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Biomedical subjects

H Maier

Publications and source records attributed to H Maier.

At least 73 records · Page 4Linked to original sources
PubMed2000

Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GFR-alpha 1) are strongly expressed in human gliomas.

Glial cell line-derived neurotrophic factor (GDNF), a sequence-related factor of the transforming growth factor-beta family, has been identified as a potent neurotrophic factor for a variety of neuronal cell populations. At present, it is still unknown whether human gliomas in vivo are also capable of producing GDNF. We studied the expression of GDNF in 14 human glioblastomas, 1 gliosarcoma and 5 astrocytomas. Using an enzyme-linked immunosorbent assay, the amount of GDNF was quantified in human gliomas and compared to GDNF-expression in C6 glioma cells, mouse fibroblasts and normal human and rat brain. Mean concentration of GDNF in gliomas was 937 +/- 140 pg GDNF/g tissue (n = 20). C6 cells revealed the highest expression levels of 2,837 +/- 813 pg/g, whereas mouse 3T3 fibroblasts showed no detectable GDNF protein. Mean GDNF tissue levels in normal human and rat brain were significantly lower. Using reverse transcriptase-polymerase chain reaction, GDNF mRNA was detected in human gliomas and in rat C6 cells. Immunohistochemistry revealed strong GDNF- and GDNF receptor-alpha 1-expressing tumor cells in human glioma tissue. These results show that glial tumors, even in the most dedifferentiated form of glioblastoma, express GDNF at concentrations up to five times higher compared to normal human brain. This overexpression of GDNF may be of biological relevance for proliferation of glial tumors in humans.

Adult↗
PubMed2000

[Neurinoma of the nasal cavity].

A 35 years old male patient presented with serous nasal secretion, relapsing epistaxis and a slowly progredient nasal obstruction. Clinical examination and CT scans showed a tumor occupying the left middle meatus and the whole nasal cavity displosing the nasal septum to the right side. The tumor was resected by a midfacial degloving approach. Histological examination showed a neurinoma. By means of the presented case report and a review of literature, diagnosis and treatment of this rare nasal tumor are discussed.

Adult↗
PubMed2000

Distribution of chromogranin B-like immunoreactivity in the human hippocampus and its changes in Alzheimer's disease.

Synapse loss is crucially involved in cognitive decline in Alzheimer's disease (AD). This study was performed to investigate the distribution and density of chromogranin B-like immunoreactivity in the hippocampus of control compared to AD brain. Chromogranin B is a large precursor molecule found in large dense-core vesicles. For immunocytochemistry we used an antiserum raised against a synthetic peptide (PE- 11) present in the chromogranin B molecule. Chromogranin B-like immunoreactivity was concentrated in the terminal field of mossy fibers, the inner molecular layer of the dentate gyrus and in layer II of the entorhinal cortex. In AD, chromogranin B was detected in neuritic plaques. The density of chromogranin B-like immunoreactivity was significantly reduced in the inner molecular layer of the dentate gyrus and in layers II, III and V of the entorhinal cortex in AD brains. The present study demonstrates that chromogranin B is a marker for human hippocampal pathways. It is particularly suitable for studying nerve fibers terminating at the inner molecular layer of the dentate gyrus. It is present in neuritic plaques, and its density is reduced in a layer-specific manner.

Aged↗
PubMed2000

Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and correlates with tumor progression.

Vascular endothelial growth factor (VEGF), a key regulatory protein in neoangiogenesis, is strongly expressed in a variety of primary brain tumors, particularly malignant gliomas. In previous studies, high levels of VEGF were also reported in tumor cysts of glioblastomas. Using an ELISA method we measured the concentration of VEGF in matched samples of aspiration fluid from tumor cysts and serum. Samples were collected from 14 patients with primary brain tumors of various histology (six glioblastomas, one protoplasmatic astrocytoma, two pilocytic astrocytomas, one ependymoma, one meningioma, and three craniopharyngiomas) and two patients with solitary cystic brain metastases from adenocarcinomas of the lung. Aspiration fluids of tumor cysts from all patients revealed high VEGF levels ranging between 882 and 1,263,000 pg/ml, which were 2 to more than 2,000 times higher than the corresponding serum levels. Maximum VEGF levels were detectable in cyst fluids from recurrent glioblastoma. Serum VEGF levels ranged between 125 and 716 pg/ml and did not differ from serum levels in 145 healthy volunteers. In a single patient with metastatic lung cancer the concentration of VEGF in serum and cyst fluid was determined during disease progression. During 60 days of follow-up VEGF concentrations in the cyst fluid collected by puncture of an Ommaya reservoir increased 650-fold, while serum levels remained rather constant. These findings indicate that immunoreactive VEGF is produced at the tumor site and abundantly released into the cyst fluid of primary and metastatic brain tumors. Interestingly, this abundant local release is not reflected in serum VEGF levels, even in the case of very high VEGF concentrations in tumor cysts. Thus, VEGF may be biologically relevant for the formation of tumor cysts in brain tumors and correlates with local disease progression.

Adolescent↗
PubMed2000

Evidence for active, nonlinear, negative feedback in the vibration response of the apical region of the in-vivo guinea-pig cochlea.

The transverse vibration response of the organ of Corti near the apical end of the guinea-pig cochlea was measured in vivo. For cochleae in good physiological condition, as ascertained with threshold compound action potentials and the endocochlear potential, increasing amounts of attenuation and phase lag were found as the intensity was decreased below 80 dB SPL. These nonlinear phenomena disappeared post mortem. The data suggest that an active, nonlinear damping mechanism exists at low intensities at the apex of the cochlea. The phase nonlinearity, evident at all frequencies except at the best frequency (BF), was limited to a total phase change of 0.25 cycles, implying negative feedback of electromechanical force from the outer hair cells into a compliant organ of Corti. The amplitude nonlinearity was largest above BF, possibly due to interaction with a second vibration mode. The high-frequency flank of the amplitude response curve was shifted to lower frequencies by as much as 0.6 octave (oct) for a 50-dB reduction of sound intensity; the reduction of BF was 0.3 oct, but there was no change of relative bandwidth (Q(10 dB)). Detailed frequency responses measured at 60 dB SPL were consistent with non-dispersive, travelling-wave motion: travel time to the place of BF (400 Hz at 60 dB SPL) was 2.9 ms, Q(10 dB) was 1.0; standing-wave motion occurred above 600 Hz. Based on comparison with neural and mechanical data from the base of the cochlea, amplitudes at the apex appear to be sufficient to yield behavioural thresholds. It is concluded that active negative feedback may be a hallmark of the entire cochlea at low stimulus frequencies and that, in contrast to the base, the apex does not require active amplification.

Acoustic Stimulation↗
PubMed2000

Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha.

Exposing human skin to ultraviolet radiation causes DNA damage, sunburn, immune alterations, and eventually, skin cancer. We wished to determine whether liposomes containing a DNA repair enzyme could prevent any of the acute effects of irradiation when applied after ultraviolet exposure. Fifteen human patients with a prior history of skin cancer were exposed to two minimal erythema doses of ultraviolet radiation on their buttock skin. Liposomes containing T4 endonuclease V or heat-inactivated enzyme were applied immediately and at 2, 4, and 5 h after ultraviolet irradiation. Transmission electron microscopy after anti-T4 endonuclease V-staining and immunogold labeling on biopsies taken at 6 h after ultraviolet exposure revealed that the enzyme was present within cells in the skin. Immunohistochemical DNA damage studies suggested a trend toward improved DNA repair at the active T4 endonuclease V liposome-treated test sites. Although the active T4 endonuclease V liposomes did not significantly affect the ultraviolet-induced erythema response and microscopic sunburn cell formation, they nearly completely prevented ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha RNA message and of interleukin-10 protein. These studies demonstrate that liposomes can be used for topical intracellular delivery of small proteins to human skin and suggest that liposomes containing DNA repair enzymes may provide a new avenue for photoprotection against some forms of ultraviolet-induced skin damage.

Administration, Topical↗
PubMed2000

Immunomodulating effects of surgical intervention in tumors of the head and neck.

The immunomodulating effect of primary surgical intervention in 33 patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx was analyzed prospectively. An operation time of longer than 7 hours was significantly associated with a decrease of total lymphocyte counts, CD4(+) T lymphocytes, and CD8(+) T lymphocytes. The CD4/CD8 ratio as a marker for the downregulation of the cellular immune response was slightly decreased but still in the normal range. CD4(+) lymphocyte counts increased within 7 days, and CD8(+) lymphocytes increased 4 weeks after the operation. The in vitro stimulation of the lymphocytes was impaired for 1 to 4 weeks. Release of interleukins, interferon-gamma, and tumor necrosis factor-alpha remained low despite the surgical trauma. The decreased lymphocyte counts, especially CD4(+) and CD8(+) lymphocytes, were significantly associated with duration of operation and volume of blood loss. Extension of trauma, age, type of anesthesia, and type of intensive care intervention were not associated with specific immunomodulating effects. However, these factors might be responsible for suppression of the immune system, which is expressed by lymphocyte depletion, lymphocyte dysfunction, and impaired upregulation of cytokine secretion.

Adult↗
PubMed2000

Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis.

A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone.

Administration, Topical↗
PubMed2000

Chromogranins in temporal lobe epilepsy.

PURPOSE: Chromogranins are neuropeptide precursors stored in large dense core vesicles. Because physiological functions have been postulated for peptides originating from chromogranins, we investigated the distribution of chromogranins A and B and secretoneurin (a peptide derived from secretogranin II) in the control and epileptic hippocampus of humans and rats. METHODS: Chromogranin immunoreactivity (IR) was investigated in paraformaldehyde-fixed hippocampal specimens from 24 temporal lobe epilepsy patients with intractable seizures, postmortem from 15 patients deceased from nonneurological disorders, in rats 30 days after kainate-induced limbic seizures, and in control rats. RESULTS: In control rats and in humans, chromogranin A and B IR and secretoneurin IR were present in mossy fibers. In addition, chromogranin B IR was found in granule cells, and chromogranin A IR was found in granule and CA2 pyramidal cells in the human hippocampus. In both species, chromogranin B and secretoneurin were unevenly distributed in the molecular layer of the dentate gyrus. The most intriguing change seen in human temporal lobe epilepsy specimens and in the kainic acid model of the rat was the prominent staining of the inner molecular layer, indicating storage of chromogranins A and B and secretoneurin in terminals of reorganized mossy fibers, from which they may be released upon nerve stimulation. CONCLUSION: Chromogranins A and B and secretoneurin are valid markers for hippocampal neurons and delineate epilepsy-induced reorganization of mossy fibers.

Animals↗
PubMed2000

Thyroid hormone deficiency before the onset of hearing causes irreversible damage to peripheral and central auditory systems.

Both a genetic or acquired neonatal thyroid hormone (TH) deficiency may result in a profound mental disability that is often accompanied by deafness. The existence of various TH-sensitive periods during inner ear development and general success of delayed, corrective TH treatment was investigated by treating pregnant and lactating rats with the goitrogen methimazole (MMI). We observed that for the establishment of normal hearing ability, maternal TH, before fetal thyroid gland function on estrus days 17-18, is obviously not required. Within a crucial time between the onset of fetal thyroid gland function and the onset of hearing at postnatal day 12 (P12), any postponement in the rise of TH-plasma levels, as can be brought about by treating lactating mothers with MMI, leads to permanent hearing defects of the adult offspring. The severity of hearing defects that were measured in 3- to 9-mo-old offspring could be increased with each additional day of TH deficiency during this critical period. Unexpectedly, the active cochlear process, assayed by distortion product otoacoustic emissions (DPOAE) measurements, and speed of auditory brain stem responses, which both until now were not thought to be controlled by TH, proved to be TH-dependent processes that were damaged by a delay of TH supply within this critical time. In contrast, no significant differences in the gross morphology and innervation of the organ of Corti or myelin gene expression in the auditory system, detected as myelin basic protein (MBP) and proteolipid protein (PLP) mRNA using Northern blot approach, were observed when TH supply was delayed for few days. These classical TH-dependent processes, however, were damaged when TH supply was delayed for several weeks. These surprising results may suggest the existence of different TH-dependent processes in the auditory system: those that respond to corrective TH supply (e.g., innervation and morphogenesis of the organ of Corti) and those that do not, but require T3 activity during a very tight time window (e.g. , active cochlear process, central processes).

Animals↗
PubMed2000

Pyuria in patients treated with indinavir is associated with renal dysfunction.

BACKGROUND: Indinavir therapy is associated with a continuum of crystal-related syndromes, including nephrolithiasis, renal colic, flank pain without recognizable stone formation, dysuria and asymptomatic crystalluria. A frank nephropathy has been recognized recently as part of the spectrum. METHODS: A retrospective analysis of 72 HIV-infected individuals receiving indinavir was performed to identify the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals treated with nucleoside analogues alone served as controls. RESULTS: Mean serum creatinine levels rose from 1.03 +/- 0.16 mg/dl to 1.11 +/- 0.22 mg/dl at week 12 and 1.15 +/- 0.27 mg/dl at week 24 (both, p < 0.01). Thirteen individuals developed serum creatinine levels > or =1.4 mg/dl. Increased serum creatinine levels were found more frequently in women (p < 0.01) and were associated with pyuria and microhematuria (p < 0.01). Frank renal colic and/or nephrolithiasis (seven patients) and urinary pH were not associated with serum creatinine levels > or =1.4 mg/dl. The mean duration of indinavir treatment, until sterile pyuria occurred, were 22 weeks and 32 weeks until the first rise of serum creatinine levels to > or =1.4 mg/dl. Ten patients showed both findings, pyuria preceded the first rise in serum creatinine levels to > or = 1.4 mg/dl (18 vs. 27 weeks, p = 0.02). Renal biopsy, done in three patients, revealed tubulointerstitial disease with crystals in collecting ducts. In 21 patients, among them 11 with pyuria, indinavir was replaced for various reasons and pyuria disappeared in nine. In these patients mean serum creatinine levels decreased from 1.43 mg/dl at withdrawal of indinavir to 1.04 mg/dl three months later (p < 0.01). CONCLUSION: Indinavir therapy is associated with a decrease in renal function which is reversible after withdrawal. In addition, indinavir-associated tubulointerstitial disease does no in patients taking indinavir may help to identify patients being at risk for nephrotoxicity.

Adult↗
PubMed1999

[Alcohol drinking and cancer of the upper aerodigestive tract in women].

BACKGROUND AND OBJECTIVE: In Germany every year approximately 2000 women die from squamous cell cancer of the oral cavity, pharynx or larynx. Until recently, excessive alcohol consumption and excessive tobacco consumption were blamed as the predominant risk factors. The present study investigated whether alcohol is an independent risk factor even in case of a moderate consumption in increasing the risk of cancer of the mouth, pharynx and larynx in females. PATIENTS AND METHODS: In a hospital based case control study the smoking and drinking patterns of 62 females with squamous cell cancer of the oral cavity, pharynx or larynx and of 248 randomly selected female control subjects were analysed. RESULTS: A regular consumption of alcohol was reported by 59.7% of the cancer patients and by 18.1% of the control subjects. The alcoholic beverages preferred by the cancer patients were beer and spirits. While only 0.8% of the control subjects reported a daily consumption of more than 30 g alcohol, this was the case in 40.3% of the cancer patients. The alcohol-associated risk increasing was dose-dependent. Compared to a daily consumption of less than 10 g alcohol, a consumption of more than 30 g/day has a relative risk of 29 (P < 0.01; adjusted for tobacco) was estimated. CONCLUSION: Even a moderate alcohol consumption (10-20 g/day) causes a significant increasing of head and neck cancer in women.

Adult↗
PubMed1999

Distinct thyroid hormone-dependent expression of TrKB and p75NGFR in nonneuronal cells during the critical TH-dependent period of the cochlea.

Analyzing the thyroid hormone (TH)-dependent period of the inner ear, we observed that the presence of triiodothyronine (T3) between postnatal day 3 (P3) and P12 is sufficient for functional maturation of the auditory system. Within this short time period, an unusual transient TH-dependent expression of nonneuronal neurotrophin receptors (NT-R) trkB and p75(NGFR) was observed in correlation with neuronal and morphogenetic processes. The availability of thyroid hormone was revealed to be invariably correlated with (a) a transient expression of full-length trkB in TRalpha1-, TRalpha2- and TRbeta1-expressing hair cells concomitant to the segregation of afferent fibers and the synaptogenesis of efferent fibers; and (b) a transient expression of p75(NGFR) in TRalpha1- and TRbeta1-expressing great epithelia ridge cells in direct spatiotemporal correlation with the appearance of apoptotic cells and morphogenetic maturation of the organ. For the first time, these data suggest a TH dependency of the expression of neurotrophin receptors in nonneuronal cells. A potential role of these peculiar neurotrophin receptor expression for the conversion of the biological function of TH on innervation patterning and morphogenesis during the critical TH-dependent period of the inner ear may be considered.

Animals↗
PubMed1999

[Construction workers as an extreme risk group for head and neck cancer?].

BACKGROUND: Workers in the construction industry carry an increased risk for head and neck cancer due to the high consumption of alcohol and tobacco plus exposure to occupational carcinogenic or co-carcinogenic agents. These latter substances include asbestos, tar products, metal dust, wood dust, cement dust and paints. RESULTS: The Heidelberg case-control studies showed a statistically increased risk of pharyngeal cancer (RR=2.5 adjusted for tobacco and alcohol) and laryngeal cancer (RR=2.3 adjusted for tobacco and alcohol) in the construction workers (23.3%) when compared to controls (8.2%). A random sample analysis of patients with head and neck cancer referred by the largest health assurance company in Heidelberg (AOK), revealed that 21.2% were employed in the construction industry. Similar results have been obtained in a number of international epidemiological studies. CONCLUSIONS: Our findings show that male construction workers who regularly consume alcohol and tobacco represent an extreme risk group for head and neck cancer. Measures for early detection are important and must be implemented carefully.

Adult↗