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Biomedical subjects

M Sauer

Publications and source records attributed to M Sauer.

At least 37 records · Page 2Linked to original sources

Sodium entry routes in principal and intercalated cells of the isolated perfused cortical collecting duct.

Transmembrane sodium transport pathways were studied in principal and intercalated cells of the isolated perfused rabbit cortical collecting duct. Intracellular electrolyte concentrations in individual collecting duct cells were measured by electron microprobe analysis during blockage of basolateral Na-K-ATPase by ouabain and simultaneous inhibition of sodium entry across the apical and/or basolateral cell membrane. In principal cells the ouabain-induced rise in cell sodium concentration could only partially be blocked by amiloride (10(-4) mol/l) in the perfusion fluid. Amiloride (10(-3) mol/l) added to the bathing solution produced a further, significant reduction of sodium influx. In principal cells the ouabain-induced increase in sodium concentration was completely prevented by amiloride in the perfusion solution in combination with omission of sodium from the peritubular bathing solution. In intercalated cells ouabain caused a less pronounced increase in sodium concentration than in principal cells. Neither amiloride in the perfusate, nor amiloride in both bathing and perfusion solution, significantly reduced the ouabain-induced rise in intercalated cell sodium concentration. These results indicate that in principal cells amiloride-sensitive sodium channels constitute the predominant pathway for sodium entry across the apical cell membrane. In addition, substantial amounts of sodium enter principal cells across the basolateral cell membrane, probably via Na-H exchange. Finally, the data suggest that in intercalated cells sodium channels and the Na-H exchange are sparse or even absent.

Amiloride

Sequence of the fhuE outer-membrane receptor gene of Escherichia coli K12 and properties of mutants.

The fhuE gene of Escherichia coli codes for an outer-membrane receptor protein required for the uptake of iron(III) via coprogen, ferrioxamine B and rhodotorulic acid. The amino acid sequence, deduced from the nucleotide sequence, consisted of 729 residues. The mature form, composed of 693 residues, has a calculated molecular weight of 77,453, which agrees with the molecular weight of 76,000 determined by polyacrylamide gel electrophoresis. The FhuE protein contains four regions of homology with other TonB-dependent receptors. A valine to proline exchange in the 'TonB box' abolished transport activity. Phenotypic revertants with substitutions of arginine, glutamine, or leucine at the valine position exhibited increasing iron-coprogen transport rates. Point mutations resulting in the replacement of glycine (127) in the second homology region with either alanine, aspartate, valine, asparagine or histidine exhibited decreased transport rates (listed in descending order). A truncated FhuE protein lacking 24 amino acids at the C-terminal end was exported to the periplasm but failed to be inserted into the outer membrane.

Amino Acid Sequence

[Behavior of pO2 on rabbit small intestine serosa, measured with the Clark electrode in different models of intestinal ischemia].

The pO2 on the surface of the small intestine serosa was measured on an isolated small intestine loop of the rabbit after synchronistic arterial and venous ligature of the mesenterium, after synchronistic arterial starvation and venous ligature, and after torsion of the mesenterium. The measurements of the pO2 were carried out by means of a Clark-electrode. Different periods for the decrease of the pO2 to zero Torr were shown in the different models of intestinal ischemia. Only the difference between the synchronistic arterial and venous ligature and torsion was statistically significant.

Animals

[Results of transabdominal chemical sympathectomy of the lower extremities directed by computer tomography].

The authors evaluated 47 transabdominal lumbar sympatectomies by ethyl alcohol with a control by computer tomography in surgically unsolved disorders in the passage through lower extremity arteries. In four fifths of the patients there was an increase in ischaemia manifestations, in one fifth there was no improvement. No substantial difference was found between the results of sympatectomy in diabetic and nondiabetic patients. The method should be applied sooner than a cutaneous ischaemic defect develops.

Adult

Effect of ouabain on electrolyte concentrations in principal and intercalated cells of the isolated perfused cortical collecting duct.

Sodium, phosphorus, chloride and potassium concentrations were measured by a new method in individual principal and intercalated cells in the cortical collecting duct in vitro. Electron microprobe analysis was applied to freeze-dried cryosections of the isolated perfused rabbit cortical collecting duct. Cell analyses were performed under control conditions and after addition of ouabain to the bath. Under control conditions similar sodium, potassium, chloride, and phosphorus concentration (means +/- SEM) were observed in principal (10.0 +/- 0.6, 126.5 +/- 2.7, 24.6 +/- 1.0, and 121.5 +/- 3.5 mmol/kg wet weight, respectively) and intercalated cells (9.0 +/- 0.9, 127.1 +/- 4.2, 27.4 +/- 1.8, and 118.7 +/- 4.9 mmol/kg wet weight, respectively). In principal cells ouabain (10 min) caused an increase in sodium and chloride concentrations by 104 and 13 mmol/kg wet weight, and a decrease in potassium and phosphorus concentrations by 106 and 32 mmol/kg wet weight. These changes in cell element concentrations can be ascribed to an exchange of intracellular potassium against extracellular sodium and to cell swelling due to influx of extracellular fluid. The effects of ouabain on intercalated cells were far less pronounced than on principal cells. This different susceptibility to ouabain of principal and intercalated cells can be ascribed to differences in active and passive transmembrane ion transport pathways.

Animals

[Hancock pericardial prosthesis. Intrinsic dysfunctions].

The frequency of primary dysfunction of 432 Hancock pericardial bioprosthesis was evaluated during a mean follow-up period of 53.1 months per patient. This frequency was 3.20% valve-year in mitral valve prosthesis and 0.92% valve-year in aortic valve prosthesis. Only one case of calcification was noted. Dysfunction was usually due to tearing of one or several pericardial cusps (25 cases), occasionally to tissue retraction (4 cases). Pathological examination of the explanted valves showed fibrin formation followed by organization into fibrous tissue in the host, retracting or fragilizing the pericardial valvular tissue. A preliminary study of the same group had led to discontinuation of Hancock prosthesis. The long follow-up period makes it possible to compare the results obtained with those of pericardial prosthesis of the same generation, to stress the need for echocardiographic monitoring of the implanted valves and to hope that new techniques of pericardial valve fitting will improve the mechanical reliability of prosthesis which, from the point of view of thrombogenesis and haemodynamics, have unquestionable advantages.

Adolescent

[Primary failure of pericardial valvular heterografts].

From July 1981 to October 1984, 79 Hancock pericardial valves were implanted in 74 patients surviving the hospital period and with a mean age of 64.2 years. Fifty-two patients underwent aortic valve replacement, 16 had mitral valve replacement, 5 bad a double replacement and 19 associated procedures were performed. The mean survival is 48 months. Until 1st June 1987, 11 primary failures have required reoperation (14.9%), 4 in the mitral position (4.6% patient-years), 7 in the aortic position (3.01% patient-years). The time to reoperation was 48.4 months for the aortic orifice and 36.5 months for the mitral orifice. The lesions most frequently encountered were tears (7 cases), calcifications (5 cases) and stretching of valvular tissue (2 cases); two patients died during the postoperative phase of this operation. Despite the small number of patients followed, this series demonstrates of high incidence of dysfunction due to primary tissue degeneration as, after the 5th year, the actuarial rate of absence of primary lesion is 85.3 +/- 8% with no significant difference between the aortic and the mitral orifices, although dysfunction appears to occur more rapidly in mitral prostheses. These results are much less favourable than those obtained with Ionescu bioprostheses in the aortic position of those obtained with porcine bioprostheses in either position. This justifies very regular clinical and echocardiographic follow-up of patients with Hancock pericardial valvular heterografts.

Actuarial Analysis

Element composition of tubule cells in the inner stripe of the renal outer medulla.

To obtain further insight into renal medullary function, element concentrations were determined in individual tubule cells of the outer medulla in the rat kidney using electron microprobe analysis on freeze-dried cryosections. In the cells of the thick ascending limb of Henle's loop the Na, P, Cl, and K concentrations (means +/- SEM) were: 9.5 +/- 0.6, 158.4 +/- 6.2, 25.6 +/- 1.2, and 135.3 +/- 4.8 mmol/kg wet weight, respectively. While similar Na, P, and K concentrations were observed in light and dark cells of the medullary collecting duct, Cl was markedly higher--55.0 +/- 2.8 mmol/kg wet weight--in the dark cells. The electrolyte concentrations of the thick ascending limb cells seen in the present study are in good agreement with ion activities reported for the isolated perfused thick ascending limb. The low cell Na and Cl concentrations provide a favorable driving force for passive cell entry of Na, Cl, and K across the apical membrane via the Na-2Cl-K cotransporter even at low tubule fluid NaCl concentrations. Although in hydropenic rats interstitial tonicity of the inner stripe is above isotonicity, electrolyte concentrations of inner stripe cells did not differ from those obtained in cortical tubule cells. This finding suggests that, similar to papillary cells, osmoadaptation of outer medullary cells is, at least partially, accomplished by organic osmolytes.

Animals

[Studies of myocardial metabolism using P-31-NMR spectroscopy and a simple heart perfusion model of slaughtered animals--an approach to avoiding in vivo animal experiments].

In research cardiology large numbers of in vivo animal experiments, mostly with dogs or pigs, are necessary. It was the aim of this study to test a simple in vitro perfusion heart model from swine harvested in the slaughterhouse as a potential substitute for in vivo animal studies. 32 unselected hearts of slaughterhouse swine after 10 to 15 min of warm ischemia were subjected to reperfusion with warm oxygenized blood and were examined for mechanical recovery, which occurred in 56%, increasing to 95% if primarily using only hearts that were in relaxation. In 21 of selected relaxed heart models the energy phosphate pattern as an index of viability was measured by P-31 MRS on a 4.7 Tesla NMR tomograph in 37 experimental runs with the following perfusion protocols: 1) immediate cardioplegia with cold Bretschneider or Collins solution, transportation under cooling, MRS after approximately 1 h; 2) immediate cardioplegia, transportation, reperfusion with oxygenated warm blood, MRS; 3) immediate blood perfusion with genuine fresh arterial blood from the slaughterhouse, cold plegia perfusion, transportation, MRS; 4) immediate blood perfusion with transportation MRS; 4) immediate blood perfusion with genuinefresh arterial blood, cold plegia perfusion, transportation, reperfusion with oxygenated warm blood, MRS during reperfusion; 5) An experimental pig heart was made plegic in vivo and reperfused with oxygenated warm blood during MRS as reference.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

A double-blind placebo controlled trial of diltiazem in Duchenne dystrophy.

The role of calcium accumulation in the pathogenesis of Duchenne muscular dystrophy (DMD) has already been discussed. Several trials with different calcium-blocking drugs have revealed no clinical benefit. In addition, the present study includes histological investigations and computer tomography to verify therapeutic effects. In a randomized placebo-controlled double-blind study, 13 DMD patients aged from 3-10 years (mean, 7 years) were treated with 5 mg/kg diltiazem daily for 1 year. Compared with before therapy, the number of calcium-positive muscular fibres was remarkably reduced in the treated DMD patients, but not in the placebo group. The evaluation of all other biochemical and clinical parameters revealed no significant effects of the diltiazem therapy. The muscular X-ray density measured by computer tomography decreased under treatment. After the evaluation of the double-blind study, the code was broken. Therapy, however, was continued in the treated group and started in the placebo group. After 3 years of diltiazem therapy the clinical status of all 26 patients of the study and 20 additional DMD patients who were treated with diltiazem was compared with 46 untreated DMD patients of the same age and stage in our department. No obvious clinical benefit of diltiazem therapy could be observed.

Calcium

Diagnosis of brain death by transcranial Doppler sonography.

The blood flow velocities in the basal cerebral arteries can be recorded at any age by transcranial Doppler sonography. We examined nine children with either initial or developing clinical signs of brain death. Soon after successful resuscitation increased diastolic flow velocities indicated a probable decrease in cerebrovascular resistance; this was of no particular prognostic importance. As soon as there was a clinical deterioration, there was a reduction in flow velocities with retrograde flow during early diastole, probably due to an increase in cerebrovascular resistance; this indicated a doubtful prognosis. In eight of the nine children with clinical signs of brain death a typical reverberating flow pattern was found, which was characterised by a counterbalancing short forward flow in systole and a short retrograde flow in early diastole. This indicated arrest of cerebral blood flow. One newborn showed normal systolic and end diastolic flow velocities in the basal cerebral arteries for two days despite clinical and electroencephalographic signs of brain death. Shunting of blood through the circle of Willis without effective cerebral perfusion may explain this phenomenon. No patient had the typical reverberating flow pattern without being clinically brain dead. Transcranial Doppler sonography is a reliable technique, which can be used at the bedside for the confirmation or the exclusion of brain death in children in addition to the clinical examination.

Basilar Artery

Ferric-coprogen receptor FhuE of Escherichia coli: processing and sequence common to all TonB-dependent outer membrane receptor proteins.

Iron transport via siderophores requires outer membrane receptor proteins and the TonB protein. The FhuE protein of Escherichia coli functions as the receptor for ferric coprogen and ferric-rhodotorulic acid. A chromosomal DNA fragment bearing the fhuE gene was cloned into pACYC184. The gene was localized by insertion mutagenesis by using the transposon Tn1000. Expression in minicells revealed a FhuE precursor with an apparent molecular weight of 82,000 and a FhuE protein with a molecular weight of 76,000. The transcription polarity of the fhuE gene was deduced from the size of truncated polypeptides derived from Tn1000 insertions, which were mapped by restriction analysis. The processing of truncated precursors that were synthesized by insertion mutants was strongly reduced even when the insertion site was close to the carboxy terminus of the FhuE protein. It is concluded that either the efficient insertion of proFhuE into the cytoplasmic membrane or the rate of cleavage of the signal peptide requires a particular conformation of the proFhuE protein, which is only formed by the complete primary structure. The amino-terminal amino acid sequence deduced from the nucleotide sequence was confirmed by gas-phase sequencing of the precursor and the mature form, which were separated by electrophoresis on polyacrylamide gels. The precursor contained an unusually long signal peptide of 36 amino acids. The amino-terminal end of the mature form contained the sequence Glu-Thr-Val Ile-Val. A pentapeptide starting with either Glu or Asp, followed by Thr, and two uncharged residues ending with Val were found in all outer membrane receptor proteins that were constituents of TonB-dependent transport systems.

Amino Acid Sequence

Functional characterization of prethymic T cells committed to alloreactivity.

The results of previous experiments on MHC fully allogenic bone marrow transplantation (BMT) in nonthymectomizd recipients indicated that anti-MHC alloreactivity starts to become irreversibly committed at the prethymic level. This is a matter of some controversy. Since it is possible that conflicting results depend on the methods chosen, we reexamined our previous results by applying two new approaches. Adult thymectomized (ATX) Balb/c mice received a syngeneic fetal thymus either 3 weeks before or 3 weeks after lethal irradiation and reconstitution with C57BL/6 BM incubated in antiserum. Since monoclonal antibodies such as anti-Thy 1 are of limited value for investigations of the above type (Thy 1 antigen crosses the prethymic/thymic border), we used two highly selective, excessively cytotoxic xenoantisera for incubation of the donor BM--either a specific anti-T cell serum (SAT) that eliminated only mature T cells, or a specific antilymphocyte serum (SAL) that reacted additionally with a subset of prethymic T cells (PTC). In both experimental approaches the results were similar: Recipients of SAT-BM developed antihost reactivity, in contrast to recipients of SAL-BM. SAT-BM recipients became immunodeficient, whereas SAL-BM chimeras were immunocompetent. Late mortality was observed only following SAT treatment. Preliminary morphological findings in the lymphoid tissue of BM recipients agree fully with the functional observations. We conclude that the data confirm our previous results in nonthymectomized BM recipients--i.e., PTCs initiate antihost reactivity in MHC fully allogeneic BMT--and PTC commitment is thymus/thymus factor independent. These conclusions are discussed with regard to the problems of MHC allogeneic clinical BMT.

Animals

A new X-linked syndrome with muscle atrophy, congenital contractures, and oculomotor apraxia.

Six men from three generations of one family had manifestations of a possible new syndrome. All had congenital contractures of the feet at birth, a slowly progressive predominantly distal muscle atrophy, dyspraxia of the eye, face, and tongue muscles, and mild mental retardation. The pedigree is compatible with X-linked recessive inheritance with no detectable manifestations in the obligate carriers. Linkage analysis excludes close linkage with the Xg locus and a polymorphic DNA sequence from the long arm of the X chromosome (DXS17).

Adolescent

Unilateral vulvar edema after intraperitoneal Hyskon administration.

Two patients are presented who developed vulvar edema after intraperitoneal instillation of Hyskon. Regardless of the route of extravasation, Hyskon's high molecular weight and osmotic effects may lead to further soft tissue swelling. Correct diagnosis warrants the exclusion of wound infection, hematoma, or seroma. Special attention to ensuring peritoneal closure may lessen the risk for the development of this complication.

Adult

Placenta previa: an analysis of three years experience.

A retrospective study of 45 cases of complete placenta previa is presented. Expectant management of the premature infant using tocolytics, blood transfusion, and cesarean section was practiced. All patients were suspected of having placenta previa based upon ultrasound examination; 90% reported third-trimester bleeding; 48% required prepartum blood transfusion; and 80% experienced one or more complications. Premature delivery occurred in 67% of patients; tocolysis was initiated in 53%. Patients with previa were older, of higher parity, and more likely to have had a previous cesarean section or abortion than matched controls.

Adult

[Disobliteration of coronary arteries by the laser. Peroperative experience].

The authors report their experience of coronary artery disobliteration by laser in 10 patients. This was a preliminary study to assess the effects of an Argon laser on atheromatous coronary stenosis in vivo. This technique was used during coronary bypass surgery. Two series of patients were treated: an initial group of 5 patients who underwent laser therapy associated with coronary bypass surgery; a second group undergoing laser therapy alone without distal bypass grafting. The results were assessed by immediate angiography in the first series and by the passage of calibrated probes in both series. Secondary control angiography after 3 weeks was carried out in all patients. The immediate results showed a constant improvement (less than 25%) in the degree of stenosis. However, secondary angiography showed secondary occlusion in 88% of cases. These preliminary results show: the immediate efficacy of Argon laser in reducing the size of atheromatous plaques, the innocuity of the method as there were no postoperative deaths, a high incidence of secondary failure which could be related to the type of indication (competitive flow in the first group and poor distal run off in the second group of patients) or to the type of laser used. The authors consider this to be a promising technique but a lot of clinical and experimental work remains to be done before it can be adopted for routine use.

Aged