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Biomedical subjects

R Lehmann

Publications and source records attributed to R Lehmann.

At least 109 records · Page 6Linked to original sources
PubMed1998

Analysis of traditional Chinese anticancer drugs by capillary electrophoresis.

The results reported in this communication demonstrate that capillary zone electrophoresis (CZE) can be used easily for the quantitative determination of the potential anticancer drugs berberine and isoguanosine in the extract of the traditional Chinese medicinal herb. Isoguanosine and berberine can be monitored selectively and sensitively at 254 nm within 14 min in the plant extract using a 100-mM sodium citrate running buffer (adjusted to pH 2.7; applied voltage 12 kV). The concentration range of 0.1-50 micrograms ml-1 proved to be sufficient for exact quantification and the peak profile showed good reproducibility [relative standard deviations (n = 32); for the migration time 0.22% (isoguanosine) and 1.32% (berberine); for the peak area 2.8% (isoguanosine) and 3.2% (berberine)]. The measured concentrations in the crude extract were 1.3 micrograms ml-1 for isoguanosine and 8.7 micrograms ml-1 for berberine. In addition to the better separation performance, CZE shows several other remarkable advantages over high-performance liquid chromatography (HPLC), such as rapidity of analysis, small sample volume, no requirement of organic solvent in the running buffer and low cost of reagents.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Capillary electrophoresis of urinary normal and modified nucleosides of cancer patients.

This paper gives a capillary electrophoretic method for the separation of 15 urinary normal and modified nucleosides from cancer patients in less than 40 min. A 500 mm x 50 microns uncoated capillary column (437.5 mm to window) was used. The effects of the voltage and the sodium dodecyl sulfate (SDS) concentration in the buffer on the separation were studied. With reproducibilities of migration times better than 1.2% (R.S.D.) and determined concentrations better than 5-25%, depending on the concentrations of nucleosides in the urine, the analytical characteristics of the method were good. Using this developed method, the concentrations of 13 normal and modified nucleosides, extracted on a phenyl boronic acid affinity chromatography column, in 25 urines from patients of 14 kinds of cancer were determined. The levels (nmol/mumol creatinine) of modified nucleosides in urines from cancer patients were increased as compared with those in normal urines.

Chromatography, Affinity↗
PubMed1998

High glucose-induced transforming growth factor beta1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells.

Previous studies revealed that exposure of mesangial cells to high glucose concentration induces the production of matrix proteins mediated by TGF-beta1. We tested if structural analogues of D-glucose may mimic the high glucose effect and found that D-glucosamine was strikingly more potent than D-glucose itself in enhancing the production of TGF-beta protein and subsequent production of the matrix components heparan sulfate proteoglycan and fibronectin in a time- and dose-dependent manner. D-Glucosamine also promoted conversion of latent TGF-beta to the active form. Therefore, we suggested that the hexosamine biosynthetic pathway (the key enzyme of which is glutamine:fructose-6-phosphate amidotransferase [GFAT]) contributes to the high glucose-induced TGF-beta1 production. Inhibition of GFAT by the substrate analogue azaserine or by inhibition of GFAT protein synthesis with antisense oligonucleotide prevented the high glucose-induced increase in cellular glucosamine metabolites and TGF-beta1 expression and bioactivity and subsequent effects on mesangial cell proliferation and matrix production. Overall, our study indicates that the flux of glucose metabolism through the GFAT catalyzed hexosamine biosynthetic pathway is involved in the glucose-induced mesangial production of TGF-beta leading to increased matrix production.

Animals↗
PubMed1998

Oculo-facio-cardio-dental (OFCD) syndrome.

The association of facial dysmorphy, congenital cataracts, microphthalmia, heart disease, and dental radiculomegaly is very rare. We describe a girl with atrial septal defect, unilateral congenital cataract, unilateral microphthalmia, radiculomegaly of incisor and canine teeth with open apices and other dental crown anomalies. This combination of symptoms clearly represents a distinct syndrome and has recently been described as oculo-facio-cardio-dental (OFCD) syndrome.

Abnormalities, Multiple↗
PubMed1998

Transient tetraparesis after intrathecal and high-dose systemic methotrexate.

Aggressive polychemotherapy, intrathecal cytostatic prophylaxis and cranial irradiation have contributed to the remarkable improvement in the prognosis of acute lymphoblastic leukemia (ALL) and subtypes of high-grade non-Hodgkin's lymphoma (NHL) and the reduction of central nervous system (CNS) relapses. Early and late neurologic changes have been observed after different CNS-directed therapies. We report on the rare event of an acute tetraparesis after methotrexate (MTX) without other CNS-directed therapy. A young female with a diffuse large B-cell lymphoma developed signs of meningeal irritation a few hours after intrathecal prophylaxis with MTX, cytosine-arabinoside and dexamethasone. She recovered quickly. Ten days after her last course of systemic chemotherapy including high dose MTX she was admitted with a tetraparesis and motoric aphasia. A computer assisted tomography (CT) scan was normal. On magnetic resonance imaging (MRI) hyperintense white matter lesions were visible in the periventricular white matter. Initially, the radiologic signs were progressive while the patient's clinical condition improved. MRI controls after complete neurologic normalization revealed delayed partial regression of the white matter abnormalities. The patient has now been free of neurologic symptoms for 16 months. This case report demonstrates acute and subacute neurotoxic effects of MTX in the same patient and illustrates that radiologic CNS changes can persist irrespective of the disappearance of clinical symptoms.

Adolescent↗
PubMed1998

Callosal and corticospinal tract function in patients with hydrocephalus: a morphometric and transcranial magnetic stimulation study.

In 15 patients with symptomatic hydrocephalus, pressure-induced morphological changes of the brain and the function of callosal and corticospinal fibres were studied. Morphometry of the corpus callosum (CC) was performed on midsagittal MR images. Focal transcranial magnetic stimulation of the motor cortex was used to assess simultaneously excitatory motor responses in contralateral hand muscle (corticospinally mediated effect) and inhibition of tonic EMG activity in ipsilateral hand muscles (transcallosal inhibition (TI) of the contralateral motor cortex). Before a shunt operation, the midsagittal area of the CC was reduced by 34% on average. The height and, to a lesser degree the length, of the CC were increased before the shunt operation. Thresholds and central motor latencies of corticospinally mediated responses were normal, response amplitudes were smaller than in normal subjects. Motor thresholds increased from 38, SD 5 to 52, SD 8% (P < 0.01) within 7 days after ventricular drainage, reflecting the increase in the distance between stimulation coil and brain. The threshold increase paralleled a restoration of normal anatomical conditions within 7 days after shunt operation and the improvement of motor symptoms and might be a predictor of successful decompression. Transcallosal inhibition could be elicited in all patients. The measurements of TI lay within the normal range except the duration, which was prolonged in 73% of 15 patients before shunt operation as a probable indicator of an increased dispersion of callosal conduction. The normalization of the area and shape of the CC after shunt operation and the normal corticospinal and callosal conduction times exclude degeneration, demyelination or functional block of a large proportion of callosal or corticospinal tract fibres or a substantial loss of nerve cells in motor cortex.

Adult↗
PubMed1998

Drinking water fluoridation: bone mineral density and hip fracture incidence.

The role of drinking water fluoride content for prevention of osteoporosis remains controversial. Therefore, we analyzed the influence of drinking water fluoridation on the incidence of osteoporotic hip fractures and bone mineral density (BMD) in two different communities in eastern Germany: in Chemnitz, drinking water was fluoridated (1 mg/L) over a period of 30 years; in Halle, the water was not fluoridated. BMD was measured in healthy hospital employees aged 20-60 years (Halle: 214 women, 98 men; Chemnitz: 201 women, 43 men, respectively) using dual-energy X-ray absorptiometry. Hip fractures in patients > or = 35 years admitted to the local hospitals in the years 1987-1989 were collected from the clinic registers. There was no difference in age, anthropometric, hormonal, or lifestyle variables between the two groups. Mean fluoride exposure in Chemnitz was 25.2 +/- 7.3 years. No correlation was found between fluoride exposure and age-adjusted BMD. We found no significant difference in spinal or femoral BMD between subjects living in Halle and Chemnitz [lumbar spine: 0.997 +/- 0.129 (g/cm2) vs. 1.045 + 0.171 (g/cm2), p = 0.08, for men; 1.055 +/- 0.112 (g/cm2) vs. 1.046 +/- 0.117 (g/cm2), p = 0.47, for women]. The fracture incidence showed an exponential increase with aging in men and women with an incidence about 3.5 times higher for women. In Chemnitz, we calculated an age-adjusted annual incidence of 142.2 per 100,000 for women and 72.5 per 100,000 for men, respectively. In Halle, the incidences were 178.5 per 100,000 for women and 89.2 per 100,000 for men. There was a lower hip fracture incidence after the age of 85 in women in Chemnitz (1391 per 100,000 in Chemnitz vs. 1957 per 100,000) in Halle, p = 0.006). Using the age-adjusted incidences, significantly fewer hip fractures occurred in Chemnitz in both men and women. In conclusion, our study suggests that optimal drinking water fluoridation (1 mg/L), which is advocated for prevention of dental caries, does not influence peak bone density but may reduce the incidence of osteoporotic hip fractures in the very old.

Adult↗
PubMed1998

[Spontaneous perimesencephalic subarachnoid hemorrhage (PMH). A disease category with good prognosis?].

Perimesencephalic subarachnoidal haemorrhage (PMH) is characterized by a typical blood distribution pattern in the basal cysterns in the CAT, missing evidence of an aneurysm in the panangiogram, a mild clinical course and a very positive prognosis. Between 1990 and 1995, 108 inpatients with non-traumatic subarachnoidal haemorrhage were treated in our clinic. Within this group 14 patients (13%) were identified retrospectively with a perimesencephalic haemorrhage distribution pattern in the CAT and a negative panangiogram. These patients experienced a mild clinical course with excellent outcome without rebleeding during the observation period of 2 to 50 months. All patients were fully able to work, and only two patients complained of frequent headaches. The mild clinical course, the negative panangiogram as well as the extremely positive outcome confirm the hypothesis of of a benign subgroup of non-traumatic subarachnoidal haemorrhages.

Adult↗
PubMed1998

zfh-1 is required for germ cell migration and gonadal mesoderm development in Drosophila.

In Drosophila as well as many vertebrate systems, germ cells form extraembryonically and migrate into the embryo before navigating toward gonadal mesodermal cells. How the gonadal mesoderm attracts migratory germ cells is not understood in any system. We have taken a genetic approach to identify genes required for germ cell migration in Drosophila. Here we describe the role of zfh-1 in germ cell migration to the gonadal mesoderm. In zfh-1 mutant embryos, the initial association of germ cells and gonadal mesoderm is blocked. Loss of zfh-1 activity disrupts the development of two distinct mesodermal populations: the caudal visceral mesoderm and the gonadal mesoderm. We demonstrate that the caudal visceral mesoderm facilitates the migration of germ cells from the endoderm to the mesoderm. Zfh-1 is also expressed in the gonadal mesoderm throughout the development of this tissue. Ectopic expression of Zfh-1 is sufficient to induce additional gonadal mesodermal cells and to alter the temporal course of gene expression within these cells. Finally, through analysis of a tinman zfh-1 double mutant, we show that zfh-1 acts in conjunction with tinman, another homeodomain protein, in the specification of lateral mesodermal derivatives, including the gonadal mesoderm.

Animals↗
PubMed1998

Identification of genes controlling germ cell migration and embryonic gonad formation in Drosophila.

Gonadogenesis in the Drosophila embryo is a complex process involving numerous cellular migratory steps and cell-cell interactions. The mechanisms guiding germ cells to move through, recognize and adhere to specific cell types are poorly understood. In order to identify genes that are required for these processes, we have conducted an extensive mutagenesis of the third chromosome and screened for mutations disrupting germ cell migration at any point in embryonic development. Phenotypic analysis of these mutants demonstrates that germ cell migration can be broken down into discrete developmental steps, with each step requiring a specific set of genes. Many of these genes are involved in the development of gonadal mesoderm, the tissue that associates with germ cells to form the embryonic gonad. Moreover, mutations that we isolated affecting embryonic patterning as well as germ cell migration suggest that the origin of gonadal mesoderm lies within the eve domain of the developing mesoderm.

Animals↗
PubMed1998

Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells.

The zinc-finger protein Nanos and the RNA-binding protein Pumilio act together to repress the translation of maternal hunchback RNA in the posterior of the Drosophila embryo, thereby allowing abdomen formation. nanos RNA is localized to the posterior pole during oogenesis and the posteriorly synthesized Nanos protein is sequestered into the germ cells as they form in the embryo. This maternally provided Nanos protein is present in germ cells throughout embryogenesis. Here we show that maternally deposited Nanos protein is essential for germ cell migration. Lack of zygotic activity of nanos and pumilio has a dramatic effect on germline development of homozygous females. Given the coordinate function of nanos and pumilio in embryonic patterning, we analyzed the role of these genes in oogenesis. We find that both genes act in the germline. Although the nanos and pumilio ovarian phenotypes have similarities and both genes ultimately affect germline stem cell development, the focus of these phenotypes appears to be different. While pumilio mutant ovaries fail to maintain stem cells and all germline cells differentiate into egg chambers, the focus of nanos function seems to lie in the differentiation of the stem cell progeny, the cystoblast. Consistent with the model that nanos and pumilio have different phenotypic foci during oogenesis, we detect high levels of Pumilio protein in the germline stem cells and high levels of Nanos in the dividing cystoblasts. We therefore suggest that, in contrast to embryonic patterning, Nanos and Pumilio may interact with different partners in the germline.

Animals↗
PubMed1998

Gonadal mesoderm and fat body initially follow a common developmental path in Drosophila.

During gastrulation, the Drosophila mesoderm invaginates and forms a single cell layer in close juxtaposition to the overlying ectoderm. Subsequently, particular cell types within the mesoderm are specified along the anteroposterior and dorsoventral axes. The exact developmental pathways that guide the specification of different cell types within the mesoderm are not well understood. We have analyzed the developmental relationship between two mesodermal tissues in the Drosophila embryo, the gonadal mesoderm and the fat body. Both tissues arise from lateral mesoderm within the eve domain. Whereas in the eve domain of parasegments 10-12 gonadal mesoderm develops from dorsolateral mesoderm and fat body from ventrolateral mesoderm, in parasegments 4-9 only fat body is specified. Our results demonstrate that the cell fate decision between gonadal mesoderm and fat body identity within dorsolateral mesoderm along the anteroposterior axis is determined by the combined actions of genes including abdA, AbdB and srp; while srp promotes fat body development, abdA allows gonadal mesoderm to develop by repressing srp function. Furthermore, we present evidence from genetic analysis suggesting that, before stage 10 of embryogenesis, gonadal mesoderm and the fat body have not yet been specified as different cell types, but exist as a common pool of precursor cells requiring the functions of the tin, zfh-1 and cli genes for their development.

Animals↗
PubMed1998

Localization and expression of adrenocorticotropic hormone receptor mRNA in normal and neoplastic human adrenal cortex.

The recent cloning of the ACTH receptor (ACTH-R) gene allows investigation of the tissue localization and relative abundance of ACTH-R mRNA in normal and neoplastic adrenal cortex. Using in situ hybridization (ISH) we studied the expression of ACTH-R mRNA in four adult adrenals of brain-dead patients, two cortisol-producing adenomas (CPA), three aldosterone-producing adenomas (APA), one non-functional adenoma (NFA), and three carcinomas. The results were compared with the mRNA expression of key steroidogenic enzymes and of the glucocorticoid receptor (GR) mRNA using Northern blotting. In adult adrenals, messenger RNA encoding ACTH-R was localized in all three zones of the adrenal cortex, in accordance with the stimulatory role of ACTH on mineralocorticoid, glucocorticoid and adrenal androgen secretion. In comparison, expression of side-chain cleavage enzyme (P450scc) showed a similar tissue distribution with mRNA abundance in all three zones, whereas 17-hydroxylase/17-20 lyase (P450c17) mRNA expression was only detected in the zona fasciculata and zona reticularis. All CPAs and APAs expressed significant levels of ACTH-R mRNA whereas an NFA showed low expression of ACTH-R mRNA. Two of three adrenocortical carcinomas expressed ACTH-R mRNA. Northern analysis using dot blot was employed to quantify ACTH-R and GR mRNA expression and confirmed the ISH data: ACTH-R mRNA expression was high in CPAs (275 and 195% vs 100 +/- 25% in adult adrenals), APAs (127, 200 and 221%) and two carcinomas (99 and 132%), but low in the NFA (7%) and in an androgen secreting carcinoma (16%). GR mRNA expression was high in the NFA (195%) and in two of three carcinomas (93, 188, 227%). We conclude that ACTH-R mRNA is upregulated in functional adenomas by yet unidentified mechanisms. The tissue distribution of ACTH-R and P450 enzyme mRNA expression is highly variable in neoplastic adrenals and does not allow a clear differentiation between benign and malignant tumors.

Adenoma↗
PubMed1998

Transplantation of allogeneic islets of Langerhans in the rat liver: effects of macrophage depletion on graft survival and microenvironment activation.

Early impairment of islet function and graft loss limit the success of allogeneic islet transplantation. Nonspecific inflammatory events occurring at the transplant site immediately after grafting, involving the production of cytokines and free radicals and sinusoidal endothelial cell (SEC) activation, may contribute to islet cell damage. To evaluate whether Kupffer cell inactivation would result in prolonged allograft survival in a model system of intrahepatic islet transplantation in rats, we systemically administered either gadolinium chloride (GdCl3) or dichloromethylene diphosphonate (Cl2MDP) to assess the effects of macrophage inactivation on rejection and on the release of proinflammatory molecules, as well as to assess the functional profile of SEC. The results obtained were compared with those observed in untreated, sham-injected animals and in rats receiving intraportal infusions of microbeads. Transient macrophage inhibition, particularly in hepatic Kupffer cells, is associated with significant prolongation of graft survival after intraportal islet allotransplantation (ITx) in rats: 7.2 days in the control group versus 11.9 days in the GdCl3 group (P < 0.01) and 15.6 days in the Cl2MDP group (P < 0.0006), respectively. Although systemic release of inflammatory mediators was observed only when islet transplantations were performed and it could be inhibited by macrophage-targeting treatments, perturbation of the functional profile of endothelial cells was also observed when microembolization was induced by the use of microbeads and could not be prevented by macrophage inhibition. These experiments provide evidence to support the concept that macrophages play a key role in early inflammatory events known to adversely affect islet engraftment and suggest that manipulation of nonspecific immune activation by inhibition of macrophage function may facilitate hepatic engraftment of islet allografts. The mechanisms mediating this effect are likely to include prevention of release of tumor necrosis factor-alpha, interleukin-1beta, and NO and interference with the rate of immune response to the islets.

Animals↗
PubMed1998

Scaling an expert system data mart: more facilities in real-time.

Clinical Data Repositories are being rapidly adopted by large healthcare organizations as a method of centralizing and unifying clinical data currently stored in diverse and isolated information systems. Once stored in a clinical data repository, healthcare organizations seek to use this centralized data to store, analyze, interpret, and influence clinical care, quality and outcomes. A recent trend in the repository field has been the adoption of data marts--specialized subsets of enterprise-wide data taken from a larger repository designed specifically to answer highly focused questions. A data mart exploits the data stored in the repository, but can use unique structures or summary statistics generated specifically for an area of study. Thus, data marts benefit from the existence of a repository, are less general than a repository, but provide more effective and efficient support for an enterprise-wide data analysis task. In previous work, we described the use of batch processing for populating data marts directly from legacy systems. In this paper, we describe an architecture that uses both primary data sources and an evolving enterprise-wide clinical data repository to create real-time data sources for a clinical data mart to support highly specialized clinical expert systems.

Computer Systems↗