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Biomedical subjects

R Braun

Publications and source records attributed to R Braun.

At least 55 records · Page 3Linked to original sources

Heat-induced gene expression as a novel targeted cancer gene therapy strategy.

One of the main advantages of gene therapy over traditional therapy is the potential to target the expression of therapeutic genes in desired cells or tissues. To achieve targeted gene expression, we experimented with a new approach based on the long-established phenomenon of the heat shock response. By using the green fluorescence protein as a reporter gene, it was demonstrated that expression of a heterologous gene with a heat shock protein 70 promoter could be elevated to 500-1000-fold over background by moderate hyperthermia (39 degrees C to 43 degrees C) in tissue cultured cells. The heat-induced green fluorescence protein expression was first detectable at 3 h after heating and reached a maximum at 18-24 h. The expression dropped back to baseline within 72 h. In addition, when cells were infected with adenovirus vectors containing the heat-inducible interleukin 12 or tumor necrosis factor alpha genes and then heated (42 degrees C, 30 min), expression was at least 13,600- or 6.8 x 10(5)-fold over background, respectively. Intralesion injection of the interleukin-12-carrying adenovirus vector in a mouse melanoma tumor model caused significant tumor growth delay only with hyperthermia treatment. Our results therefore support heat-induced gene expression as a feasible approach for targeted cancer gene therapy.

Adenoviridae↗

[UV-B comb versus betamethasone solution in scalp psoriasis].

BACKGROUND: The aim of the study was to assess the effectiveness of a UV-B-comb on scalp psoriasis versus betamethasone valerate solution. MATERIAL AND METHODS: Of 44 adult patients with scalp psoriasis, 22 were treated with a dermalight 80 psoracomb and 22 with betamethasone valerate solution, five times a week for three weeks. RESULTS: No difference in effect was found at the end of treatment. Two weeks after end of treatment a higher proportion of patients treated with UV-B-comb (7/22) had remained in remission than those treated with betamethasone valerate solution (3/22; p < 0.05). INTERPRETATION: Treatment with a UV-B-comb offers a good alternative to topical corticosteroids for patients with scalp psoriasis.

Administration, Topical↗

Putting priming into perspective - from cellular heterogeneity to cellular plasticity.

The concept of priming is widely used in cell biology and has come to mean the functional enhancement of a given cell by cytokines. 'Primed' cells have a number of other cellular alterations, although the relationship between functional and phenotypical diversity has not been established. Here, Claus Kroegel and colleagues discuss the dynamic nature of inflammatory-cell priming, which might be part of a broader means of comprehending cell function in disease.

Cell Adhesion Molecules↗

Impaired vascular contractility and blood pressure homeostasis in the smooth muscle alpha-actin null mouse.

The smooth muscle (SM) alpha-actin gene activated during the early stages of embryonic cardiovascular development is switched off in late stage heart tissue and replaced by cardiac and skeletal alpha-actins. SM alpha-actin also appears during vascular development, but becomes the single most abundant protein in adult vascular smooth muscle cells. Tissue-specific expression of SM alpha-actin is thought to be required for the principal force-generating capacity of the vascular smooth muscle cell. We wanted to determine whether SM alpha-actin gene expression actually relates to an actin isoform's function. Analysis of SM alpha-actin null mice indicated that SM alpha-actin is not required for the formation of the cardiovascular system. Also, SM alpha-actin null mice appeared to have no difficulty feeding or reproducing. Survival in the absence of SM alpha-actin may result from other actin isoforms partially substituting for this isoform. In fact, skeletal alpha-actin gene, an actin isoform not usually expressed in vascular smooth muscle, was activated in the aortas of these SM alpha-actin null mice. However, even with a modest increase in skeletal alpha-actin activity, highly compromised vascular contractility, tone, and blood flow were detected in SM alpha-actin-defective mice. This study supports the concept that SM alpha-actin has a central role in regulating vascular contractility and blood pressure homeostasis, but is not required for the formation of the cardiovascular system.

Actins↗

Ozone-induced epithelial injury in the ferret is similar to nonhuman primates.

Extrapolation to humans from rodent ozone exposure is limited by the anatomic differences between the species. Ferrets have similar pulmonary structures to humans, with well developed respiratory bronchioles and submucosal glands. We exposed adult ferrets, monkeys, and rats to 1 ppm ozone (O(3)) or filtered air for 8 h followed by 1 h in filtered air. Bronchoalveolar lavage (BAL) analysis, histopathology, and confocal microscopy were used to evaluate ozone-induced epithelial injury and inflammation. BAL showed significantly increased numbers of neutrophils in ozone-exposed as compared with filtered air ferrets, monkeys, and rats. However, there were 3- to 4-fold more neutrophils in monkeys and ferrets per milliliter of BAL than in rats. Ozone-exposed lungs showed a severe, acute infiltration of neutrophils in regions with necrotic epithelial cells, especially in the centriacinar region that was more severe in ferrets and monkeys than rats. We conclude that acute ozone exposure in ferrets induce severe epithelial necrosis and inflammation, results in similar epithelial injury compared with monkeys, and represents a better model of humans than rodents.

Animals↗

Teledermoscopy--results of a multicentre study on 43 pigmented skin lesions.

We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.

Adolescent↗

Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'.

The parasitic nematode Ascaris lumbricoides infects one billion people worldwide. Its perienteric fluid contains an octameric haemoglobin that binds oxygen nearly 25,000 times more tightly than does human haemoglobin. Despite numerous investigations, the biological function of this molecule has remained elusive. The distal haem pocket contains a metal, oxygen and thiol, all of which are known to be reactive with nitric oxide. Here we show that Ascaris haemoglobin enzymatically consumes oxygen in a reaction driven by nitric oxide, thus keeping the perienteric fluid hypoxic. The mechanism of this reaction involves unprecedented chemistry of a haem group, a thiol and nitric oxide. We propose that Ascaris haemoglobin functions as a 'deoxygenase', using nitric oxide to detoxify oxygen. The structural and functional adaptations of Ascaris haemoglobin suggest that the molecular evolution of haemoglobin can be rationalized by its nitric oxide related functions.

Anaerobiosis↗

Post-stripping sclerodermiform dermatitis.

BACKGROUND: Cutaneous sclerosis, a process that results in hardening of the skin, is the hallmark of scleroderma and sclerodermoid disorders. Cutaneous sclerosis is usually classified as secondary or primary, depending on the presence or absence of underlying diseases. Primary cutaneous sclerosis is a feature of idiopathic inflammatory processes that are often associated with autoimmune disorders, whereas secondary cutaneous sclerosis arises in the context of many pathological processes of varying causes, including chronic graft-vs-host disease, defined metabolic or genetic disorders, and exposure to certain infectious organisms, drugs, or chemicals. OBSERVATIONS: Three patients had localized cutaneous sclerosis overlying the site of a surgically removed (stripped) great saphenous vein. In all 3 patients, lesions were clinically characterized by multiple hypopigmented and indurated plaques distributed linearly along the path of the preexisting vein. Extensive history, physical examination, and diagnostic tests did not reveal known predisposing factors for cutaneous sclerosis. CONCLUSIONS: Although the observed association of sclerodermiform dermatitis and venous stripping in these 3 patients does not imply a causal relationship, the absence of other identifiable predisposing factors and the striking linear distribution of the cutaneous lesions along the path of the preexisting vein are suggestive. This poststripping sclerodermiform dermatitis may be a rare late complication of saphenous vein stripping.

Adult↗

Effects of nitrogen limitation on biofilm formation in a hydrocarbon-degrading trickle-bed filter.

The effect of nitrogen limitation on young and mature steady-state biofilm in a trickle-bed filter was studied. Toluene and n-heptane were the sole carbon source. Biomass concentration, respiration, substrate-induced respiration, metabolic quotient, and total hydrocarbon degradation efficiency were measured. The aim of the experiment was to control excess biomass production in the trickle-bed filter by limiting the mineral nutrients and to achieve increased mineralization of the carbon source. Biofilm growth responded strongly to the amount of available nitrogen, whereas hydrocarbon degradation efficiency reached a maximum of 60% and could not be increased even by further addition of nitrogen. The experiments showed that 95% of the adsorbed carbon was mineralized completely and only 5% was used for biofilm formation. This complete mineralization can also be concluded from the metabolic quotient. The value of the latter was about 6-10 mg CO2-C g-1 Cmic h-1, indicating an expanded energy demand due to stress effects in the presence of nutrient deficiency. It was postulated that determination of the metabolic quotient could be an simple instrument to measure the rate of mineralization of carbon sources and also the rate of biomass formation in trickle-bed filters or biofilters.

Biofilms↗