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Biomedical subjects

H Hoensch

Publications and source records attributed to H Hoensch.

At least 19 recordsLinked to original sources

Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines.

From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.

Animals

[Differential diagnosis in fever of unknown origin: significance of concomitant clinical symptoms].

Between 1978 and 1984, 169 patients were admitted to the hospital for fever of unknown origin which was repeatedly above 38.3 degrees C. After a retrospective analysis of their records the patients were divided into two groups on the basis of the following new criteria. The first group (74 patients) was described as having "monosymptomatic fever", i.e. fever without any other physical signs, whereas the second group (95 patients) had "polysymptomatic fever", i.e. fever with additional physical signs. In 56 patients (76%) of the monosymptomatic group fever had lasted longer than 3 weeks prior to admission. In 86% of these patients case history, physical examination, microbiological tests, serological tests for microorganisms and outoimune antibodies, and microscopic inspections of tissue and/or bone marrow led to a diagnosis. Malignancies, factitious fever and fever of unknown origin were found only in this group. The patients with malignancies were generally older than the rest of the patients (p less than 0.05), and eight of ten patients suffering from connective tissue diseases also had monosymptomatic fever. The incidence of infections in this group was 42% (31 cases), in contrast to 88% (84 cases) in the polysymptomatic group (p less than 0.05). Whereas the latter had significantly more bacterial infections (p less than 0.05), viral infections prevailed in the monosymptomatic group (p less than 0.05). Thus, the etiology of polysymptomatic fever distinctly differed from that of monosymptomatic fever. Since the frequency distribution of etiologies in the monosymptomatic group corresponded to that of the cases of fever of unknown origin in the literature, differentiation into monosymptomatic and polysymptomatic fever might be helpful in determining further diagnostic workup of patients with fever of unknown origin.

Adult

Distribution of glutathione and its related enzymes in small intestinal mucosa of rats.

Glutathione (GSH) concentration of whole mucosa was 2.96 +/- 0.26 (mean +/- SEM) mumol/g wet weight in all segments: however the tip cell layer contained significantly less GSH than the lower mucosal cells. GSH S-transferase (GSH-T) activities displayed a striking gradient with highest values in the duodenum and lowest in the terminal ileum. gamma-glutamyl transpeptidase (GGT) activities were also highest in the proximal segment but lowest in the fifth segment among eight divided segments. Along the villus/crypt axis GGT and to a lesser degree GSH-T were also polarized with highest activities in the villus tip cell region. GSH peroxidase (GSH-Px) and glutathione reductase (GSSG-R) had an even distribution along the intestinal tube and among the mucosal cell populations. This distinct pattern of distribution suggests a functional adaptation of GSH and its related enzymes; GSH-T might be important for detoxification of exogenous luminal compounds which enter the body in the upper intestinal segments while GSH-Px might be responsible for peroxidation of endogenously produced compounds.

Animals

Cyclophosphamide-induced remission in Weber-Christian panniculitis.

A patient with Weber-Christian panniculitis is described in this report in which treatment with prednisone and hydroxychloroquine caused no improvement of the disease, and even led to a worsening of the symptoms. In contrast, administration of oral cyclophosphamide led to a rapid remission of the disease. As Weber-Christian disease has no known aetiology and no specific treatment has been established, the successful therapy with the cytostatic drug cyclophosphamide may shed light on the pathogenesis of Weber-Christian panniculitis.

Adult

Monooxygenase enzyme activity in alcoholics with varying degrees of liver damage.

Monooxygenase enzymes are involved in the biotransformation of drugs and of environmental carcinogens. The activity of 7-ethoxycoumarin 0-deethylase and associated NADPH-cytochrome c reductase was determined in 9000 g supernatant from bioptically obtained liver specimens from patients with various liver diseases in order to study in vitro drug metabolising capacity. Monooxygenase and reductase activity was significantly higher in the livers of 21 patients with alcoholic liver disease (fatty liver, alcoholic hepatitis, cirrhosis of the liver) than in 22 normal controls or in six patients with chronic active hepatitis. The raised activity of drug-metabolising enzymes obtained from alcoholics with liver damage differs from normal values found in five alcoholics without liver disease. Both groups were comparable in respect to the amount of alcohol consumed and duration of abuse. A strikingly low monooxygenase activity was observed in eight patients with cirrhosis of the liver and ascites, with, however, no apparent effect on reductase activity. The results show that alcoholic liver disease is associated with enhanced monooxygenase and reductase activity, but alcoholism, per se, is not. This rise of drug-metabolising enzyme activity could lead to selectively increased rates of biotransformation in patients with alcoholic liver damage.

Alcoholism

[Small bowel biopsy as a cause of pseudomonas aeruginosa septicemia in a patient with intestinal lymphoma? (author's transl)].

A patient with intestinal lymphoma developed a gram-negative septicemia 48 hours following a peroral biopsy of the small intestine. The bacteriological examination of the instrument proved the same bacteria (Pseudomonas aeruginosa) which was the cause of septicemia. On the basis of our observation and of other reports it seems reasonable besides gassterilization or effective disinfection of the instruments to carry out cultural examinations of the instrument before and following endoscopic and bioptic investigations of patients with impaired resistance; it would then be possible to start an appropriate antibiotic treatment in case of a septic complication.

Adult

Determination of microsomal UDP-glucuronyltransferase in needle-biopsy specimens of human liver.

Sensitive, reliable and convenient assays are described for the study of human liver microsomal UDP-glucuronyltransferase. Using 14C-1-naphthol as substrate about 2 mg of a liver biopsy specimen and for 14C-morphine about 20 mg of tissue will suffice for enzyme estimation. Lack of inhibition of 1-naphthol glucuronidation by morphine suggests that the substrates are glucuronidated by different forms of the enzyme. Enzyme levels in the native and activated state were studied in biopsies from patients grouped according to histopathological and clinical criteria. The enzyme assays may help to characterize UDP-glucuronyltransferases in human tissues and their induction by drugs and environmental chemicals, as well as their alteration in various diseases.

Animals

[Small-nodular liver cirrhosis with marked portal hypertension due to vitamin A intoxication resulting from psoriasis treatment (author's transl)].

Clinical and histological signs of small nodular liver cirrhosis with portal hypertension were present in a 36-year-old man, three-and-a-half years after a seven-week course of treatment of psoriasis vulgaris with high doses of vitamin a (70 X 10(6) IU orally). Although there is no increase in serum level of vitamin A now, increased deposits of vitamin A in the perisinusoidal lipid storage cells (Ito cells) are still demonstrated by fluorescencespectrophotometry and under the electron microscope. Fundectomy with resection of the terminal oesophagus was necessary because of bleeding from oesophageal varices.

Adult

Oxidative metabolism of foreign compounds in rat small intestine: cellular localization and dependence on dietary iron.

Oxidative metabolism of foreign compounds was measured in the intestinal mucosa of male rats. Activities of benzpyrene hydroxylase, p-nitroanisole O-demethylase, and NADPH-cytochrome P-450 reductase and cytochrome P-450 content were 3 to 10 times higher in epithelial cells of the upper villus than in mucosal crypt cells. Villous tip cells of the upper small intestine exhibited much higher cytochrome P-450 content and drug-metabolizing enzyme activity than did tip cells of lower intestinal segments. In rats fed commercial chow diet, cytochrome P-450 content and drug-metabolizing enzyme activity in villous tip cells of duodenal mucosa were higher than in animals fed a semisynthetic diet, but cytochrome b5 and NADPH-cytochrome P-450 reductase were unaffected. On restriction of dietary iron intake, cytochrome P-450 and oxidative enzyme activity fell sharply, but were completely restored in 24 hr by oral iron supplementation, whereas parenteral iron administration was ineffective. These findings suggest that intestinal drug metabolism is localized primarily in the upper villous cells of the proximal intestinal mucosa, that cytochrome P-450 is synthesized in maturing epithelial cells as they migrate from the crypts to the tip of the mucosal villi, and that this process is dependent critically upon absorption of iron from the intestinal lumen.

Animals