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Biomedical subjects

K Schmidt

Publications and source records attributed to K Schmidt.

At least 271 records · Page 15Linked to original sources
PubMed1995

Tumor necrosis factor-alpha and basic fibroblast growth factor decrease glial fibrillary acidic protein and its encoding mRNA in astrocyte cultures and glioblastoma cells.

Tumor necrosis factor-alpha is a pluripotent cytokine that is reportedly mitogenic to astrocytes. We examined expression of the astrocyte intermediate filament component glial fibrillary acidic protein in astrocyte cultures and the U373 glioblastoma cell line after treatment with tumor necrosis factor-alpha. Treatment with tumor necrosis factor-alpha for 72 h resulted in a decrease in content of glial fibrillary acidic protein and its encoding mRNA. At the same time, tumor necrosis factor-alpha treatment increased the expression of the cytokine interleukin-6 by astrocytes. The decrease in glial fibrillary acidic protein expression was greater when cells were subconfluent than when they were confluent. Thymidine uptake studies demonstrated that U373 cells proliferated in response to tumor necrosis factor-alpha, but primary neonatal astrocytes did not. However, in both U373 cells and primary astrocytes tumor necrosis factor-alpha induced an increase in total cellular protein content. Treatment of astrocytes and U373 cells for 72 h with the mitogenic cytokine basic fibroblast growth factor also induced a decrease in glial fibrillary acidic protein content and an increase in total protein level, demonstrating that this effect is not specific for tumor necrosis factor-alpha. The decrease in content of glial fibrillary acidic protein detected after tumor necrosis factor-alpha treatment is most likely due to dilution by other proteins that are synthesized rapidly in response to cytokine stimulation.

Animals↗
PubMed1995

Long-term adherence to intensified conventional insulin therapy.

All diabetic patients of the outpatient clinic of the University of Frankfurt/Main, who started intensified conventional insulin therapy (ICT) between 1980 and 1991, and who could be followed for at least one year (n = 141) were evaluated retrospectively. Fourteen patients changed from ICT to continuous subcutaneous insulin infusion (CSII). No patient changed back permanently to conventional insulin therapy. Mean glycosylated hemoglobin-levels (HbA1) decreased significantly in the first year from 9.3% to 8.5% and remained at a near normal level in the following years. HbA1-levels were found not to be associated with age, age at diagnosis, weight gain, frequency of visits to the outpatient clinic, number of consultations with the dietician as well as the frequency of attendance at special seminars for ICT. These results demonstrate that ICT lowered blood glucose levels permanently, that patients were highly compliant, and that ICT was practicable and safe for long-term treatment under routine conditions without initial hospitalization and with an acceptable expenditure of time for patients and medical staff.

Adult↗
PubMed1995

Autoimmune phenomena in non-Hodgkin's lymphoma.

In order to obtain valid data on the pattern, frequency and prognostic significance of autoimmune derangements in non-Hodgkin's lymphoma (NHL) we studied 626 consecutive adult NHL patients participating in a population-based lymphoma registry. A total of 86 patients, corresponding to 13.7%, showed autoimmune phenomena (AP). Of these, 7.8% exhibited clinical autoimmune phenomena (CAP), and 5.9% showed immunohaematological phenomena (IHP). The distribution of histological subgroups of NHL in the AP and non-AP patients was similar. The same holds true for the CAP and IHP patients. A slight, non-significant overrepresentation of NHL, T-cell phenotype was found in patients with AP. CAP preceded the diagnosis of NHL in most patients, whereas IHP was associated with active lymphoma disease. AP as a whole did not predict for time to complete response, time to relapse or for survival. The finding that IHP patients relapsed earlier than CAP patients was not reflected in a significant difference in survival.

Adolescent↗
PubMed1995

Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one.

In brain and other tissues, nitric oxide (NO) operates as a diffusible second messenger that stimulates the soluble form of the guanylyl cylase enzyme and so elicits an accumulation of cGMP in target cells. Inhibitors of NO synthesis have been used to implicate NO in a wide spectrum of physiological and pathophysiological mechanisms in the nervous system and elsewhere. The function of cGMP in most tissues, however, has remained obscure. We have now identified a compound, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), that potently and selectively inhibits NO-stimulated guanylyl cyclase activity. In incubated slices of cerebellum, ODQ reversibly inhibited the NO-dependent cGMP response to glutamate receptor agonists (IC50 approximately nM) but did not affect NO synthase activity. The compound did not affect synaptic glutamate receptor function, as assessed in hippocampal slices, nor did it chemically inactivate NO. ODQ did, however, potentially inhibit cGMP generation in response to NO-donating compounds. An action on NO-stimulated soluble guanylyl cyclase was confirmed in studies with the purified enzyme. ODQ failed to inhibit NO-mediated macrophage toxicity, a phenomenon that is unrelated to cGMP, nor did it affect the activity of particulate guanylyl cyclase or adenylyl cyclase. ODQ is the first inhibitor that acts selectively at the level of a physiological NO "receptor" and, as such, it is likely to prove useful for investigating the function of the cGMP pathway in NO signal transduction.

Amino Acid Oxidoreductases↗
PubMed1995

[Detection of amphetamine derivatives in chemical toxicological studies 1987-1993 in the greater Frankfurt area].

Chemical-toxicological testing during the period from 1987 to 1993 revealed a remarkable increase in amphetamine positive cases in the greater Frankfurt area. Amphetamine abuse is particularly worrying in car drivers, where the proportion of amphetamine positive cases increased from 0.49% in 1987 to 9.40% in 1993. Considering the fact, that the only samples tested were the ones of drivers exhibiting an impaired driving performance, the number of cases remaining undetected is most certainly higher. This study also demonstrated that amphetamine derivatives are rarely consumed on their own. In most cases (80%) they are consumed in conjunction with cannabis. The additional use of tranquillisers occurred more often than that of cocaine. It seems that amphetamine abuse plays only a minor role with heroin users. This is emphasised by the low number of drug fatalities.

Amphetamines↗
PubMed1995

[Recurrent tumor after R0 resection of colorectal liver metastases. Incidence, resectability and prognosis].

In the period 1960 to 1992 a total of 366 patients underwent macroscopic and histologic complete resection (R0) of colorectal liver metastases. Excluding 16 operative deaths and 4 patients with incomplete follow-up information, 346 patients form the basis for this report. Of them, 240 (69.4%) developed recurrent disease involving the liver in 136 (39.3%) instances. 71 patients underwent a tumor related reoperation with a re-resection performed in 60 cases. This involved the liver in 22 patients. 47 of these procedures (19.6% of all recurrences), and 16 re-resections of the liver (11.8% of hepatic recurrences) were ultimately classified R0. Additional 9 patients who had the initial liver resection performed in other hospitals underwent hepatic re-resection which was classified R0 in 8. Out of 8 subsequent reoperations, 3 addressed the liver. Operative mortality in the 34 re-resections at the liver was 2.9% while nonlethal morbidity was 17.7%. After a minimum and median follow-up time of 18 and 49 months, resp., 27 patients are alive without recurrent disease, including 11 patients with hepatic re-resection. Another 4 patients are alive with disease, one of them after repeat liver resection. 5-year survival from re-resection is 39.0% for the entire group of 55 R0-patients, and 45.6% for the 24 who underwent hepatic R0-re-resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Expression of rat brain nitric oxide synthase in baculovirus-infected insect cells and characterization of the purified enzyme.

Rat brain nitric oxide synthase was expressed to a high level in baculovirus-infected insect cells and purified to apparent homogeneity by affinity chromatography. The enzyme had a specific activity of approximately 1 mumol of citrulline.min-1.mg of protein-1 and contained 0.93, 0.45, 0.18 and 0.23 mol of haem, (6R)-5,6,7,8-tetrahydro-L-biopterin (H4biopterin), FAD and FMN per mol of subunit respectively.

Amino Acid Oxidoreductases↗
PubMed1994

Identification of imidazole as L-arginine-competitive inhibitor of porcine brain nitric oxide synthase.

Imidazole acts as a heme-site inhibitor of nitric oxide synthase (NOS). We used this compound to investigate whether the substrate L-arginine binds directly to the heme or to a separate domain of brain NOS. Enzyme kinetic experiments showed that imidazole enhanced the apparent Km for L-arginine without affecting maximal enzyme activity, and binding studies revealed that the inhibitor displaced the radioligand NG-nitro-L-[3H]arginine in a concentration-dependent fashion. These results demonstrate that imidazole exerts its effects on NOS in an L-arginine-competitive manner and that the substrate site of the enzyme may be identical with the prosthetic heme group.

Amino Acid Oxidoreductases↗
PubMed1994

[Prognosis after ruptured intracranial aneurysm in men and women].

Of 1076 patients with aneurysmal subarachnoid haemorrhage, 674 were females and 402 males. No significant differences between females and males were seen as regards age, clinical condition on admission, pre-existing arterial hypertension and number of rebleeds. Angiographically demonstrated vasospasm was seen with a significantly higher incidence in females, which may possibly explain a significantly poorer outcome in females compared to males, despite a much higher rate in females of internal carotid artery aneurysms which have a significantly better prognosis compared with aneurysms at other sites.

Aneurysm, Ruptured↗
PubMed1994

Reaction of peroxynitrite with oxyhaemoglobin: interference with photometrical determination of nitric oxide.

A frequently applied photometrical assay of NO is based on the reaction of NO with oxyhaemoglobin. This study shows that peroxynitrite induces spectral changes of oxyhaemoglobin identical with those elicited by NO. Like a variety of other agents, peroxynitrite did not interfere with NO measurements using a Clark-type electrode, demonstrating that electrochemical detection has an advantage over the oxyhaemoglobin method for specific determination of NO.

Electrochemistry↗
PubMed1994

Uptake of nitric oxide synthase inhibitors by macrophage RAW 264.7 cells.

Uptake of the nitric oxide synthase inhibitors NG-methyl-L-arginine (L-NMA) and NG-nitro-L-arginine (L-NNA) by macrophages is mediated by two different mechanisms. Activation of the cells with cytokines resulted in an up-regulation of L-NMA uptake but did not affect L-NNA transport. Characterization of the transport sites revealed that uptake of L-NMA is mediated by a cationic amino acid transporter (system y+) whereas a neutral amino acid transporter (system L) accounts for the uptake of L-NNA.

Amino Acid Oxidoreductases↗
PubMed1994

The pteridine binding site of brain nitric oxide synthase. Tetrahydrobiopterin binding kinetics, specificity, and allosteric interaction with the substrate domain.

Nitric oxide (NO) synthases contain FAD, FMN, heme, and (6R)-5,6,7,8-tetrahydro-L-biopterin as prosthetic groups. We have characterized the pteridine-binding site of purified brain NO synthase, using 3H-labeled (6R)-5,6,7,8-tetrahydro-L-biopterin as radioligand. Association of [3H]tetrahydrobiopterin followed second-order kinetics (kon = 1.3 x 10(6) M-1 min-1), the dissociation reaction was reversible and first-order (koff = 3.2 x 10(-1) min-1), yielding a kinetic KD of 0.25 microM. Binding of the radioligand was competitively antagonized by several pteridine derivatives with the following order of potency (KI): 7,8-dihydro-L-biopterin (2.2 microM), (6S)-5,6,7,8-tetrahydro-L-biopterin (19 microM), (6R,S)-6-methyl-5,6,7,8-tetrahydropterin (240 microM), and 6,7-dimethyl-5,6,7,8-tetrahydropterin (> 1 mM). The affinity of NO synthase for tetrahydrobiopterin was increased 6-fold in the presence of 0.1 mM L-arginine (KD = 37 nM), and, conversely, tetrahydrobiopterin enhanced the affinity of the enzyme for 3H-labeled NG-nitro-L-arginine about 2-fold. 7-Nitroindazole, which presumably binds to the heme group of NO synthase, competitively inhibited binding of [3H]tetrahydrobiopterin and [3H]NG-nitro-L-arginine with similar Ki values (0.1 microM). Functional as well as binding studies revealed that 7-nitroindazole was competitive with both L-arginine and tetrahydrobiopterin. Our data indicate that brain NO synthase exhibits a highly specific binding site for (6R)-5,6,7,8-tetrahydro-L-biopterin, which allosterically interacts with the substrate domain and may be located proximal to the prosthetic heme group of NO synthase.

Allosteric Regulation↗
PubMed1994

Inhibitors of brain nitric oxide synthase. Binding kinetics, metabolism, and enzyme inactivation.

Nitric oxide (NO) is synthesized from L-arginine by different NO synthase isozymes, which are inhibited by the substrate analogs NG-methyl- and NG-nitro-L-arginine. We studied binding of 3H-labeled NG-nitro-L-arginine to purified brain NO synthase and compared the data with results obtained in enzyme kinetic experiments. Binding data revealed a single binding site for NG-nitro-L-[3H]arginine (KD = 0.17 microM). Binding was competitively antagonized by L-arginine (KI = 2.9 microM). The half-time of dissociation was remarkably slow (9.4 min) and closely correlated with the time necessary for surmounting NO synthase inhibition by dilution. Although an apparently less potent inhibitor, NG-methyl-L-arginine exhibited the same affinity for brain NO synthase as the nitro derivative (KI = 0.17 microM), and in initial rate experiments, almost equal KI values were obtained for NG-methyl-L-arginine (0.61 microM) and NG-nitro-L-arginine (0.53 microM). However, after prolonged incubation periods, NG-nitro-L-arginine induced a rapid inactivation of the enzyme, whereas the methyl derivative turned out to be a substrate of NO synthase, which was slowly converted into stoichiometric amounts of NO and L-citrulline.

Amino Acid Oxidoreductases↗