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U Pfeifer

Publications and source records attributed to U Pfeifer.

At least 91 records · Page 5Linked to original sources
PubMed1984

Methods in laboratory investigation. Application of test substances to the surface of rat liver in situ: opposite effects of insulin and isoproterenol on cellular autophagy.

Small plastic rings were applied to the surface of intact rat liver and used as microvessels in short-term experiments (10 to 20 minutes) for the local surface application of test substances. Tissue within the ring was then fixed using OsO4 in phosphate buffer. Excellent ultrastructural preservation of hepatocytes and sinusoids, including their contents, was obtained in the superficial tissue layer. By combining this method with quantitative electron microscopy we found that insulin decreased the volume fraction and numerical density of autophagic vacuoles, in comparison with control areas of the same livers exposed to Ringer's solution alone. Isoproterenol had opposite effects. One of the advantages of this method is that counterregulation, which must always be considered following systemic application of test substances, can be excluded as a possible explanation of the effects observed.

Animals↗
PubMed1984

[Electron microscopy findings in non-A, non-B hepatitis].

Contrary to some reports electron microscopy up to now has not yielded any characteristic or specific changes of liver parenchyma in hepatitis non-A-non-B of man. In man as well as in chimpanzees intranuclear particles of 20-27 nm diameter (interchromatin granula) have been found; however, they are unspecific. In chimpanzees characteristic changes of cytoplasma (type I-IV) have been demonstrated; however, there is no equivalent of that in human liver tissue to be observed.

Animals↗
PubMed1983

Interference between non-A, non-B and hepatitis B virus infection in chimpanzees.

Pre-existing chronic or concurrent acute non-A, non-B (NANB) virus infection has been found to interfere with hepatitis B virus (HBV) replication and to delay and moderate markedly the appearance of disease related to HBV infection in chimpanzees. The mechanism for this phenomenon remains unclear. These findings are of practical significance for vaccine safety testing and evaluation of methods for virus inactivation in chimpanzees. The possible occurrence of dual NANB and HBV infection requires that prolonged follow-up be carried out. Attempts to carry out inactivation studies on materials containing both types of virus may also provide misleading observations.

Alanine Transaminase↗
PubMed1983

Cardiac hypertrophy in rats after supravalvular aortic constriction. I. Size and number of cardiomyocytes, endothelial and interstitial cells.

The ascending aorta of 22 adult male Sprague-Dawley rats was constricted with a silver ring, and 25 animals were subjected to a sham-operation. The hearts, including the main arteries, were fixed by retrograde perfusion 3, 7, 14, 21 and 35 days after the operation. The cross-sectional area of the aorta was reduced by the constriction to an average of 20% of the values found after sham-operation. Twenty-one days after the constriction the weight of the left ventricular myocardium including the septum was increased 1.7-fold compared with controls. No further increase in weight was observed 35 days after the operation. The relative volumes of the tissue components remained largely constant in the subepicardial myocardium. In the subendocardial myocardium, however, the volume fraction of interstitial and, to a lesser extent, of endothelial tissue was significantly increased. Twenty-one days after constriction the estimated total volumes of the different myocardial components per left ventricle were increased 1.7-fold for heart muscle parenchyma, 1.8-fold for endothelial tissue, 2.9-fold for interstitial tissue, and 1.3-fold for capillary lumina compared with controls. At 35 days, only the interstitial tissue showed a further increase to 4.8-fold of control values. The mean cardiomyocyte volume was increased after aortic constriction in proportion to the increase in left ventricular weight, i.e. 1.7-fold over controls at 21 days. After 35 days its value was 29,500 +/- 790 micron 3 in rats subjected to aortic constriction compared with 16,800 +/- 640 micron 3 in controls. At this time the estimated number of cardiomyocytes per left ventricle showed no significant differences between experimental animals (2.9 X 10(7)) and controls (3.1 X 10(7)). Endothelial and interstitial cells were not only increased in average single cell volume (1.3-fold and 2.0-fold, respectively), but also in number per left ventricle (1.4-fold and 2.7-fold, respectively). Two-dimensional parameters indicated that during hypertrophy the capillary supply lagged behind the overall mass increase but achieved control levels on termination of hypertrophic growth at 35 days. These results show that even in pronounced hypertrophy the increase in mass of the myocardial parenchyma in the rat is due exclusively to an enlargement of cardiomyocytes (hypertrophy), whereas in endothelial and interstitial tissues enlargement of cells as well as increase in cell number (hyperplasia) also plays a role.

Animals↗
PubMed1983

Cardiac hypertrophy in rats after supravalvular aortic constriction. II. Inhibition of cellular autophagy in hypertrophying cardiomyocytes.

Adult male Sprague-Dawley rats were killed by retrograde perfusion fixation 3, 7, 14, 21 and 35 days after supravalvular aortic constriction (n = 33) or sham-operation (n = 25). Subepicardial specimens of the left ventricular myocardium were evaluated by conventional electron microscopic morphometry, and in addition were examined for the occurrence of autophagic vacuoles (AVs) using large test areas (3.9 X 10(4) micron 2 per animal). The quotient of mitochondrial to myofibrillar volume fraction was largely unchanged during hypertrophy but was reduced by 25% compared with controls after termination of growth at 35 days. During the process of hypertrophy which eventually led to an increase in average single cell volume of the cardiomyocytes by 78%, the volume fraction and the numerical density of AVs was significantly lower than in sham-operated rats. The most striking difference was observed 7 days after the operations, the stage at which the growth rate of the cardiomyocytes relative to controls was at its maximum of 4.5% per day. At this point the volume fraction as well as the numerical density of AVs were reduced by about 50% compared with controls. At 14 and 21 days after operation, when the relative growth rate of the hypertrophying cardiomyocytes was still 2% and 1% per day, the AV volume fraction was reduced to a lesser extent (by 47% and 28%, respectively). After termination of adaptive growth at 35 days significant differences in fractional volume and numerical density of AVs were no longer detectable. These results suggest that degradation of cytoplasmic components is inhibited in cardiomyocytes undergoing hypertrophy. Such an anticatabolic reaction seems to play an important role in establishing the positive balance of cellular metabolism generally required for growth processes.

Animals↗
PubMed1983

Inhibition by insulin of cellular autophagy in proximal tubular cells of rat kidney.

Adult male Sprague-Dawley rats were injected intraperitoneally with 5 U insulin/kg body wt (45 animals). As determined by quantitative electron microscopy, the volume fraction and the numerical density of autophagic vacuoles (AV) in proximal tubular cells decreased within 10 min by 46 and 26%, respectively. A partial recovery of the AV volume fraction was observed 20 and 30 min after the injection contrary to our previous findings with liver (J. Cell Biol. 78: 152-167, 1978). In an additional experiment (12 animals) it was shown that an insulin dose of 0.5 U but not of 0.05 U/kg body wt reduced the AV volume fraction to an extent similar to that of 5 U. To eliminate possible secondary effects, Ringer solution containing 0.8 microM insulin was dropped intravitally for 15 min to one pole of the decapsulated kidney and Ringer solution without additions to the other pole (8 animals). After intravital fixation, the AV volume fraction and numerical density in proximal tubular cells was found to be reduced under the influence of insulin by 22 and 36%, respectively. This data shows that insulin inhibits the process of cellular autophagy in proximal tubular cells of the kidney.

Animals↗
PubMed1983

Safety and potency aspects in the preparation of an experimental HBsAg vaccine.

No experimental setting is available to exclude residual infectivity in HBsAg vaccines derived from human plasma. Thus, safety can be achieved only by means of their preparation. To reduce infectivity of the starting material, only plasma from healthy anti-HBe positive donors was used. In the FRG, 50% of all healthy HBsAg carriers with anti-HBe have a suitable serum level of 5 to 20 micrograms/ml. The purification procedure removed hepatitis B virus by a factor greater than 10(4). The purified product contained only the HBsAg proteins and no serum protein, as shown by SDS gel electrophoresis. The pure HBsAg was treated with formalin 1:500 at 37 degrees C for 4 days. A loss of 30 to 50% antigenicity was tolerated to achieve the highest possible destruction of known and unknown infectious agents. After inactivation, the HBsAg was bound to aluminium hydroxide gel. The gel was washed repeatedly to remove the formalin. Doses of 40 micrograms or 20 micrograms absorbed HBsAg protein were given to greater than 2500 persons without serious side effects. In greater than 97% anti-HBs was formed with a median titer of 1900 I.U./ml.

Follow-Up Studies↗
PubMed1983

Specificity and significance of hepatocellular ultrastructural changes in non-A, non-B hepatitis in chimpanzees.

324 liver biopsies from 71 chimpanzees with and without non-A, non-B (NANB) hepatitis have been examined by electron microscopy (E.M.) for hepatocellular changes reported to be associated with this disease. At least 2 types of ultrastructural cytoplasmic alterations were found in each of 23 cases of acute and 6 cases of chronic NANB hepatitis. Nuclear modifications were never seen. Similar ultrastructural alterations were found in infections derived from 9 different human blood borne NANB cases. In 9 animals which had received 5 different inocula, Pfeifer Type I, II, III and IV changes were seen; 3 of the 4 types occurred in 10 animals and 2 of the types in 5 animals. Type II and III changes were almost always seen together. All 4 types of alteration were usually found in biopsies taken near the peak of ALT elevation. Five of 6 animals in whom E.M. changes were detected in serial samples over a 1 1/2 to 4 1/2 year period had concurrent chronic ALT abnormality. Two of these 6 animals did not develop ALT abnormality until years after the original acute episode though E.M. changes were detected throughout this period. There was generally a good correlation between onset and duration of ALT abnormality and period when E.M. changes were detected. All samples from animals not exposed to NANB virus(es) were negative by E.M. Our findings indicate the ultrastructural cytoplasmic alterations to be highly specific for NANB infection. Since each of the 9 isolates produced essentially the same pattern of E.M. changes, it is likely that a single NANB hepatitis virus group accounts for most blood borne NANB hepatitis.

Alanine Transaminase↗
PubMed1982

[Preparation and testing of a hepatitis B vaccine (author's transl)].

Starting with 41.5 l of plasma from anti-HBe positive carriers of HBs antigen, 11,400 doses of a hepatitis B vaccine with 42 micrograms HBsAg-protein and 11,300 national units HBsAg activity per dose were obtained. After purification, HBsAg is obtained in 99% purity with a yield of more than 90% protein. A possible residual infectivity was inactivated by a diluted formalin solution. The infectivity test in chimpanzees confirmed the absence of infectious hepatitis viruses (HBV and nonA-nonB). In guinea pigs the immunogenicity of the vaccine was comparable to that of the reference preparation from the U.S. National Institute of Health. The presence of Al(OH)3 in the vaccine increased the anti-HBs titre by factors of 30-50. After vaccination with two doses 41 of 45 persons became anti-HBs positive, with three doses 42 of 45 persons developed anti-HBs. Median anti-HBs titre after the third doses: schedule I (three doses in intervals of 6 weeks) 427 mWHO-U/ml; schedule II (two doses at an interval of 4 weeks, third doses 4 months after the first doses) 1535 mWHO-U/ml. The vaccine was well tolerated. There were minor local reactions only.

Animals↗
PubMed1981

A simple method for incubation of tissue sections in immunohistochemistry.

The construction of a simple "incubation chamber" is presented by which a homogeneous incubation of tissue sections with calculable amounts of immunoreagents is guaranteed. The incubation of large area sections, and parallel incubations of 10 slides are possible. As an example of application a case of alpha-1-antitrypsin deficiency in the liver is demonstrated.

Histological Techniques↗
PubMed1981

Acute effects of isoproterenol on cellular autophagy. Inhibition in myocardium but stimulation in liver parenchyma.

The influence of isoproterenol (IPR) on cellular autophagy was examined in left ventricular myocardium and in liver parenchyma of rats two hours after a subcutaneous injection of a low dose (3 mg/kg body weight). 4 animals were treated with IPR, 4 controls received Ringer solution. The average cytoplasmic volume fraction of the autophagic vacuoles (AV) was 1.6 X 10(-4) in the heart muscle of the controls. After treatment with IPR this value was reduced by 70% to 0.5 X 10(-4). This inhibition of cellular autophagy is interpreted as an initial anticatabolic reaction which might be responsible for the myocardial hypertrophy after chronic administration of IPR. An opposite influence of IPR was observed in the hepatocytes. The volume fraction of AV's increased twofold to 8.7 X 10(-4) after IPR, compared to 4.0 X 10(-4) in control animals. In the controls, the volume fraction of AV's in heart muscle was 57% of the value found in the liver. Comparing liver tissue after fixation by immersion and by perfusion, no statistically significant differences in the volume fractions and in the numerical densities of AV's were observed.

Animals↗
PubMed1981

Hepatocellular fibrinogen storage in familial hypofibrinogenemia.

In the cytoplasm of hepatocytes of liver biopsy from a 30 year old man, there were proteinaceous inclusions which by use of the peroxidase-antiperoxidase method reacted strongly with antihuman-fibrinogen IgG, but gave a negative reaction with antihuman-alpha-1-antitrypsin IgG and with antihuman-albumin IgG. As shown in the electron microscope, these protein inclusions were composed of densely packed, irregularly arranged tubules of 40 nm diameter. Clinically, the patient and members of his family showed primary hypofibrinogenemia which on the basis of the morphological findings has to be interpreted as the consequence of a disturbance in the secretion of fibrinogen. Besides the well known alpha-1-antitrypsin deficiency, familial hypofibrinogenemia with hepatocellular fibrinogen storage appears to represent another example of a plasma deficiency due to failure of hepatic secretion.

Adult↗
PubMed1981

The significance of serologic, histologic, and immunohistologic findings in the prognosis of 88 asymptomatic carriers of hepatitis B surface antigen.

Eighty-eight asymptomatic carriers of hepatitis B surface antigen (HBsAg) were followed with biochemical, serologic, histologic, and immunohistologic studies over a period of four years. None of the 78 HBsAg carriers with normal or minimally changed liver tissue, antibody to hepatitis B e antigen (HBeAg) in serum, and no intranuclear hepatitis B core antigen (HBcAg) developed a chronic inflammatory liver disease. Four individuals lost circulatory HBsAg, and at least two individuals terminated their HBsAg carrier state. Seven asymptomatic HBsAg carriers with chronic hepatitis were characterized by HBeAg in serum and intranuclear HBcAg. However, three HBsAg carriers with chronic hepatitis and an absence of intrahepatocellular HBcAg were positive for antibody to HBeAg over the observation period. The mechanism that leads to chronic hepatitis in these patients remains to be determined.

Adult↗