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Biomedical subjects

G Herrmann

Publications and source records attributed to G Herrmann.

At least 109 records · Page 6Linked to original sources

[Sialadenitis at an unusual site in acute infectious mononucleosis].

Infectious mononucleosis is found worldwide. The clinical manifestations vary widely. We report a case with impressive swelling of the hard and soft palate. Inflammation in the region of the efferent ducts of the palatinal glands resulted in congestion in the region of the mucinous salivary glands. The subsequent secretory stasis caused degeneration of the acini and rupture of a salivary retention cyst. The surrounding connective tissue was soaked with mucin, and unspecific chronic granular inflammation was found. Immunohistochemical examination with a monoclonal EBV antibody was necessary to show that the exceptional clinical picture was due to infectious mononucleosis.

Adult↗

[Neurochemical studies of adrenergic reinnervation after heart transplantation].

Heart transplantation causes sympathetic cardiac denervation. Measurements of plasma concentrations of the main presynaptic noradrenaline metabolite, dihydroxyphenylglycol (DOPEG, the plasma pool of which is exclusively neuronal in origin), were used to examine sympathetic reinnervation of the transplanted human heart. We determined arterial and coronary-venous plasma concentrations of DOPEG in 27 heart transplant recipients (transplant age ranging from 0.5 to 5 years) and in 9 control patients. In each of the control patients the DOPEG concentration was higher in coronary venous plasma than in arterial plasma (mean arterio-venous increment: 57.3 +/- 8.7%; p < 0.001). However, in heart transplant recipients, 18 out of 27 patients showed an arteriovenous increment in plasma DOPEG (mean increment in all patients 12.6 +/- 2.0%; p < 0.05). The ratio of the coronary-venous to arterial DOPEG concentration was positively correlated with the time after transplantation (p = 0.02 for individual results and p < 0.01 for mean group results). Thus, our data provide evidence for a time-dependent partial sympathetic reinnervation of the transplanted heart.

Adrenergic Fibers↗

Computer-assisted prediction, classification, and delimitation of protein binding sites in nucleic acids.

We present a method to determine the location and extent of protein binding regions in nucleic acids by computer-assisted analysis of sequence data. The program ConsIndex establishes a library of consensus descriptions based on sequence sets containing known regulatory elements. These defined consensus descriptions are used by the program ConsInspector to predict binding sites in new sequences. We show the programs to correctly determine the significant regions involved in transcriptional control of seven sequence elements. The internal profile of relative variability of individual nucleotide positions within these regions paralleled experimental profiles of biological significance. Consensus descriptions are determined by employing an anchored alignment scheme, the results of which are then evaluated by a novel method which is superior to cluster algorithms. The alignment procedure is able to include several closely related sequences without biasing the consensus description. Moreover, the algorithm detects additional elements on the basis of a moderate distance correlation and is capable of discriminating between real binding sites and false positive matches. The software is well suited to cope with the frequent phenomenon of optional elements present in a subset of functionally similar sequences, while taking maximal advantage of the existing sequence data base. Since it requires only a minimum of seven sequences for a single element, it is applicable to a wide range of binding sites.

Algorithms↗

[Orthotopic liver transplantation with arterial re-anastomosis in the rat--a detailed description of technique and analysis of possible errors].

Liver transplantation (LTX) in the rat is a frequently used transplantation model. In the present study we give a detailed description of the suture technique for all anastomoses, except the bile duct, with arterialization of the transplanted liver over an aortoceliac segment to the recipient's aorta. Using this technique, we finally achieved survival rates of 80%. During the development stages, the main cause of death was an exceedingly long anhepatic time (> 20 min); later on, complications occurred only from insufficient anastomoses. The advantage of the suture technique over the cuff technique is that a more physiological anastomosis is obtained with less trauma to the recipient when using rearterialization. Despite the complicated suture technique, the anhepatic time can be well reduced to below 20 min.

Anastomosis, Surgical↗

Left main coronary artery stenosis after aortic valve replacement: genetic disposition for accelerated arteriosclerosis after injury of the intact human coronary artery?

BACKGROUND: Left main coronary artery stenosis is a rare but life-threatening complication after aortic valve replacement because of coronary perfusion-related trauma to the vessel wall with cannulation of the coronary ostia. We investigated whether this complication still occurs in the 1990s despite the use of more advanced catheter materials and modern surgical preservation techniques. METHODS: Four years after identification of the first two cases in 1987, five further patients had developed left main coronary artery stenosis after aortic valve replacement (incidence, 0.9%) at the cardiothoracic clinic of the J.W. Goethe University and were studied for contributing factors. RESULTS: Severe coronary ostial stenosis developed within 1 to 6 months after aortic valve replacement. In one such case, intimal proliferation was seen in a biopsy specimen that was comparable to the restenosis induced by coronary angioplasty. The clinical characteristics of the patients developing the complication, the surgical technique, and the intraoperative course did not differ from the other patients. However, five of the seven patients (71%) had a common genetic trait concerning their apolipoprotein E genotype (the epsilon 4 allele) that is normally present in only 10% to 15% of patients screened (P < 0.01). CONCLUSIONS: These lesions seem to result from a uniform response of the vessel wall to injury. Their incidence is probably related in part to the degree of injury after trauma to the coronary ostia during cannulation for myocardial protection. Patients with the epsilon 4 allele might be genetically predisposed for a pathologically increased response of proliferative repair mechanisms after arterial injury. The complication can be avoided by not instrumenting the coronary ostia for direct antegrade cardioplegia but using retrograde delivery as an alternative method of myocardial protection.

Adult↗

UVA-induced autocrine stimulation of fibroblast-derived-collagenase by IL-6: a possible mechanism in dermal photodamage?

Like other cytokines, IL-6 has been reported to stimulate collagenase. In this study we were interested in whether IL-6 is involved in the ultraviolet (UV) mediated up-regulation of fibroblast-derived collagenase. Confluent fibroblast monolayers were irradiated under standardized conditions. Following UVA irradiation the bioactivity of IL-6 increased up to fiftyfold in the supernatants of irradiated compared to mock-irradiated fibroblasts. As determined by Northern blot analysis this was also reflected on the pre-translational level by a tenfold increase of IL-6-specific mRNA following UVA irradiation. Induction of IL-6-specific mRNA was maximal at 6 h post-irradiation, thus clearly preceding the maximal induction of collagenase mRNA at 24 h post-irradiation. To elucidate the regulatory role of IL-6 in the UVA induction of fibroblast-derived collagenase, monospecific polyclonal neutralizing antibodies directed against recombinant human IL-6 and antisense oligonucleotides specifically inhibiting the translation of IL-6 mRNA were used at various concentrations. The amount of UVA-induced collagenase mRNA was reduced in a dose-dependent manner when antibodies or specific antisense oligonucleotides were present during and after irradiation. Taken together our data provide first evidence that UVA enhances IL-6 synthesis and secretion in fibroblasts. IL-6 induces via an autocrine mechanism collagenase and may thus contribute to the actinic damage of the dermis.

Actinin↗

UVA irradiation stimulates the synthesis of various matrix-metalloproteinases (MMPs) in cultured human fibroblasts.

UVA irradiation leads to photoaging including clinical features such as wrinkle formation, reduced recoil capacity and blister formation of the skin. Besides synthesis of the extracellular matrix, its regulated degradation by various matrix-metalloproteinases (MMPs) determines the amount and the composition of the extracellular matrix within the dermis and the basement membrane of the dermo-epidermal junction. In this study we therefore ascertained whether UV irradiation could modulate the synthesis of MMPs with substrate specificities for dermal (collagen I, III, V) and basement membrane compounds (collagen IV, VII, proteoglycans, laminin) and whether synthesis of the counteracting tissue inhibitor of metalloproteinases (TIMP-1) was also affected. Following UVA irradiation specific mRNAs of MMPs 1, 2 and 3 were induced concomitantly up to 5-fold compared to mock irradiated controls. In contrast, TIMP-1 mRNA levels remained unaltered. Immunoprecipitation indicated that after UVA irradiation synthesis and secretion of MMPs 1, 2 and 3 into the supernatant increased. Taken together, our data show that UVA irradiation coordinately induced MMPs 1, 2 and 3 implying similar mechanisms in their regulatory pathways, while TIMP-1 synthesis was not altered. Hence, unbalanced synthesis of MMPs potentially contributes to the dissolution of dermal and basement membrane compounds finally leading to blister formation and cutaneous photoaging.

Actins↗

[Morphometric, cytochemical and immunohistochemical studies on the proliferative activity of urinary bladder carcinomas].

58 carcinomas of the urinary bladder as well as 11 carcinomata in situ and 10 biopsies of normal mucosa were investigated for their proliferative activity by means of nuclear area morphometry, silver staining of nucleolar organizing regions (NOR) and immunohistochemical staining of the proliferating cell nuclear antigen (PCNA) and the Ki67 antigen. In comparison to normal bladder mucosa, the values were increased significantly (p < 0.05) in all carcinomata in situ and carcinomas. Within the carcinomas, there was an increase from G1- to G3-carcinomas. For all four parameters, the values of the carcinomata in situ and the G2-carcinomas were similar. All parameters correlated with each other and allowed a significant differentiation between G1- and G2-carcinomas (p < 0.05), whereas they allowed only a less optimal differentiation between G2- and G3-carcinomas. Of all markers of proliferation, the Ki67 antigen was the most useful criterium to differentiate between invasive and noninvasive carcinomas. A Ki67 index of 30% seems to be a borderline between these two groups. This could be of prognostic relevance especially for the heterogeneous G2-carcinomas.

Aged↗

Establishment and immunological characterization of cultured human gallbladder epithelial cells.

Biliary epithelial cells are a primary site of damage in liver allograft rejection and in immunologically mediated diseases such as primary biliary cirrhosis. Human leukocyte antigens and adhesion molecules on the biliary epithelium are associated with T-lymphocytic binding, recognition and destruction. To investigate relevant cellular immunological mechanisms under standard conditions, we have established an in vitro model using human gallbladder epithelial cells. Although not directly affected in these aberrations, gallbladder epithelial cells are excellent objects for immunological investigations. More than 10(8) highly purified cells were isolated and cultured longer than 6 wk in confluent monolayers. Cell growth was routinely established on uncoated plastic culture dishes, and serum-free media could be applied for immunological experiments. Cell characterization was performed by means of specific monoclonal antibodies typical for biliary epithelial cells. Cytokeratins 1 through 8, 18 and 19 and human epithelial cell antibody 125 always showed strong positive staining. Antigen patterns were examined before and after treatment with interferon-gamma by use of immunohistochemical staining methods. Untreated human gallbladder epithelial cells expressed human leukocyte class I antigens but few or no class II antigens. After stimulation with interferon-gamma induction of human leukocyte antigen-DR, -DP and -DQ was detected. In addition, intercellular adhesion molecule 1 was induced on these gallbladder epithelial cells. Therefore an immunological competence similar to that of biliary epithelial cells could be demonstrated. In vitro cell cultures of gallbladder epithelial cells offer a promising tool for subsequent investigations concerning intrahepatic biliary epithelial cells and their interactions with cells of the immune system.

Biomarkers↗

[Heart volume determination as an indication of rejection after orthotopic heart transplantation].

Endomyocardial biopsy in cardiac transplantation is still the most exact test (gold standard) to confirm or exclude a suspected rejection. Up to now, all available noninvasive tests suffer from a low sensitivity and specificity. For a further reduction of biopsies early available noninvasive methods are desirable. In the data presented a comparison between histological findings and heart volume measurements is shown in 40 patients (112 histological findings) after orthotopic cardiac transplantation. In 46 cases with no evidence of histological rejection the echocardiographically or radiologically determined heart volume was 869 +/- 142 ml/1.73 m2 body surface area, compared to 1026 +/- 178 ml/1.73 m2 in 29 cases with mild cardiac rejection. In 37 cases with a moderate or severe rejection heart volume as 1094 +/- 181 ml/1.73 m2. The diagnosis of a moderate or severe rejection by biopsy is combined with a heart volume above 950 ml/1.73 m2 with a sensitivity of 78% and a specificity of 73%. Intramyocardial edema as well as an increase in right and left ventricular volumes due to heart failure may be the causes for heart volume increase in rejection. Thus, heart volume measurement which can be performed easily during routine echocardiography gives additional information about whether a rejection has to be assumed or can be excluded. Today, sensitivity and specificity of the test does not allow a reduction of biopsy frequency. Further investigations are necessary to analyze the course of heart volume changes during an episode of rejection.

Biopsy↗

Automated compounder for adding ingredients to parenteral nutrient base solutions.

The effects of using an automated compounder for adding ingredients to parenteral nutrient (PN) base solutions was evaluated. Work-sampling methods were used to determine the amount of time spent by pharmacists and technicians in the production of PN solutions before and after the implementation of an automated device for adding ingredients to PN base solutions. Costs of materials and supplies were evaluated before and after the PN compounder was implemented. Qualitative (sterility) and quantitative (accuracy) analyses were performed by the hospital laboratory. A personnel time savings of 5.4 minutes per PN solution (1.0 full-time equivalent [FTE]) was shown. There was also an additional 0.5 FTE saved in activities not directly related to PN production. There was a 1.5% increase in pharmacist time (mean +/- S.D. preimplementation, 12.66 +/- 2.33 minutes; postimplementation, 12.85 +/- 1.96 minutes) and a significant 27.9% decrease in technician time (mean +/- S.D. preimplementation, 20.29 +/- 2.47 minutes; postimplementation, 14.62 +/- 2.24 minutes) per PN solution. The break-even point for personnel and supply costs was 33 PN solutions. Qualitative analysis resulted in one positive culture preimplementation and no positive cultures postimplementation. Quantitative analysis showed an improvement in compounding accuracy. The use of an automated compounder for adding ingredients to PN base solutions resulted in personnel time savings and improved accuracy.

Automation↗

[An aortopulmonary shunt after a knife wound].

An extensive hemopneumothorax developed in a 23-year-old man after having been knifed in the region of the left nipple. After general surgical care a Bülau suction drain was inserted. Cardiological examination became necessary a week later when a chest X-ray film demonstrated an enlarged cardiac silhouette. Echocardiography revealed pericardial effusion (about 600 ml) which was removed by pericardial aspiration. Cross-sectional and colour Doppler echocardiography showed a shunt between the aorta and right ventricular outflow tract at the origin of the pulmonary artery. At surgery a fistula between the root of the aorta and the pulmonary artery was identified (the posterior sinus near the anulus was nearly completely detached). The fistula was closed and the pulmonary valve reconstructed. The early and late postoperative course was unremarkable.

Adult↗

[Proliferation kinetic studies in the syngeneic liver transplantation mode in the rat. Effect of re-arterialization on the transplant].

Successful orthotopic liver transplantation (OLT) can be achieved in the rat. We used bromo-2-deoxyuridine (BrdU) as a proliferation marker to document morphological differences between OLT with and without rearterialization. Animals with portal anastomosis alone had a significantly increased proliferation rate of hepatocytes, Kupffer cells, and bile duct epithelial cells, as indicated by strong staining with BrdU, 8 days post-transplant compared to animals with rearterialization. Regeneration of ischemically damaged liver parenchymal cells may account for this observation. Thus, OLT with rearterialization appears to be the more physiological transplant model.

Anastomosis, Surgical↗

Structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BV-araU, V-araU) in inhibition of Epstein-Barr virus replication.

The structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BV-araU and V-araU) in inhibition of Epstein-Barr virus (EBV) was evaluated. Both V-araU and BV-araU effectively inhibited EBV replication in virus-producer P3HR-1(LS) cells, as determined by DNA-DNA hybridization. The 50% effective doses (ED50) for viral DNA replication were 0.005 and 0.3 microM for V-araU and BV-araU, respectively. The in vitro therapeutic index was 4000 for V-araU and 1300 for BV-araU. Synthesis of EBV-induced polypeptides with molecular weights of 145,000 (145, 140, 130, and 110 kDa) was significantly inhibited by both drugs. Only V-araU inhibited the synthesis of 85-, 55-, and 32-kDa polypeptides by approx. 50%. Kinetic analysis of inhibition and reversibility of EBV DNA replication after removal of the drugs indicated that BV-araU has a more prolonged inhibitory effect than V-araU. These results indicate that the substitution of H by Br in the 5-vinyl group results in marked reduction in anti-EBV activity while prolonging the drug effect and diminishing cytotoxicity.

Antiviral Agents↗

Immunocytochemical characterization of cytomegalovirus (CMV) infected giant cells in perinatal acquired human immunodeficiency virus (HIV) infection.

In a pediatric case of necrotizing CMV myelitis after perinatal HIV infection characteristic cytomegalic cells, which could not be attached to a particular cell line by cell morphology, were studied after immunostaining with monoclonal and polyclonal antibodies raised against GFAP, S100 protein, NSE, synaptophysin, factor VIII, vimentin, macrophages, leukocytes, CMV, HSV I + II, toxoplasma, and HIV 1 gp41. Astrocytes, oligodendrocytes, neurons, ependymal and endothelial cells, macrophages, and Schwann cells stained positively with CMV antiserum. With regard to their immunological features the majority of cytomegalic cells ("owl eye cells") was identified as astrocytes, and in decreasing frequency, the remainder was characterized as macrophages, mesenchymal, and endothelial cells. It is concluded that CMV giant cells represent one phase of virus induced cell transformation, not only one single, but numerous cell types are exposed to after CMV infection.

Acquired Immunodeficiency Syndrome↗

Rapid development of giant aneurysm at the base of the brain in an 8-year-old boy with perinatal HIV infection.

An 8-year-old boy with perinatal HIV infection developed a large fusiform aneurysm in the circle of Willis two years prior to death which was confirmed by radiological studies. The postmortem examinations revealed a predominantly intimal, proliferative lesion, and partial destruction of the internal elastic lamina in the involved arteries. Within the intima hyperplasia of fibroblasts and smooth muscle cells was observed. No inflammatory alterations, no granulomas and no multinucleated giant cells could be noted in the vascular walls and in the cerebral parenchyma. A small ischemic infarct was present in the left thalamus. Cerebellum, brainstem and medulla showed multiple areas of progressive multifocal leukoencephalopathy (PML). Immunohistochemistry with anti-gp41, a monoclonal antibody against HIV envelope did not exhibit any positive results. These findings implicate that the vascular lesion might be attributed to primary infection of the brain by HIV which led to a defect of elastic lamina and consecutive intimal hyperplasia. A second hypothesis could be based on the effect of extremely high dose AZT therapy avoiding inflammatory reaction after HIV infection.

Acquired Immunodeficiency Syndrome↗

Stimulation of cell division and fibroblast focus formation by antisense repression of retinoblastoma protein synthesis.

Circumstantial evidence supports a role for the retinoblastoma susceptibility gene, Rb-1, in the maintenance of normal cell growth, in that loss of its function results in abnormal growth and malignancy. Here we report that a high rate of mitosis and efficient dense focus formation in human embryonic lung fibroblasts (HEL cells) is induced by antisense oligonucleotide-directed inhibition of synthesis of p105-Rb, the product of the Rb-1 gene. mRNA specific for p105-Rb is truncated at the site of base pairing with the antisense oligonucleotide, and no synthesis of p105-Rb is observed. The rate of mitosis is considerably increased and the frequency of dense focus formation is extremely high in treated cells. However, although phosphothioate oligodeoxyribonucleotides taken up by the cells remain stable for at least 4 weeks, the recipient cells do not become immortal; nor are they able to induce tumor formation in nude mice. Thus, loss of Rb-1 function is not sufficient per se to allow malignant transformation.

Base Sequence↗