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Peter Jeppesen

Publications and source records attributed to Peter Jeppesen.

10 recordsLinked to original sources

The age-dependent decrease in the myogenic response of retinal arterioles as studied with the Retinal Vessel Analyzer.

PURPOSE: To study the age-dependent change in myogenic response of retinal arterioles. METHODS: Fifty-one healthy volunteers with at least ten persons in each of the five age decades (I-V) between 20 and 69 years were subjected to diameter measurement of retinal arterioles using the Retinal Vessel Analyzer (RVA) during rest and during an increase in the systemic blood pressure when lifting hand weights. The transmural pressure in the retinal arterioles during the procedures was estimated from the blood pressure and the intraocular pressure and was compared to the accompanying diameter response. RESULTS: The retinal arteriolar diameter showed a significant decrease as a function of increasing weight for the two younger age groups below the age of 40 years (P=0.007, group I, and P=0.049, group II), compatible with perfect autoregulation, whereas no such change was observed in persons above this age (P=0.41, 0.053, 0.29 for groups III-V, respectively). CONCLUSION: Studies on autoregulation in retinal disease should consider the normal age-related decrease in diameter response of retinal arterioles when the blood pressure is changed.

Adult↗

Heterochromatin and tri-methylated lysine 20 of histone H4 in animals.

Tri-methylated lysine 20 on histone H4 (Me(3)K20H4) is a marker of constitutive heterochromatin in murine interphase and metaphase cells. Heterochromatin marked by Me(3)K20H4 replicates late during S phase of the cell cycle. Serum starvation increases the number of cells that exhibit high levels of Me(3)K20H4 at constitutive heterochromatin. Me(3)K20H4 is also present at the centromeric heterochromatin of most meiotic chromosomes during spermatogenesis and at the pseudoautosomal region, as well as at some telomeres. It is not present on the XY-body. During murine embryogenesis the maternal pronucleus contains Me(3)K20H4; Me(3)K20H4 is absent from the paternal pronucleus. On Drosophila polytene chromosomes Me(3)K20H4 is present in a 'punctate pattern' at many chromosomal bands, including the chromocenter. In coccids it is present on the facultatively heterochromatinised paternal chromosome set. We also present evidence that Me(3)K20H4 is dependent upon H3-specific Suv(3)9 histone methyltransferase activity, suggesting that there may be 'epigenetic cross-talk' between histones H3 and H4.

Animals↗

The occurrence and causes of registered blindness in diabetes patients in Arhus County, Denmark.

PURPOSE: To report the occurrence of registered blindness among diabetes patients in Arhus County, Denmark during 1993-2002. METHODS: Data were obtained from a database of 7527 diabetes patients, which included all patients in the county who had been treated for or had experienced visual loss due to diabetic retinopathy since 1992. Of these, 1949 had type 1 diabetes and represented 90% of the type 1 diabetes patient population in the county, and 5459 had type 2 diabetes and represented 40% of the type 2 diabetes patient population in the county. RESULTS: The point prevalence of legal blindness was 0.6% for type 1 and 1.5% for type 2 diabetes patients at January 1st, 2003. In type 1 diabetes patients, the major cause of blindness was proliferative diabetic retinopathy (PDR) (66.2% of all blind eyes); in type 2 diabetes patients the major causes were age-related macular degeneration (21.9%), PDR (18.0%) and diabetic maculopathy (DMac) (18.5%). During 1993-2002 there was a significant decrease in the number of blind eyes secondary to PDR (p = 0.008) in type 1 diabetes patients, and a significant increase in the number of blind eyes secondary to DMac (p = 0.005) in type 2 diabetes patients. CONCLUSION: The major challenge in reducing diabetes-related blindness is related to the detection and treatment of an increased incidence of diabetic maculopathy in type 2 diabetes patients.

Adult↗

Characterization of vasomotion in porcine retinal arterioles.

PURPOSE: To characterize vasomotion in porcine retinal arterioles in vitro using isobaric (pressure myograph) and isometric (wire myograph) methods. METHODS: Pressure myograph: 208 small porcine retinal arterioles (outer diameter 68 +/- 4 microm) were studied under isobaric conditions in a double-barrelled pipette system. Diameter changes of the arterioles were registered by video recordings. Wire myograph: 60 large porcine retinal arterioles (inner diameter 147 +/- 1.6 microm) were studied under isometric conditions in a small vessel myograph for force measurements. RESULTS: The rates of success in initiating vasomotion were 7.2% using the pressure myograph and 43% using the wire myograph (p < 0.001). The small vessels studied under isobaric conditions oscillated with a frequency of 0.014 Hz and the episodes lasted 6.0 +/- 1.0 min, whereas the large vessels under isometric conditions oscillated with a significantly faster frequency of 0.043 Hz and lasted 32.1 +/- 4.9 min (p = 0.026). CONCLUSION: Retinal vasomotion can be studied in vitro using both pressure myograph and wire myograph techniques. The wire myograph is superior to the pressure myograph in initiating and maintaining vasomotion in vitro.

Animals↗

Myogenic response in isolated porcine retinal arterioles.

PURPOSE: To study the myogenic response in large and small porcine retinal arterioles and the effects of blockade of L-type voltage gated calcium channels on the myogenic response. METHODS: Eleven large (outer diameter 137.7 +/- 4.5 micro m) and fourteen small (77.3 +/- 3.7 micro m) isolated porcine retinal arterioles were studied for myogenic response while mounted between two double-barrelled pipette systems. The intraluminal pressure was varied from 0 to 140 cm H( 2)O (0-103 mmHg) and the diameter changes of the arterioles were registered. The pressure-diameter relation was determined for arterioles in calcium-containing and calcium free solutions and during inhibition of the L-type voltage gated calcium channels with nifedipine. RESULTS: Both large and small retinal arterioles showed a decrease in diameter as the intraluminal pressure was increased, but no significant difference was found between large and small arterioles (p = 0.39). Blockade of voltage gated calcium channels significantly abolished the myogenic response (p = 0.010 and p = 0.005, large and small arterioles respectively). CONCLUSIONS: The results indicate that myogenic responses are present throughout the retinal arteriolar system and that L-type voltage gated calcium channels are involved in transforming the stretch of retinal vascular smooth muscle cells induced by an increase in intraluminal pressure into a contraction.

Animals↗

Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals.

We show that methylated lysine 9 of histone H3 (Me9H3) is a marker of heterochromatin in divergent animal species. It localises to both constitutive and facultative heterochromatin and replicates late in S-phase of the cell cycle. Significantly, Me9H3 is enriched in the inactive mammalian X chromosome (Xi) in female cells, as well as in the XY body during meiosis in the male, and forms a G-band pattern along the arms of the autosomes. Me9H3 is a constituent of imprinted chromosomes that are repressed. The paternal and maternal pronuclei in one-cell mouse embryos show a striking non-equivalence in Me9H3: the paternal pronucleus contains no immunocytologically detectable Me9H3. The levels of Me9H3 on the parental chromosomes only become equivalent after the two-cell stage. Finally, we provide evidence that Me9H3 is neither necessary nor sufficient for localisation of heterochromatin protein 1 (HP1) to chromosomal DNA.

Animals↗

Allele-specific underacetylation of histone H4 downstream from promoters is associated with X-inactivation in human cells.

We have used a novel approach to investigate the histone H4 acetylation status at X-inactivated genes compared with their active counterparts. Immunoprecipitation with a sheep antibody that preferentially binds multiply-acetylated H4 isoforms was used to select hyperacetylated chromatin from a human female lymphoblastoid cell line exhibiting non-random X-inactivation as a result of an X/autosome translocation. The distribution of active and inactive gene sequences between the immunoprecipitated and bulk chromatin was compared at four X-linked loci containing intragenic polymorphic microsatellite repeats to allow identification of individual alleles by polymerase chain reaction. We find that DNA sequences corresponding to transcriptionally silent alleles are consistently under-represented in the hyperacetylated fraction. As the microsatellite repeat sequences used to identify alleles range in distance from 6.5 kb to 25 kb downstream of promoters, we conclude that differential H4 acetylation of active and silent chromatin is not confined to regions involved in the initiation of transcription, contrary to previous reports.

Acetylation↗

Adenosine relaxation in small retinal arterioles requires functional Na-K pumps and K(ATP) channels.

PURPOSE: To study the effect of Na-K pump and K(ATP) channel inhibition on the diameter and the adenosine-induced vasodilation of small retinal arterioles. METHODS: Thirty isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barrelled pipette system placed in an organ bath, and diameter changes were studied under isobaric no-flow conditions. After an equilibration period, the arterioles were incubated with the Na-K pump inhibitors ouabain and low K(+) medium or the K(ATP) channel inhibitor glibenclamide, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted and the adenosine concentration response curve was measured with and without the presence of inhibitors. RESULTS: Inhibition of the Na-K pump elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.047), whereas no change in the spontaneous diameter was induced by inhibition of the K(ATP) channels (P = 0.754). Inhibition of the Na-K pump with ouabain or with low K(+) medium, as well as inhibition of the K(ATP) channels with glibenclamide, both diminished the adenosine induced vasodilation (P = 0.003, P = 0.01, and P = 0.003, respectively). CONCLUSION: The adenosine-induced vasodilation of small retinal arterioles involves the K(ATP) channels and the Na-K pump. Changes in the metabolism of adenosine as well as the activity of the K(ATP) channels or the Na-K pump can be expected to influence the retinal blood flow.

Adenosine↗

Bradykinin relaxation in small porcine retinal arterioles.

PURPOSE: To study changes in the spontaneous diameter of small retinal arterioles and bradykinin (BK)-induced vasodilation during inhibition of the synthesis of nitric oxide (NO), prostaglandins (PGs), and cytochrome P450 2C8/9-dependent endothelial-derived hyperpolarizing factor (EDHF). METHODS: Forty-eight isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barreled pipette system placed in an organ bath, and diameter changes were studied under isobaric conditions. After an equilibration period, the arterioles were incubated with inhibitors of the synthesis of NO, PGs, or cytochrome P450 2C8/9-dependent EDHF, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted, and the diameter was assessed after addition of BK in cumulative concentrations. RESULTS: Inhibition of NOS elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.028), whereas no change in the spontaneous diameter was induced by inhibition of PG or cytochrome P450 2C8/9 dependent EDHF synthesis (P = 0.35 and P = 0.75, respectively). The vasodilating effect of BK was decreased by inhibition of NO (P = 0.002) but not by inhibition of prostaglandin or cytochrome P450 2C8/9-dependent EDHF synthesis (P = 0.82 and P = 0.94, respectively). CONCLUSIONS: The results suggest the presence of a spontaneous release of NO, which keeps the retinal microcirculation dilated under normal conditions. The finding of BK-induced relaxation being dependent on the NO synthase (NOS), but not on PGs or cytochrome P450 2C8/9-dependent EDHF may be of importance for understanding the microcirculatory effects of pharmacologic compounds affecting the BK metabolism, such as angiotensin-converting enzyme (ACE) inhibitors.

Animals↗