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Biomedical subjects

T Hintze

Publications and source records attributed to T Hintze.

7 recordsLinked to original sources

Role of superoxide radicals in anoxia reoxygenation-mediated vascular contraction.

To determine the mechanism of anoxic vasoconstriction, precontracted rat aortic rings were exposed to 95% N2, which caused additional contraction. Reoxygenation (95% O2) resulted in initial relaxation followed by contraction. Indomethacin did not affect anoxic contraction or reoxygenation-mediated events, but NG-monomethyl-1-arginine, which inhibits EDRF synthesis, and oxyhemoglobin, which reduces EDRF activity, markedly decreased anoxic contraction and reoxygenation relaxation, and potentiated subsequent contraction. Superoxide dismutase did not affect anoxic contraction, but potentiated reoxygenation relaxation and attenuated subsequent contraction. Endothelin concentrations remained unchanged throughout anoxia and reoxygenation. Thus, anoxic contraction and reoxygenation-mediated early relaxation appear to be due to changes in EDRF. On the other hand, reoxygenation-induced contraction appears related to release of superoxide radicals.

Animals↗

Biotinylated epidermal growth factor: a useful tool for the histochemical analysis of specific binding sites.

Epidermal growth factor (EGF) was labelled with biotin via modification of either the amino or carboxyl groups, using suitable reagents, namely biotinyl-N-hydroxysuccinimide ester or biotinamidocaproyl hydrazide. To assure that the specific binding capacity of EGF is retained despite its chemical modification, displacement of the EGF by biotinylated derivatives in a routine binding assay was performed. The inhibitory potency compared to unmodified EGF was only slightly reduced. This result is the prerequisite for testing the usefulness of biotinylated EGF in histochemistry. The biotinylated probes were applied to sections of human tumour tissue and of monkey organs (liver, kidney, uterus of Cynomolgus and Rhesus monkey) to localize the specific binding sites for EGF. Formalin-fixed, paraffin-embedded tissue sections were deparaffinized and incubated with the probes at a concentration of 10 micrograms ml-1 at room temperature for 60 min. Specific binding of the EGF was visualized by the avidin-biotin techniques (ABC). A positive reaction in conjunction with appropriate controls by competitive inhibition was seen for all monkey tissue sections and for the following number of cancer cases: breast carcinoma: 7/10; mesothelioma: 2/4; lung carcinoma: 1/3; colon carcinoma: 1/3. The staining properties were similar for both types of probes that differed in the functional group that is involved in modification by biotin attachment. However, the batches with modification of the amino groups stained more intensely and more distinctly than the carboxyl modified EGF. Overall, the data indicate that the ligand properties of the EGF are not impaired by biotinylation of the two types of functional groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differentiation-related expression of epidermal growth factor receptors in human lung carcinoma demonstrated histochemically by biotinylated epidermal growth factor.

Biotin-labeled epidermal growth factor (EGF) was applied to routinely processed sections of 64 cases of human lung carcinoma as a histochemical tool for demonstrating EGF-specific receptors. Formalin-fixed, paraffin-embedded tissue sections were deparaffinized and incubated with the labeled EGF (10 micrograms/ml) for 60 min at room temperature. The specific binding of the growth factor to its receptor was visualized by the avidin-biotin complex (ABC) technique. Positive binding capacities were obtained for the following cases: 15/16 epidermoid carcinoma; 13/15 adenocarcinoma; 2/11 large cell anaplastic carcinoma; 12/20 small cell anaplastic carcinoma; 0/11 normal lung tissue; 0/6 main bronchi; 0/1 hamartoma; 0/1 primary fibrosarcoma of lung. In addition, a strong positive reaction was seen for neutrophilic granulocytes present within the tumorous tissue. Data indicate that EGF receptors are frequently expressed in more differentiated carcinoma in comparison with anaplastic carcinoma of lung.

Aged↗

Relationship between plasma atriopeptin concentration and function in the conscious primate.

The renal actions of atriopeptins (APs) 24, 21 and 28 were examined in the conscious primate, macaca fascicularis. AP-24 increased urine flow rate and sodium excretion 20- and 100-fold, respectively. The circulating form of the atriopeptins, AP-28, had similar, even slightly greater (25%) effects when compared to AP-24. AP-21 on the other hand had dramatically reduced effects, less than 20%, when compared to either AP-24 or AP-28. Infusion of AP-24 resulted in marked increases in plasma immunoreactive AP and in renal function. There were direct, significant linear relations between plasma levels and arterial pressure, heart rate, glomerular flow rate, urine flow rate, sodium and potassium excretion. However, the threshold for these effects was generally higher than expected, i.e., greater than 100 pg/ml. Interestingly, there was a 4-fold greater slope for sodium excretion when compared to other renal functions implying a distinctly different mechanism of action. Whereas, the plasma half-life of the peptide was 2 to 3 min, the biological half-life varied from 6 min for sodium excretion to 10 min for urine flow and potassium excretion. The increased slope for the relationship between sodium excretion and plasma AP concentration and the short half-life for sodium excretion indicate that the change in renal sodium handling is independent of urine flow rate and glomerular filtration rate. There is a direct and linear relationship between plasma peptides and renal function which may imply a cause and effect relationship. This extrapolation may, however, be valid only when plasma peptide levels are elevated markedly.

Animals↗

Cytochrome P-450 oxidation of alkanes originating as scission products during lipid peroxidation.

Alkanes of low molecular weight, as well as malondialdehyde, originate during lipid peroxidation. Ethane and pentane are the most prominent and are probably scission products of omega-3 and omega-6 unsaturated fatty acids, respectively. Measurement of exhaled alkanes is the most reliable procedure for determining lipid peroxidation in vivo. Alkanes appear in the breath of rats 15 min after administration of CBrCl3 i.p., and are also formed in small amounts endogenously. Alkanes exhaled from untreated rats in a closed system, in which CO2 is absorbed and O2 supplied, reached steady-state levels after different times, indicating that these volatile gases are metabolized at variable rates. Metabolism was verified by injecting alkanes into the closed system. Pentane was metabolized 5-10 times faster than ethane, and was species- and strain-dependent. Administration of drugs which inhibit or induce cytochrome P-450 indicated that a particular isoenzyme might be involved in the oxidation of small alkanes. SKF 525-A or benzoflavone did not inhibit, but tetrahydrofuran and ethanol were effective inhibitors. Inducing effects of phenobarbital, methylcholanthrene or ethanol were insignificant. Incubation of microsomes with NADPH and O2, either with or without Fe-ADP, to elicit lipid peroxidation confirmed the findings in vivo. Ethane and pentane were formed in similar quantities. Inhibition of alkane oxidation with CO or ethanol increased the amount of pentane three- to four-fold, indicating that inhibition of metabolism enhances alkane release. The ratio of unmetabolized pentane to ethane reflects the membrane ratio of omega-6 to omega-3 unsaturated acids. Different types of alkane release were observed following administration of paracetamol or CCl4 to mice, indicating differences in the peroxidative attack. CCl4 destroys cytochrome P-450 dose dependently, so that it loses its capacity to oxidize pentane, whereas paracetamol does not inactivate the mono-oxygenase. Monitoring the elimination rate of injected pentane is recommended as a reliable non-invasive procedure for testing the functional state of hepatic cytochrome P-450.

Alkanes↗