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Biomedical subjects

P K Jensen

Publications and source records attributed to P K Jensen.

At least 19 recordsLinked to original sources

Is there an association between bacteriological drinking water quality and childhood diarrhoea in developing countries?

To investigate the association between bacteriological drinking water quality and incidence of diarrhoea, we conducted a 1-year prospective study in the southern Punjab, Pakistan. Diarrhoea episodes, drinking water sources and drinking water quality were monitored weekly among children younger than 5 years in 200 households. We found no association between the incidence of childhood diarrhoea and the number of Escherichia coli in the drinking water sources (the public domain). A possible trend was seen relating the number of E. coli in the household storage containers (the domestic domain) and diarrhoea incidence, but this did not reach statistical significance. Faecal contamination levels in household water containers were generally high even when the source water was of good quality. Under conditions such as this, it is questionable whether public water treatment will have a significant impact on the incidence of endemic childhood diarrhoea.

Child, Preschool↗

Diameter variations of retinal blood vessels during and after treatment with hyperbaric oxygen.

AIMS: To quantify retinal vascular change during and after hyperbaric oxygenation (HO) for 6x5 weekly 90 minute treatments. METHODS: Fundus photographs were taken before, during, and after HO at 2.5 atmospheres absolute pressure (ATA) on days 1, 2, 3, 10, 20, 29, and 30 of treatment on three patients using a specially developed hand held ophthalmoscope with a digital colour camera. Blood vessel diameter was estimated on red free retinal images. The mean of three measurements of arterioles and venoles close to the optic disc was calculated. Consistency and repeatability of the method was verified by estimating the diameter of the vessels by three measurements in each of seven images taken within 70 seconds on the same person. Analysis of variance with Bonferroni correction for multiple comparisons was conducted to ascertain whether significant intergroup differences existed. RESULTS: Breathing 100% oxygen at 2.5 ATA constricts retinal arterioles by 9.6% (standard deviation 0.3%) and venoles by 20.6% (SD 0.3%) of their size in air at ambient pressure. Constriction escalates during treatment. Ten minutes after the HO, arterioles dilate to 94.5% (SD 0.3%) and venoles to 89.0% (SD 0.3%) of their primary size. This pattern is the same for each day of measurement. Heart frequency falls continually during HO. Systolic, diastolic, and mean arterial pressures stay constant. CONCLUSION: Exposure to hyperbaric oxygen causes constriction of the retinal vessels. It is found that this constriction is constant through the series of treatments. This suggests that oxygen or products thereof are responsible for the vascular changes during and after hyperbaric oxygenation probably through autoregulation of the retinal vessels.

Aged↗

Optic nerve oxygen tension: the effects of timolol and dorzolamide.

BACKGROUND/AIMS: The authors have previously reported that carbonic anhydrase inhibitors such as acetazolamide and dorzolamide raise optic nerve oxygen tension (ONPO(2)) in pigs. The purpose of the present study was to investigate whether timolol, which belongs to another group of glaucoma drugs called beta blockers, has a similar effect. In addition, the effect of dorzolamide and timolol in combination was studied. METHODS: Polarographic oxygen electrodes were placed transvitreally over the optic disc in anaesthetised pigs and ONPO(2) was recorded continually. Drugs were administered intravenously either as 100 mg timolol followed by 500 mg dorzolamide (n = 5), 500 mg dorzolamide followed by 100 mg timolol (n = 5), or 100 mg timolol and 500 mg dorzolamide given simultaneously (n = 5). Arterial blood pressure, blood gasses, and heart rate were recorded. RESULTS: ONPO(2) was unaffected by administration of 100 mg timolol as an intravenous injection (n = 5). Administration of 500 mg dorzolamide by itself significantly increased ONPO(2) from 2.96 (SD 0.62) kPa to 3.69 (SD 0.88) kPa (n = 4, p = 0.035). The dorzolamide induced ONPO(2) increase was not significantly different from the ONPO(2) increases were seen when dorzolamide was administered simultaneous with (n = 5) or 35 minutes (n = 5) after 100 mg timolol. CONCLUSION: Systemic administration of timolol does not affect the optic nerve oxygen tension despite its lowering effect on the intraocular pressure. Additionally, timolol does not affect the ONPO(2) increasing effect of dorzolamide.

Adrenergic beta-Antagonists↗

Indomethacin lowers optic nerve oxygen tension and reduces the effect of carbonic anhydrase inhibition and carbon dioxide breathing.

BACKGROUND/AIMS: Prostaglandins are important in blood flow regulation. Carbon dioxide (CO(2)) breathing and carbonic anhydrase inhibition increase the oxygen tension in the retina and optic nerve. To study the mechanism of this effect and the role of cyclo-oxygenase in the regulation of optic nerve oxygen tension (ONPO(2)), the authors investigated how indomethacin affects ONPO(2) and the ONPO(2) increases caused by CO(2) breathing and carbonic anhydrase inhibition in the pig. METHODS: Optic nerve oxygen tension was measured in 11 pigs with a polarographic oxygen electrode. The tip of the electrode was placed 0.5 mm above the optic disc. The effects of indomethacin, CO(2) breathing (3%) before and after indomethacin treatment, and carbonic anhydrase inhibition with or without indomethacin treatment were investigated. RESULTS: Administration of 300 mg indomethacin decreased optic nerve oxygen tension significantly. Carbonic anhydrase inhibition and CO(2) breathing increased ONPO(2) significantly. After indomethacin had been given, the rise in ONPO(2) caused by CO(2) breathing and carbonic anhydrase inhibition was significantly reduced. CONCLUSION: Systemic administration of indomethacin decreases the optic nerve oxygen tension; this is probably the result of decreased blood flow through vasoconstriction of vessels in the optic nerve. Additionally, indomethacin diminishes the ONPO(2) increasing effect of CO(2) breathing and carbonic anhydrase inhibition, thus affecting the reactivity of vessels in the optic nerve.

Animals↗

[The molecular genetic background of hereditary craniosynostoses and chondrodysplasias].

Fibroblast growth factors are structurally related proteins associated with cell growth, differentiation, migration, wound healing, angiogenesis, and oncogenesis. At the cellular level, their function is mediated by transmembrane tyrosinekinase receptors, fibroblast growth factor receptors. Four genes encoding fibroblast growth factor receptors have been identified, and mutations in three of these, FGFR1, FGFR2, and FGFR3, can cause different congenital, autosomal dominant disorders affecting the craniofacial and skeletal development: craniosynostosis and chondrodysplasias. The craniosynostosis syndromes: Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Muenke syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome can be caused by mutation in either FGFR1, FGFR2, or FGFR3. Saethre-Chotzen syndrome can also be caused by mutation in a functionally related gene, ACS. The same mutation can cause different syndromes, and the same syndrome can be caused by mutations in different genes. The chondrodysplasias: achondroplasia, hypochondroplasia, and thanatophoric dysplasia are all caused by mutations in FGFR3.

Bone Diseases, Developmental↗

Basicity of the amino groups of the aminoglycoside amikacin using capillary electrophoresis and coupled CE-MS-MS techniques.

This paper describes the use of capillary electrophoresis (CE), and coupled CE and mass spectrometric techniques, to measure the values of the pKa of the amino groups of the aminoglycoside antibiotic amikacin and of its acetylated derivatives. These values of pKa (8.4, 6.7, 9.7, 8.4) were determined by measuring the electrophoretic mobilities of the molecules as a function of pH; they are within 0.7 unit of certain values reported in the literature (by 13C and 15N NMR spectroscopies) but resolved ambiguities left by these earlier studies. The range of values of pKa of amino groups also indicates the complex dependence of the acidity of a functional group (and thus the extent of ionization at a specified value of pH) on the molecular environment of that group.

Acetylation↗

[Ophthalmoscopy].

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Contraindications↗

Rapid quantitative measurements of proteomes by Fourier transform ion cyclotron resonance mass spectrometry.

The patterns of gene expression, post-translational modifications, protein/biomolecular interactions, and how these may be affected by changes in the environment, cannot be accurately predicted from DNA sequences. Approaches for proteome characterization are generally based upon mass spectrometric analysis of in-gel digested two dimensional polyacrylamide gel electrophoresis (2-D PAGE) separated proteins, allowing relatively rapid protein identification compared to conventional approaches. This technique, however, is constrained by the speed of the 2-D PAGE separations, the sensitivity limits intrinsic to staining necessary for protein visualization, the speed and sensitivity of subsequent mass spectrometric analyses for identification, and the limited ability for accurate quantitative measurements based on differences in spot intensity. We are presently developing alternative approaches for proteomics based upon the combination of fast capillary electrophoresis, or other suitable chromatographic separations, and the high mass accuracy and sensitivity obtainable with unique Fourier transform ion cyclotron resonance (FTICR) mass spectrometers available at our laboratory. Several approaches are presently being pursued; one based upon the analysis of intact proteins and the second upon approaches for global protein digestion and accurate peptide mass analysis. Quantitation of protein/peptide levels are based on using two or more stable-isotope labeled versions of proteomes which are combined to obtain precise quantitation of relative protein abundances. We describe the status of our efforts towards the development of a high-throughput proteomics capability and present initial results for application to several microorganisms and discuss our efforts for extending the developed capability to mammalian proteomes.

Bacterial Proteins↗

Specificity for field enumeration of Escherichia coli in tropical surface waters.

In remote rural areas in developing countries, bacteriological monitoring often depends on the use of commercial field media. This paper evaluates a commercial field medium used for the enumeration of Escherichia coli in different surface waters under primitive field conditions in rural Pakistan. In order to verify the field kit, 117 presumptive E. coli isolates have been tested, finding a specificity of only 40%. By excluding some strains based on colony colours, the calculated specificity could be increased to 65%. Thus, it is suggested that prior to use in a tropical environment, the specificity of any commercial medium used should be tested with representative tropical isolates, in order to increase the specificity.

Colony Count, Microbial↗

Exercise and iris concavity in healthy eyes.

PURPOSE: To study the effect of exercise on the configuration of the anterior chamber angle in healthy persons. METHODS: Both eyes of 22 healthy persons were scanned by Ultrasound Biomicroscopy. Before and after 10 minutes of exercise the anterior chamber angle and the area of the peripheral anterior chamber were measured on the scannings. RESULTS: After exercise the anterior chamber angle/peripheral area increases in all eyes due to changes in the iris configuration. The myopic group shows the largest change. CONCLUSION: Reverse pupillary block (iris concavity) is not pathognomonic in pigmentary glaucoma, it occurs in all normal eyes after exercise, most pronounced in myopics. Consequently, the difference between physiological and pathological reverse pupillary block has to be clarified.

Adult↗

Irrigation water as a source of drinking water: is safe use possible?

BACKGROUND: In arid and semi-arid countries there are often large areas where groundwater is brackish and where people have to obtain water from irrigation canals for all uses, including domestic ones. An alternative to drawing drinking water directly from irrigation canals or village water reservoirs is to use the water that has seeped from the irrigation canals and irrigated fields and that has formed a small layer of fresh water on top of the brackish groundwater. The objective of this study was to assess whether use of irrigation seepage water for drinking results in less diarrhoea than direct use of irrigation water and how irrigation water management would impact on health. METHODS: The study was undertaken in an irrigated area in the southern Punjab, Pakistan. Over a one-year period, drinking water sources used and diarrhoea episodes were recorded each day for all individuals of 200 households in 10 villages. Separate surveys were undertaken to collect information on hygiene behaviour, sanitary facilities, and socio-economic status. RESULTS: Seepage water was of much better quality than surface water, but this did not translate into less diarrhoea. This could only be partially explained by the generally poor quality of water in the in-house storage vessels, reflecting considerable in-house contamination of drinking water. Risk factors for diarrhoea were absence of a water connection and water storage facility, lack of a toilet, low standard of hygiene, and low socio-economic status. The association between water quality and diarrhoea varied by the level of water availability and the presence or absence of a toilet. Among people having a high quantity of water available and a toilet, the incidence rate of diarrhoea was higher when surface water was used for drinking than when seepage water was used (relative risk 1.68; 95% CI 1.31-2.15). For people with less water available the direction of the association between water quality and diarrhoea was different (relative risk 0.80; 95% CI 0.69-0.93). This indicates that good quality drinking water provides additional health benefits only when sufficient quantities of water and a toilet are available. In a multivariate analysis no association was found between water quality and diarrhoea but there was a significant effect of water quantity on diarrhoea which was to a large extent mediated through sanitation and hygiene behaviour. CONCLUSIONS: Increasing the availability of water in the house by having a household connection and a storage facility is the most important factor associated with reduced diarrhoea in this area. Safe use of canal irrigation water seems possible if households can pump seepage water to a large storage tank in their house and have a continuous water supply for sanitation and hygiene. Irrigation water management clearly has an impact on health and bridging the gap between the irrigation and drinking water supply sectors could provide important health benefits by taking into account the domestic water availability when managing irrigation water.

Adolescent↗

Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene.

The Mohr-Tranebjaerg syndrome (MIM 304700) and the Jensen syndrome (MIM 311150) were previously reported as separate X-linked recessive deafness syndromes associated with progressive visual deterioration, dystonia, dementia, and psychiatric abnormalities. In the most extensively studied Norwegian family, the Mohr-Tranebjaerg syndrome was reported to be caused by a one-basepair deletion (151delT) in the deafness/dystonia peptide (DDP) gene at Xq22. This gene has been renamed TIMM8a. We identified a stop mutation (E24X) in the TIMM8a gene segregating with the disease in the original Danish family with the Jensen syndrome, which confirms that the two disorders are allelic conditions. We also report abnormal VEP examinations and neuropathological abnormalities in affected males from the two unrelated families with different mutations. The findings included neuronal cell loss in the optic nerve, retina, striate cortex, basal ganglia, and dorsal roots of the spinal cord. The demonstration of mitochondrial abnormalities in skeletal muscle biopsies in some patients is compatible with the suggestion from recent research that the TIMM8a protein is the human counterpart of an intermembrane mitochondrial transport protein, Tim8p, recently characterized in yeast. The clinical and neuropathological abnormalities associated with mutations in the TIMM8a gene support that this X-linked deafness-dystonia-optic neuropathy syndrome is an example of progressive neurodegeneration due to mutations in a nuclear gene necessary for some, yet unknown mitochondrial transport function. We recommend sequencing the TIMM8a gene, thorough ophthalmological examination, and measuring visual evoked potentials in clinically suspected male patients with either progressive hearing impairment, dystonia, or visual disability in order to establish an early diagnosis and provide appropriate genetic counselling.

Adolescent↗

Identification of human candidate genes for male infertility by digital differential display.

Evidence for the importance of genetic factors in male fertility is accumulating. In the literature and the Mendelian Cytogenetics Network database, 265 cases of infertile males with balanced reciprocal translocations have been described. The candidacy for infertility of 14 testis-expressed transcripts (TETs) were examined by comparing their chromosomal mapping position to the position of balanced reciprocal translocation breakpoints found in the 265 infertile males. The 14 TETs were selected by using digital differential display (electronic subtraction) to search for apparently testis-specific transcripts in the TIGR database. The testis specificity of the 14 TETs was further examined by reverse transcription-polymerase chain reaction (RT-PCR) on adult and fetal tissues showing that four TETs (TET1 to TET4) were testis-expressed only, six TETs (TET5 to TET10) appeared to be differentially expressed and the remaining four TETs (TET11 to TET14) were ubiquitously expressed. Interestingly, the two tesis expressed-only transcripts, TET1 and TET2, mapped to chromosomal regions where seven and six translocation breakpoints have been reported in infertile males respectively. Furthermore, one ubiquitously, but predominantly testis-expressed, transcript, TET11, mapped to 1p32-33, where 13 translocation breakpoints have been found in infertile males. Interestingly, the mouse mutation, skeletal fusions with sterility, sks, maps to the syntenic region in the mouse genome. Another transcript, TET7, was the human homologue of rat Tpx-1, which functions in the specific interaction of spermatogenic cells with Sertoli cells. TPX-1 maps to 6p21 where three cases of chromosomal breakpoints in infertile males have been reported. Finally, TET8 was a novel transcript which in the fetal stage is testis-specific, but in the adult is expressed in multiple tissues, including testis. We named this novel transcript fetal and adult testis-expressed transcript (FATE).

Chromosome Mapping↗

[Keratin diseases].

The rapid development in human genome research has resulted in a tremendous increase in our understanding of the molecular basis of many genetic skin diseases. One outstanding example of this is diseases caused by mutations in keratin genes, which comprise several disorders of the epidermis, as for example the different types of epidermolysis bullosa simplex. In this respect, the most important questions have been to 1. Define the molecular defect. 2. Unravel the pathophysiological mechanisms that lead to the characteristic phenotype and 3. Design of new therapeutic strategies. Molecular research has contributed significantly to the first two issues whereas a therapeutic break-through has yet to appear.

Epidermolysis Bullosa Simplex↗

[Epidermolysis bullosa simplex: genotype-phenotype correlation in Danish patients].

Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant inherited skin disorders caused by mutations in the keratin genes K5 or K14. We examined five Danish families with EBS-Weber-Cockayne (WC) or EBS-Koebner (K) and two sporadic cases of EBS-Dowling-Meara (DM) in order to investigate the mutational spectrum and evaluate the genotype-phenotype correlation in Danish patients. Three new K14 mutations, one new and one previously described K5 mutation were identified by DNA sequence analysis. The positions of the EBS-DM mutations were consistent with previous studies, whereas the EBS-WC and EBS-K mutations were found in regions of the keratin genes not typically associated with this type of EBS mutations. In conclusion, we found a strict genotype-phenotype correlation. Furthermore, we found that the position of the mutation in the keratin gene is not the only determinant for severity of the disease; the nature of the amino acid substitution should also be considered when predicting the severity of the EBS disorder.

DNA Mutational Analysis↗

Mass spectrometric detection for capillary isoelectric focusing separations of complex protein mixtures.

Capillary isoelectric focusing (CIEF) can provide high-resolution separations of complex protein mixtures, but until recently it has primarily been used with conventional UV detection. This technique would be greatly enhanced by much more information-rich detection methods that can aid in protein characterization. We describe progress in the development of the combination of CIEF with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry and its application to proteome characterization. Studies have revealed 400-1000 putative proteins in the mass range of 2-100 kDa from total injections of approximately 300 ng protein in single CIEF-FTICR analyses of cell lysates for both Escherichia coli (E. coli) and Deinococcus radiodurans (D. radiodurans). We also demonstrate the use of isotope labeling of the cell growth media to improve mass measurement accuracy and provide a means for quantitative proteome-wide measurements of protein expression. The ability to make such comprehensive and precise measurements of differences in protein expression in response to cellular perturbations should provide new insights into complex cellular processes.

Bacterial Proteins↗