mutation type and location of the tumour, since mutations in the conserved areas of the p53 gene have been suggested to result in a poorer outcome of colorectal cancer than mutations outside these areas. Exons 5 to 8 of the p53 gene were studied in specimens from 72 colorectal-cancer patients. Polymerase-chain-reaction-amplified products of tumour DNA were analyzed by automated direct sequencing. Of the mutations detected in distal cancers, 71% were located in conserved regions of the gene, while only 42% of the mutations in proximal cancers were in these areas. In rectal cancers, 81% of the mutations were located in conserved regions. The tumours with mutations in the conserved regions were more often poorly differentiated (23%) than those with other mutations (0%). Our results indicate that mutations in the conserved regions of the p53 gene accumulate in distal but not in proximal tumours. This difference may be related to the more aggressive behaviour and to different aetiological factors associated with distal tumours.

Adult↗

Quinolone antibacterials: a new class of photochemical carcinogens.

Hairless mice were exposed orally to antibiotics of the fluoroquinolone group alone and in combination with irradiation with UVA over an extended period of time to determine the possible skin carcinogenicity in comparison with that with 8-methoxypsoralen, i.e. a known photochemical skin carcinogen. Animals exposed to UVA and fleroxacin, ciprofloxacin, nalidixic acid and ofloxacin exhibited an increase in the number of benign skin tumors when compared with animals exposed to UVA alone. Animals exposed to lomefloxacin and UVA exhibited a specific type of neoplastic progression. In addition to benign papillomas and solar keratoses, a number of cystic squamous cell carcinomas were observed. In the positive control group, which was given 8-methoxypsoralen and UVA, a number of papillomas and superficial squamous cell carcinomas were found. In animals exposed to UVA alone, only a few benign tumors were seen; in unexposed animals, no cutaneous neoplasms were observed. It is concluded that fluoroquinolones warrant further study, because they have potential photocarcinogenic properties.

Animals↗

Oncogenes and growth factors as indicators of carcinogen exposure.

The occurrence of different components of the cell growth regulation pathway as expressed in experimental skin carcinogenesis in haired carcinogen-sensitive NMRI, in haired carcinogen resistant DBA/2 mice and in hairless SKH/1 mice was studied by morphological and immunohistochemical methods. The results were compared with respect to neoplastic response, number of tumors, tumor behaviour and to the inducing agent (UV irradiation or chemical carcinogen), in order to increase our understanding of specific alterations in neoplastic development caused by extraneous agents and to determine their possible usefulness as indicators of carcinogen exposure. The expression of growth factors (transforming growth factor alpha and epidermal growth factor), growth factor receptors (epidermal growth factor receptor/c-erbB-1 and c-erbB-2/neu), cell signalling component c-myc, the nuclear transcription factor Harvey-Ras and the tumor suppressor gene p53, were studied in carcinogen- and UV-induced tumor formation in mouse. The results showed increased oncogene expression as well as growth factor expression in the skin during tumor development appearing early in neoplastic and premalignant conditions and becoming more distinct during neoplastic progression. Efforts to delineate specifically initiated cells prior to the appearance of morphologically detectable alterations including dysplasia, papilloma formation and squamous cell carcinomas, were unsuccessful. Increased staining by antibodies to growth factors and oncogenes were also observed in DBA/2 animals resistant to tumor formation. It is concluded that oncogene expression and growth factor protein deposits are associated with carcinogenic effects, partly explaining the mechanism of action of these agents, but the applicability, as such, for the analysis of potential hazardous agents needs further studies.

Animals↗