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Biomedical subjects

G Heinrich

Publications and source records attributed to G Heinrich.

At least 19 recordsLinked to original sources
PubMed2006

What really enhances the adsorption of polymers onto chemically nonuniform surfaces: surface randomness or its heterogeneity?

We theoretically perform a comparative analysis of the adsorption of polymers onto the regularly and randomly nonuniform surfaces. By developing and making use of the self-consistent perturbation expansion we calculate the surface excesses of the polymers adsorbed on the random and periodically patterned surfaces. In both cases the enhancement of the polymer adsorption is indicated, as compared to the adsorption onto the homogeneous surface that has the same average affinity for polymers. Moreover, the results obtained for the randomly nonuniform and periodically patterned adsorbing surfaces show striking quantitative similarity, when compared at the same characteristic sizes of inhomogeneities of these surfaces. This finding leads to the conclusion that the adsorption ability of the nonuniform surface primarily depends on the characteristic size of the surface inhomogeneity, rather than on the spatial distribution of the inhomogeneities on this surface. In all cases, the calculated total surface excess is found to be a decaying function of the ratio of the radius of gyration of polymers to the characteristic size of the surface inhomogeneity. The effect of the excluded volume is found to reduce the polymer adsorption.

Journal Article↗
PubMed2006

Biweekly pegylated liposomal doxorubicin in patients with relapsed ovarian cancer: results of a multicenter phase-II trial.

BACKGROUND: The obvious benefit of pegylated liposomal doxorubicin (PLD) for tumour control in recurrent ovarian cancer is frequently offset by severe palmar-plantar erythrodysesthesia (PPE). There is evidence that dose reduction from 50 to 40 mg/m(2) reduces the incidence of PPE without compromising cytotoxic activity. We set out to investigate whether biweekly application further improves the therapeutic index of PLD. PATIENTS AND METHODS: Patients with recurrent ovarian cancer after surgery and adjuvant chemotherapy with platinum and taxane compounds were eligible to participate in this multi-institutional phase II study. PLD was administered at a dose of 20 mg/m(2) every two weeks. Eligible patients had ECOG performance status of < or =2, and sufficient organ function. We employed an optimized two-stage design to test the hypothesis that biweekly application of PLD reduces the frequency of grade III and IV PPE from 25% to 10%. Response and survival were addressed descriptively. RESULTS: Between October 2001 and February 2004, 64 patients with median age of 59 (range 38-81) years were recruited onto this trial. We evaluated 553 (median 7, range 1-25) courses of PLD treatment. Most patients were in their third or fourth line of chemotherapy. PPE was noted in 30 patients (47.6%), but only three participants progressed to grade 3 severity (4.7%, 95% confidence interval 1.0-13.1%). Partial response, stable disease, and tumour progression were observed in 5, 13, and 24 patients, respectively. Median overall and progression-free survival were 18.2 (range, 1.4-34.0) and 4.3 (range 0.5-22.3) months. CONCLUSIONS: Biweekly PLD may reduce the incidence of PPE while retaining efficacy in relapsed ovarian cancer. Our data support the need for a randomized trial to strengthen these assumptions.

Adult↗
PubMed2005

In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study.

BACKGROUND: Response to the first two cycles of preoperative chemotherapy might differentiate subgroups of breast cancer patients with high or minimal chances for a pathologic complete response (pCR) and may be used as an in vivo chemosensitivity test. METHODS: Breast cancer patients were treated with two cycles of TAC (docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2) every 21 days). Patients whose tumors showed a response received four more cycles. Patients whose tumors did not respond were randomized to four additional cycles TAC or NX (vinorelbine 25 mg/m(2) days 1 and 8, capecitabine 2000 mg/m(2) days 1-14, every 21 days). The primary end point was pCR at surgery. RESULTS: Two hundred and eighty-five patients showed a clinical response, in 73.0% after two cycles, in 88.4% at surgery, and a pCR was seen in 17.9%. Breast conservation was possible in 72.2%. Responding patients obtained a pCR in 22.6% whereas non-responding patients reached a pCR in 7.3% and 3.1% with TAC or NX, respectively. Grade III/IV neutropenia and febrile neutropenia were observed during TAC in 70.2% and 13.5%, respectively. Significantly less toxicity were observed with NX. CONCLUSION: Early response to TAC can reliably identify patients with a high chance of achieving a pCR. New effective treatments need to be explored for patients without an early response.

Adult↗
PubMed2005

Identification and characterization of an SKN7 homologue in Cryptococcus neoformans.

Cryptococcus neoformans is an encapsulated fungal pathogen that primarily infects the central nervous system of immunocompromised individuals, causing life-threatening meningoencephalitis. The capacity of C. neoformans to subvert host defenses and disseminate by intracellular parasitism of alveolar macrophages in the immune-compromised host has led to studies to evaluate genes associated with C. neoformans resistance to oxidative stress. In the present study, we identify and characterize a C. neoformans homologue to SKN7, a transcription factor in Saccharomyces cerevisiae that regulates the oxidative stress response, cell cycle, and cell wall biosynthesis. To examine the contribution of SKN7 in the pathogenesis of fungal infections, we created skn7 mutants via targeted disruption. The skn7 mutants were observed to be more susceptible to reactive oxygen species in vitro and were significantly less virulent than the wild-type strain and a reconstituted strain as measured by cumulative survival in the mouse inhalational model. The Skn7 protein was observed to be important for expression of thioredoxin reductase in response to oxidative challenge. Interestingly, skn7 mutants were also observed to flocculate following in vitro culture, a novel phenotype not observed in skn7 mutants derived from other fungi. These findings demonstrate that SKN7 contributes to the virulence composite but is not required for pathogenicity in C. neoformans. In addition, flocculation of C. neoformans skn7 mutants suggests a potentially unique function of SKN7 not previously observed in other cryptococcal strains or skn7 mutants.

Animals↗
PubMed2002

A phase II study of topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy.

BACKGROUND: Second-line chemotherapy for patients with ovarian cancer who failed platinum and paclitaxel treatment remains a therapeutic challenge. We investigated the toxicity profile and therapeutic efficacy of a novel combination regimen, topotecan plus gemcitabine, in a clinical phase II study. PATIENTS AND METHODS: Women with relapsed epithelial ovarian cancer after platinum and paclitaxel treatment were eligible to participate in this trial. Topotecan was given at an initial dose of 0.5 mg/m(2) daily (days 1-5), combined with gemcitabine 800 mg/m(2) and 600 mg/m(2) on days 1 and 8, respectively. Precluding good tolerability, this protocol facilitated subsequent dose increases of topotecan up to 1.0 mg/m(2). The primary objective was to determine the dose-limiting toxicity, whereas secondary objectives comprised measurable and CA-125 response rates, disease-free and overall survival. RESULTS: The twenty-one patients (median age 57 years, range 37-70 years) who were allocated to this trial received a total of 94 courses of chemotherapy. Median follow-up was 20.5 months. Topotecan dosage could be escalated to 0.75 mg/m(2) in nine patients and 1 mg/m(2) in another two patients. Dose reduction was not necessary in any case. There were no episodes of neutropenic fever, sepsis or chemotherapy-related fatalities. Only one patient developed CTC grade 4 leukopenia after the first treatment cycle, whereas three patients showed grade 3/4 anaemia. Five patients experienced thrombocytopenia grade 4 without clinical sequelae. Non-hematological toxicities were mild and rare. Eleven patients could be evaluated for clinical tumour response, with three complete, and four partial remissions. Two patients each had stable and progressive diseases. The median progression-free survival rate was 8.8 months [95% confidence interval (CI) 6.3-13.4 months]. The median overall survival rate was 21.1 months (95% CI 14.8-22.1 months). CONCLUSIONS: Topotecan combined with gemcitabine has a favourable toxicity profile and encouraging efficacy in patients with recurrent ovarian cancer.

Adult↗
PubMed2002

Glandular hairs of Sigesbeckia jorullensis Kunth (Asteraceae): morphology, histochemistry and composition of essential oil.

Long-stalked glandular hairs of outer and inner involucral bracts of Sigesbeckia jorullensis, which are important for epizoic fruit propagation, were investigated using light and scanning electron microscopy. The essential oil secreted by the hairs was analysed by chromatographic methods including gas chromatography/mass spectrometry and with a laser microprobe mass analyser. The glandular hairs consisted of a large multicellular stalk and a multicellular secreting head. The apical layer of glandular head cells was characterized by leucoplasts and calcium oxalate crystals. Below the apical cells there were up to six layers of cells containing many chloroplasts around the nucleus and surrounded by vacuoles filled with flavonoids and tannins. The essential oil originating in the head cells was secreted into the subcuticular space and may be liberated by rupture of the cuticle. It was mainly composed of sesqui- and diterpenes, with the sesquiterpene hydrocarbon germacrene-D as the main component. Monoterpenes, n-alkanes and their derivatives as well as flavonoid aglycones were also detected. The stickiness of the essential oil is probably associated with the high content of oxygenated sesqui- and diterpenes. In addition to long-stalked trichomes, small biseriate trichomes occurred, secreting small quantities of essential oil into a subcuticular space.

Asteraceae↗
PubMed2001

Regulative fine-tuning of the two novel DAHP isoenzymes aroFp and aroGp of the filamentous fungus Aspergillus nidulans.

Two novel genes, aroF and aroG, from the filamentous fungus Aspergillus nidulans were isolated and the regulative fine-tuning between the encoded, differentially regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthases was analyzed. A wide range of DAHP synthase isoenzymes of various organisms are known, but only a few have been characterized further. DAHP synthases (EC 4.1.2.15) catalyze the first committed step of the shikimate pathway, which is a putative target for anti-weed drugs. The reaction is the condensation of erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) to yield DAHP. The two purified DAHP synthases showed different affinities for the substrates: 175 microM for PEP and 341 microM for E4P for the aroFp isoenzyme and weaker affinities of 239 microM (PEP) and 475 microM (E4P) for the aroGp isoenzyme. The enzymes are differentially regulated by tyrosine (aroFp) and phenylalanine (aroGp). The calculated kcat values are 7.0 s-1 for the tyrosine-inhibitable (aroFp) and 5.5 s-1 for the phenylalanine inhibitable (aroGp) enzyme. Tyrosine is a competitive inhibitor of the aroFp DAHP synthase in its reaction with PEP. Phenylalanine is a competitive inhibitor of the isoenzyme aroGp in its reaction with E4P. Both enzymes are inhibited by the chelating agent EDTA, which indicates a metal ion as cofactor.

3-Deoxy-7-Phosphoheptulonate Synthase↗
PubMed2001

Brain-derived neurotrophic factor and TrkB tyrosine kinase receptor gene expression in zebrafish embryo and larva.

The genes that encode the neurotrophin family of secreted polypeptides and the Trk family of high affinity neurotrophin transmembrane protein tyrosine kinase receptors are induced at the time of neurogenesis in mammals and are known to play critical roles in nervous system development. We show here that in contrast to mammals, the genes encoding the neurotrophin brain-derived neurotrophic factor (BDNF) and the neurotrophin receptor TrkB are expressed throughout embryonic development in the zebrafish. At the embryonic stages preceding transcription of endogenous genes all cells contain BDNF transcripts and immunoreactive BDNF and the trkB transcripts lack the region that encodes a kinase domain. As development proceeds, progressively fewer cells contain BDNF transcripts and by the time of neurogenesis the trkB transcripts encode a kinase-domain. In the 4-day-old larva, a small subset of specialized sensory cells on the surface and cells in deeper structures including the gill arches, fin, and cloaca express the BDNF gene at high levels in a promoter-specific fashion. This progressive restriction of BDNF gene expression must involve an extinction of BDNF gene transcription in some and induction of high levels of transcription in a promoter-specific fashion in other cells.

Aging↗
PubMed2001

Brain-derived neurotrophic factor gene organization and transcription in the zebrafish embryo.

The gene encoding zebrafish brain-derived neurotrophic factor (BDNF) was cloned from a PAC genomic DNA library. The entire transcription unit was contained in two independently isolated clones that together encompass 120 kb of genomic DNA. The intron/exon organization of the zebrafish gene was found to be identical to that of the mammalian gene but only one promoter has so far been identified. The associated 5' exon is 67% identical to exon 1c of the rat BDNF gene. A search of the 5' flank of the cloned promoter for sequence similarities with known transcription factor binding sites revealed potential AP-1, CREB, and SP1 binding sites. Fusion constructs containing the cloned promoter and 1.7 kb of 5' flank and an enhanced green fluorescent protein reporter that becomes membrane-anchored were injected into 1-8 cell stage embryos. Expression was seen in notochord, muscle, epithelial and endothelial cells of the 1-day-old embryo in consonance with the endogenous gene. These results demonstrate that the cloned promoter mediates cell-specific expression.

Animals↗
PubMed2001

[Diagnosis of urethral diverticula and periurethral masses].

AIM: To give recommendations for the standard diagnostic assessment of urethral diverticula and periurethral masses based on an evaluation of our results and a survey of the recent literature. METHODS: Group I (1981-1993) included 47 women in whom urethral diverticula (n = 34), periurethral cysts (n = 11), and periurethral leiomyomas (n = 2) were diagnosed and the results compared with the intraoperative findings. Diagnostic work-up comprised history taking, vaginal palpation, introitus ultrasound, double-balloon urethrography (DBU), voiding cystourethroscopy (VCU), excretion urography (EU), and urethrocystoscopy. Group II (1994-1996) included 12 women with urethral diverticula who were examined by DBU, 2D and 3D introitus ultrasound. The diagnostic accuracy of the different methods was assessed. RESULTS: Group I: The diagnostic accuracy in identifying urethral diverticula was 85.3% for palpation, 61.5% for introitus ultrasound, 93.8% for DBU, 37.5% for EU, and 30.0% for urethrocystoscopy. Of all imaging modalities used, only introitus ultrasound depicted periurethral cysts and leiomyomas. Group II: The DBU, 2D and 3D introitus ultrasound had a diagnostic accuracy of 100% in identifying urethral diverticula. CONCLUSIONS: Introitus ultrasound should be used as the basic diagnostic tool in clinically suspected urethral diverticula or periurethral masses and additional DBU should be restricted to cases with inconclusive findings.

Adult↗
PubMed1999

[Effect of various dressings on the point of entry of an intravenous drip].

In modern health care systems nosocomial infection is a major cause of patient suffering and leads to high financial costs. Overall nursing care that is part of nursing staff's daily routine is not brought under scrutiny often enough. The goal of this research project is to look at a small part only of optimal intravenous drip care. The focus of the paper is the influence that the use of two different kinds of dressings and two different types of cleansing methods have on the general appearance, as well as the microbiological results at the point of entry of the i.v. drip into the central veins. In order to examine this, test patients from different types of intensive care units were used for an experiment under highly controlled conditions. The results show that a variation in nursing care of the i.v. drip leads to a variation in germ development and in the general appearance at the point of entry.

Bandages↗
PubMed1998

Cloning and functional characterization of PACAP-specific receptors in zebrafish.

Two PACAP receptors were isolated from total zebrafish cDNA library prepared from 6-day old fish by a homology-based cloning strategy. The two zebrafish PACAP receptors have the same topology as the one found in other members of this class of seven membrane-spanning G-protein-coupled receptors. Each of the two zebrafish PACAP receptors shares about 70% sequence identity at the amino acid level with the human PACAP-type 1 receptor, and about 50% amino acid identity with PACAP/VIP R-1 and PACAP/VIP R-2 receptors. One of these zebrafish receptors contains the hop2 configuration found in the human and rat PACAP-type 1 receptors. On the basis of these structural characteristics the zebrafish PACAP receptors were classified as PACAP-type 1 and PACAP-type 2 receptors. In competitive binding experiments zebrafish PACAP-type 1 and PACAP-type 2 receptors showed similar binding specificity for zebrafish and human PACAP-38 and PACAP-27. Furthermore, the specificity of PACAP-type 1 and PACAP-type 2 receptors for zebrafish and human PACAPs is about 1,000-fold higher than for human VIP. These results demonstrate that zebrafish PACAP-type 1 receptor is a structural and pharmacological homolog of the mammalian PACAP-type 1 receptor. Additional pharmacological characterization is needed in order to classify the zebrafish PACAP-type 2 receptor.

Amino Acid Sequence↗
PubMed1998

Sequence and expression of glutamic acid decarboxylase isoforms in the developing zebrafish.

We describe the isolation two glutamic acid decarboxylase (GAD) cDNAs from zebrafish with over 84% identity to human GAD65 and GAD67. In situ hybridization studies revealed that both GAD65 and GAD67 were expressed in the early zebrafish embryo during the period of axonogenesis, suggesting a role for GABA prior to synapse formation. Both GAD genes were detected in the telencephalon, in the nucleus of the medial longitudinal fasciculus in the midbrain, and at the border regions of the rhombomeres in the rostral hindbrain. In the caudal hindbrain, only GAD67 was detected (in neurons with large-caliber axons). In the spinal cord, both GAD genes were detected in dorsal longitudinal neurons, commissural secondary ascending neurons, ventral longitudinal neurons, and Kolmer-Agduhr neurons. Immunohistochemistry for gamma-aminobutyric acid (GABA) revealed that GABA is produced at all sites of GAD expression, including the novel cells in the caudal hindbrain. These results are discussed in the context of the hindbrain circuitry that supports the escape response. We conclude that fish, like mammals, have two GAD genes. The zebrafish GAD65 and GAD67 are present in identified neurons in the forebrain, midbrain, hindbrain, and spinal cord, and they catalyze the production of GABA in the developing embryo.

Amino Acid Sequence↗
PubMed1998

Zebrafish TrkC1 and TrkC2 receptors define two different cell populations in the nervous system during the period of axonogenesis.

We identified previously five distinct trk genes in the zebrafish. The structures of two of these, TrkC1 and TrkC2, are most similar to mammalian TrkC. Detailed sequence comparisons reported here indicate that although the similarities to TrkC are greatest in those regions of the extracellular domain implicated in ligand binding, the two sequences also differ significantly in these regions. Whole-mount in situ hybridization experiments in the early embryo revealed full-length trkC1 but no trkC2 transcripts in the cranial ganglia and in a subset of Rohon-Beard neurons. At the same time, full-length trkC2 but no trkC1 transcripts were detected laterally in the spinal cord, in the caudal hindbrain, in reticulospinal neurons of rhombomeres 4, 5, and 6, and in the midbrain. Both types of transcripts were expressed in clusters of cells in the dorsal telencephalon and the nucleus of the tract of the postoptic commissure. These results suggest distinct functions of trkC1 and trkC2 in nervous system development. The expression patterns define two different neuronal populations in the zebrafish.

Amino Acid Sequence↗
PubMed1997

Brain-derived neurotrophic factor gene expression in the developing zebrafish.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of polypeptides that includes NGF, NT-3, NT-4/5 and NT-6. Although neurotrophins are known to be expressed in teleost fishes little is known about their functions in the development of these vertebrates. We are therefore studying BDNF in the zebrafish, Danio rerio. The structure of zebrafish BDNF mRNA was established using PCR and cDNA cloning. The encoded BDNF was 91% identical to mammalian BDNF. Southern blot analysis revealed a unique BDNF gene. Northern blot analysis detected two heterogeneous populations of BDNF transcripts centered at 1.6 and 2 kb. BDNF transcripts were first measurable 24 h post-fertilization (pf). Their abundance relative to total transcripts increased 6-fold between 1 day and 3 days pf and again 2-fold by 7 days pf. In situ hybridization analyses of 4-day-old larvae revealed BDNF transcripts in the retina, brain, otic vesicle, pectoral fin and the hair cells of the neuromast. The early onset and cellular sites of expression suggest that BDNF functions in nervous system and fin development in the zebrafish.

Aging↗