[Margareta wants: prohibit prostitution!. Interview by Christina Mörk].
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Biomedical subjects
Publications and source records attributed to M Appel.
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The upper liver veins of fifty adult people were dissected from their orifices up to their second ramifications. The courses of the hepatic veins to the main portal fissure and umbilical fissure were determined. Three large upper hepatic veins can be expected in 74%, an accessory one occurs in 26%. The three or four upper hepatic veins join V. cava inferior by two (66%) or three (34%) common terminal branches (length 0.9 cm). Mean diameters of right hepatic vein 1.5 cm, middle hepatic and left hepatic veins 1 cm, accessory upper hepatic vein 0.6 cm. The course of the middle hepatic vein to "cava-gallbladder-line" was determined. The most common vein of the umbilical fissure joins the left, occasionally the middle hepatic vein. The intrahepatic distribution of the liver veins was projected to the surface of the liver considering the typical resection lines. We recommend the following anatomical way of proceeding: right extended and left lateral lobectomy remain right to lig. falciforme hepatis; right lobectomy 1 cm right, left lobectomy 1 cm left to "cava-gallbladder-line".
Retroviral-mediated gene transfer to multipotent and committed hematopoietic stem cells and marrow stromal cells was evaluated in long-term bone marrow cultures (LTBMCs). The retroviral vector pZIP-Neo(SV)(X) carrying the bacterial neomycin resistance (neor) gene that confers resistance to the neomycin analog G418 in mammalian cells was packaged in a Moloney envelope either as a replication-competent or replication-defective virus. Virus was introduced by infection of long-term marrow cultures at day 7. During a period of 12 weeks in culture, 10%-50% of harvested hematopoietic progenitor cells that formed differentiated CFU-GEMM colonies in response to pokeweed mitogen-containing spleen cell-conditioned medium (SCCM) and erythropoietin expressed the neor gene. In contrast, 1%-10% of hematopoietic progenitor cells that formed colonies in agar in response to WEHI-3B- or L-cell-conditioned medium expressed resistance to G418. The percentage of resistant progenitors was not detectably enhanced when replication-competent Moloney murine leukemia virus (M-MuLV) was present as helper virus, even though M-MuLV infected greater than 90% of cells in the long-term marrow cultures. In a separate CFU-F assay, 12%-17% of the adherent stromal cells in LTBMCs were found to express the neor gene. Thus gene transfer is limited by the fraction of progenitor cells that can integrate and express the transferred genetic sequences, rather than by the fraction of cells that are initially infected by the vector.
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The in vivo kinetic of removal of 3H asialo-orosomucoid from plasma was investigated in control and streptozotocin-diabetic rats after intravenous injection of 1 mg of asialo-orosomucoid/100 g body wt. Michaelis-Menten kinetics of disappearance were observed. In diabetic rats the maximal rate (Vmax) of disappearance of 3H asialo-orosomucoid was decreased by 30% with no modification of Michaelis constant. Since no accumulation of desialylated orosomucoid in the circulation was observed, the slower rate of removal of 3H asialo-orosomucoid was attributed to a decrease in the number of hepatic asialoglycoprotein receptors which are largely involved in the catabolism of asialoglycoproteins. Our estimate on in vivo maximal rates was 10- to 20-fold greater than our previous in vitro estimate of the maximal rate of endocytosis. In contrast, the values of the Michaelis constant obtained in vivo and in vitro were very similar.
In a prospective study on Coronary Heart Disease (CHD) orthogonal electrocardiograms (Frank) were recorded annually for ten years from 1,444 asymptomatic, middle-aged males with a mean age of 57.4 +/- 10.6 years. Cases with overt or suspected CHD were excluded. The purpose of the study was to identify risk indicators in electrocardiograms and to compare them with other known risk factors used for prediction of acute CHD events such as myocardial infarction (MI) and/or cardiac death (CD). Such acute events occurred in 88 cases. Pre-event ECGs of these acute events were compared with all others without events, using logistic regression analysis. Identified ECG risk indicators were then compared with other known risk factors such as smoking, blood pressure, cholesterol, age, weight, etc. The predictive power of the ECG, derived mainly from the ST-T complex, exceeded all others by a wide margin. The amplitude of the first 1/8 of the ST-T complex in lead x (similar to V5-V6) together with relative body weight proved best when one pre-event record was available. Prediction improved when ECG changes between two pre-event recordings were included. Precision of measurements by computer appeared essential for improvements in CHD prediction.
The influence of some extreme body postures on vital capacity (VC) was examined in young adult humans. Two postures required full support of body weight by the arms: arms up, hanging from a bar, and arms down with hands gripping parallel bars. Three involved muscles that flex and extend the trunk: a partial sit-up position while supine and nearly maximal spinal extension and flexion while standing. Changes at the inspiratory and expiratory volume extremes were recognized by having the subjects do two VC efforts: the first standing and the second in the posture in question while continuing to breathe on the spirometer. Control observations in which the second of a VC pair was performed in an unstressed posture allowed correction for the influence of rebreathing. The changes in corrected VC were small, the greatest being an average reduction of approximately 8% in the partial sit-up position. During full support of body weight by the arms, the VC was slightly increased due to a significant increase in the inspiratory extreme and no change in the expiratory extreme. Spinal extension produced small increases in lung volume at both extremes with no significant change in VC, whereas spinal flexion did not influence the upper extreme but did increase lung volume at the lower extreme. The changes are discussed in terms of trunk muscle action.
The binding of the 3'-[1,5-(dimethylamino)naphthoyl] (DAN) derivatives of AMP, ADP, and ATP to the solubilized ADP/ATP carrier is studied, evaluating primarily the fluorescence enhancement and 3H-labeled compound binding. DAN nucleotides also fluoresce when adsorbed to Triton X-100 micelles that are used for solubilization of the carrier. The partition of DAN-AMP between water and Triton X-100 micelles is measured, and it is shown to be shifted toward a higher content in Triton micelles with increasing salt concentration. In order to maintain a low level of fluorescence, the Triton content is decreased. The fraction of DAN nucleotide fluorescence due to carrier binding is determined by the suppression with bongkrekate (BKA). In contrast to the membrane-bound carrier, the solubilized preparation shows an increase of total BKA-sensitive fluorescence by 30-60% upon addition of ATP or ADP. In the solubilized atractylate-protein complex, the ADP-stimulated fluorescence amounts even to 80%. The suppression of fluorescence by BKA is independent of the presence of ADP or ATP, while that by carboxyatractylate (CAT) depends on ADP or ATP. The quantitation with [3H]BKA and [3H]CAT of these ligand interactions with DAN-AMP fluorescence shows that DAN-AMP fluorescence reflects the "m"-state carrier population and its redistribution under the influence of ADP or ATP. Thus, besides the "c"/"m" distribution, the kinetics of the c to m transition in the solubilized carrier also can be determined. The m share is increased to 80% when SO4, Pi, or pyrophosphate is present during solubilization. The rate of the ADP- or ATP-stimulated transition to the m state is markedly dependent on pH and on the presence of various anions, whereas the extent is little varied. The affinity decreases 4-fold going from DAN-AMP to DAN-ADP and to DAN-ATP (KD = 0.9, 1.6, and 3.2 microM). Comparison with physical binding of [3H]DAN nucleotides shows that the fluorescence yield of bound DAN-AMP is about 1.4 times higher than that of bound DAN-ATP. DAN substitution causes more than a 100-fold affinity increase for AMP and a 50-fold increase for ADP or ATP, probably because of interaction of the DAN group with a hydrophobic niche. A less specific, low-affinity displacement of DAN nucleotides by GDP, ADP, GTP and ATP (Ki = 1-2 mM) probably reflects primarily the ionic interactions at the binding center.
The utilization of fructose by isolated hepatocytes was investigated in fed obese Zucker fa/fa rats compared with their lean littermates (Fa/?) and Sprague-Dawley rats. Hepatocytes were incubated during 3 h using U14C fructose (20 mM). Our results show: a significant increase of fructose consumption, glucose, lactate and pyruvate production and faster turnover of glycogen by fa/fa rats. In these animals, synthesis of acylglycerol was also significantly enhanced. Our results suggest that fructose in fa/fa rats was used preferentially as precursor for lipid synthesis not only by the liver but also by the adipose tissue after a prior transformation into glucose by hepatocytes. All these abnormalities result in an accumulation of acylglycerols maintaining an obesity state in fa/fa rats.
Hepatocytes isolated from streptozotocin treated Rats bind less asialotransferrin than hepatocytes isolated from normal rats. This decrease is parallel with a decrease in the sialic acid content. Insulin therapy restored simultaneously membrane sialic acid content and asialotransferrin binding capacity.
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A novel procedure for storing blood at a controlled pH consists in collecting blood in a pH 8.20, Tris-CPD solution and storing it in a special recipient including a gas permeable membrane under a CO2 atmosphere. The recipient is placed in an atmosphere of variable CO2 content, so that the initial alkalinity of the preservative is balanced by dissolved CO2, the proportion of which is diminished when lactate production increases with storage. 2,3-DPG and ATP were studied at three different pH levels of approximately 7.25, 7.45, and 7.65 at 4 degrees C. The best pH for the simultaneous maintenance of 2,3-DPG and ATP was 7.65. Under these conditions, 2,3-DPG is maintained at its initial level and ATP at 55% of its initial level at the 30th day. Lactate production is linear and hemolysis moderate.
Several infectious agents are involved in the kennel cough complex in dogs. They include canine parainfluenza virus (SV5), canine adenovirus 2, Bordetella bronchiseptica, and possibly several mycoplasma species. The importance of each of these agents in the disease syndrome is discussed as well as possible prevention or treatment.
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The kinetics of myocardial calcium washout using a calcium free perfusion were studied in controls and animals after a short period of ischaemia. A significantly higher rate for k3 was found after ischaemia. This may represent a greater lability of membrane-bound calcium.
An investigation into the contents (mumol/g w.w.) of the creatine phosphate (CP) and adenosine triphosphate (ATP) of various myocardial regions was performed on the empty beating isolated blood perfused dog heart. Across the myocardial wall, CP concentration was higher in the outer portion (9.03 +/- 0.18) than in the inner portion (8.59 +/- 0.20) (P less than 0.05). In addition to this transmural gradient, a longitudinal gradient was found: tissue contents of both CP and ATP decrease significantly from the base (CP: 9.70 +/- 0.28, ATP: 5.84 +/- 0.20) to the apex (CP: 8.69 +/- 0.27, ATP: 5.57 +/- 0.17) (P less than 0.01 and P less than 0.05 respectively). The gradients of metabolites in the well oxygenated empty beating heart suggest that a permanent metabolic adaptation to less adequate regional O2 reserves is physiologically operating in the subendocardial layer and the apex region of the left ventricle.
Isolation of a viral agent (107) directly from brain explants of a 15-month-old heifer with symptoms of a sporadic encephalomyelitis is described. The virus shares properties with the paramyxovirus family. It grows in a variety of cell cultures from different species, and induces nuclear and cytoplasmic inclusion bodies in infected cells. Nucleocapsids measuring 17 nm in diameter were found in the nucleus and cytoplasm of these cells when studied electron microscopically, thus indicating a close relationship of the agent to the measles-distemper-rinderpest group. No infectious virus was released from infected cells, although alignment of nucleocapsids was observed beneath the cell membrane, and no hemagglutinating activity could be detected with the methods employed. The 107 agent was compared serologically with parainfluenza viruses type 1, 2 and 3, simian virus 5, mumps and Newcastle disease virus (NDV), two bovine respiratory syncytial viruses and measles/subacute sclerosing panencephalitis, distemper and rinderpest viruses, always using 107 virus infected CV1 cells and antiserum of the different viruses in indirect FA tests. Positive FA reactions were observed only with two sera obtained from SSPE patients with high antibody titer to SSPE virus, and with one rabbit-anti-rinderpest serum. The titers of these sera to 107 virus, however, were significantly lower than those against homologous viruses. Five out of 9 sera from randomly selected healthy cattle showed antibody titers between 1:10 and 1:80 to 107 virus in FA tests. The significance of these results is discussed with respect to the epidemiology of SSPE in children and its possible implication with rinderpest in Europe.