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Biomedical subjects

K H Neumann

Publications and source records attributed to K H Neumann.

13 recordsLinked to original sources
PubMed1992

Decrease in beta 1- and increase in beta 2-adrenoceptors in long-term follow-up after orthotopic cardiac transplantation.

Total beta 1- and beta 2- subtype distribution were examined in right ventricular biopsies taken from 100 patients 1-60 months after orthotopic cardiac transplantation and from eight prospective transplant donor hearts serving as controls. The patients were classified into eight groups depending on the time after transplantation that the biopsies were taken: 1-3 (n = 15), 4-7 (n = 15), 8-11 (n = 6), 12 (n = 15), 24 (n = 15), 36 (n = 12), 48 (n = 12) and 60 months (n = 10). The non-selective beta-adrenoceptor antagonist (-)-[125I]-iodocyanopindolol (ICYP) was used as a radioligand to assess total beta-adrenoceptor density. The beta 1- and beta 2-subtype distribution was determined with a beta 1-adrenoceptor saturating concentration of the selective beta 1-adrenoceptor antagonist CGP 20712A (300 nmol/l). In transplant donor hearts the total beta-adrenoceptor density was found to be 70.8 +/- 7.1 fmol/mg protein including a beta 1:beta 2-adrenoceptor ratio of about 80:20%. Until 36 months after cardiac transplantation the total number of beta-adrenoceptors showed no significant change. A slight but insignificant decrease was observed after 48 (16.2%) and 60 (21.2%) months. In contrast, from 12 to 60 months after cardiac transplantation the beta 1:beta 2-adrenoceptor ratio was shifted significantly (66:33% to 61:39%) as compared with transplant donor hearts which was due to an increase in beta 2- and a decrease in beta 1-adrenoceptor number. Thus, the surgically denervated, transplanted human heart exhibits a beta 2-adrenoceptor up-regulation during long-term follow-up. It is suggested that this up-regulation of the beta 2-adrenoceptor subtype could be owing to an increased importance of circulating catecholamines in modulating positive chronotropic and inotropic effects.

Adult↗
PubMed1992

Mechanisms of ciclosporin A-induced vasoconstriction in the isolated perfused rat kidney.

Hypertension is a well-known side effect of ciclosporin A (CsA). In the present study the mechanisms of vasoconstriction in renal vessels were examined in the isolated perfused rat kidney. Kidneys were perfused with constant flow at a temperature of 37 degrees C with Tyrode's solution equilibrated with 95% O2/5% CO2. CsA was dissolved in ethanol. 500 and 2000 ng/ml increased resistance of renal vessels by 0.97 +/- 0.55 x 10(5) and 2.29 +/- 1.33 x 10(5) dyn s cm-5, respectively (mean values +/- SD, n = 12). The vasoconstriction developed gradually over 4 min. The vasopressor effect of CsA was not changed by saralasin (10(-6) M), nifedipine (10(-6) M) and ketanserin (10(-6) M), but was completely blocked by phentolamine and prazosin (each 10(-6) M). CsA-induced vasoconstriction was not prevented by perfusion with Ca(2+)-free solution containing 2 mmol EGTA. Similarly, pretreatment with reserpine to deplete sympathetic nerve endings from catecholamines did not affect CsA-induced vasoconstriction. The findings suggest that CsA-induced vasoconstriction is mediated by stimulation of alpha 1-receptors. Ca2+ influx does not play a role for CsA-induced vasoconstriction. Prolonged perfusion of rat kidneys with the vehicle cremophor EL elicits an irreversible increase in perfusion pressure.

Animals↗
PubMed1992

The physiological and pathophysiological basis of glomerular permeability for plasma proteins and erythrocytes.

The barrier function of glomerular capillaries in vivo, which prevents the leakage of plasma proteins and cellular elements, depends on the basic morphological and electro-chemical fine structure of the glomerular capillary wall, and on a functional barrier maintained by components obtained from blood, which effect the definitive barrier against the leakage of plasma proteins and cellular elements. The functional component of the barrier may explain the variability and some of the phenomena known as functional proteinuria. A certain size and number of morphological "defects" are thought to represent the normal condition, but under pathological conditions they may increase in size and number, resulting in a shift to an increasing permeability for higher molecular mass proteins; also an increase of the size and number of larger defects may enable more red cells to pass the barrier compared with the normal condition. These defects are different from the minimal glomerular lesions which are due to charge defects in the glomerular capillary membrane, primarily the lamina rara interna and the lamina rara externa of the basement membrane.

Animals↗
PubMed1990

Ca2+ release in permeabilized human neutrophils induced by ciclosporin.

In suspensions of permeabilized human neutrophils, the free Ca2+ concentration was measured to test the effects of ciclosporin. Free Ca2+ concentration was measured with a Ca2(+)-selective electrode. Ciclosporin (500 ng/ml) induced a transient increase in free Ca2+ concentration (maximum delta pCa, 0.41 +/- 0.17). Thereafter, the free Ca2+ concentration decreased again, but did not reach the baseline level in most experiments. Ruthenium red, but not orthovanadate, abolished the slow decline of free Ca2+ concentration after the initial increase. The experiments suggest that ciclosporin may induce a release of Ca2+ from cellular organelles, e.g. the endoplasmic reticulum, and a partial reuptake in mitochondria. A release of cellular Ca2+ may play a role in ciclosporin-induced hypertension.

Calcium↗
PubMed1990

Correlation of free phenytoin to serum albumin in cancer patients.

The objectives of this study were to compare the total and free phenytoin serum concentrations of cancer patients with hypoalbuminemia with those of cancer patients with normal serum albumin and to correlate the percentage of free phenytoin with the albumin concentration. A total of 22 patients were studied, 13 with normal albumin concentration and 9 with low albumin. The mean free phenytoin in the normal albumin group was 9.9 (+/- 1.3) percent and 17.6 (+/- 4.6) percent in the low albumin group. With the groups combined, the mean free phenytoin was 13.1 percent (range 8.3-22.2) with the albumin range of 20-45 g/L. There was a significant negative correlation (r = -0.9, p less than 0.001) between the percentage of free phenytoin and the measured serum albumin. In cancer patients, the serum albumin concentration appears to be the key factor that determines the percentage of free phenytoin. In cancer patients with low serum albumin concentration, the total and free phenytoin concentration should be measured for adequate assessment of phenytoin therapy.

Female↗
PubMed1989

Amyloid goiter and arthritides after kidney transplantation in a patient with systemic amyloidosis and Muckle-Wells syndrome.

A case of hereditary AA amyloidosis with Muckle-Wells syndrome is described. After a successful kidney transplantation for chronic renal failure due to renal amyloid deposits at age 21, the patient, a white female now 26 years of age, developed a large amyloid goiter as a manifestation of the systemic amyloidosis and recurrent monarthritides. Both observations are novel for this disease. Subtotal thyroidectomy and oral colchicine administration, known to be effective in preventing complications of familial Mediterranean fever, another hereditary type of AA amyloidosis, proved highly effective in the management of this unusual case.

Adult↗
PubMed1978

The nucleotide sequence of the 5' untranslated region of human gamma-globin mRNA.

The nucleotide sequence of the entire 5' untranslated region of human gamma-globin mRNA has been determined. This was accomplished by analyzing complementary DNA (cRNA) synthesized from the mRNA with reverse transcriptase. The CDNA was labeled at its 3' end with 32"p using terminal deoxynucleotidyl transferase, digested with the restriction endonuclease Hae III and the end-labeled fragment isolated ans sequenced by the method of Maxam and Gilbert. Including the initiation codon AUG, the 5' untranslated region of human gamma-globin mRNA contains 57 nucleotides, compared to 41 in alpha- and 54 in beta-globin mRNA. There is very little homology between alpha and gamma sequences in the 5' region. There is considerable homology between beta- and gamma-globin mRNAs in the regions proximal and distal to the initiation codon, but the entire sequence shows less homology than the human and rabbit beta-globin mRNAs. The hexanucleotide sequence CUUCUG is found near the 5' ends of all three human globin mRNAs, suggesting a possible role of this sequence or ribosomal binding. Both guanosine and cytidine were found at the 19th nucleotide position from the 5' end of the gamma mRNA. We believe this heterogeneity arises from the difference in nucleotide sequence between the A gamma and G gamma loci.

Base Sequence↗
PubMed1977

The nucleotide sequences of the untranslated 5' regions of human alpha- and beta-globin mRNAs.

The complete sequences of the untranslated 5' regions of human alpha- and beta-globin mRNAs were determined by sequence analysis of full-length cDNAs. The single-stranded cDNAs were digested with the restriction endonuclease Hae III, and the two 3'-terminal fragments of 75 and 132 nucleotides, complementary to the 5' termini of the alpha- and beta-globin mRNAs, respectively, were isolated and sequenced. Including the initiation codon AUG, the untranslated 5' regions of human alpha- and beta-globin mRNAs contain 41 and 54 nucleotides, respectively, and exhibit striking homologies with the corresponding sequences in the rabbit. Human alpha- and beta-globin mRNAs have five bases in the region of the initiation codon that may form base pairs with the 3' terminus of 18S rRNA. Stable secondary structures with hairpin loops can be constructed in the untranslated 5' regions.

Base Sequence↗
PubMed1976

Mechanism of NaCl and water reabsorption in the proximal convoluted tubule of rat kidney.

The role of chloride concentration gradients in proximal NaCl and water reabsorption was examined in superficial proximal tubules of the rat by using perfusion and collection techniques. Reabsorptive rates (Jv), chloride concentrations, and transtubular potential difference were measured during perfusion with solutions (A) simulating an ultrafiltrate of plasma; (B) similar to (A) except that 20 meq/liter bicarbonate was replaced with acetate; (C) resembling late proximal fluid (glucose, amino acid, acetate-free, low bicarbonate, and high chloride); and (D) in which glucose and amino acids were replaced with raffinose and bicarbonate was partially replaced by poorly reabsorbable anions (cyclamate,sulfate, and methyl sulfate). In tubules perfused with solutions A and B, Jv were 2.17 and 2.7 nl mm-1 min-1 and chloride concentrations were 131.5 +/- 3.1 and 135 +/- 395 meq/liter, respectively, indicating that reabsorption is qualitatively similar to free-flow conditions and that acetate adequately replaces bicarbonate. With solution C, Jv was 2.10 nl mm-1 min-1 and potential difference was +1.5 +/- 0.2 mV, indicating that the combined presence of glucose, alanine, acetate, and bicarbonate per se is not an absolute requirement. Fluid reabsorption was virtually abolished when tubules were perfused with D solutions; Jv was not significantly different from zero despite sodium and chloride concentrations similar to plasma; chloride concentration was 110.8 +/- 0.2 meq/liter and potential difference was -0.98 mV indicating that chloride was close to electrochemical equilibrium. These results suggest the importance of the chloride gradient to proximal tubule reabsorption in regions where actively reabsorbable solutes (glucose, alanine, acetate, and bicarbonate) are lacking and provide further evidence for a passive model of NaCl and water transport.

Absorption↗