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M Lauritzen

Publications and source records attributed to M Lauritzen.

99 records · Page 6Linked to original sources

A comparison of the properties of renin isolated from pig and rat kidney.

1. On isoelectric focusing, renin from rat kidneys showed three activity peaks with pI values at pH 5.0, 5.2 and 5.4 after a purification procedure involving differential centrifugation, acidification, chromatography on Sephadex G-75 and dialysis. 2. The preparation (purified 140-fold) was compared with a crude kidney extract in the absence and presence of 3 M-urea by isoelectric focusing. The pattern of activity distribution was confirmed by these experiments and the content of isoenzymes in the three groups calculated. 3. Pig renin was prepared and compared with rat renin with regard to molecular weight, acid activation, behaviour on isoelectric focusing, immunogenicity and substrate affinity. 4. Extracts of rat kidney contained multiple forms of renin with mol.wt. between 39000and 42000, whereas active pig renin had an approximate mol.wt. of 40000. Acidification of rat renal extracts did not increase the activity of renin, indicating the absence of an inactive form of renin in rat kidneys, whereas pig renin was activated by this procedure. Pig renin has isoelectric points at pH 4.6, 4.8, 5.05 and 5.2, significantly lower than for rat renin. The isoenzymes from the two species had no antigenicity in common, as shown by crossed immunoelectrophoresis or rocket immunoelectrophoresis. 5. The Michaelis constants for pig and rat renin were in the same range, 1 X 10(-6) M, when rat renin substrate was used. The relative content of rat isoenzyme with pI in the pH ranges 4.9-5.1, 5.1-5.3 and 5.3-5.5 was approx. 20, 27 and 53% respectively. Purified pig renin prepared in two different ways had isoenzymes with pI in the pH regions 4.5-4.7, 4.7-4.9, 4.9-5.05 and 5.05-5.20 in the approximate proportions 14, 24, 28 and 29%.

Animals↗

Regional cerebral blood flow assessed by 133Xe inhalation and emission tomography: normal values.

Regional cerebral blood flow (rCBF) in the cerebral hemispheres and the cerebellum was measured by single photon emission computed tomography with inhalation of 133Xe in 39 normal volunteers at test. The goal of this study was to assess the normal flow pattern and its variations. Five parallel tomographic slices through the brain were recorded with a resolution element of 1.7 X 1.7 X 2.0 cm (full width at half maximum). The blood flow distribution showed that the predominantly gray matter areas displayed flow approximately double that of the predominantly white matter regions. The CBF distribution was practically symmetrical with a side-to-side difference averaging 1.4 +/- 1.4 ml/100 g/min. This means that a difference exceeding 4.2 ml/100 g/min (approximately 9% of mean CBF) is abnormal with a confidence level of below 5%. The measured average CBF and cerebellar blood flow were 56 +/- 7 and 54 +/- 6 ml/100 g/min (mean +/- 1 SD), respectively. A significant correlation was found between CBF and PCO2, and between CBF and age. Repeat measurements in an additional 30 subjects showed a day-to-day variability of -0.2 +/- 6.4 ml/100 g/min of the difference between the first and the second measurement. This corresponds to random methodological and biological errors of 6.4/square root 2 = 4.6 ml/100 g/min and is a measure of the overall intraindividual variability. Xenon-133 tomography is atraumatic and affords rCBF images free of the superposition artifacts that practically invalidate the nontomographic approaches in the studies of cerebrovascular disease. The rCBF tomograms are blurred, particularly due to Compton scatter. Relative to this factor, the errors caused by local variations in the tissue:blood partition coefficient are less important.

Adult↗

Surface charge of red blood cells in insulin-dependent diabetic patients with incipient and overt nephropathy.

The negative surface charge of red blood cells was studied in adults with insulin-dependent diabetes mellitus, using a chemical assay based on the binding of the cationic dye Alcian-blue 8GX to anionic sites on the cell surface. Twenty-one healthy non-diabetic adults, 21 normo-albuminuric diabetic patients, 25 diabetic patients with incipient nephropathy, and 19 diabetic patients with overt nephropathy were studied. The diabetic patients were matched for age, duration of diabetes, and glycaemic control. The red cell surface charge was nearly identical in the four groups studied. Our study does not suggest that loss of membrane negative charge is a generalized phenomenon in insulin-dependent diabetic patients with albuminuria.

Adolescent↗

Scanning laser-Doppler flowmetry of rat cerebral circulation during cortical spreading depression.

Scanning laser-Doppler flowmetry (SLDF) generates two-dimensional images of blood flow. This study compared SLDF to conventional laser-Doppler flowmetry (LDF) in the cerebral circulation. Test stimuli were episodes of cortical spreading depression (CSD) elicited in brains of halothane anaesthetised rats (n = 9). The LDF instrument used two wavelengths of laser light to record relative changes of cerebral blood flow (CBF) up to an approximate depth of 250 microm (543 nm) and 500 microm (780 nm). Under resting conditions, SLDF images showed a heterogeneous pattern of flow in pial vessels with high flow rates in arterioles, and lower rates in venules and small vessels (<30 microm). Arterioles constituted about 6%, venules 12% and small vessels 2% of the image area, while approximately 80% were background with a laser-Doppler signal corresponding to zero calibration. During CSD, the relative increase of area was largest for small vessels and less for venules and arterioles. Similar changes were observed for blood flow in the three vessel structures. For both wavelengths of LDF, flow changes correlated with SLDF (r approximately 0.7). In conclusion, SLDF provides images of flow in pial vessels and capillaries at, or just beneath the cortical surface. SLDF and LDF are complementary, but cannot substitute for one another as they measure flow in different layers of the cortex.

Animals↗

Nitric oxide synthase expression of oligodendrogliomas.

In the central nervous system, nitric oxide (NO) has a variety of biological functions including vasorelaxation and neurotransmission. The synthesis of NO is catalyzed by NO synthases (NOS) existing in 3 isoforms, neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). NO synthase has implications in the pathophysiology of primary glial brain tumors with enhanced expression of nNOS and eNOS in high-grade astrocytic tumors, WHO grades III and IV. Only minor groups of pure oligodendrogliomas have been investigated. The aim of the investigation was to study the expression of the 3 NOS isoforms in this genetically divergent group of primary gliomas and to correlate the findings with tumor grade and expression pattern for the major group of gliomas--the astrocytomas. We examined the NOS expression in 35 oligodendrogliomas, WHO grade II, and 7 anaplastic oligodendrogliomas, WHO grade III, by immunohistochemical methods using formalin-fixed paraffin-embedded material. We observed only a minor expression of nNOS and sparse expression of eNOS in the tumor cells, but a vivid expression of eNOS in the vascular endothelial cells in both the tumor and the surrounding tissue. The rich expression of eNOS in oligodendroglioma vessels independent of tumor grade may suggest that blood flow and angiogenesis in these richly vascularized tumors are modified by NO. Interestingly, enhanced expression of inducible NOS was observed in the oligodendroglial tumor cells in 19 of 35 oligodendrogliomas (54%) and in 2 of 7 anaplastic oligodendrogliomas (29%). This is diverging for iNOS expression in astroglial tumors and the data could be indicative of iNOS exerting anti-tumor activity which may protract the progression from low-grade oligodendrogliomas to more anaplastic types.

Brain Neoplasms↗

Nitric oxide synthase expression and enzymatic activity in human brain tumors.

Nitric oxide (NO) is synthesized by NO synthases (NOS), existing in 3 isoforms. NO influences a great variety of vital functions including vascular tone and neurotransmission. Under conditions of excessive formation, NO emerges as an important mediator of neurotoxicity in a variety of disorders of the central nervous system (CNS). Inhibitors of NOS are available that may modify the activity of all isoforms, which may be of clinical relevance. The expression of the 3 NOS isoforms nNOS, iNOS and eNOS and NOS enzymatic activity was examined in 40 patients with primary CNS tumors (gliomas WHO grades I - IV and meningeomas WHO grades I - III) and in 13 patients with metastases from adenocarcinomas or malignant melanomas. A polyclonal antibody directed against nNOS and monoclonal antibodies directed against iNOS and eNOS were used for immunohistochemical staining. NOS enzymatic activity, measured by labeled arginine to citrulline conversion, was assessed in tissue specimens obtained from the same tumors. NOS data were compared with clinical variables and the degree of edema as judged from MR scanning. nNOS expression was increased in tumor cells of glial neoplasms and most pronounced in high-grade tumors, WHO grades III and IV, and in the carcinoma and melanoma metastases. Low-grade gliomas, WHO grades I and II and meningeomas expressed no or only little nNOS. iNOS was only expressed in a few tumors. eNOS was expressed sporadically in the tumor cells while the expression was increased in vascular endothelial cells in both the tumor itself and the peritumoral area of glial neoplasms, and in metastases. eNOS expression was sporadic in endothelial cells of meningeomas. NOS enzymatic activities were heterogeneous among tumor types (0 - 13.8 pmol/min/mg of protein) without correlation to the NOS expression found by immunohistochemical techniques. Likewise, NOS activity and expression was not correlated to the clinical scores or brain edema. In conclusion, nNOS expression may be a putative useful indicator of brain tumor differentiation and malignancy. The enhanced expression of eNOS in vascular endothelial cells of glial neoplasms and metastases raises the possibility that NO production in tumor endothelial cells may contribute to tumor blood flow regulation and possibly brain edema.

Adenocarcinoma↗