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Biomedical subjects

H Maier

Publications and source records attributed to H Maier.

At least 55 records · Page 3Linked to original sources

Apoptosis signals in sporadic amyotrophic lateral sclerosis: an immunocytochemical study.

Sporadic amyotrophic lateral sclerosis (sALS) is a neurodegenerative disorder of unknown cause characterized by selective loss of both upper and lower motor neurons. Whether neuronal death in sALS is due to apoptosis has so far not been clarified. In this study, the expression and distribution patterns of pro- and anti-apoptotic bcl-2 family members as well as the executioner caspase-3 were investigated in post-mortem CNS tissue of eight sALS patients and seven age-matched controls. Sparse motor neurons were immunoreactive for bcl-2, bax, bak, and CM1 on serial sections through the spinal cord and motor cortex of individual sALS patients and controls. However, there was no obvious difference in the numbers of immunoreactive (IR) neurons between the two groups. The study did not find evidence for apoptosis as a major mechanism of motor neuronal cell death in sALS.

Aged↗

[The role of yaws in the serologic screening of treponematoses in blood donors in Martinique].

Using TPHA instead of VDRL for syphilis blood-screening since 1995 showed an important increase of positive blood donors in Martinique. Yaws, another treponema disease, has been present on the island until 1975-1980. Usual tests are unable to identify which type--venereal or non venereal--of treponema is involved. Our study, carried out from January 1995 to May 1999, compares actual serological and epidemiological characteristics of TPHA reactive donors to former studies. In our results, the frequency of reactive TPHA is about 1.04% in blood donations. Donors are carrying serological tracks of a past treponema disease with very low rate of antibodies, sometimes linked to yaws. Among donors aged 18 to 30, prevalence is low and is going to become similar to the rate observed in Continental France. This means that this problem will disappear in new donor generations. We suggest the possibility for them to continue blood donation, if their personal preliminary enquiry fits the admission criteria for blood giving.

Adolescent↗

Change of ultraviolet absorbance of sunscreens by exposure to solar-simulated radiation.

Regarding the outdoor behavior of the Caucasian population, modern sunscreens should provide high and broad-spectrum ultraviolet protection in the ultraviolet B as well as in the ultraviolet A range and should be photochemically stable for ultraviolet doses, which can be expected in solar radiation. At present an assessment of the photostability of suncare products is not a general requirement before marketing. In order to evaluate the photostability of suncare products we conducted an in vitro test and measured the spectral absorbance of 16 sunscreens before, and after exposure to increasing biologically weighted standard erythema doses (5, 12.5, 25, 50) of solar-simulated radiation. Seven of 16 suncare products showed a significant dose- and wavelength-dependent decrease of the ultraviolet A protective capacity, whereas the ability to absorb ultraviolet B was not affected. In the ultraviolet A range, the decrease of absorbance (photoinactivation), respectively, the increase of transmission was 12-48% for an ultraviolet exposure of 25 standard erythema dose. Photoinactivation started in the wavelength range between 320 and 335 nm with a maximum above 350 nm. Furthermore, our analysis showed that the behavior of suncare products was not predictable from its individual ingredients. Neither complex combinations of organic filters nor addition of inorganic filters could absolutely prevent photoinactivation. The inclusion of a single photounstable filter did not mean photoinstability of the complete suncare product. Photoinactivation of sunscreens appears to be an underestimated hazard to the skin, first, by formation of free radicals, second, by increased ultraviolet A transmission.

Dose-Response Relationship, Radiation↗

Cytokeratin expression and epithelial differentiation in Warthin's tumour and its metaplastic (infarcted) variant.

AIMS: Warthin's tumour is characterized by a bilayered columnar epithelium. Transformation into metaplastic (infarcted) Warthin's tumour includes squamous metaplasia of the epithelium along with regressive changes in the stroma. Misinterpretation of metaplastic Warthin's tumour for malignancy is a serious diagnostic pitfall. This study assesses the utility of cytokeratin expression in Warthin's tumour and its metaplastic variant. METHODS AND RESULTS: Twenty-six cases of Warthin's tumour, among them eight metaplastic Warthin's tumours, were investigated employing immunohistochemistry. Both Warthin's tumour and its metaplastic variant regularly expressed cytokeratins (CK) 7, 8, 18, and 19. Staining results with antibodies to CK10, 10/13, 1/2/10/11, and 20 were negative in all specimens. Immunoreactivity for CK 5/14 and 17 was restricted to basal cells in Warthin's tumour, but involved basal as well as surface cells in metaplastic Warthin's tumour. CONCLUSIONS: Warthin's tumour and its metaplastic (infarcted) variant both express CK 7, 8, 18, and 19, which are typical for columnar differentiation. Cytokeratins typical of squamous differentiation are absent from Warthin's tumour and its metaplastic variant, irrespective of the squamous morphology of the epithelium in metaplastic Warthin's tumour. The expression of CK 5/14 and 17, which are typical of regenerative cells, is restricted to basal cells in Warthin's tumour, but is expressed also in surface cells in metaplastic Warthin's tumour.

Adenolymphoma↗

[Use and results of universal newborn hearing screening with ALGO portable device].

BACKGROUND: Congenital hearing disorder, which has an occurrence of 1 in 1000 newborn babies, is a health problem that should be taken seriously. Once it has been discovered too late, it leads to lifelong language, intellectual, emotional and social problems. The aim of this project was the critical evaluation of a universal, ABR-based newborn hearing screening, looking at the specificity and the success of the method used as well as the organisational requirements and costs involved with this method. METHODS: From August 1999 until March 2000, 464 newborn babies, born at the University Hospital Eppendorf in Hamburg, were examined with the Algo portable. Another 31 children, all younger than 6 months, were also examined with the Algo portable, because of suspected hearing loss. When a child got a refer twice by the Algo portable, the child was examined again, using the conventional ERA-machine (Evoselect) to confirm the suspected hearing loss and to assess its grade. RESULTS: 98% of the newborns at our hospital were examined. Up to now, out of 13 conspicuous children, the majority of which belonged to the risk group, 6 have been identified as unambiguously bilateral and 2 as unilateral hard of hearing. After an introductory period of two months, the average costs per examination could be set at 38.65 DM and app. 3200 DM per bilateral hearing loss discovered. CONCLUSION: A Universal Newborn Hearing Screening is necessary and can be executed with calculable effort with concern to personnel, time and finance.

Age Factors↗

Patterns of p21(waf1/cip1) expression in non-papillomatous nasal mucosa, endophytic sinonasal papillomas, and associated carcinomas.

AIMS: To clarify p21(waf1/cip1) expression in sinonasal lesions. METHODS: Archived surgical specimens from 38 patients were investigated by means of immunohistochemistry. p21(waf1/cip1) staining was evaluated in the different layers of the epithelium. In addition, human papillomavirus (HPV) infection and p53 protein overexpression were assessed and correlated with p21(waf1/cip1) expression. RESULTS: p21(waf1/cip1) staining was negative in non-papillomatous nasal mucosa. HPV infection and p53 protein overexpression were not seen. Sixteen of 20 inverted papillomas showed p21(waf1/cip1) expression. HPV infection was found in 16 cases and p53 protein overexpression was present in 13 specimens. Expression of p21(waf1/cip1) was restricted to surface cells in five cases, but involved basal/parabasal cells in 11 specimens. Immunoreactivity for p21(waf1/cip1) in basal/parabasal cells colocalised with p53 protein overexpression. Enhanced expression rates for p21(waf1/cip1) were seen in transitional and squamous epithelium compared with columnar epithelium. p21(waf1/cip1) expression involved only surface cells in cylindrical cell papillomas. HPV infection and p53 protein overexpression were detected in all specimens. One of five squamous cell carcinomas showed p21(waf1/cip1) expression. HPV infection was seen in two cases, and all carcinomas showed p53 protein overexpression. CONCLUSIONS: Expression of p21(waf1/cip1) is associated with terminal differentiation in surface cells in inverted papillomas and cylindrical cell papillomas, but not in non-papillomatous nasal mucosa. Overexpression of p53 protein colocalises with p21(waf1/cip1) expression in basal/parabasal cells in inverted papillomas but not in cylindrical cell papillomas. Expression of p21(waf1/cip1) in squamous cell carcinomas involves a subset of tumours with p53 protein overexpression.

Adolescent↗

Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/dilution and mass spectrometry.

Production rates of dihydrotestosterone (DHT) were determined in healthy men (n = 8), in healthy women during the follicular phase of their menstrual cycle (n = 7), and in young men with male pattern baldness (n = 8) using the stable isotope dilution technique and mass spectrometry. [2,3,4-(13)C]DHT was infused for 10 h at doses of 15 microg/h (men) and 2 microg/h (women), and blood samples were obtained at 20-min intervals during the last 4 h of the observation period. Production rates estimated between April and June were 2.9 +/- 1.1 microg/h (women) and 17.8 +/- 6.2 microg/h (men). In men production rates of DHT were similar (16.2 +/- 7.7 microg/h) when the investigation was repeated between October and December. Mean production rates of DHT in young men with male pattern baldness (60 +/- 50 microg/h) were higher than those in healthy men (P < 0.005). Although this group included two individuals with normal production rates of DHT, the production rate of DHT was markedly elevated (range, 32.0-161.0 microg/h) in the remaining patients. Stable isotope-labeled infusions of DHT are suitable for clinical use in a routine setting to obtain analytically correct estimates of DHT production in vivo. In the majority of men with male pattern baldness endogenous production of DHT is markedly increased, providing a rationale for therapeutic 5 alpha-reductase inhibition in this disorder.

Adult↗

Coexpression of cytokeratins typical for columnar and squamous differentiation in sinonasal inverted papillomas.

Cytokeratin (CK) expression was studied in 22 sinonasal inverted papillomas. Columnar (respiratory) epithelium in inverted papillomas abundantly expressed CK7, CK8, CK18, and CK19. Immunoreactivity for CK5/14 and CK17 was found in basal and parabasal/suprabasal cells. Transitional (cuboidal) and squamous epithelium in inverted papillomas comparably expressed CK7, CK8, CK18, and CK19. In addition CK13 was found in subluminal and surface cells. Immunoreactivity for CK5/14 and CK17 involved all layers of the epithelium. In nonpapillomatous nasal mucosa adjacent to inverted papillomas, CK expression in columnar (respiratory) epithelium exactly matched the findings in inverted papillomas. Transitional (cuboidal) and squamous epithelium in nonpaillomatous mucosa were negative for CK7, CK8, CK18, and CK19. CK13 was expressed in subluminal and surface cells. Immunoreactivity for CK5/14 and CK17 was restricted to basal and parabasal/suprabasal cells. Conclusively, transitional (cuboidal) and squamous epithelium in inverted papillomas but not in the adjacent mucosa coexpress CKs typical for columnar and squamous differentiation.

Adult↗

Overexpression of p53 in tumor-distant epithelia of head and neck cancer patients is associated with an increased incidence of second primary carcinoma.

Second primary carcinoma is a peculiar feature of head and neck cancer and represents a form of treatment failure distinct from the recurrence of the primary tumor. Whether altered p53 expression in tumor-distant epithelia at the time of diagnosis is of clinical value as a biomarker for second primary carcinoma development has not been rigorously answered because of the lack of long-term follow-up studies involving a sufficiently large patient cohort. In this prospective study, we have investigated p53 expression in tumor-distant epithelia and in the corresponding primary tumors of 105 head and neck cancer patients by immunohistochemistry on frozen sections. After a median follow-up of 55 months, the clinical course of disease parameters, i.e., local recurrences, lymph node and distant metastasis, incidence of second primary carcinoma, and survival, was evaluated. Overexpression of p53 in tumor-distant epithelia was found in 49 patients (46.7%), and it was independent of the p53 protein status of the primary tumor and of the tumor site, size, stage, and grading. Mucosal p53 overexpression was not associated with local primary recurrences, lymph node or distant metastases, or overall survival. Importantly, mucosal p53 overexpression, but not overexpression in the primary tumors, was significantly associated with an increased incidence of second primary carcinomas (P = 0.0001; Fisher's exact test). When the times to second primary tumor occurrence were analyzed by the Kaplan-Meier method, the difference remained significant (P = 0.005; log rank test). We conclude that IHC staining for p53 overexpression in tumor-distant epithelia provides a simple and rapid tool to identify head and neck cancer patients at increased risk of developing second primary tumors. Because p53 overexpression in these epithelia in our patient cohort was specifically associated with second primary cancer but not with recurrences, at least a fraction of the second primary cancers appears to have resulted from genetic events in the mucosa ("field cancerization").

Carcinoma, Squamous Cell↗

The mCK-5 multiprobe RNase protection assay kit can yield erroneous results for the murine chemokines IP-10 and MCP-1.

The ribonuclease protection assay (RPA) represents a sensitive method to detect and quantify RNA levels. It can be adapted to allow the simultaneous analysis of more than 10 different mRNAs. The multiprobe RPA kit mCK-5 from PharMingen was used to analyze the expression of chemokines in CCR5 chemokine receptor knockout mice. Upon careful analysis it was found that the mCK-5 kit is defective and can lead to false results for the chemokines IP-10 and MCP-1. The problem is caused by a long-known sequence polymorphism within the 3'-untranslated region of the murine IP-10 gene. This polymorphism leads to a protected IP-10 fragment approximately 20 nucleotides shorter than expected, yielding a length similar to the protected MCP-1 fragment from the mCK-5 kit. Since the identification of specific transcripts with this kit is based exclusively on the size of the various protected fragments, false-negative results for IP-10 together with false-positive results for MCP-1 can be obtained. Interestingly, the polymorphism was found not only in 129/CD-1 mice, but also in MRL and SJL/J mice. To facilitate troubleshooting in the future, all templates from the mCK-5 set were isolated and sequenced.

Animals↗

Poliomyelitic-like illness in central European encephalitis.

Central European encephalitis (CEE) may be accompanied by myeloradiculitic symptoms in up to 5% of patients. The authors report six patients with a myelitic form of CEE mimicking acute poliomyelitis with bulbar and arm predominance and a poor prognosis. Three patients died. Of the survivors, only one can perform most activities of daily living, but still needs assisted ventilation at night. Autopsy in one patient showed severe cervicothoracic inflammation with changes almost exclusively in anterior horn cells and roots, as typically seen in poliomyelitis.

Adult↗

Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis.

OBJECTIVE: To determine the value of vascular endothelial growth factor (VEGF) in CSF as a marker for carcinomatous meningitis (CM). METHODS: The concentration of VEGF was measured by ELISA in matched samples of CSF and serum collected from 162 patients. These included patients with solid tumors with CM (n = 11) or brain metastases without concomitant CM (n = 12), paraneoplastic neurologic syndromes (n = 4), viral (n = 15) and bacterial (n = 20) meningitis, and a variety of non-neoplastic and noninfectious neurologic diseases (n = 100). Using CSF/serum albumin ratios, the VEGF index was calculated to estimate the proportion of intrathecally produced VEGF. Immunohistochemical staining for VEGF was performed in a brain metastasis from a mammary carcinoma associated with CM. RESULTS: High VEGF levels (median 6,794.8 pg/mL) were found in CSF of all patients with CM, whereas VEGF levels in matched sera were comparable to other disease groups. In patients with CM, the concentration of VEGF in CSF decreased significantly following antineoplastic treatment. In CSF samples from patients with brain metastases without concomitant CM, VEGF was not detectable. Median VEGF concentration in CSF from patients with acute bacterial meningitis was 38.6 pg/mL, with only 9 of these 17 patients showing detectable VEGF levels in CSF. The VEGF indices in patients with bacterial meningitis were significantly lower than in tumor patients with CM (<22.8 versus >62.3), suggesting that the proportion of intrathecally produced VEGF is much higher in patients with CM as compared with patients with bacterial meningitis. Patients without neoplastic or infectious neurologic disorders consistently showed VEGF levels in CSF below the assay detection limit of 25 pg/mL. Immunohistochemistry revealed strong cytoplasmic staining for VEGF in a metastatic lesion from breast cancer infiltrating the meninges. CONCLUSION: In patients with carcinomatous meningitis, significant amounts of VEGF are released into CSF. This study yields preliminary evidence that VEGF in CSF may be a useful biologic marker for both the diagnosis and evaluation of treatment response in carcinomatous meningitis.

Adolescent↗

Laryngeal mucosa of head and neck cancer patients shows increased DNA damage as detected by single cell microgel electrophoresis.

Major risk factors for cancer of the oral cavity, pharynx and larynx are smoking and excess alcohol consumption. Since long-term survival rates of head and neck cancer patients have not substantially been improved, new preventive strategies including the use of cancer chemopreventive agents have to be developed. With the aim of developing biomarkers which can verify the efficacy of chemopreventive interventions, a standardised alkaline microgel electrophoresis (MGE) assay was applied as a sensitive and rapid tool to detect DNA damage on a single cell level. Macroscopically normal laryngeal mucosa biopsies obtained by surgery from head and neck cancer patients (n=29) and from hospital controls (n=22) were analysed by MGE in a pilot study. As compared to controls, cells from head and neck cancer patients showed a significantly elevated DNA damage without any further genotoxic treatment (P<0.01). We conclude that this increased background DNA damage in laryngeal epithelia could result from genetic alterations caused by smoking and alcohol leading, in accord with the field cancerisation hypothesis, to a gradual decrease of genomic stability and malignancy. MGE should now be explored as a rapid screening method in larger clinical studies: (i) to identify high-risk subjects carrying cells with decreased genomic stability and (ii) to verify the efficacy of chemopreventive regimens to prevent or slow down the development of head and neck cancer in high-risk persons.

Adult↗

Progressive multifocal leukoencephalopathy presenting with an isolated focal movement disorder.

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal papovavirus infection of the central nervous system predominantly affecting immunocompromised patients. Although the basal ganglia circuitry may be involved in the pathology of PML, movement disorders are exceedingly rare as presenting symptoms and have not been described as isolated features in such patients. We report a previously healthy, immunocompetent 24-year-old woman with histologically proven PML who presented with a focal movement disorder of the left arm as an isolated symptom for many months before diagnosis.

Adult↗

Exogenous neopterin causes cardiac contractile dysfunction in the isolated perfused rat heart.

Neopterin is known in humans as a sensitive marker for diseases associated with increased activity of the cellular immune system. Recent studies report neopterin also to exhibit distinct effects: neopterin induces inducible nitric oxide synthase expression in rat vascular smooth muscle cells and activates translocation of nuclear factor- kappa B. Neopterin may also induce oxidative stress causing apoptotic cell death, or superinduce tumor necrosis factor- alpha -mediated apoptosis. Observing these effects in cell cultures, we were interested in possible consequences of neopterin on cardiac function in the isolated perfused rat heart. The influence of neopterin in three different concentrations (10 micromol/l, 50 micromol/l, 100 micromol/l) on cardiac contractility parameters and coronary vascular resistance were studied in 67 male Sprague-Dawley rats using the temperature-controlled and pressure-constant Langendorff apparatus with retrograde perfusion of the aorta with a Krebs-Henseleit buffer. Treatment with 100 micromol/l neopterin resulted in a significant decrease in coronary flow and cardiac contractility. Coronary flow decreased from 15.2 to 9.5 ml/min (P=0.002), left ventricular pressure from 80 to 52 mmHg (P=0. 002), rate of pressure fall from 1605 to 923 mmHg/s (P=0.001) and rate of pressure rise from 2862 to 1709 mmHg/s (P=0.001). Concentrations lower than 100 micromol/l neopterin had no significant effect on cardiac function. Our study demonstrates a considerable influence of exogenous neopterin on cardiac performance in the Langendorff model of isolated perfused rat hearts. This has to be considered a potential pathogenic factor of cardiac disturbances in diseases in which high concentrations of neopterin are released due to immune activation. At present the exact mechanism remains unclear.

Animals↗