Biomedical subjects
Publications and source records attributed to U Fischer.
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In conscious dogs the peripheral venous blood glucose profile of an OGTT (1.0 g/kg) was individually duplicated by a computed i.v. glucose infusion. The correspondence reached between both tests was demonstrated by the correlation between the paired increments of the reactive blood glucose concentration areas. The average total dose needed for duplication was 0.52 +/-0.04 g/kg (no. = 11). There was a more rapid and greater IRI increase in OGTT than in the infusion test. When 1.0 g glucose per kg was given according to the same pattern by a computed infusion, the integrated areas both of blood glucose and of IRI was twice that in OGTT. We concluded that the IRI increase in OGTT reinforced by enteral mechanisms favors the direct hepatic uptake of absorbed glucose. This could also protect the body from an excessive insulin release provoked by the entire oral load if it reached the peripheral circulation.
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One approach of improving metabolic control in type I diabetic patients is the application of computer-aided procedures aimed at supporting the decision on optimal therapeutic regimens. To accomplish this, a complex strategy was developed which in an individual patient permits (1) the evaluation of metabolic data by means of statistical and graphical methods, and (2) the prediction of the outcome in feedback and in non-feedback-controlled insulin therapy. The latter is realized by means of simulation, employing a structured model of the glucose-insulin control system where the model parameters can either be identified individually or be taken at random. The practical applicability was validated in C-peptide-negative type I diabetic patients who were on intensified insulin injection therapy. The comparison between theoretical predictions and daily glycaemic profiles measured by the patients under ambulatory conditions showed close correspondence which justifies the application of this method as a clinical decision support.
To verify a structured model of the glucose-insulin system, metabolic measurements were compared with model-based simulations in insulin-dependent diabetic dogs which had been previously identified in terms of model parameters. Glycaemia, glucosuria, plasma insulin, and the rates of appearance Ra and disappearance Rd of glucose (kinetics of double-labelled glucose, evaluated according to Steele's equation in its non-steady-state version) were observed under the following conditions, starting from normoglycaemia during glucose-controlled insulin infusion (GCII): (I) insulin withdrawal, (II) insulin withdrawal and glucose infusion, (III) constant i.v. infusion of glucose and insulin, (IV) glucose infusion during GCII. After fitting the patterns of glycaemia, simulations of the other state variables were accomplished, employing the individual model parameters, the preset experimental inputs, and the GCII control constants (test IV only). Under nearly all conditions, correspondence was excellent between measured and simulated data. There were, however, the following exceptions: incomplete representation by the model of kinetics in glucose utilisation after interruption of insulin supply, overestimation of glucosuria by the model in the presence of insulin. It is concluded that the model provides a reasonable representation of metabolic processes which are of importance in the treatment of insulin-dependent diabetes mellitus and that it might thus appropriately simulate the outcome of metabolic regimens.
Cell-mediated cytotoxicity of clonal ginbuna crucian carp leukocytes against allogeneic erythrocytes is described using a sensitive non-radioactive in vitro assay. Hemoglobin released from target erythrocytes after cell-mediated erythrolysis was detected by tetramethylbenzidine (TMB). TMB assay showed clear correlation with a 51Cr-release assay and even exhibited higher cytotoxicity. The use of erythrocytes as target cells has several advantages over a conventional 51Cr-release assay. Erythrocytes do not have cytotoxic activity, are relatively homogeneous, are available in large numbers and erythrocyte donors need not be killed. Leukocytes from fish sensitized by erythrocyte injection or scale grafting efficiently lysed allogeneic erythrocytes, but did not kill isogeneic or autologous erythrocytes. In contrast, leukocytes from unsensitized fish did not lyse allogeneic erythrocytes and repeated sensitizations by allogeneic grafts were necessary to induce cytotoxic cells. Effector cells isolated from peripheral blood showed a higher cytotoxic effect toward allogeneic target cells than effector cells isolated from kidney. These studies support the hypothesis that fish are capable of a genetically restricted specific cell-mediated cytotoxicity.
Tumor recurrence in patients with cervical cancer after primary radical surgery with complete tumor resection (R0) may be caused by occult tumor cell deposits (OTCD) in potentially tumor-bearing pelvic tissue. New surgical techniques, like liposuction-assisted nerve-sparing radical abdominal hysterectomy (LANS-RH) might be performed to remove this tissue. In a preliminary study of 30 cases, treated with LANS-RH, the liposuction specimens were examined on hematoxylin & eosin (H&E)-stained step sections and at immunohistochemical levels, using the antibody cocktails MNF 116 and AE1/AE3 for cytokeratins to detect occult tumor cells. In nine cases microscopically tumor-free lymph nodes were detected in the liposuction material. One case presented lymphovascular space involvement in the capsular region of a node on H&E stained slides. Two additional cases showed tumor cell deposits in pelvic perinodal fatty tissue on immunohistochemical examination. We conclude that the LANS-RH technique is capable of resecting potentially tumor-bearing pelvic tissue. Careful histologic handling and immunohistochemical techniques may improve the detection of OTCD.
It is currently in discussion whether or not established liver cell lines can be used for an extracorporeal liver assist device. Thus, metabolic features of primary hepatocytes, immortalized hepatocytes, and hepatoma cells were compared. The ability of these cells to process toxic blood of patients with hepatic failure was investigated by testing their viability in toxin enriched medium that was obtained by toxin separation from patients' blood via a molecular adsorbents recirculating system (MARS). In addition, glucose metabolism, urea synthesis, P450 dependent verapamil metabolism using high performance liquid chromatography, and interleukin-6 induced "acute phase" reaction by sulfodesoxysalicylic acid-polyacrylamide gel electrophoresis detected changes of albumin synthesis were determined in primary hepatocytes and in established liver cells. The viability of hepatoma cells after contact with the toxic compounds coming from the patients' blood was significantly decreased in comparison to that of immortalized hepatocytes and primary hepatocytes. Immortalized hepatocytes and hepatoma cells showed a significantly higher consumption of glucose associated with a significantly higher lactate synthesis. A basic urea synthesis rate could be measured in immortalized hepatocytes and hepatoma cells, but it was significantly lower than that of primary cells. P450 with its subenzyme CYP2C was inducible only in primary hepatocytes and in immortalized cells, but in the latter the enzymatic activity was lower than that of primary cells. The incubation with acute phase mediators resulted in a decrease of albumin synthesis in primary hepatocytes and in hepatoma cells, but it increased the albumin synthesis in immortalized hepatocytes. Summarizing these data, partially beneficial effects can be assumed if established cells are used in an extracorporeal liver assist device. These might include synthesis of some compounds and basic metabolic activities, such as urea synthesis. However, established liver cells showed clearly altered metabolic characteristics. The sufficient removal of toxic compounds requires additional strategies for detoxification by primary hepatocytes in sufficient amounts.
OBJECTIVE: We describe and evaluate a preoperative MRI localization procedure for suspected breast lesions. MATERIALS AND METHODS: Fourteen consecutive patients underwent MR localization of suspected breast lesions discovered with contrast-enhanced MRI but not detected by conventional mammography or ultrasound. In each case diagnostic MRI was repeated after the application of special skin markers. A non-magnetic wire was subsequently inserted into the breast and a second MRI performed to document the position of the wire tip relative to the lesion. RESULTS: The procedure was successful in all 14 patients, enabling excision of the lesion and allowing histological diagnoses. CONCLUSION: We found the described procedure to be quite useful.
PURPOSE: Our goal was to investigate the role of Gd-DTPA-enhanced dynamic MRI in the evaluation of renal ischemic lesions. METHOD: With a turbo FLASH sequence before and after injection of Gd-DTPA, nine foxhound dogs after 60-120 min of renal ischemia underwent MR examination. In addition, five patients with a tumor in a solitary kidney were examined before and after nephron-sparing renal surgery to evaluate renal perfusion and function. The experimental and clinical findings were correlated with conventional measurements of kidney function and with histological findings. RESULTS: Complete renal ischemia leads to a poor corticomedullary differentiation in Gd-DTPA-enhanced turbo FLASH MRI. The signal-intensity-versus-time plots of kidneys with significant postischemic changes show a less steep increase of signal intensity in the cortex and a steeper increase of signal intensity in the medulla than those of normal kidneys. CONCLUSION: Dynamic MRI demonstrate renal morphology and reflect the functional status of renal vasculature.
PURPOSE: Our goal was to demonstrate possible pitfalls in the CT diagnosis of retained surgical sponges (textilomas) and to evaluate the impact of gas bubbles inside a textiloma. METHOD: Thirteen patients with textilomas were investigated with CT 3 weeks to 8 years after surgery. Twelve of the 13 textilomas were removed within 3 weeks after the first CT examination. Eight samples of surgical sponges were placed in a water bath for 6 months. Serial CT was performed to document the presence and persistence of gas bubbles. RESULTS: The radiopaque marker inside the textiloma was seen in nine patients but did not lead to the diagnosis in all patients. In seven patients gas bubbles were found inside the textiloma with a typical pattern. None of these patients had an abscess formation. In vitro studies demonstrated gas bubbles in all surgical sponges scanned 1 h afterward. The number of gas bubbles was not significantly reduced after 6 months. CONCLUSION: The variable appearance of retained surgical sponges can lead to diagnostic misinterpretations. If present, typical spongiform pattern with gas bubbles is the most specific sign for the detection of textilomas but does not indicate an abscess formation.
PURPOSE: Our goal was to evaluate possible diagnostic advantages of ultrafast MRI of the breast in comparison with dynamic MRI. METHOD: Thirty patients with 35 hypervascularized lesions were selected prospectively after undergoing standard dynamic MRI (temporal resolution 87 s). Patients underwent additional ultrafast imaging (temporal resolution 2 s). Onset, rate, and pattern of enhancement were analyzed. RESULTS: Histopathology revealed 15 malignant and 20 benign lesions (3-40 mm). Enhancement pattern was centripetal in 2 benign and 4 malignant lesions, centrifugal in 5 and 3, and homogeneous in 13 and 8. The onset of lesion enhancement ranged from 3 to 13 s (parenchymal enhancement 4-14 s) and the rate of enhancement from 3 to 70%/s, both without any correlation to the histologic diagnosis. There was no significant difference between ultrafast and standard dynamic MRI. CONCLUSION: Ultrafast MRI does not provide additional information in comparison with standard dynamic MRI.
Two soluble acidic c-type cytochromes--c' and c-552--were isolated by ion exchange chromatography, gel filtration and ammonium sulfate fractionation. Cytochrome c' is a high-spin cytochrome with maxima at 399 nm, 490 nm, and 634 nm in the oxidized form and at 550 nm, 425 nm and a characteristic shoulder at 434 nm in the reduced state. The best purity index obtained (A280/A399) was 0.35. Cytochrome c' is autoxidizable, has a molecular weight of 12000 (estimated by sodium dodecylsulfate electrophoresis), a midpoint redoxpotential of +10 mV and an isoelectric point at pH 4.0. The reduced cytochrome c' reacts with carbon monoxide. The reaction is reversible. Cytochrome c-552 shows maxima at 552 nm, 523 nm and 417 nm in the reduced form and at 408 nm in the oxidized state. The best purity index obtained (A280/A408) was 0.94. Cytochrome c-552 has a molecular weight of 30000 and an isoelectric point between pH 4.3 and 5.0. Chromatium warmingii also contains a membrane-bound cytochrome c-552. During anaerobic sulfide oxidation, elemental sulfur and sulfate were formed at the same time. When all sulfide was consumed by the cells, the remaining intracellular elemental sulfur was further oxidized to sulfate.
High potential iron sulfur protein (HIPIP) of the purple sulfur bacterium Chromatium warmingii was purified to homogeneity by ion exchange chromatography, gel filtration and ammonium sulfate fractionation. The acidic protein was isolated in the reduced form. The best purity index (A280/A388) obtained was 2.52, and 3.8 mumol of the protein was isolated out of 100 g wet cell material. The molecular weights estimated by sodium dodecylsulfate polyacrylamide gel electrophoresis and gel filtration through Sephacryl S-200 were 8900 and 10 500, respectively. The protein has an isoelectric point at pH 3.6 for the reduced form and at pH 3.8 for the oxidized form, and a midpoint redox potential of +355 mV. One mol of HIPIP contains 4 mol nonheme iron and 4 mol acid-labile sulfur.
In addition to the previous isolated and sequenced polypeptides from green photosynthetic sulfur bacteria, which are presumably involved in binding BChl c and e, an analogous polypeptide has been purified from the BChl d-containing bacterium Chlorobium vibrioforme f. thiosulfatophilum. The primary structure of this 6.15 kDa polypeptide was determined. It shows an extremely high homology (98.3%) to the corresponding polypeptide from Pelodictyon luteolum, indicative of an important functional role.
The profiles of blood glucose and of insulin dosage were compared between the first and second of 2 consecutive days of Biostator administration under constant conditions in 12 brittle type I diabetic inpatients. All blood glucose criteria and the daily insulin doses were reproducible between these 2 days for the entire group of patients. In nearly all patients, however, there were distinct but unsystematic differences between the 2 days in the diurnal patterns of insulin dose distribution. These differences could be ascribed to some stress reaction or inherent metabolic lability. It is concluded that, in these extremely labile diabetic patients, due to the insufficient short-term reproducibility of the outcome of an extracorporal artificial beta-cell, caution must be used when constant profiles are to be predicted from these doses for open-loop insulin delivery systems or for conventional subcutaneous injection therapy.
Multiple chromosomal aberrations have been reported in head and neck squamous cell carcinoma (HNSCC). But less information is available on specific patterns of chromosomal amplifications which distinguish different areas of head and neck tumors. To elucidate genetic mechanisms causing the aggressive growth and high proliferation of hypopharyngeal squamous cell carcinoma (SCC), we performed reverse chromosome painting (RCP) on a total of eight hypopharyngeal SCC including invasive carcinoma and preinvasive tissue. Five hypopharyngeal invasive carcinomas showed amplifications on chromosome 3q. Furthermore, we detected gains on chromosomes 11q and 6p. Compared to the histologically classified preinvasive tissues, we found amplified alterations on chromosome 6p, 11q and 12q, but none of them showed gains on chromosome 3q. This observed heterogeneity in hypopharyngeal SCC might reflect a specific role of chromosome 3q as a late event in the highly invasive capacity of these SCC.
Exogenous insulin exists primarily as the monomer in human plasma. However, in U100 regular insulin formulations, the concentrations of zinc and peptide are such that the insulin hexamer predominates. The biologic result is further disassociation to the monomer after subcutaneous or i.v. administration. Because of this, human plasma from seven normal controls dissolved 20-30 microm hexagonal insulin crystals in 3-8 min. This ability was inhibited by acid titration to a stable pH of 6.30, at which point bicarbonate depletion could be suggested. Repletion of bicarbonate remarkably restored the solvent effect, while back-titration to the initial pH without repleting bicarbonate had only a moderate result. To establish whether the in vivo reduction of bicarbonate in pathologic states had similar results, plasma from five Type I diabetics in severe acidosis (pH 7.06 +/- 0.04, HCO3 -7.3 +/- 0.6 mmol/l) was similarly studied after stabilization under 5% CO2 (pH, 6.97-7.17). In all cases, the dissolution of insulin crystals was inhibited (dissolution times greater than 25 min). When bicarbonate was replenished (HCO3- 24.1-26.7 mmol/l) and pH accordingly renormalized (pH 7.39-7.43), the dissolution of insulin crystals was completely restored. Because of these observations, we conclude that both plasma bicarbonate and pH markedly affect the dissolution of insulin and that reduced bicarbonate/pH in diabetic ketoacidosis may limit the availability of the biologically active monomer. These influences may play a role in the initial insensitivity to insulin frequently seen in severe insulin deficiency and ketoacidosis.