Mandatory or elective?
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Decision Making↗
Biomedical subjects
J M Jensen
Publications and source records attributed to J M Jensen.
Association of coronary heart disease with age-adjusted aortocoronary calcification in patients with familial hypercholesterolaemia.
OBJECTIVES: Existing algorithms of risk of coronary heart disease (CHD) do not pertain to patients with familial hypercholesterolaemia (FH), whose arteries have been exposed to hypercholesterolaemia since birth. We studied a cohort of FH patients to compare four diagnostic models of CHD: traditional risk factors of CHD (age, sex, cholesterol, hypertension, smoking and body mass index), cholesterol year score, and aortic as well as coronary calcium measured by spiral computed tomography (CT). SUBJECTS: We invited 88 individuals with molecularly defined FH of whom 80 (91%) decided to participate. RESULTS: Analysis of receiver operating characteristic curves showed that the age-adjusted coronary calcium score was more strongly associated with clinical manifestations of CHD than were traditional risk factors (P < 0.002), cholesterol year score (P << 0.0001), and the age-adjusted aortic calcium score (P < 0.0004). CONCLUSIONS: Age-adjusted coronary calcium score shows promise as an indicator of CHD in FH patients.
Adult↗
Impaired cutaneous permeability barrier function, skin hydration, and sphingomyelinase activity in keratin 10 deficient mice.
Point mutations in the suprabasal cytokeratins 1 (K1) or 10 (K10) in humans have been shown to be the cause of the congenital ichthyosis epidermolytic hyperkeratosis. Recently, a K10 deficient mouse model was established serving as a model for epidermolytic hyperkeratosis. Homozygotes suffered from severe skin fragility and died shortly after birth. Heterozygotes developed hyperkeratosis with age. To see whether phenotypic abnormalities in the mouse model were associated with changes in skin barrier function and skin water content we studied basal transepidermal water loss and capacity for barrier repair after experimental barrier disruption as well as stratum corneum hydration. Also, we determined the activities of acid and neutral sphingomyelinase key enzymes of the tumor necrosis factor and interleukin-1 signal transduction pathways generating the ceramides most important for epidermal permeability barrier homeostasis. Neonatal homozygotes showed an 8-fold increase in basal transepidermal water loss compared with wild type controls. Adult heterozygotes exhibited delayed barrier repair after experimental barrier disruption. Stratum corneum hydration was reduced in homozygous and heterozygous mice. Acid sphingomyelinase activity, which is localized in the epidermal lamellar bodies and generates ceramides for extracellular lipid lamellae in the stratum corneum permeability barrier, was reduced in homozygous as well as heterozygous animals. Neutral sphingomyelinase activity, which has a different location and generates ceramides involved in cell signaling, was increased. The reduction in acid sphingomyelinase activity may explain the recently described decreased ratio of ceramides to total lipids in K10 deficient mice. In summary, our results demonstrate the crucial role of the keratin filament for permeability barrier function and stratum corneum hydration.
Animals↗
Evaluation of anthelmintic activity in captive wild ruminants by fecal egg reduction tests and a larval development assay.
The effectiveness of anthelmintics was evaluated in four herds of captive ruminants, wapiti (Cervus elaphus), Armenian red sheep (Ovis orientalis), giraffe (Giraffa camelopardalis), and pronghorn (Antilocapra americana), by the use of fecal egg reduction tests (FERTs) and a commercial larval development assay (LDA) designed to evaluate susceptibility or resistance of nematodes to anthelmintics. Haemonchus sp. was the predominant nematode in the red sheep, giraffe, and pronghorn herds, whereas Ostertagia sp. and Trichostrongylus sp. were predominant in the wapiti. The LDA data indicated susceptibility by the worms to benzimidazoles except in the red sheep flock, which showed a high level of resistance. High levels of resistance to levamisole were seen in the worm populations from the wapiti and red sheep, moderate resistance in the pronghorn herd, and susceptibility in the giraffe herd. Worms were susceptible in all four herds to a combination of benzimidazole/levamisole. There was suspected avermectin resistance by Trichostrongylus sp. in the wapiti herd and by Haemonchus sp. in the giraffe. The FERTs agreed with the LDA in showing the Haemonchus in the giraffe was susceptible to fenbendazole and had suspected resistance to ivermectin, whereas Haemonchus in the red sheep and pronghorn were susceptible to ivermectin. There was correlation between the tests evaluating anthelmintics. The LDA is useful as a screening test in the selection of an anthelmintic for use in grazing ruminants, but the effectiveness of a drug in a host species may depend as much on the dose used, and the method of administration, as it does on the parasite's sensitivity to the anthelmintic.
Animals↗
[The biologically equivalent dose (BED): how solid is the calculation of this factor? A consideration of margins of error of biologically equivalent dose].
To predict the effect on tumours in radiotherapy, especially relating to irreversible effects, but also to realize the retrospective assessment the so called L-Q-model is relied on at present. Internal specific organ parameters, such as alpha, beta, gamma, Tp, Tk, and rho, as well as external parameters, so as D, d, n, V, and Vref, were used for determination of the biologically equivalent dose BED. While the external parameters are determinable with small deviations, the internal parameters depend on biological varieties and dispersions: in some cases the lowest value is assumed to be delta = +/- 25%. This margin of error goes on to the biologically equivalent dose by means of the principle of superposition of errors. In some selected cases (lung, kidney, skin, rectum) these margins of error were calculated exemplarily. The input errors especially of the internal parameters cause a mean error delta on the biologically equivalent dose and a dispersion of the single fraction dose d dependent on the organ taking into consideration, of approximately 8-30%. Hence it follows only a very critical and cautious application of those L-Q-algorithms in expert proceedings, and in radiotherapy more experienced based decisions are recommended, instead of acting only upon simple two-dimensional mechanistic ideas.
Algorithms↗
Impaired neutral sphingomyelinase activation and cutaneous barrier repair in FAN-deficient mice.
The WD-40 repeat protein FAN binds to a distinct domain of the p55 receptor for tumor necrosis factor (TNF) and signals the activation of neutral sphingomyelinase (N-SMase). To analyze the physiological role of FAN in vivo, we generated FAN-deficient mice by targeted gene disruption. Mice lacking a functional FAN protein do not show any overt phenotypic abnormalities; in particular, the architecture and cellular composition of lymphoid organs appeared to be unaltered. An essential role of FAN in the TNF-induced activation of N-SMase was demonstrated using thymocytes from FAN knockout mice. Activation of extracellular signal-regulated kinases in response to TNF treatment, however, was not impaired by the absence of the FAN protein. FAN-deficient mice show delayed kinetics of recovery after cutaneous barrier disruption suggesting a physiological role of FAN in epidermal barrier repair. Although FAN exhibits striking structural homologies with the CHS/Beige proteins, FAN-deficient mice did not reproduce the phenotype of beige mice.
Amino Acid Sequence↗
Linking genotype to aorto-coronary atherosclerosis: a model using familial hypercholesterolemia and aorto-coronary calcification.
Most studies of the pathogenesis of coronary heart disease occur between gene variants and biochemical or physiological variables known to be atherogenic. In many situations, however, the gene products are not necessarily known. We studied 17 families (n = 122) with mutations in the low density lipoprotein (LDL) receptor gene as a model in which to test formally for linkage directly between an atherogenic genotype and ischemic heart disease (IHD) or aorto-coronary calcified atherosclerosis. In each family one of three different mutations was found: the Trp66-Gly mutation, the Trp23-Stop mutation, or a ten kilobase deletion removing exons 3-6 of the LDL receptor gene. Genomic DNA was used to determine these mutations by either enzymatic cleavage assays or Southern blotting. Aorto-coronary calcification was significantly associated with age and plasma cholesterol. Sex, hypertension, BMI and smoking were not associated with aorto-coronary calcification. Nonparametric analysis indicated significant linkage of the LDL receptor gene locus to aortic (p < 0.00005) and to aorto-coronary calcified atherosclerosis (p < 0.00001). Assuming a dominant mode of inheritance, significant linkage was detected for aortic (LOD = 3.89) and aorto-coronary calcified atherosclerosis (LOD = 4.10). We suggest that the atherogenicity of variations in other genes could be assessed by a similar approach.
Adult↗
Inpatient alcohol treatment in a private healthcare setting: which patients benefit and at what cost?
This study investigated whether selected patients have better outcomes with inpatient than outpatient treatment. There were 93 inpatients and 80 outpatients with alcohol dependence who were evaluated at treatment entry to a private healthcare setting. Patients with multiple drinking-related consequences were less likely to return to significant drinking in the first 3 months after treatment ended if they had attended inpatient compared to outpatient treatment. Thus, inpatient appeared to have some advantage over outpatient treatment in the early recovery period for patients with multiple drinking-related consequences. The gap between inpatient and outpatient costs was also reduced when computed as a cost-effectiveness ratio, although treatment costs continued to remain proportionally higher with inpatient than outpatient treatment.
Adult↗
Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier.
Epidermal TNF expression increases in response to cutaneous permeability barrier disruption and wound healing. TNF signaling is mediated by acid and neutral sphingomyelinases (A- and N-SMase), which generate ceramide, an important regulator of proliferation, differentiation, and apoptosis. In the epidermis, ceramide is known to be an integral part of the extracellular stratum corneum (SC) lipid bilayers that constitute the permeability barrier of the skin. We show here that topical application of TNF after experimental injury to the SC of hairless mice (hr(-/-)) enhances barrier repair. In TNF receptor p55-deficient (TNF-R55-deficient) mice (hr(+/+)), cutaneous barrier repair was delayed compared with wild-type (hr(+/+)) or TNF-R75-deficient (hr(+/+)) animals. After barrier disruption in hairless (hr(-/-)) and wild-type (hr(+/+)), but not in TNF-R55-deficient (hr(+/+)) mice, the enzymatic activities of both A-SMase and N-SMase were significantly enhanced. Stimulation of SMase activities was accompanied by an increase in C(24)-ceramide levels. Most A-SMase activity in hairless mice (hr(-/-)) was found in the outer epidermal cell layers and colocalized in the lamellar bodies with A-SMase and sphingomyelin. Reduction of epidermal A-SMase activity by the inhibitor imipramine resulted in delayed permeability barrier repair after SC injury. Together, these results suggest that TNF-R55 signaling pathways contribute to cutaneous permeability barrier repair through SMase-mediated generation of ceramide.
Animals↗
[A linear quadratic offset filter for contrast improvement in digital reconstruction of radiography imaging for virtual simulation in radiotherapy].
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Computer Simulation↗
Current ratite therapy.
This article describes the use of drugs and therapeutic techniques in the treatment of ratite diseases. Effective routes of administration are documented. Appropriate selection and dose regimens are provided for bacterial and parasitic conditions. This article includes empirical formularies for antibiotics and anthelmintics. Metabolic drug dosage and nutrient scaling for ratites are outlined.
Animal Feed↗
Expression of epidermal keratins and the cornified envelope protein involucrin is influenced by permeability barrier disruption.
In previous studies we have shown that experimental permeability barrier disruption leads to an increase in epidermal lipid and DNA synthesis. Here we investigate whether barrier disruption also influences keratins and cornified envelope proteins as major structural keratinocyte proteins. Cutaneous barrier disruption was achieved in hairless mouse skin by treatments with acetone +/- occlusion, sodium dodecyl sulfate, or tape-stripping. As a chronic model for barrier disruption, we used essential fatty acid deficient mice. Epidermal keratins were determined by one- and two-dimensional gel electrophoresis, immunoblots, and anti-keratin antibodies in biopsy samples. In addition, the expression of the cornified envelope proteins loricrin and involucrin after barrier disruption was determined by specific antibodies in human skin. Acute as well as chronic barrier disruption resulted in the induction of the expression of keratins K6, K16, and K17. Occlusion after acute disruption led to a slight reduction of keratin K6 and K16 expression. Expression of basal keratins K5 and K14 was reduced after both methods of barrier disruption. Suprabasal keratin K10 expression was increased after acute barrier disruption and K1 as well as K10 expression was increased after chronic barrier disruption. Loricrin expression in mouse and in human skin was unchanged after barrier disruption. In contrast, involucrin expression, which was restricted to the granular and upper spinous layers in normal human skin, showed an extension to the lower spinous layers 24 h after acetone treatment. In summary, our results document that acute or chronic barrier disruption leads to expression of keratins K6, K16, and K17 and to a premature expression of involucrin. We suggest that the coordinated regulation of lipid, DNA, keratin, and involucrin synthesis is critical for epidermal permeability barrier function.
Animals↗
Hepatotoxicity and secondary photosensitization in a red kangaroo (Megaleia rufus) due to ingestion of Lantana camara.
Three red kangaroos (Megaleira rufus), an adult male, an adult female, and a yearling, were exposed in bedding and food to coastal bermuda hay that contained the toxic plant Lantana camara. The adult male exhibited signs of anorexia, depression, lethargy, and jaundice. The adult female was presented dead. After 1 wk, following exposure to sunlight, the adult male and a yearling joey developed exudative dermatitis of the ear margins, eyelids, muzzle, and scrotum and opacity of the corneas. The adult male had a leucocytosis, anemia, bilirubinemia, bilirubinuria, hyperproteinemia, and elevated alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, and bile acid serum levels. Postmortem examination of the adult male revealed jaundice, and the liver was swollen, mottled, and pale yellow to reddish yellow. The gall bladder was markedly distended. Histopathologically, there was hepatocellular enlargement with vesiculation of the nuclei and sporadic feathery degeneration of the cytoplasm. The yearling joey survived and was treated symptomatically with i.v. fluids and antibiotics. The history, clinical signs, diagnostic findings, necropsy findings, and exposure to the toxic plant Lantana camara support the diagnosis of secondary photosensitization and hepatoxicity.
Alanine Transaminase↗
Disseminated coccidioidomycosis in a mandrill baboon (Mandrillus sphinx): a case report.
A case of disseminated coccidioidomycosis caused by a dimorphic fungus Coccidioides immitis in a mandrill baboon (Mandrillus sphinx) was diagnosed following radiography, ultrasound-guided aspiration of thoracic lesions, and aspiration cytology of skeletal lesions of the left sixth rib. The diagnosis was confirmed by fungal culture and serum quantitative immunodiffusion for antibodies against C. immitis.
Animals↗
[A new parameter for the determination of dose distribution in radiotherapy].
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Dose Fractionation, Radiation↗
[A new method of 3-dimensional imaging of dose distribution in radiotherapy].
Beside the documentation it is the object of the graphical presentation of dose distribution in radiotherapy to clarify for better judgement. A three-dimensional graphical presentation could rise the understanding. Auto-stereographical presentation of isodoses opens the practicability for a three-dimensional view without the use of additional auxiliarities, such as stereoscope, or spectacles. This is shown by some isodose distribution charts (fixed field-, box-, multiple field- and rotation-technique, AL-treatment).
Dose Fractionation, Radiation↗
Effects of xerosis and ageing on epidermal proliferation and differentiation.
The hallmarks of dry skin (xerosis) are scaliness and loss of elasticity. Decreased hydration and a disturbed lipid content of the stratum corneum are also well-known features. The frequency of dry skin increases with ageing. The aim of this study was to examine if these known features of dry skin are related to changes in epidermal proliferation and differentiation. In addition, age-related changes in normal and in dry skin were examined: 62 volunteers were divided by clinical grading and biophysical measurements into groups with young/normal, young/dry, aged/normal and aged/dry skin. Biopsy samples from the lower legs (most severe dryness) were examined by two-dimensional gel electrophoresis and by immunohistochemistry for epidermal proliferation, epidermal keratins and cornified envelope proteins. There was a slight increase in proliferation in both groups with dry skin compared with normal skin of the corresponding age. In aged/normal compared with young/normal skin there was a significant decrease in proliferation. However, epidermal proliferation was the same in aged/dry skin as in young/normal skin. For epidermal differentiation, an age-independent decrease of keratins K1 and K10 and an associated increase in the basal keratins K5 and K14 was detected in dry skin. There was also an age-independent premature expression of the cornified envelope protein involucrin. In contrast, loricrin expression was not influenced by dry skin conditions. In summary, epidermal proliferation was significantly decreased in aged/normal compared with young/normal skin. Dry skin showed significant changes in the epidermal expression of basal and differentiation-related keratins, and a premature expression of involucrin irrespective of age.
Adult↗
Topical vitamin D3 derivatives impair the epidermal permeability barrier in normal mouse skin.
BACKGROUND: Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 are potent drugs for the treatment of psoriasis. It has recently been published that these compounds induce epidermal hyperproliferation in hairless mouse skin. OBJECTIVE: The aim of our study was to examine the effect of vitamin D3 derivatives on epidermal growth, keratinization and permeability barrier function in vivo. METHODS: Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 in isopropanol or in an ointment formula were applied to normal hairless mouse skin. Transepidermal water loss (TEWL), a marker of cutaneous barrier function, and epidermal proliferation were determined at different time points 0-264 h after treatment. In addition, light and electron microscopy studies were performed. RESULTS: A single treatment in solution led to a transient (2- to 3-fold) increase in TEWL after application of calcipotriol or 1,25(OH)2D3 and to a 3- to 6-fold increase in epidermal proliferation after application of each of the compounds. Repeated applications also resulted in an up to 3-fold increase in TEWL which persisted for 3 days after the end of the treatment. By light microscopy an increase in epidermal thickness was observed. There was no sign of inflammation. Electron microscopy studies showed the formation of a transitional cell zone as a sign of a premature keratinization. CONCLUSION: These results demonstrate that in normal mouse skin vitamin D3 and its analogues disrupt the epidermal permeability barrier by induction of epidermal proliferation and premature keratinization but without morphological signs of inflammation.
1-Propanol↗