[Porphyria: from clinics to molecular genetics].
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Biomedical subjects
Publications and source records attributed to J Frank.
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Microvascular ingrowth into damaged tissue is an essential component of the normal healing process. In fact, wound therapy is often aimed at promoting neovascularization. However, little is known about the mechanisms that regulate microvascular ingrowth into a healing wound. This limited knowledge is largely due to the lack of adequate models in which microvascular ingrowth can be quantitatively analyzed throughout the healing process. To address this deficiency, we developed a model in which a wound was created on the ear of the hairless mouse-a well established model for directly viewing and measuring skin microcirculation. While the animals were under ketamine and xylazine anesthesia, 2.25 mm diameter full-thickness wounds were created on the dorsum of hairless mouse ears down to but not including the cartilage (0.125 mm depth). With the use of video microscopy and computer-assisted digitized planimetry, the precise epithelial and neovascular wound edge was viewed and measured regularly throughout healing. Therefore, this model can provide objective data on wound epithelialization and neovascularization throughout healing. This model was used to examine the effect of topical wound agents on epithelialization and neovascularization. Differential effects by these anti-microbial agents on these two processes were observed, which suggests clinical implications for their use.
BACKGROUND: Borreliosis is the most common vector transmitted disease in childhood. Although the disease manifests with an erythema migrans in 80 % of the patients, multilocular skin manifestations are only observed in 2-18 % of these. Differential diagnoses of erythema migrans include erysipelas, persistent insect bite reaction, and fixed drug eruption, in particular when the clinical history does not reveal a tick bite. PATIENT: We report on a 5-year-old boy showing nine erythemas with central pallor on his face, trunk, arms and legs. He recalled a tick bite 3 weeks before. RESULTS: Serological studies revealed an acute infection with Borrelia burgdorferi. After antibiotic treatment with orally administered amoxicillin skin manifestations resolved within three days. During a follow-up period of six months the patient revealed no signs of persistent borreliosis. CONCLUSION: Multilocular erythema migrans is a possible manifestation of borreliosis and is classified as disseminated early infection which is frequently associated with systemic reactions, including malaise, arthritis, carditis, headache and even meningeal signs. Treatment is based on antibiotics, which should preferably be given intravenously in case of systemic signs.
A new electromechanical energy converting system has been developed to yield an efficient and durable orthotopic total artificial heart (TAH). The energy converter we developed transforms the unidirectional rotational motion of the motor into a longitudinal forward-reverse movement of an internal geared oval, linked directly to pusher plates on both sides. To ensure a permanent positive connection between the drive gear and the internally geared wheel, a ball bearing runs inside an oval shaped guide track. Motor, gear unit, and conical pusher plates are seated between alternately ejecting and filling ventricles. The unidirectional motion of the brushless DC motor affords easier motor control, reduces energy demand, and ensures longer life of the motor when compared with a bidirectional motion system. In vitro testing has been performed on a mock circulation loop. The overall system efficiency of the TAH Ovalis was 27-39% (mean, 36%) for the pump output range of 2-7 L/min. The maximum output of 7 L/min can be obtained with a pump rate of 130 min(-1) and an afterload pressure of 140 mm Hg. For an average sized human with a mean cardiac output of 6 L/min at a mean aortic pressure of 120 mm Hg, 5 watts of input power would be required. The size of the prototype is 560 cm3, the weight is 950 g. Our first in vitro studies demonstrated the excellent efficiency and pump performance of this new electromechanical energy converter. The results prove the feasibility of this new concept's use as an energy converter for a total artificial heart.
The morphology of the Escherichia coli ribosome, i.e., its shape at moderate to low (20-40 A (1 A = 0.1 nm)) resolution, provides important constraints in modeling both the folding of ribosomal RNA and the translational process. A new reconstruction, obtained by low-dose cryoelectron microscopy and image processing of single ribosomes, contains clues to the way in which the ribosome interacts with the key functional ligands: the mRNA and the A- and P-site tRNAs. It also suggests possible pathways of the nascent polypeptide chain. From an interpretation of these clues in the light of existing knowledge, a plausible model for the locations and interactions of key components of protein synthesis is suggested.
The porphyrias are disorders that result from the inherited or acquired dysregulation of one of the eight enzymes in the porphyrin-heme biosynthetic pathway. The different types of porphyrias often show overlapping findings with regard to clinical and/or biochemical features. Therefore, the establishment of screening methods for the identification of underlying mutations on the basis of direct DNA analysis may provide a more reliable approach for diagnosis of the different types of porphyrias. Here, we provide an overview of molecular biological screening techniques for mutations and the molecular bases of the porphyrias.
Variegate porphyria, one of the acute hepatic porphyrias, is characterized by a partial reduction in protoporphyrinogen oxidase, the seventh enzyme of the heme biosynthetic pathway. For a long time, this disease has caused confusion among the porphyrias because it presents with clinical symptoms and biochemical findings that can be similar to those found in other types of porphyrias. Here, we provide an overview of historical, clinical, biochemical, genetical, and other aspects of variegate porphyria that might be helpful in providing more insight into this rare disorder.
The porphyrias comprise a group of fascinating disorders resulting from predominantly inherited as well as acquired deficiencies of one of the eight enzymes along the pathway of heme biosynthesis. On the basis of clinical aspects, the different types of porphyrias can be classified in acute and non-acute forms. However, an exact classification is often difficult since the porphyrias might reveal unspecific clinical symptoms and/or overlapping biochemical features. In particular, this is true for the acute porphyrias which can present with life-threatening acute neurovisceral attacks that require immediate medical intervention. Due to the multiple facets of these disorders, the diagnosis and treatment of the acute porphyrias should always imply a close interdisciplinary collaboration to serve patients and their families most effectively.
The effects of isolated limb perfusion were studied in 12 patients suffering from peripheral arterial occlusion. The hemodynamic investigations show that the vascular resistance decreases considerably during isolated limb perfusion. After administration of a vasodilator cocktail, added to the perfusion, the vascular resistance continues to decrease. Angiographic records, made before, during and after the perfusion, suggest that the calibre of the collateral vessels increases significantly and besides new collaterals can also be observed. The mechanism of the effects of isolated hyperbaric limb perfusion and its clinical value are discussed.
PURPOSE: This study tested the reliability and validity of a pain scale that was developed at University of Wisconsin Children's Hospital for the preverbal child (less than 3 years old) and the nonverbal child (children who cognitively were not able to communicate a pain rating on traditional pain scales). METHOD: Content validity was established by expert review. Construct validity was demonstrated by having the nurse rate the child's pain before and after analgesic and during a procedure. Inter-rater reliability was achieved by two nurses simultaneously and independently rating the child's pain. Criterion validity was determined by comparing ratings with those obtained on the Wong-Baker Faces scale. Internal consistency was calculated using Cronbach's alpha. FINDINGS: Seventy-four patients provided data for 124 observation times. At 58 of the observation times, two nurses independently used the newly developed University of Wisconsin Children's Hospital (UWCH) scale, resulting in 182 pain ratings. Internal consistency of the scale (Cronbach's alpha) was 0.93. Mean pain scores were significantly higher prior to pain medication administration and during procedures than following analgesic administration. Inter-rater reliability was 0.92. Correlation of the new scale with the Wong-Baker Faces Scale was r = .62. CONCLUSIONS: Initial testing of the construct validity, internal reliability, and internal consistency of the UWCH Pain Scale for Preverbal and Nonverbal Children were acceptable. Parents provided ratings for most of the faces scale, which could account for the low correlation in the construct validity testing.
The porphyrias comprise a clinically and genetically heterogeneous group of diseases mostly arising from a genetically determined dysfunction of specific enzymes along the pathway of heme biosynthesis. Based on the occurrence or absence of cutaneous symptoms and life-threatening acute neurological attacks, the different types of porphyrias can either be classified into cutaneous and non-cutaneous forms or acute and non-acute forms. Establishing an accurate diagnosis might be difficult for two reasons: i) the porphyrias can manifest with a broad but unspecific spectrum of clinical symptoms mimicking several other disorders, and ii) biochemical examination of urine, feces, and blood can reveal overlapping findings. Fortunately, however, the advances in the fields of molecular genetics during recent years have provided us with the possibility of overcoming these diagnostic pitfalls. Therefore, in controversial cases the correct diagnosis can finally be made using molecular biological techniques. Due to the various facets of the porphyrias, diagnosis and treatment should always imply a close interdisciplinary collaboration to counsel and help patients and their families most efficiently.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The pathogenesis of renal interstitial fibrosis is not fully understood at present. As renal interstitial fibrosis occurs mainly in association with interstitial cell infiltrates, several cytokines, e.g. PDGF, TGF-beta, IL-6, are thought to play a major role in the induction and progression of renal interstitial fibrosis. In order to prove whether renal tubular epithelial cells produce cytokines which are known to modulate renal interstitial fibroblasts, RNA was isolated from human renal tubular epithelial cells and from human renal fibroblasts. The expression of specific cytokines and growth factors was analysed by Northern blot analysis using cDNA probes for IL-1 alpha, IL-1 beta, IL-6, INF-gamma, TNF-alpha, a-FGF, b-FGF, GM-CSF, PDGF-B and oligonucleotides for IL-2 and TGF-beta 1. In renal tubular epithelial cells from normal and diseased kidneys, mRNA transcripts for PDGF-B, IL-6 and GM-CSF could be detected. Quantitative analysis of the mRNA transcripts of the cytokines expressed revealed consistently higher amounts of GM-CSF and PDGF-B mRNA in tubular epithelial cells from diseased in comparison to normal kidneys. Furthermore, higher amounts of GM-CSF and PDGF-B mRNA transcripts were detected in tubular epithelial cells derived from kidneys with interstitial fibrosis as compared to tubular epithelial cells from diseased but nonfibrotic kidneys. Renal fibroblasts from normal and fibrotic kidneys showed a weak signal for IL-6, but PDGF-B and GM-CSF were not expressed in these cells. By means of colony assays, using human bone marrow cells in the presence or absence of neutralizing antibodies, the release of biologically active colony-stimulating factors GM-CSF and M-CSF by renal tubular epithelial cells from normal and diseased kidneys could be demonstrated. The present results probably indicate interactions between renal tubular epithelial cells and renal fibroblasts in the progression of renal diseases.