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Biomedical subjects

S Wagner

Publications and source records attributed to S Wagner.

At least 19 recordsLinked to original sources
PubMed1998

cDNA cloning of the 43-kDa latex allergen Hev b 7 with sequence similarity to patatins and its expression in the yeast Pichia pastoris.

IgE-mediated hypersensitivity to latex proteins present in health care products, particularly in latex gloves, has become an important public health problem in recent years. We purified natural Hev b 7, a 43-kDa patatin-like allergen from the latex of Hevea brasiliensis and determined several internal peptide sequences. A heterologous hybridization probe of a patatin gene of potato, to which these peptides could be aligned best, was used to screen a latex cDNA library. The cDNA encoded an acidic protein of 388 amino acids with a molecular mass of 42.9 kDa. The deduced amino acid sequence had 39-42% identity to patatins from Solanum tuberosum. The purified recombinant Hev b 7 expressed in the yeast Pichia pastoris displayed, similarly to patatins from S. tuberosum, esterase activity. Both natural and recombinant Hev b 7 were recognized by IgE from sera of latex-sensitized allergic individuals. In contrast to patatins from S. tuberosum and Nicotiana tabacum, natural Hev b 7 lacked an N-terminal leader peptide for targeting to the endoplasmatic reticulum and was not glycosylated. These results establish the 43-kDa patatin-like protein as a latex allergen and raise the possibility of different cellular localization and function compared to S. tuberosum patatins.

Allergens↗
PubMed1998

Mechanism of gamma sigma T-cell-mediated inhibition of stem cell differentiation in vitro: possible relevance for myelosuppression in HIV-infected individuals.

We investigated whether gamma delta T cells contribute to the suppression of myelopoiesis in HIV infection. Freshly isolated gamma delta T cells from HIV seropositive patients suppressed CFU-GM growth in vitro. Preactivation of gamma delta T cells with IL-2 and/or IL-15 further reduced the number of CFU-GM. Natural killer cells and to a lower extent CD4+ and CD8+ cells also inhibited CFU-GM growth. In contrast to gamma delta T cells, this effect was not dependent on IL-15 or IL-2 preactivation. Moreover, no enhanced inhibitory effect of CD56+ and CD4+ cells was observed in HIV+ subjects compared to HIV- donors. The myelosuppressive effect of supernatants of gamma delta T cells could be inhibited by antibodies against IFN-gamma or TNF-alpha. Accordingly, we found increased numbers of TNF-alpha or IFN-gamma-secreting CD8+ gamma delta T cells in HIV+ patients. We conclude that the increased fraction of activated gamma delta T cells producing myelosuppressive cytokines might contribute to the dyshematopoiesis frequently observed in HIV-infected individuals.

Cell Differentiation↗
PubMed1998

The dominant chloride channel mutant G200R causing fluctuating myotonia: clinical findings, electrophysiology, and channel pathology.

Clinical, electrophysiological, and molecular findings are reported for a family with dominant myotonia congenita in which all affected members have experienced long-term fluctuations of the symptom of myotonia. In some patients myotonia is combined with myalgia. The myotonia-causing mutation in this family is in the gene encoding the muscular chloride channel, hCIC-1, predicting the amino acid exchange G200R. We have constructed recombinant DNA vectors for expression of the mutant protein in tsA201 cells and investigation of the properties of the mutant channel. The most prominent alteration was a +100-mV shift of the midpoint of the activation curve. Therefore, within the physiological range the open probability of the mutant channel is markedly smaller than in wild-type. This shift is likely to be responsible for the myotonia in the patients. The fluctuating symptoms of this chloride channelopathy are discussed with respect to short-term fluctuations of myotonia in the sodium channelopathy of potassium-aggravated myotonia.

Adolescent↗
PubMed1998

Targeting of ultrasmall superparamagnetic iron oxide (USPIO) particles to tumor cells in vivo by using transferrin receptor pathways.

Human transferrin was covalently coupled to ultrasmall superparamagnetic iron oxide (USPIO) particles, and the transferrin-USPIO obtained was investigated in vivo in experimental SMT/2A tumor-bearing rats (rat mammary carcinoma). Physicochemical characterization showed an overall size of 36 nm (DLS) with a core size of 5 nm (TEM). Relaxivities were R1 = 23.6 and R2 = 52.1 liter/mmol.s (0.47 T). Bound transferrin was 280 micrograms/mg of iron. Pharmacokinetic investigations revealed a half-life of 17 min in normal rats. The MR evaluation of tumor signal intensity over time showed a 40% (range 25-55%) signal reduction 150 min after injection with the reduction persisting for at least 8 h. Control experiments using the parent USPIO compound or USPIO labeled with a nonspecific human serum albumin (HSA-USPIO) showed a change of only 10% (range 5-15%) in tumor signal intensity over time. The results demonstrate that a combination of the USPIO relaxivity properties with the specificity of transferrin-mediated endocytosis allows in vivo detection of tumors by MR imaging.

Animals↗
PubMed1998

Myelin splitting, Schwann cell injury and demyelination in feline diabetic neuropathy.

Nerve biopsy samples from two cats with spontaneously occurring diabetes were examined. The predominant nerve fiber abnormalities observed were restricted to the myelin sheath and Schwann cell. Reactive, degenerative and proliferative Schwann cell changes were evident but the most striking abnormality encountered was splitting and ballooning of the myelin sheath. These observations highlight the significance of Schwann cell injury in the pathogenesis of diabetic neuropathy.

Animals↗
PubMed1998

The Helicobacter pylori fatty acid cis-9,10-methyleneoctadecanoic acid stimulates protein kinase C and increases DNA synthesis of gastric HM02 cells.

Protein kinase C (PKC) has been implicated in the control of epithelial proliferative activity and in the process of malignant transformation. Helicobacter pylori (H.p.) infection is associated with increased gastric epithelial cell proliferation and has been linked with gastric carcinoma. In the present study, we report that the H.p. fatty acid cis-9,10-methyleneoctadecanoic acid (MOA) directly activates PKC (Ka 3.3 microM). The effect of MOA upon PKC activation was Ca2+ dependent but did not require phosphatidylserine as phospholipid cofactor. MOA increased the stimulatory effect of phosphatidylserine at low Ca2+ (1 microM) concentrations. These findings indicate that MOA interacts at the phospholipid- and the diacylglycerol-binding domain to elicit PKC activation. Treatment of gastric mucous cells HM02 caused translocation of PKC from the cytosol to the nuclear, mitochondrial and membrane fraction. Furthermore, MOA stimulated [3H]thymidine incorporation into the DNA of HM02 cells. Our results show that the H.p. fatty acid MOA activates PKC and increases DNA synthesis in gastric epithelial cells.

Animals↗
PubMed1998

The 60 Minutes Myocardial Infarction Project. Characteristics on admission and clinical outcome in patients with reinfarction compared to patients with a first infarction.

PURPOSE: The purpose of the study was to evaluate parameters that characterize patients with myocardial reinfarction as compared to patients with a first infarction in clinical practice, and possibly to determine their clinical outcome. METHODS: The 60 minutes Myocardial Project is a German multicentre prospective observational study in which 136 hospitals are participating. Fourteen thousand, nine hundred and eighty consecutive patients with acute Q wave myocardial infarction were included from July 1992 to September 1994. RESULTS: Out of these 14,980 patients, there were 2854 (19%) with reinfarction and 12,126 (81%) with a first infarction. Patients with a reinfarction arrived at the hospital 24 min earlier than patients with a first infarction (pre-hospital delay 156 vs 180 min; P < 0.001); the door-to-needle time with reinfarction was longer (38 vs 30 min; P < 0.001); however, patients with reinfarction were older (69 vs 66 years; P < 0.001), had a lower rate of a diagnostic first ECG (54 vs 71%; P < 0.001) and received thrombolytic therapy less frequently than patients with a first infarction (46 vs 52%; P < 0.001). A low number of patients received primary PTCA ( n = 205) since only a few hospitals offered a primary PTCA service at the time the study was performed. In patients with reinfarction, there were more reasons as to why thrombolytic therapy was not given (24 vs 21%; P < 0.001). Left bundle branch block occurred more frequently in patients with reinfarction (15 vs 8%; P < 0.001). The intra-hospital course in patients with reinfarction was associated with an increase of complications and intra-hospital death (23 vs 15%; P < 0.001. CONCLUSIONS: Although reinfarction patients arrived earlier at hospital than patients with a first infarction, the former received thrombolytic therapy less frequently than the latter. Patients with reinfarction were older, more frequently had a non-diagnostic ECG on admission and had a higher rate of contraindications against thrombolytic therapy.

Adult↗
PubMed1998

Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence.

OBJECTIVE: Survival after surgery and radiotherapy for the treatment of malignant gliomas is linked to the completeness of tumor removal. Therefore, methods that permit intraoperative identification of residual tumor tissue may be of benefit. In a preliminary investigation, we have studied the value of fluorescent porphyrins that accumulate in malignant tissue after administration of a precursor (5-aminolevulinic acid) for labeling of malignant gliomas in nine patients. METHODS: Three hours before the induction of anesthesia, 10 mg 5-aminolevulinic acid/kg body weight was administered orally. Intraoperatively, red porphyrin fluorescence was observed with a 455-nm long-pass filter after excitation with violet-blue (375-440 nm) xenon light and was verified by analysis of fluorescence spectra. Fluorescing and nonfluorescing samples taken from the tumor perimeters were examined histologically or used to study the photobleaching of porphyrins by excitation light and white light from the operating microscope. Plasma and erythrocyte porphyrin levels were determined by fluorescence photometry. RESULTS: Normal brain tissue revealed no porphyrin fluorescence, whereas tumor tissue was distinguished by bright red fluorescence. For a total of 89 tissue biopsies, sensitivity was 85% and specificity was 100% for the detection of malignant tissue. For seven of nine patients, visible porphyrin fluorescence led to further resection of the tumor. Under operating light conditions, fluorescence decayed to 36% in 25 minutes for violet-blue light and in 87 minutes for white light. Plasma and erythrocyte porphyrin contents increased slightly, without exceeding normal levels. CONCLUSION: Our observations suggest that 5-aminolevulinic acid-induced porphyrin fluorescence may label malignant gliomas safely and accurately enough to enhance the completeness of tumor removal.

Aged↗
PubMed1998

Percutaneous sonographic gastrostomy: method, indications, and problems.

OBJECTIVES: This study evaluated the application of ultrasound (US) guidance in the percutaneous placement of gastric feeding tubes in patients in whom endoscopic placement of a nutrition tube is not possible. METHODS: Thirty-eight patients with upper gastrointestinal obstruction were entered in a prospective study with US-guided nutrition tube application. Feasibility of placement, side effects, and nutritional states were monitored for a mean follow-up of 4 months. RESULTS: Ultrasound allowed rapid puncture after filling of the stomach with water through a nasal tube in 34/38 cases. In four cases a total upper gastrointestinal obstruction required an initial stomach insufflation through a direct puncture. Puncture-related major complications were not observed. Minor complications during the observation time were one late dislocation, five cases with broken material after about 6 months (four could be changed by using the Seldinger technique), and two minor local infections. The nutrition through feeding tubes stabilized body weight and body composition parameters. CONCLUSION: The percutaneous sonographic gastrostomy (PSG) is a safe and minimally invasive procedure for enteral nutrition in all cases with upper gastrointestinal obstruction when endoscopic placement of a feeding tube is not possible. Percutaneous sonographic gastrostomy may help to stabilize the nutritional parameters and general condition in patients with malignant diseases.

Adult↗
PubMed1998

Hepatoma with severe non-islet cell tumor hypoglycemia.

We report a 22-yr-old male patient with chronic hepatitis B and a large, well differentiated hepatoma who developed episodes of symptomatic fasting hypoglycemia, which were caused by paraneoplastic secretion of unprocessed "big" insulin-like growth factor-II. Initially, the patient presented with normal liver function, which deteriorated during the clinical course. Therapeutic attempts to reduce tumor mass failed and the patient subsequently died because of metastases of the hepatoma. The pathophysiology of non-islet cell tumor hypoglycemia, differential diagnosis, and therapeutic options are discussed.

Adult↗
PubMed1998

In vitro activities of terbinafine against cutaneous isolates of Candida albicans and other pathogenic yeasts.

Terbinafine is active in vitro against a wide range of pathogenic fungi, including dermatophytes, molds, dimorphic fungi, and some yeasts, but earlier studies indicated that the drug had little activity against Candida albicans. In contrast, clinical studies have shown topical and oral terbinafine to be active in cutaneous candidiasis and Candida nail infections. In order to define the anti-Candida activity of terbinafine, we tested the drug against 350 fresh clinical isolates and additional strains by using a broth dilution assay standardized according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) M27-A assay. Terbinafine was found to have an MIC of 1 microg/ml for reference C. albicans strains. For 259 clinical isolates, the MIC at which 50% of the isolates are inhibited (MIC50) of terbinafine was 1 microg/ml (fluconazole, 0.5 microg/ml), and the MIC90 was 4 microg/ml (fluconazole, 1 microg/ml). Terbinafine was highly active against Candida parapsilosis (MIC90, 0.125 microg/ml) and showed potentially interesting activity against isolates of Candida dubliniensis, Candida guilliermondii, Candida humicola, and Candida lusitaniae. It was not active against the Candida glabrata, Candida krusei, and Candida tropicalis isolates in this assay. Cryptococcus laurentii and Cryptococcus neoformans were highly susceptible to terbinafine, with MICs of 0.06 to 0.25 microg/ml. The NCCLS macrodilution assay provides reproducible in vitro data for terbinafine against Candida and other yeasts. The MICs for C. albicans and C. parapsilosis are compatible with the known clinical efficacy of terbinafine in cutaneous infections, while the clinical relevance of its activities against the other species has yet to be determined.

Antifungal Agents↗
PubMed1998

Clinical outcome of transfemoral embolisation in patients with arteriovenous malformations of the liver in hereditary haemorrhagic telangiectasia (Weber-Rendu-Osler disease).

BACKGROUND: Arteriovenous malformations of the liver in Osler's disease may present as high output cardiac failure. A few case reports suggested that treatment with arterial embolisation may have beneficial effects in such patients. AIMS: To investigate the efficacy and safety of this treatment modality in a prospective pilot study. PATIENTS AND METHODS: Four women and one man (aged 39-59 years) with the dominant hepatic manifestation of Osler's disease presented with symptoms of cardiac failure and elevated cardiac output. Arteriovenous malformations were treated in three to five sessions with arterial embolisation using coils. The outcome was analysed by measurement of cardiac output and scoring of clinical symptoms. RESULTS: Embolisation was technically feasible in all patients and adequate occlusion of vascular malformations was achieved in four patients. After completion of therapy symptoms improved in four patients, while one patient suffered from abdominal pain due to cholangitis. One patient died seven months after the embolisation treatment from variceal bleeding. Mean cardiac output significantly decreased from 14.2 (range 12-17.3) l/min to 8 (range 5.9-10.6) l/min (p = 0.043). After a median follow up of 23 months (range 7-50 months), three of five patients had a long lasting improvement of clinical symptoms and cardiac function. CONCLUSIONS: This first treatment series of patients with dominant hepatic involvement in Osler's disease indicates that arterial embolisation may prevent cardiac failure by significantly lowering cardiac output.

Adult↗
PubMed1998

Prevalence of Helicobacter pylori-associated gastritis in chronic urticaria.

BACKGROUND: Chronic urticaria and concurrent angioedema are frustrating problems for both physicians and patients. METHODS: 100 patients with chronic urticaria (mean duration 33.3+/-48.2 months) attending the urticaria consulting hour of our Department of Dermatology within 1 year were carefully analyzed for pathogenesis to avoid extensive unnecessary diagnostic approach in the future. RESULTS: In 43 cases a potential infectious trigger could be identified, 35 were of idiopathic origin, and 15 demonstrated pseudoallergic reactions to acetylsalicylic acid or food additives, 5 had antibodies to thyroid gland, and 2 had malignant diseases. Of patients with foci, 26 had Helicobacter pylori-associated gastritis, 9 chronic tonsillitis or sinusitis, 4 infections with Epstein-Barr virus or cytomegalovirus, 2 dental focal infections and 2 suffered from Yersinia infection. High prevalence of H. pylori gastritis was found since 47% of patients showed elevated H. pylori-specific IgA and/or IgG antibodies. 27 patients underwent endoscopy and in all but 1 (96%) antral H. pylori infection was found. In contrast, a prevalence rate of 37% among asymptomatic adults has been published. Disappearance (67%) or improvement of urticaria (24%) occurred in most antimicrobially treated patients after 3-12 weeks. In contrast, only 50% of untreated H. pylori-seropositive patients with chronic urticaria showed spontaneous remission or improvement within 12 weeks. Prevalence of H. pylori infection may even be underestimated since only 27/100 patients underwent endoscopy. It is suggested that H. pylori infection may be present at least in all seropositive subjects (47%). Moreover, we found H. pylori infection in 2 seronegative subjects demonstrating gastric complaints. CONCLUSIONS: Thus, measurement of H. pylori-specific antibodies and/or gastroscopy should be included in the diagnostic management of chronic urticaria to identify patients who may profit from eradication treatment with disappearance of long-standing and annoying urticaria symptomatology.

Adolescent↗
PubMed1998

Assessing information in T2-weighted MRI scans from secondary progressive MS patients.

BACKGROUND: Magnetic resonance imaging is used routinely for diagnosing MS and for objective assessment of the extent of disease as a marker of treatment efficacy in MS clinical trials. Nevertheless, in many clinical studies only weak correlations have been reported between MRI findings and clinical outcome measures. PURPOSE: The purpose of this study is to compare clinical outcome measures (neurologic scales) with MRI findings (evaluation of T2-weighted MRI scans using a semiautomated quantitative technique and with an independent assessment by a neurologist) in the context of a randomized clinical trial evaluating the efficacy of cladribine for treatment in secondary progressive MS. METHODS: Baseline, 6-month, and 12-month scans from 41 secondary progressive MS patients were examined and ranked in terms of lesion burden from the quantitative assessment and independently in terms of severity by neurologic evaluation. Comparison is made to monthly Expanded Disability Status Scale (EDSS) and Scripps Neurologic Rating Scale (SNRS) determinations in these patients with a nonparametric statistical procedure. RESULTS: Average rank correlations between any of the MRI assessment procedures and either clinical outcome measure were less than 0.15 in absolute magnitude. The average rank correlation between the two MRI assessment procedures was 0.10. There is only a weak degree of association between the MRI assessment procedures and the clinical parameters, although the study has statistical power in excess of 0.90 to find even a moderate level of association between them. CONCLUSIONS: Disease-related activity in T2-weighted scans of secondary progressive MS patients is a multidimensional construct, and is not summarized adequately solely by quantification of overall lesion burden or by assessment of severity. Neither method of summarizing information from T2-weighted scans is strongly related to measures of the clinical course of disease as assessed by the EDSS or SNRS.

Disease Progression↗
PubMed1998

A rare case of bloody diarrhea: thrombosis of the V. mesenterica inferior following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has become the standard treatment for symptomatic cholecystolithiasis. The most common complications, as current experiences show, are bleeding, bile duct injury and non-technical complications like pneumonia. In some individual cases ischemic lesions of bowel by injury or thrombosis of intestinal vessels are described. Here we report the rare case of intestinal venous thrombosis following laparoscopic cholecystectomy. The complication clinically appeared within 24 h after operation starting with bloody diarrhea and mimicking inflammatory bowel disease. The patient, a 41-year old man, was treated with high-dose heparin and could be discharged after 44 days without complaints. Coloscopy six months after the event showed a restitution ad integrum.

Adult↗
PubMed1998

[Enteroparesis caused by progressive fibrosis of the muscularis propria].

We would like to present the case of a 54-year-old patient who was admitted to the hospital with complaints of recurrent vomitus after food intake and associated weight loss. Endoscopy. barium X-ray of the small bowel and scintigraphy showed enteroparesis. Full-thickness biopsies achieved by explorative laparotomy revealed the pathological changes. The inner circular muscular layer was atrophic and replaced by fibrosis. The pathological findings were consistened with either visceral myopathy or isolated intestinal progressive systemic sclerosis. A sporadic nonfamilial type of visceral myopathy seems to be the most likely diagnosis in this case. Progressive systemic sclerosis seems to be unlikely as the patient presented with isolated gastrointestinal involvement and lack of appropriate autoantibodies. The diseases progression made an enteral supplementation impossible. Therefore a parenteral nutrition was started, which was characterized by a complicated clinical course. Persisting gastrointestinal complaints, recurrent port infections and lack of perspectives led to patient's diminished motivation for adequate sterile use of the port-system. This case report shows that besides the use of modern port-systems and antibiotics the psychological situation of patients treated with total parenteral nutrition is of great interest for optimal patient care.

Diagnosis, Differential↗