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Biomedical subjects

J Wiltfang

Publications and source records attributed to J Wiltfang.

142 records · Page 8Linked to original sources

Soluble intercellular adhesion molecule-1 in cerebrospinal fluid: an indicator for the inflammatory impairment of the blood-cerebrospinal fluid barrier.

A soluble form of the intercellular adhesion molecule-1 (sICAM-1) was measured in paired cerebrospinal fluid (CSF)/blood samples from 123 patients with different neurological diseases. Mean levels of circulating ICAM-1 in the blood were mean +/- SD = 423 +/- 184.6 ng ml-1 (range 44-1115 ng ml-1). Considerable differences of sICAM-1 in the CSF of patients were observed between disease groups. In acute bacterial meningitis, sICAM-1 levels as high as 1/5 of the serum concentration were detected in the CSF (n = 24; mean +/- SD = 33.0 +/- 23.7 ng ml-1; range: 4.8-93.9 ng ml-1). These changes coincided with a severe blood-CSF barrier dysfunction as indicated by a high CSF/blood ratio for albumin (mean +/- SD = 46.7 +/- 52.2; range: 16.8-249.3). In patients with polyradiculitis (n = 9; mean +/- SD = 14.5 +/- 11.9 ng ml-1; range: 2.6-43.7 ng ml-1) a similar covariation between the albumin and sICAM CSF/blood ratios was detected. In patients with multiple sclerosis (n = 9; mean +/- SD = 5 +/- 4.3; range: 0-12.7 ng ml-1) or HIV infection with neurological symptoms (n = 18; mean +/- SD = 4.9 +/- 3.2; range; 1-11.9 ng ml-1) low levels of sICAM-1 were detected in the CSF associated with intact blood-CSF barrier function in most patients. Among 13 patients with viral meningitis, only four had detectable levels of sICAM-1 in their CSF (mean +/- SD = 1.0 +/- 1.5 ng ml-1; range: 0-3.7).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

A new multiphasic buffer system for sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins and peptides with molecular masses 100,000-1000, and their detection with picomolar sensitivity.

A novel multiphasic buffer system for high resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis of dansylated and nondansylated proteins/peptides in the relative molecular mass (Mr) range of 100,000-1000 is described. The system, based on Jovin's theory of multiphasic zone electrophoresis, allows complete stacking and destacking of proteins/peptides within the above Mr range. The buffer system uses Bicine and sulfate as trailing and leading ion, respectively, and Bistris and Tris as counter ions in the stacking and separating phase, respectively. Through selection of two different counter ions--the characteristic feature of the present ionic system--the stacking limits of a multiphasic buffer system can be further widened, thus making it applicable to gel electrophoresis of a larger spectrum of rapidly migrating species, such as sodium dodecyl sulfate-proteins/peptides and nucleic acids, than has been possible previously. Highly sensitive detection methods for proteins as well as for polypeptides down to approximately Mr 1000 are described. Dansylated proteins/peptides were detected by their fluorescence either directly within the gel or following electroblotting into anion-exchange or polyvinylidene difluoride membranes. The latter procedure resulted in detection sensitivities of approximately 1 ng. Nondansylated proteins/peptides were either detected within the gel by colloidal Coomassie staining or by electroblotting into polyvinylidene difluoride membranes, followed by colloidal gold staining. Prior to both staining procedures the proteins/peptides were pretreated with glutardialdehyde in the presence of borate at near neutral pH values to generate protein/peptide polymers of poor solubility. For a given pH the efficiency of the latter procedure was significantly influenced by the nature of the buffer ion used in the fixation buffer. In contrast to conventional fixation procedures even small polypeptides (Mr 1000) were immobilized and approximately 15 ng and 0.75 ng could be detected after colloidal Coomassie and colloidal gold staining, respectively.

Buffers↗

[Mandibular condyle fractures in childhood: effects on growth and function].

Long-term follow-up findings in 29 patients having had childhood condylar fractures and 13 patients having had childhood mandibular body fractures combined with condylar fractures are presented. In only 12% of all cases moderate to severe mandibular growth abnormalities were observed. About 2/3 of these patients showed growth retardation on the condylar fracture side. 1/3 of this group, however, demonstrated more pronounced growth on the fracture side compared to the nonfracture side. Cephalometric measurements proved to be the most effective method for evaluation of growth disorders, whereas clinical examination and photographs were less efficient. Although function and anatomical remodelling was good, the probability of complete remodelling and functional rehabilitation is higher in younger children.

Child↗

[Prophylaxis of the bacterial endocarditis in dental surgery].

Bacterial endocarditis is a disease with high morbidity and lethality. Bacteremia following diagnostic or therapeutic procedures in oral surgery may cause bacterial endocarditis. Patients with certain kinds of heart diseases are at higher risk to develop bacterial endocarditis. Especially these patients have to be protected by means of systemic and local prophylactic regimens.

Anti-Bacterial Agents↗

[Anaesthesia and spontaneous return of sensation following resection of the mandibular continuity with primary alloplastic materials].

Resection affecting the continuity of the mandible and the mandible nerve leads to complete anaesthesia of the lower lip and mental area, furthermore to deformity and functional disturbance like uncontrolled salivation. In our long term follow up study on multimodal neurological investigation sensibility is reported to have uncomplete regenerated spontaneously often already after one year. Complete sensory, however, could not be found; the incomplete sensory return was to be measured in individually different degrees of hypaesthesia. Furthermore the axonal qualities of the mandible nerve show different regenerative potential: the receptor function for pressure and contact sensitivity could be demonstrated in the most of cases, whereas the heat- and painreceptor qualities could not be revealed in all cases.

Adult↗

Neurophysiological assessment of early hepatic encephalopathy.

The spontaneous EEG, pattern reversal VEPs, and the P300 wave were studied in patients with liver cirrhosis and early stages of hepatic encephalopathy (HE). The sensitivities of the different neurophysiological methods in the early stages of hepatic encephalopathy were compared with each other and with several neuropsychological tests. P300 latency was shown to be the most appropriate neurophysiological method for detection of early HE. The diagnostic sensitivity of the P300 latency resembled that of the number connection test (NCT). These results are discussed with regard to methodological considerations and the clinical use of both methods.

Adult↗

[Studies on mandibular fractures during the growth period and late results of surgical treatment].

Because of their etiology, localization and therapy, mandibular fractures in children occupy a special position. At the University Hospital in Göttingen 70 children with a total of 112 mandibular fractures were treated between 1979 and 1988. 30 out of 36 mandibular body fractures were treated with plate fixation, i.e. predominantly minicompression plates. This type of treatment requires no postoperative intermaxillary fixation. Furthermore, it allows immediate functional treatment for a possible concomitant condylar neck fracture. Neither clinically nor radiographically was there any major inhibition of mandibular growth or nonunion in the 24 patients examined (mean follow-up period 4.7 years). The results demonstrate that rigid plate fixation of mandibular fractures may also be recommended in children.

Adolescent↗

Gas-phase sequencing after electroblotting on polyvinylidene difluoride membranes assigns correct molecular weights to myoglobin molecular weight markers.

Commercially available polypeptide marker kits containing peptides generated by cyanogen bromide cleavage of either horse heart myoglobin or sperm whale myoglobin have been investigated by sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE), followed by electroblotting on polyvinylidene difluoride membranes, and gas-phase sequencing. It could be shown that the molecular weights assigned to the SDS-PAGE bands by the companies are incorrect. Arranged in descending order, the marker kits are composed of the following polypeptide fragments from myoglobin: positions 1-153, 1-131, 56-153, 56-131, 1-55, and 132-153. A polypeptide comprising residues 1-14 was not found. According to these results the log Mr versus Rf plot used for calibration must be revised. For the separation of low molecular weight polypeptides and peptides a new gel system based on the theory of multiphasic zone electrophoresis combined with a modified Coomassie staining procedure is reported.

Amino Acid Sequence↗

Paracetamol as a test drug to determine glucuronide formation in man. Effects of inducers and of smoking.

A simple, noninvasive procedure was developed to monitor glucuronidation and sulphation in patients using paracetamol as the test drug. Urinary paracetamol and its metabolites were determined by UV absorption and electrochemical detection after separation by HPLC. The metabolite to paracetamol ratio (M/P) was used as an approximation of the partial clearance due to metabolite formation. In 14 healthy volunteers, all nonsmokers without medication, M/P was 18 +/- 5 for glucuronides and 12 +/- 4 for sulphate esters. The test was validated in patients treated with enzyme inducers. In 10 patients with epilepsy given phenytoin 0.3 g/day, and in 10 patients with tuberculosis treated with rifampicin 0.6 g/day, the M/P value for glucuronidation was significantly increased to 41 +/- 11 and 35 +/- 7, respectively. In contrast, M/P values for sulphation were not significantly different from untreated controls. In 9 heavy smokers (about 40 cigarettes/day) M/P values for glucuronidation were also significantly increased to 33 +/- 11. However, in 4 moderate smokers (about 10 cigarettes/day) no significant increase was found. The results suggest that in man glucuronidation of paracetamol is inducible both by phenobarbital- and 3-methylcholanthrene-type inducers. Monitoring the ratios of various urinary paracetamol conjugates/paracetamol may be useful as a new tool for the evaluation of factors determining glucuronide and sulphate ester formation in man.

Acetaminophen↗

Improved electrophoretic separation and immunoblotting of beta-amyloid (A beta) peptides 1-40, 1-42, and 1-43.

Beta-amyloid peptides (A beta peptides) form the main protein component of the amyloid deposits found in the brains of Alzheimer's disease (AD) patients. Soluble A beta peptides, which are proteolytic fragments of the amyloid-precursor protein (APP) are constitutively secreted by cells expressing APP during normal metabolism [1] and are also present in human plasma and cerebrospinal fluid [2]. Missense mutations in Codon 717 of the APP gene are responsible for a small percentage of inherited AD cases (FAD) and increase the amount of A beta peptides containing additional carboxy terminal amino acids (A beta 1-42, A beta 1-43) [3, 4]. Recent findings indicate that FAD mutations in the presenilin 1 and 2 genes also increase the amount of these longer A beta peptides [5]. A beta 1-42 polymerizes more rapidly in vitro [6] than A beta 1-40 and has been identified as the major component of the brain amyloid deposits [7-9]. We recently developed a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) system [10] for the separation of these two peptides. Here we describe a modified version of the original SDS-PAGE procedure, which allows the separation of A beta 1-40, A beta 1-42, and A beta 1-43 for the first time. Detection of the three A beta peptides in the lower ng and pg range is realized by optimized silver staining or immunoblot procedures. These nonradioactive methods may validate results obtained by ELISA procedures used to study the metabolic fate of APP. They may help to define the neurotoxic potential of the longer A beta peptides in relation to their aggregation state.

Amyloid beta-Peptides↗

Growth and transplantation of a custom vascularised bone graft in a man.

BACKGROUND: A major goal of research in bone transplantation is the ability to avoid creation of secondary bone defects. We aimed to repair an extended mandibular discontinuity defect by growth of a custom bone transplant inside the latissimus dorsi muscle of an adult male patient. METHODS: Three-dimensional computed tomography (CT) scanning and computer-aided design techniques were used to produce an ideal virtual replacement for the mandibular defect. These data were used to create a titanium mesh cage that was filled with bone mineral blocks and infiltrated with 7 mg recombinant human bone morphogenetic protein 7 and 20 mL of the patient's bone marrow. Thus prepared, the transplant was implanted into the latissimus dorsi muscle and 7 weeks later transplanted as a free bone-muscle flap to repair the mandibular defect. FINDINGS: In-vivo skeletal scintigraphy showed bone remodelling and mineralisation inside the mandibular transplant both before and after transplantation. CT provided radiological evidence of new bone formation. Postoperatively, the patient had an improved degree of mastication and was satisfied with the aesthetic outcome of the procedure. INTERPRETATION: Heterotopic bone induction to form a mandibular replacement inside the latissimus dorsi muscle in a human being is possible. This technique allows for a lower operative burden compared with conventional techniques by avoiding creation of a secondary bone defect. It also provides a good three-dimensional outcome.

Activin Receptors, Type I↗

Elevated homocysteine levels in alcohol withdrawal.

Ethanol exerts its behavioural effects largely by interacting with receptors for brain neurotransmitters. However, the molecular mechanisms involving these interactions and the pathogenesis of alcohol-withdrawal symptomatology are still not well understood. Until recently, no data were available about homocysteine (Hcy) levels in acute alcohol intoxication of chronic alcoholics and in patients undergoing withdrawal from alcohol. Hcy, blood-alcohol concentrations, vitamins B6, B12, and folate concentrations were assessed in 29 chronic alcoholics, who underwent withdrawal from alcohol. We observed increased Hcy levels in most patients. Hcy levels steadily decreased during the observation period. We postulate that hyperhomocysteinaemia and excitatory amino acid neurotransmitters, by their agonism at the N-methyl-D-aspartate receptor, may partly mediate alcohol-associated withdrawal symptomatology. The importance of assessing serum Hcy levels in order to detect methylation deficiency in patients with chronic alcoholism and for possible therapeutic strategies is discussed.

Adult↗

Molecular biology of Alzheimer's dementia and its clinical relevance to early diagnosis and new therapeutic strategies.

Over the past few years, molecular biological research has considerably deepened our understanding of the pathophysiological basis of Alzheimer's dementia (AD). Although different genetic origins of the disease have been identified, all of the findings point to a common terminal sequence in familial AD. This consists of an increased production of beta-amyloid peptides from beta-amyloid precursor protein. For the cases of sporadic AD, which far outweigh the number of cases of familial AD, an impaired catabolism of the beta-amyloid peptides may also be pathophysiologically decisive according to the latest findings. Research into the molecular level of AD makes it possible to identify points of attack for rational drug treatment of the disease, while molecular markers of AD are increasingly being used as a part of early and differential neurochemical diagnostics.

Alzheimer Disease↗

Correlation of telomerase activity, clinical prognosis and therapy in oral carcinogenesis.

Telomerase activity is associated with most malignant tumors. To evaluate the role of telomerase reactivation as a diagnostic and prognostic marker in oral carcinogenesis activity was investigated in mortal and immortal cell lines in eight oral leukoplakias (OL) and 46 oral squamous cell carcinomas (OSCC). Activity was also investigated in 13 histopathologically unaffected mucosas from distant sites or tumor-free margins of the same patients using a modified, highly sensitive, non-radioactive telomeric repeat amplification protocol (TRAP). This was correlated with histopathological stages and the clinical course of the disease. 50% of OL and 46% of OSCC showed activity. One patient with positive, high dysplastic OL developed an OSCC 11 month later. One of three specimens of adjacent tissue presented activity and a recurrence occurred after 6 months. Out of 10 tissues of distal normal mucosa, 2 demonstrated activity which could also be proved in the corresponding tumor. Detection of telomerase reactivation may be a novel method for early detection of immortalised cell clones and malignant cells in histopathologically normal oral squamous epithelium.

Carcinoma, Squamous Cell↗

Comparative study of guided bone regeneration using absorbable and permanent barrier membranes: a histologic report.

In an experimental study using the Göttingen minipig, Gore-Tex, Gore Resolut, and Vicryl barrier membranes were tested for their efficacy in guided bone regeneration. The results were compared to those of autologous periosteum. The strongest reossification was seen in the bone defects covered with Gore-Tex; however, time-dependent disintegration phenomena, which had already been observed in preliminary examinations, were clearly established. After investigations of cell cultures to which human macrophages were added, the latter findings can be interpreted as the result of a physicochemical process, since a direct attack by the macrophages was not seen in vitro. Of the membranes used, the absorbable ones tended to collapse, depending on the size of the defect that was used, and they did not enhance reossification as much as did the permanent membranes. The periosteum-covered defects showed a satisfactory degree of regeneration, and no differences were observed between freely transplanted and pedunculate periosteum.

Animals↗