Search PubMed⌕ Search

Biomedical subjects

J Schmidt

Publications and source records attributed to J Schmidt.

At least 217 records · Page 12Linked to original sources
PubMed1999

Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas.

PURPOSE: To assess the effects of intravitreal injection of recombinant tissue plasminogen activator (rTPA) and gas on submacular hemorrhage in age-related macular degeneration (ARMD). METHODS: Eleven consecutive patients (11 eyes) with subretinal hemorrhage due to ARMD involving the fovea with elevation of the neurosensory retina were included in this study. Subretinal hemorrhage occured 12 h to 14 days before onset of therapy. Injection of rTPA through the pars plana in a dose of 50 or 100 microg was performed. Gas instillation (0.2-0.4 ml) followed rTPA injection, either immediately after injection (7 patients) or during the following day (4 patients). RESULTS: After intravitreal injection of rTPA, subretinal clots were totally or partially liquefied when treatment started up to 3 days after onset of bleeding. In all patients treated with 100 microg rTPA a large exudative retinal detachment of the inferior retina resulted, which reabsorbed spontaneously within 2 weeks. After reattachment of the exudative retinal detachment hyperpigmentation of the retinal pigment epithelium was noted. Temporary opacification of the vitreous was observed between the 2nd and 7th postoperative day in 5 eyes (45.5%). Postoperative visual acuity increased in 5 patients (45.5%). CONCLUSION: Intravitreal application of rTPA followed by gas injection is a sufficient and convenient technique for effective removal of freshly formed submacular hemorrhage. Removal is mediated through combined enzymatic (rTPA) and mechanical (gas) effects. This technique offers a quick recovery of vision in eyes with less severe ARMD.

Acute Disease↗
PubMed1999

Onset and dynamics of osteosclerosis in mice induced by Reilly-Finkel-Biskis (RFB) murine leukemia virus. Increase in bone mass precedes lymphomagenesis.

Newborn NMRI strain mice were infected with Reilly-Finkel-Biskis (RFB) murine leukemia virus (MuLV), a murine leukemia virus that has been shown to induce lymphomas, osteosclerosis, and osteomas in susceptible strains of mice. Bone histomorphometry of the distal femoral metaphyses at 3-month intervals showed osteosclerosis 3 (100%), 6 (100%), and 9 (93%) months after infection. This was represented by significantly augmented cancellous bone mass and accompanied by distinct changes in bone architecture. High numbers of provirus copies were detected at 2-4 weeks in femora, humeri, and calvaria, and viral protein was highly expressed in trabecular and cortical bone cells, particularly in osteocytes. Infected mice showed enhanced bone formation and smaller numbers of osteoclasts relative to sex- and age-matched controls. Osteoclastic differentiation was significantly reduced in cocultures of spleen or bone marrow cells with RFB MuLV-infected osteoclastogenic, osteoblast-like cells. However, RFB MuLV did not impair the activity of mature osteoclasts. In infected mice lymphomas were only observed at 6 (22%) and 9 months (40%) of age. At 3 months, IgG gene and TCR-beta gene rearrangements were not detectable, and new proviruses showed a heterogeneous integration pattern, indicating the absence of lymphoma in early osteosclerotic mice. In contrast, lymphomas, which developed in 8- to 9-month-old infected mice, showed IgG rearrangements indicating development of B-cell lymphomas, together with mono- or oligoclonal expansion of distinct patterns of proviral integrations. These results indicate that RFB MuLV-induced osteosclerosis develops within 3 months after infection and precedes lymphomagenesis. It may therefore be considered an independent skeletal lesion in MuLV-infected mice.

3T3 Cells↗
PubMed1999

Biochemical strategy of sequestration of pyrrolizidine alkaloids by adults and larvae of chrysomelid leaf beetles.

Tracer feeding experiments with (14)C-labeled senecionine and senecionine N-oxide were carried out to identify the biochemical mechanisms of pyrrolizidine alkaloid sequestration in the alkaloid-adapted leaf beetle Oreina cacaliae (Chrysomelidae). The taxonomically closely related mint beetle (Chrysolina coerulans) which in its life history never faces pyrrolizidine alkaloids was chosen as a 'biochemically naive' control. In C. coerulans ingestion of the two tracers resulted in a transient occurrence of low levels of radioactivity in the hemolymph (1-5% of radioactivity fed). With both tracers, up to 90% of the radioactivity recovered from the hemolymph was senecionine. This indicates reduction of the alkaloid N-oxide in the gut. Adults and larvae of O. cacaliae sequester ingested senecionine N-oxide almost unchanged in their bodies (up to 95% of sequestered total radioactivity), whereas the tertiary alkaloid is converted into a polar metabolite (up to 90% of total sequestered radioactivity). This polar metabolite, which accumulates in the hemolymph and body, was identified by LC/MS analysis as an alkaloid glycoside, most likely senecionine O-glucoside. The following mechanism of alkaloid sequestration in O. cacaliae is suggested to have developed during the evolutionary adaptation of O. cacaliae to its alkaloid containing host plant: (i) suppression of the gut specific reduction of the alkaloid N-oxides, (ii) efficient uptake of the alkaloid N-oxides, and (iii) detoxification of the tertiary alkaloids by O-glucosylation. The biochemical mechanisms of sequestration of pyrrolizidine alkaloid N-oxides in Chysomelidae leaf beetles and Lepidoptera are compared with respect to toxicity, safe storage and defensive role of the alkaloids.

Journal Article↗
PubMed1999

Improved glucose tolerance in rats treated with the dipeptidyl peptidase IV (CD26) inhibitor Ile-thiazolidide.

The incretins glucose-dependent insulinotropic polypeptide (GIP1-42) and truncated forms of glucagon-like peptide-1 (GLP-1) are hormones released from the gut in response to ingested nutrients, which act on the pancreas to potentiate glucose-induced insulin secretion. These hormones are rapidly inactivated by the circulating enzyme dipeptidyl peptidase IV ([DPIV] CD26). This study describes the effect on glucose tolerance and insulin secretion of inhibiting endogenous DPIV in the rat using Ile-thiazolidide, a specific DPIV inhibitor. High-performance liquid chromatography (HPLC) analysis of plasma following in vivo administration of 125I-labeled peptides showed that inhibition of DPIV by about 70% prevented the degradation of 90.0% of injected 125I-GLP-17-36 after 5 minutes, while only 13.4% remained unhydrolyzed in rats not treated with the DPIV-inhibiting agent after only 2 minutes. Ile-thiazolidide treatment also increased the circulating half-life of intact GLP-17-36 released in response to intraduodenal (ID) glucose (as measured by N-terminal specific radioimmunoassay [RIA]). In addition, inhibition of DPIV in vivo resulted in an earlier increase and peak of plasma insulin and a more rapid clearance of blood glucose in response to ID glucose challenge. When considered with the HPLC data, these results suggest that the altered insulin profile is an incretin-mediated response. DPIV inhibition resulting in improved glucose tolerance may have therapeutic potential for the management of type 2 diabetes mellitus.

Animals↗
PubMed1999

Light-induced betacyanin and flavonol accumulation in bladder cells of Mesembryanthemum crystallinum.

Treatment of the halophyte Mesembryanthemum crystallinum L. (ice plant) (Aizoaceae) with high intensities of white light resulted in a rapid cell-specific accumulation of betacyanins and flavonoids with 6-methoxyisorhamnetin 3-O-¿[(2"'-E-feruloyl)-3"'-O-(beta-D- glucopyranosyl)](2"-O-beta-D-xylopyranosyl)]-beta-D-glucopyranoside (mesembryanthin) as the predominant component, within bladder cells of the leaf epidermis. Induced accumulation of these metabolites was first detected 18 h after the initiation of light treatment in bladder cells located at the tip of young leaves followed by the bladder cells located on the epidermis of fully expanded leaves. UV-A light apparently is sufficient to induce accumulation of betacyanins and flavonoids. Application of 2-aminoindan 2-phosphonic acid, a specific inhibitor of phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), not only inhibited the accumulation of flavonoids but also reduced betacyanin formation. Based on these observations we suggest these bladder cells as a model system to study regulation of betacyanin and flavonoid biosyntheses.

Anthocyanins↗
PubMed1999

Effects of exogenous superoxide anion and nitric oxide on the scavenging function and electron microscopic appearance of the sinusoidal endothelium in the isolated, perfused rat liver.

BACKGROUND/AIMS: Functional and morphological alterations of the hepatic sinusoidal endothelial cell occur in several models of experimental liver injury and in clinical settings. The causes of these alterations are multiple. The aim of this study was to test the hypothesis that the early functional impairment and morphological alterations of the sinusoidal endothelial cell and hepatic sinusoid associated with liver injury are mediated by free radical species, such as superoxide anion and nitric oxide. METHODS: Isolated rat livers were perfused by recirculation with hemoglobin-free, Krebs-Henseleit bicarbonate buffer and presented with a source of superoxide anion (xanthine oxidase+hypoxanthine) or nitric oxide (S-nitroso-N-acetyl penicillamine). Hyaluronan uptake (an index of sinusoidal endothelial cell scavenging function), thiobarbituric acid-reactive substances content of the tissue (a marker of lipid peroxidation), reduced and oxidized glutathione (a marker of the thiol system oxidation/reduction state), lactate dehydrogenase and alanine aminotransferase activities (markers of cytolysis), as well as scanning and transmission electron microscopic appearance of the sinusoid were evaluated. RESULTS: At the high concentrations used, both free radical generating systems suppressed hyaluronan uptake, increased malondialdehyde content of the tissue, enhanced the release of both liver enzymes, decreased the total glutathione content of the liver, and altered the ratio of reduced/oxidized glutathione. Both free radical species induced dose-dependent morphological alterations of the sinusoid, consisting of the appearance of large gaps replacing the sieve-plated fenestration. CONCLUSIONS: The free radical species-induced functional impairment and morphological alterations of the liver sinusoid, presented in this study, closely resemble the early in vivo changes associated with liver injury under a variety of conditions, such as preservation and reperfusion, or administration of hepatotoxicants such as D-galactosamine, Gram-negative bacterial lipopolysaccharides, acetaminophen, alcohol and others. Therefore, we suggest that early liver sinusoid injury, observed under these conditions, can be attributed to the action of free radicals, such as superoxide anion and nitric oxide.

Alanine Transaminase↗
PubMed1999

Genetically modified organisms in food-screening and specific detection by polymerase chain reaction.

PCR methods for the detection of genetically modified organisms (GMOs) were developed that can be used for screening purposes and for specific detection of glyphosate-tolerant soybean and insect-resistant maize in food. Primers were designed to amplify parts of the 35S promoter derived from Cauliflower Mosaic Virus, the NOS terminator derived from Agrobacterium tumefaciens and the antibiotic marker gene NPTII (neomycin-phosphotransferase II), to allow for general screening of foods. PCR/hybridization protocols were established for the detection of glyphosate-tolerant RoundUp Ready soybean and insect-resistant Bt-maize. Besides hybridization, confirmation of the results using restriction analysis was also possible. The described methods enabled a highly sensitive and specific detection of GMOs and thus provide a useful tool for routine analysis of raw and processed food products.

Blotting, Southern↗
PubMed1999

Sequence and functional analysis of the left-hand part of the T-region from the nopaline-type Ti plasmid, pTiC58.

The Agrobacterium tumefaciens nopaline strain C58 transfers a large, 29 kb T-DNA into plant cells during infection. Part of this DNA (the 'common DNA') is also found on the T-DNA of octopine strains, the remaining DNA is nopaline strain-specific. Up to now, only parts of the C58 T-DNA and related T37 T-DNA have been sequenced. We have sequenced the remainder of the nopaline-specific T-DNA (containing genes a to d) and acs to iaaM. Gene c codes for a new unknown T-DNA protein. Gene a is homologous to the agrocinopine synthase gene. Genes b, c', d and e are part of a larger family: they are related to the T-DNA genes 5, rolB, lso and 3'. Genes 5, rolB and lso induce or modify plant growth and have been called T-DNA oncogenes. Our studies show that gene 3' (located on the TR-DNA of octopine strains) is also oncogenic. Although the b-e T-DNA fragment from C58 and its individual genes lack growth-inducing activity, an a-acs deletion mutant was distinctly less virulent on Kalanchoe daigremontiana and showed reduced shoot formation on Kalanchoe tubiflora. Shoot formation could be restored by genes c and c' in co-infection experiments. Contrary to an earlier report, a C58 e gene deletion mutant was fully virulent on all plants tested.

Agrobacterium tumefaciens↗
PubMed1999

Trypsinogen activation peptides (TAP) in peritoneal fluid as predictors of late histopathologic injury in necrotizing pancreatitis of the rat.

The levels of trypsinogen activation peptides (TAP) were quantified by ELISA immunoassay in acute pancreatitis of the rat and compared to the degree of late histopathological sequelae and exocrine functional impairment 4 and 12 weeks after the acute phase of the disease. For this purpose acute pancreatitis of different severity was induced using a suitable rat model recently described. Forty five surviving animals were studied. The level of TAP in peritoneal exudate measured 3 and 6 hr after pancreatitis induction correlated well with the amount of the late histopathological injury at the end of the corresponding observation period (at 4 weeks after 3 hr: r = 0.75, P = 0.003, after 6 hr: r = 0.72, P = 0.005, Pearson; and at 12 weeks after 3 hr: r = 0.86, P = 0.0001, after 6 hr: r = 0.84, P = 0.0001, Pearson). A negative correlation of TAP with the impairment of exocrine function was found only at 4 weeks for the secretion of total protein (r = -0.76 after 3 hr; r = -0.62 after 6 hr) and for exocrine function (r = -0.67 after 3 hr, r = -0.57 after 6 hr), but not at 12 weeks after acute pancreatitis. No correlation with plasma amylase and lipase was found. We conclude that quantitation of TAP in ascites provides an accurate prediction of late histopathologic sequelae. Pancreatic exocrine function could be predicted by TAP assay only in the early stage after pancreatitis induction (eg, four weeks). In later stages of the disease (eg, 12 weeks) remaining pancreatic tissue seems to compensate for any exocrine deficits that have occurred.

Animals↗
PubMed1999

Peptide-mediated glial responses to leydig neuron activity in the leech central nervous system.

Neuronal activity may lead to a variety of responses in neighbouring glial cells; in general, an ensemble of neurons needs to be active to evoke a K+- and/or neurotransmitter-induced glial membrane potential change. We have now detected a signal transfer from a single neuromodulatory Leydig neuron to the giant neuropil glial cells in the central nervous system of the leech Hirudo medicinalis. Activation of a Leydig neuron, two of which are located in each segmental ganglion, elicits a hyperpolarization in the giant neuropil glial cells. This hyperpolarization could be mimicked by bath application of the peptide myomodulin A (1 nM-1.0 microM). Myomodulin-like immunoreactivity has recently been found to be present in a set of leech neurons, including Leydig neurons (Keating & Sahley 1996, J. Neurobiol., 30, 374-384). The glial responses to Leydig neuron stimulation persisted in a high-divalent cation saline, when polysynaptic pathways are suppressed, indicating that the effects on the glial cell were direct. The glial responses to myomodulin A application persisted in high-Mg2+/low-Ca2+ saline, when chemical synaptic transmission is suppressed, indicating a direct effect of myomodulin A on the glial membrane. The glial hyperpolarization evoked by myomodulin A was dose dependent (EC50 = 50 nM) and accompanied by a membrane conductance increase of approximately 25%. Ion substitution experiments indicated that myomodulin A triggered a Ca2+-independent K+ conductance. Thus, our results suggest, for the first time, direct signal transmission from an identified modulatory neuron to an identified glial cell using a myomodulin-like peptide.

Animals↗
PubMed1999

[Self-sealing, sutureless sclerotomy in pars plana vitrectomy].

BACKGROUND: If sutures are used in the regular closure of sclerotomies a trauma to the bulbus can be inflicted and intraocular bleeding might result. Phases of intraocular hypotony accompany the intraoperative exchange of instruments. Like in no-stitch cataract surgery we employed this type of self-sealing wound closure in pars-plana vitrectomies. A less traumatizing technique yielding a tight and effective closure is an alternative to the conventional approach and results of our experiences are presented. MATERIALS AND METHODS: A modified approach for sutureless sclerotomy closure was applied in 50 eyes (150 sclerotomies). A sclera-covered sclerotomy is performed after preparation of adequate scleral pouches in conventional positions. A minimal conjunctival peritomy allows at the end of surgery an electric cauterization, thus using no suture material in the whole course of vitrectomy. RESULTS: Sutureless vitrectomies can only be installed in the primary operation. However, re-operations on 3 eyes were possible in the same manner using the old sclerotomy sites up to 6 weeks after initial surgery. In 12 eyes the sclerotomy had to be covered with a single suture to obtain adequate wound closure. A repetitive change of instruments during the surgical procedure is possible with this technique and all types of intraocular instruments can be employed. CONCLUSIONS: Self-sealing sclerotomies are a simple and atraumatic approach for wound closure in pars-plana vitrectomies and allow a control of intraocular pressure during surgery.

Follow-Up Studies↗
PubMed1999

Interferon-alpha upregulates gene expression of aquaporin-5 in human parotid glands.

Aquaporins are a family of homologous membrane proteins that function as highly selective water channels. Aquaporin-5 (AQP5) is uniquely present in lacrimal and salivary glands, where it accounts for normal tear and saliva production. We tested the hypothesis that orally administered human interferon-alpha (HuIFN-alpha) benefits persons with xerostomia by augmenting the production of AQP5 protein by parotid gland epithelium. Cells from three human parotid glands were cultured with and without human lymphoblastoid IFN-alpha, and assayed for AQP5 mRNA levels by reverse transcriptase polymerase chain reaction (RT-PCR), and AQP5 protein levels by Western blot. Intracellular localization of AQP5 protein was done using confocal microscopy. The functional integrity of the glandular tissue was confirmed by RT-PCR analysis of alpha-amylase 1 and basic proline-rich protein transcripts. AQP5 was constitutively expressed in human parotid gland tissue, with AQP5 protein restricted to the plasma membranes and cytoplasmic vesicles of acinar cells. IFN-alpha augmented AQP5 transcription and protein production in a concentration-dependent manner, and increased the size of intensity of staining of AQP5-containing cytoplasmic vesicles in acinar cells. We conclude that IFN-alpha upregulates AQP5 gene expression in human parotid acinar cells in vitro. To our knowledge, this is the first demonstration that IFN-alpha regulates the gene expression of an aquaporin.

Administration, Oral↗
PubMed1999

Clinical experience with spirapril in human hypertension.

The efficacy and tolerability of spirapril were evaluated in a prospective, multicentre, post-marketing surveillance study on the treatment of arterial hypertension in 5000 patients, most of whom had received a single daily dose of 6 mg spirapril. The study was carried out by internists and general practitioners. In accordance with placebo-controlled clinical trials, spirapril was proven to be a very effective antihypertensive drug, in respect of both the mean reduction in systolic and diastolic blood pressure achieved as well as the responder rate of 89.4% and 85.4% for systolic and diastolic blood pressure, respectively. Efficacy was equally good in single drug treatment and combination treatment. Differentiated evaluation of blood pressure values in respect of the severity of hypertension on the basis of the World Health Organization classification showed a clear relationship between the baseline blood pressure and the reduction in blood pressure. The higher the baseline blood pressure, the more pronounced was the antihypertensive efficacy; a particular reduction in diastolic blood pressure being observed. Tolerability was also good, with an incidence of side effects of only 2.9%. Coughing was observed in only 0.88% of patients. Thus spirapril is seen to be an effective and well-tolerated antihypertensive drug whose efficacy is clearly related to baseline blood pressure and thus is also very effective in the treatment of severe forms of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Posttraumatic hypertension secondary to adrenal hemorrhage mimicking pheochromocytoma: case report.

We report the case of a 68-year-old man who presented with a mass 3 x 4 cm in size located in the right adrenal gland together with extreme hypertension, tripled urine levels for normetanephrine, and normal plasmatic levels of metanephrines. The patient had suffered a fall from a height of 2.5 meters before hospitalization. [123I]MIBG-scan was repeatedly positive in the area of the right adrenal gland. At laparotomy under alpha-adrenergic blocking agents, the suspected pheochromocytoma was histologically confirmed as hematoma. After resection of the adrenal gland, blood pressure returned to normal without drug therapy as did metanephrine levels in urine. Although adrenal insufficiency after distension of the gland caused by hemorrhage has been reported, there are no data available regarding the mimicking of a hormonally active pheochromocytoma. We conclude that intra-adrenal pressure rise caused by hematoma may cause partial ischemic necrosis to the gland but may also induce reactive hyperplasia with periodic excessive secretion of catecholamines. This interpretation is consistent with the finding that plasma levels of catecholamines were normal in contrast to the urinary normetanephrines in the presented case. It might be worthwhile to investigate patients with intra-adrenal hemorrhage immediately after sustaining multiple injuries and in the posttraumatic course of several months up to 1 or more years together with verification of abnormal urinary excretion of metanephrines as a sign of impaired adrenal function.

Adrenal Gland Diseases↗
PubMed1999

Infection of Chinese hamster ovary cells by pseudorabies virus.

Chinese hamster ovary (CHO) cells have recently been used for identification of receptors for several alphaherpesviruses, including pseudorabies virus (PrV) (R. J. Geraghty, C. Krummenacher, G. H. Cohen, R. J. Eisenberg, and P. G. Spear, Science 280:1618-1620, 1998). The experiments were based on the fact that CHO cells are inefficient target cells for PrV. However, a detailed analysis of the interaction between PrV and CHO wild-type and recombinant PrV-receptor bearing cells has not been performed. We show here that PrV has a growth defect on CHO cells which leads to a ca. 100-fold reduction in plating efficiency, strongly delayed penetration kinetics, and a 10(4)-fold reduction in one-step growth. Entry of PrV into CHO cells is significantly delayed but is not affected by inhibitors of endocytosis, suggesting that the mechanism of penetration resembles that on permissive cells. The defects in plating efficiency and penetration could be corrected by expression of herpesvirus entry mediators B (HveB), HveC, or HveD, with HveC being the most effective. However, the defects in one-step growth and plaque formation were not corrected by expression of PrV receptors, indicating an additional restriction in viral replication after entry. Surprisingly, PrV infection of CHO cells was sensitive to neutralization by a gB-specific monoclonal antibody, which does not inhibit PrV infection of other host cells. Moreover, the same monoclonal antibody neutralized PrV infectivity on cells displaying the interference phenomenon by overexpression of gD and subsequent intracellular sequestration of gD receptors. Thus, absence of gD receptors on two different host cells leads to an increased sensitivity of PrV toward gB neutralization. We hypothesize that this is due to the increased requirement for interaction of gB with a cellular surface protein in the absence of the gD-gD receptor interaction. As expected, CHO cells are as susceptible as other host cells to infection by PrV gD(-) Pass, an infectious gD-negative PrV mutant. However, PrV gD(-) Pass was also not able to form plaques on CHO cells.

Animals↗
PubMed1999

The kissing-loop motif is a preferred site of 5' leader recombination during replication of SL3-3 murine leukemia viruses in mice.

A panel of mouse T-cell lymphomas induced by SL3-3 murine leukemia virus (MLV) and three primer binding site mutants thereof (A. H. Lund, J. Schmidt, A. Luz, A. B. Sorensen, M. Duch, and F. S. Pedersen, J. Virol. 73:6117-6122, 1999) were analyzed for the occurrence of recombination between the exogenous input virus and endogenous MLV-like sequences within the 5' leader region. Evidence of recombination within the region studied was found in 14 of 52 tumors analyzed. Sequence analysis of a approximately 330-bp fragment of 44 chimeric proviruses, encompassing the U5, the primer binding site, and the upstream part of the 5' untranslated region, enabled us to map recombination sites, guided by distinct scattered nucleotide differences. In 30 of 44 analyzed sequences, recombination was mapped to a 33-nucleotide similarity window coinciding with the kissing-loop stem-loop motif implicated in dimerization of the diploid genome. Interestingly, the recombination pattern preference found in replication-competent viruses from T-cell tumors is very similar to the pattern previously reported for retroviral vectors in cell culture experiments. The data therefore sustain the hypothesis that the kissing loop, presumably via a role in RNA dimer formation, constitutes a hot spot for reverse transcriptase-mediated recombination in MLV.

5' Untranslated Regions↗