Biomedical subjects

H Nagel

Publications and source records attributed to H Nagel.

At least 19 recordsLinked to original sources

PubMed2004

Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1, -2, and -3 in benign and malignant tumours of the salivary gland.

AIMS: The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is involved in the morphogenesis of the normal salivary gland as well as in mechanisms of tumour invasion and metastasis. Our aim was to analyse protein and mRNA expression of MMPs and TIMPs in normal salivary gland tissue and in various salivary gland neoplasms. METHODS AND RESULTS: Immunohistochemistry for MMP-2, MMP-9, TIMP-1, -2 and -3 was performed in 20 malignant and six benign salivary gland tumours. The immunoscores of MMP-2 were significantly higher in carcinomas compared with adenomas (P = 0.0028). The MMP/TIMP ratio was significantly higher in carcinomas than in adenomas (P = 0.0097). In mucoepidermoid carcinomas MMP-2 expression was preferentially observed in the intermediate cell type. Neoplastic acinar cells of acinic cell carcinoma demonstrated de novo expression of MMP-2, MMP-9, TIMP-1, and TIMP-2. Immunoscores of TIMP-3 were not decreased in malignant tumours compared with adenomas. In accordance with the immunostaining of MMP-2 and -9, gelatinolytic activity could be demonstrated by in-situ zymography. The mRNA expression of MMPs and TIMPs analysed by real-time reverse transcriptase-polymerase chain reaction in three malignant and two benign tumours and their corresponding normal tissue did not generally correlate with their protein expression. CONCLUSIONS: Our findings suggest a disturbed balance between MMP and TIMP in malignant salivary gland tumours. MMP-2 expression in particular seems to be related to the invasive properties and the malignant potential of these tumours.

Adenoma↗

PubMed2003

The alphavbeta5 integrin of hematopoietic and nonhematopoietic cells is a transduction receptor of RGD-4C fiber-modified adenoviruses.

Epithelial and endothelial cells expressing the primary Coxsackie virus B adenovirus (Ad) receptor (CAR) and integrin coreceptors are natural targets of human Ad infections. The fiber knob of species A, C, D, E and F Ad serotypes binds CAR by mimicking the CAR-homodimer interface, and the penton base containing arginine-glycine-aspartate (RGD) motifs binds with low affinity to alphav integrins inducing cell activation. Here, we generated seven different genetically modified Ad vectors with RGD sequences inserted into the HI loop of fiber knob. All mutants bound and infected CAR and alphav integrin-positive epithelial cells with equal efficiencies. However, the Ads containing two additional cysteines, both N and C terminals of the RGD sequence (RGD-4C), were uniquely capable of transducing CAR-less hematopoietic and nonhematopoietic human tumor cell lines and primary melanoma cells. Both binding and transduction of RGD-4C Ad were blocked by soluble RGD peptides. Flow cytometry of cell surface integrins and virus binding to CAR-less cells in the presence of function-blocking anti-integrin antibodies indicated that the alphavbeta5 integrin, but not alphavbeta3, alphaIIbbeta3 or beta1,alpha5 or alpha6-containing integrins served as a functional transduction receptor of the RGD-4C Ads. However, in cells with low levels of alphavbeta5 integrin, the function-blocking anti-alphavbeta5 antibodies were not effective, unlike soluble RGD peptides. Collectively, our data demonstrate that the alphavbeta5 integrin is a functional transduction receptor of RGD-4C Ads in the absence of CAR, and that additional RGD receptors are targets of these viruses. The RGD-4C vectors further extend the tropism of Ads towards potential human therapies.

Adenoviridae↗

PubMed2003

Analysis of the tumour suppressor genes, FHIT and WT-1, and the tumour rejection genes, BAGE, GAGE-1/2, HAGE, MAGE-1, and MAGE-3, in benign and malignant neoplasms of the salivary glands.

AIMS: Molecular genetic changes involved in tumorigenesis and malignant transformation of human tumours are novel targets of cancer diagnosis and treatment. This study aimed to analyse the expression of putative tumour suppressor genes, FHIT and WT-1, and tumour rejection genes, BAGE, GAGE-1/2, MAGE-1, MAGE-3, and HAGE (which are reported to be important in human cancers), in salivary gland neoplasms. METHODS: Gene expression was analysed by reverse transcription polymerase chain reaction (RT-PCR) in normal salivary gland tissue and 44 benign and malignant salivary gland tumours. RESULTS: Aberrant FHIT transcripts were found in one of 38 normal salivary glands, three of 28 adenomas, and two of 16 carcinomas. WT-1 mRNA was detectable in two adenomas and five carcinomas. Immunoblotting showed that WT-1 mRNA expression was associated with raised WT-1 protein concentrations. RT-PCR for detection of BAGE, GAGE, and MAGE gene expression was positive in two adenomas and nine carcinomas, but negative in normal salivary gland tissue. HAGE mRNA was found in two normal salivary glands, 11 benign, and eight malignant tumours. CONCLUSIONS: FHIT mRNA splicing does not appear to be involved in the genesis of salivary gland neoplasms. The upregulation of WT-1 mRNA in tumours of epithelial/myoepithelial phenotype may imply a potential role of WT-1 in the genesis and/or cellular differentiation of these salivary gland tumours. The tumour rejection genes were more frequently, but not exclusively, expressed in malignant salivary gland tumours than in benign neoplasms, although none was suitable as a diagnostic marker of malignancy in salivary gland neoplasms.

Acid Anhydride Hydrolases↗

PubMed2001

Gene expression analysis of the catalytic subunit of human telomerase (hEST2) in the differential diagnosis of serous effusions.

Diagnostic accuracy in effusion cytology based on morphologic examination is not always satisfactory. Therefore, various diagnostic adjuncts such as immunocytochemistry or deoxyribonucleic acid cytometry are employed in this diagnostic field. Recently, demonstration of telomerase activity has been proposed as a possible marker for malignancy. In this study a seminested reverse transcription-polymerase chain reaction (RT-PCR) strategy for expression analysis of the catalytic subunit of human telomerase (hEST2) was used in 58 serous effusions. RT-PCR results correlated with cytologic diagnoses in 14 of 17 malignant effusions. In eight effusions cytologically suspicious for malignancy, PCR results were in accordance with the clinical follow-up. However, hEST2 RT-PCR was also positive in six of 15 cytologically benign effusions that consisted predominantly of inflammatory and mesothelial cells. Using the telomeric repeat amplification protocol, it could be demonstrated that cultured, proliferating benign mesothelial cells may present a weak telomerase activity, as is known in other benign cells including activated lymphocytes. In conclusion, the simple and rapid method of hEST2 RT-PCR serves to support the cytologic diagnosis of malignancy, but false-positive PCR results resulting from activated lymphocytes and proliferating mesothelial cells must be considered.

Ascitic Fluid↗

PubMed2001

Genetic analysis of the human oncoprotein MDM2 in benign and malignant tumors of the salivary gland.

INTRODUCTION: Genetic alterations of oncogene MDM2 promote malignant transformation of several human tumors. In tumors of the salivary gland, however, the genetic status of MDM2 has not been evaluated so far. METHODS AND RESULTS: Benign and malignant tumors of the salivary gland (6 pleomorphic adenomas, 3 Warthin's tumors, 1 adenocarcinoma, 1 basal cell adenocarcinoma, 1 mucoepidermoid carcinoma, 3 acinic cell carcinomas, 2 adenoid cystic carcinoma, 1 squamous cell carcinoma) were analyzed by fluorescence-based PCR techniques and immunochemistry for MDM2 gene amplification, MDM2 gene expression, MDM2 gene mutation, MDM2 RNA splicing and MDM2 accumulation. Data show that all samples contained nonamplified MDM2 genes with nonmutant zinc finger regions. However, in two benign and two malignant samples, novel MDM2 mRNA splicing variant types 1 and 2 were detected. Furthermore, three malignant tumors revealed significant nuclear MDM2 accumulation. Correlation between levels of MDM2 mRNA and MDM2 protein could not be detected in the specimens. CONCLUSION: The present study suggests that MDM2 gene mutation and gene amplification do not contribute to MDM2 accumulation detected in malignant tumors of the salivary gland. However, the role of novel MDM2 splicing variants in MDM2 expression and malignant transformation must be elucidated further.

Adenoma↗

PubMed2000

Long-term photoepilation using a broad-spectrum intense pulsed light source.

BACKGROUND: The goal of laser or flashlamp photoepilation is to produce long-term, cosmetically significant hair removal. We document the long-term efficacy achieved with an intense pulsed light source for photoepilation. DESIGN: Prospective study comparing long-term results of single vs multiple treatments, and effects of anatomic site and skin type on efficacy of photoepilation with a device emitting broad-spectrum, noncoherent (nonlaser) radiation from 550- to 1200-nm wavelengths, in macropulses divided into 2 to 5 minipulses. SETTING: Private dermatology practice. PATIENTS: Thirty-four patients (8 men, 26 women) with hirsutism. INTERVENTIONS: Parameters for the study were wavelength of 615 to 695 nm, pulse duration of 2.6 to 3.3 milliseconds, fluence of 34 to 42 J/cm(2), 10 x 45-mm exposure field, and application of 1 degrees C cooling gel. MAIN OUTCOME MEASURES: Hair removal efficiency, calculated as percentage ratio of the number of hairs present compared with baseline counts, and patient satisfaction questionnaire completed at last follow-up. RESULTS: The mean hair removal efficiency achieved was 76% after a mean of 3.7 treatments. More than 94% of the sites reached mean hair removal efficiency values greater than 50%. Hair removal efficiency was not significantly related to skin type, hair color, anatomic site, or number of treatments. Side effects were mild and reversible and occurred in a minority of patients (hyperpigmentation in 3 and superficial crusting in 2). CONCLUSIONS: Our data document the long-term clinical efficacy of intense pulsed light source-induced hair removal in light and dark skin phenotypes. Maximal photoepilation was achieved from the initial 1 to 3 treatments; only a small added benefit was seen after more treatments.

Adolescent↗

PubMed2000

Cytologic diagnosis of medullary carcinoma of the thyroid gland.

The cytomorphologic features in fine-needle aspiration (FNA) biopsies from 91 histologiacally verified medullary carcinomas of the thyroid (MCT) were investigated. FNA was able to diagnose neoplasms with indications of surgical removal in 98.9% of cases and moreover, was accurate in specific tumor typing in 89% of cases. The most important cytologic criteria of MCT with FNA are: dispersed cell-pattern of polygonal or triangular cells, azurophilic cytoplasmic granules, and extremely eccentrically placed nuclei with coarse granular chromatin and amyloid. These and other cytologic features of MCT are discussed in detail. Fourteen cases of thyroid tumors originally diagnosed as MCT by cytology are illustrated to discuss the differential diagnosis of MCT and its potential pitfalls. If MCT is cytologically presumed but amyloid and azurophilic cytoplasmic granules are not demonstrated, the use of immunostaining is necessary for a correct tumor typing. The application of immunocytochemistry in MCT is discussed.

Adult↗

PubMed2000

Diagnostic value of urinary alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase in comparison to alpha 1-microglobulin as a marker in evaluating tubular dysfunction in glomerulonephritis patients.

To estimate the diagnostic value of tubular parameters, the urinary alanine aminopeptidase (AAP), N-acetyl-beta-D-glucosaminidase (NAG) and the alpha(1)-microglobulin (a1M) of 150 patients with histologically proven glomerulonephritis (GN) were determined. In addition, the reabsorption rate of the proximal tubule and the fractional excretion of sodium, the free water clearance and the renal function were assessed by inulin and p-aminohippurate (PAH) clearance. Compared to healthy controls, urinary AAP, NAG and a1M were found significantly elevated in GN patients. Morphological tubular changes were confirmed by significant differences in urinary laboratory parameters. In patients with tubular atrophy, the diagnostic sensitivity and specificity were calculated as follows: AAP (0.94/0.35), NAG (0.75/0.59) and a1M (0.73/0.52). In patients showing tubular protein droplets, the values were 0.90/0.17 for AAP, 0.78/0.76 for NAG and 0.84/0.74 for a1M and in patients with interstitial fibrosis, the values were AAP (0.95/0.35), NAG (0.75/0. 46) and a1M (68/0.38). Urinary AAP, NAG and a1M reflect histologically proven tubulus alteration in GN, although in most cases, the renal function is still intact. AAP indicates very early tubular impairment and, in some cases, AAP is elevated although NAG and a1M are still within normal ranges. We suggest that the enzyme activities are useful in the diagnostics of early stages of the disease.

Acetylglucosaminidase↗

PubMed1999

Cytologic diagnosis of adenoid cystic carcinoma of salivary glands.

The cytomorphologic features in fine-needle aspiration (FNA) biopsies from 31 primary and 33 recurrent adenoid cystic carcinomas (ACC) were investigated. The correct FNA diagnosis was established in 24 of 31 primary ACC (77%). The diagnostic clue in aspirates from ACC are large globules of extracellular matrix, partially surrounded by basaloid tumor cells. In FNAs with predominance of basaloid tumor cells, but lacking characteristic globules, all other benign and malignant salivary gland tumors of epithelial-myoepithelial differentiation should be considered in the cytologic diagnosis. Pleomorphic adenoma is most frequently confused with ACC, and therefore, the cytologic findings in FNAs from 50 pleomorphic adenomas were compared with those diagnosed as ACC. Furthermore, rare neoplasms of salivary glands with epithelial-myoepithelial cell differentiation, including basal-cell adenoma and carcinoma, epithelial-myoepithelial carcinoma, and polymorphous low-grade adenocarcinoma, as well as some nonsalivary gland neoplasms presenting an adenoid cystic pattern, must be considered. The cytologic features of these entities are discussed in detail with respect to the cytologic diagnostic criteria of ACC.

Adenoma, Pleomorphic↗

PubMed1999

Plexiform leiomyoma of the uterus in a patient with breast carcinoma: case report and review of the literature.

Plexiform leiomyomas of the uterus are incidental findings in hysterectomy specimens. Histogenetically, these rare tumors are classified as a variant of epithelioid leiomyomas. Most of the plexiform leiomyomas reported range in size from microscopically small lesions to less than 1 cm in largest diameter, and they macroscopically present as a nodular white-yellowish cut surface. Microscopically, the "Indian-file" pattern of epithelial-like tumor cells of plexiform leiomyomas may be confused with metastatic breast carcinoma, in particular lobular breast carcinoma, i.e.; one of the most frequent extragenital neoplasms metastasizing to the uterus. This report describes the occurrence of a large plexiform leiomyoma in a patient with a history of breast carcinoma, and draws attention to the histological differential diagnosis between these lesions. The results of immunohistochemical stainings for cytokeratin and smooth muscle actin confirmed the final diagnosis of plexiform leiomyoma.

Aged↗

PubMed1998

The value of anti-calretinin antibody in the differential diagnosis of normal and reactive mesothelia versus metastatic tumors in effusion cytology.

In effusion cytology the distinction of reactive mesothelia from metastatic carcinoma cells may be a diagnostic challenge. Immunocytochemistry using antibodies suitable to detect epithelial cells must be considered carefully due to limited sensitivity and specificity of these antibodies. Efficient results in histological differential diagnosis of malignant mesothelioma versus lung-adenocarcinoma applying a novel antiserum against the calcium binding protein calretinin inspirated us to investigate the value of anti-calretinin antibody in effusion cytology combined with an epithelial marker. Cytoslides prepared by cytocentrifugation from 42 malignant and 65 reactive effusion specimens were immunostained using antibodies against calretinin and the epithelial marker Ber-EP4. Positive immunoreaction for calretinin in normal and reactive mesothelial cells was noted in 93% of the cases, whereas immunoreaction for calretinin was completely negative in the metastatic cells in 95% of the malignant effusions. Metastatic carcinoma cells were detected with anti-Ber-EP4 in 83% of malignant effusions. Non-specific positive reactions for Ber-EP4 in single mesothelial cells were observed in 16% of all cases and, moreover, frequently with macrophages or neutrophilic granulocytes. Our results demonstrate high sensitivity and specificity of anti-calretinin antibody for mesothelial cells in effusion specimens. They support its application to improve the diagnostic reliability of epithelial markers, especially because anti-calretinin antibody could be helpful in the assessment of false positive and false negative reactions of epithelial markers.

Antibodies, Monoclonal↗

PubMed1998

The in situ polymerase chain reaction for detection of chlamydia trachomatis.

The in situ polymerase chain reaction (PCR) is a technique that has important applications in the diagnosis of viral and bacterial diseases. This study investigated an in situ PCR assay established to detect the presence of Chlamydia trachomatis in endocervical swabs. In addition, histological sections of endocervical squamous cell carcinoma were analyzed because previous studies had revealed a significant association with C. trachomatis. A total of 20 cervical neoplasms (squamous cell carcinoma in situ; n = 10; invasive squamous cell carcinoma; n = 10) and endocervical smears taken from five patients with and without inflammatory changes were analyzed by conventional PCR. Chlamydial DNA was found in 10 histological samples (six carcinomas in situ, four invasive carcinomas) and in one endocervical swab from a patient with known C. trachomatis infection. Positive specimens were used for establishing an in situ PCR assay (IS-PCR). After IS-PCR, these samples showed dense cytoplasmic staining of endocervical cells (smears) and non-neoplastic epithelial cells (cervical neoplasms). The other tumor samples and smears did not demonstrate positive PCR reaction. The results indicate that in situ PCR is an effective technique for localizing C. trachomatis in target cells because IS-PCR detection of chlamydial DNA correlated with histological and cytological features.

Adult↗

PubMed1997

Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumours.

This study investigates the human oncoprotein MDM2, which interferes with regulation of cell division and apoptosis. Fifteen mixed-type follicular non-Hodgkin's lymphomas, ten leukaemias, two hepatocellular carcinomas, one osteosarcoma, and ten normal cell lines (fibroblasts, osteoblasts, mesothelium, peripheral lymphocytes) were tested for MDM2 expression and MDM2 gene mutation by reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and nucleotide sequence analysis. Two follicular lymphomas, three leukaemias, both hepatocellular carcinomas, and the osteosarcoma sample showed transcription of the activated MDM2 gene. These samples lacked amplified MDM2 genes and carried mis-sense, non-sense and frame-shift mutations in a zinc finger region of MDM2, altering the amino acid sequence or causing premature termination of transcription. The mis-sense mutations were found in tumour cells that showed significant accumulation of MDM2 and lack of nuclear p53. Non-sense mutations and frame-shift mutations were found in tumours lacking MDM2 proteins. The mutations may affect the biological properties of MDM2 proteins.

Amino Acid Sequence↗

PubMed1997

Cytologic diagnosis of acinic-cell carcinoma of salivary glands.

The cytologic findings in fine-needle aspiration (FNA) biopsies obtained from 40 primary and 18 recurrent acinic-cell carcinomas (ACC) were retrospectively analyzed. Cytomorphologically, ACC is characterized by acinar differentiated tumor cells. In addition to these diagnostic clue cells, other types of neoplastic cells including vacuolated cells, cells resembling oncocytes, and nonspecific glandular cells are encountered. A pronounced lymphocytic reaction is a hallmark in 10% of ACC aspirates. Both the variety of tumor cell differentiation and the pronounced lymphocytic reaction observed in ACC aspirates may result in confusion with other salivary gland lesions. The differential diagnosis of ACC encompasses adenocarcinoma, mucoepidermoid carcinoma, pleomorphic adenoma, Warthin tumor, sebaceous lymphadenoma, benign lymphoepithelial lesion, sialoadenosis, sialadenitis caused by radiotherapy, and lymphadenitis. Primary ACCs were correctly diagnosed in 68%; additionally, ACC was suspected or included in the differential diagnosis in 15%. Increased familiarity with the spectrum of cytomorphologic findings and the potential diagnostic pitfalls in ACC will improve the cytodiagnosis of this neoplasm.

Biopsy, Needle↗

PubMed1997

Interstitial adenosine and serotonin in the feline lumbar spinal cord during short-term ischaemia.

During controlled ischaemia (aortal snare occlusion) of the lumbar spinal cord, microcirculatory (laser-Doppler flowmetry) and segmental neurophysiological parameters (monosynaptic reflexes, polysynaptic reflexes, cord dorsum potential=CDP) as well as interstitial concentrations of adenosine and serotonin (5-HT) were determined in the grey matter using the microdialysis/HPLC method. Ischaemic periods of 1-7 min with a residual blood flow in the lumbar spinal cord of 10-30 % of the preischaemic control blood flow caused a blockade of spinal pathways and an increase of concentrations of interstitial adenosine and 5-HT. This increase started immediately after the initiation of the ischaemic period and reached a maximum at the end or shortly after the end of the ischaemic period during postischaemic hyperaemia. A close correlation between the duration of ischaemia and the interstitial concentration of adenosine and 5-HT was not found. Repetition of ischaemic periods in an experiment did not lead to an extracellular accumulation or an exhaustion of the release of 5-HT, whereas some indication was found for an exhaustion of adenosine release. The course of the increase of interstitial adenosine and 5-HT was partly found to correlate to the loss and recovery of the CDP following ischaemia. The concentrations usually reached control levels before spinal reflexes reappeared. The highly dynamic changes in concentrations of adenosine and 5-HT in the extracellular space of the spinal cord during and after short-term ischaemia revealed some relation to the time course of recovery of segmental spinal functions by reflecting the course of spinal neuronal metabolism.

Adenosine↗

PubMed1995

The hypothalamic-pituitary-adrenal axis in obesity.

The hypothalamic-pituitary-adrenal (HPA) axis normally maintains the concentration of cortisol within a narrow range with a diurnal variation characterized by higher cortisol concentrations in the morning and reduced levels in the evening. Excessive or deficient secretion of cortisol is associated with pathologic changes. Obesity has been linked with age, sex and racial alterations in the functioning of the HPA axis which are reviewed. The possible relationship of altered HPA axis activity with the long-term complications of obesity are considered.

Adrenocorticotropic Hormone↗

PubMed1994

Sterylsulfatase expression in normal and transformed human placental cells.

Isolated cytotrophoblast cells and choriocarcinoma cell lines are commonly applied in-vitro systems for the study of human placental endocrine function. We tested these normal and transformed placental cells for expression of the enzyme sterylsulfatase which is necessary for the production of free steroids from sulfoconjugated precursors in the placenta as well as in other human tissues, and compared the results with respective data obtained from term placental tissue. Specific sterylsulfatase activity was highest in placental homogenates but was lower by about a factor of 5 to 10 in homogenates of freshly isolated cytotrophoblast or JEG-3 cells and by about a factor of 100 in BeWo cell homogenates; the enzyme activity could not be detected in Jar cells. Sterylsulfatase mRNA levels as analyzed by Northern blotting roughly paralleled the levels of enzyme activity measured in cytotrophoblast, JEG-3, and BeWo cells; in Jar cells, RNA species complementary to the specific probe were clearly detectable but differed by size from the mRNA species found in the other cells. Our results indicate that sterylsulfatase activity is differently expressed in normal and transformed placental cells due to different rates or products of gene transcription in these cells.

Arylsulfatases↗

PubMed1994

[Expectant management of premature rupture of fetal membranes before completion of the 35th week of pregnancy--retrospective analysis of 44 cases].

44 cases of preterm premature rupture of fetal membranes (PPROM) before 35 completed weeks of gestation were analyzed retrospectively. Expectative management was based on infection diagnosis, vaginal disinfection and in case of signs of infection on systemic antibiotic therapy. Glucocorticoids for induction of lung maturity were generally administered. Perinatal mortality was 11.4%, after exclusion of one congenital anomaly 9.3% respectively. Lung immaturity was the main cause of neonatal death. Only 5 neonates developed clinical infection, with 4 of these showing prepartal maternal signs of infection. Maternal signs of infection are not a specific signal for later neonatal infection. Cerebral bleeding complications and pathological neurologic status occurred in 10/39 and 8/39 cases respectively. Cesarean section rate amounted to 15/44 (34%).

Adolescent↗