Search PubMed⌕ Search

Biomedical subjects

W Huber

Publications and source records attributed to W Huber.

At least 91 records · Page 5Linked to original sources
PubMed1993

Glutathione S-transferase isoenzyme patterns in different subtypes of enzyme-altered rat liver foci treated with the peroxisome proliferator nafenopin or with phenobarbital.

It is known that phenobarbital (PB) and the peroxisome proliferator (PP) nafenopin (NAF) promote tumor formation by stimulating selective growth of different subtypes of liver foci. While PB enhanced the gamma-glutamyltranspeptidase (GGT)-positive eosinophilic-clear cell foci (ECF), NAF amplified the GGT-negative weakly basophilic foci (WBF). These findings provide the possibility of using the occurrence of these foci subtypes as early indicators for the carcinogenic potential of PB- and PP-type promoters. In order to improve the methods for the discrimination between ECF and WBF we studied further differences in their phenotype, as determined by the expression pattern of glutathione S-transferase (GST) subunits. GST subunits of the alpha (Ya, Yc), mu (Yb1, Yb2) and pi family (Yp), which compose different GST isoenzymes, were demonstrated by immunohistochemical methods. ECF were the only foci subpopulation that expressed GST subunit Yp, while this subunit was always absent in WBF and in another focus subtype, the tigroid foci (TF). Neither PB nor NAF changed this pattern. Thus Yp expression was rather a function of the focus type than of the promoter used. Upon PB treatment expression of the GST subunits Yb1 and Yb2 was frequently elevated in ECF, while Ya and Yc remained more or less unchanged. In NAF-treated livers large WBF, however, showed diminished expression of all investigated GST subunits of the alpha and mu family. In conclusion, PB seems to promote mostly ECF with elevated levels of mu and pi class GSTs, while low levels or absence of all GSTs tested may be associated with growth selection of WBF through the PP NAF.

Adenoma↗
PubMed1993

Peroxisomal enzyme induction uncoupled from enhanced DNA synthesis in putative preneoplastic liver foci of rats treated with a single dose of the peroxisome proliferator nafenopin.

Putative preneoplastic foci of spontaneous origin could be detected in the livers of 2 year old, untreated male Wistar rats. The unaltered and preneoplastic hepatocytes showed an identical expression of the peroxisomal marker enzyme acyl-CoA oxidase, as determined by immunohistochemical staining. A single dose of the peroxisome proliferator (PP) nafenopin (NAF) induced the enzyme predominantly in hepatocytes around the central venules and cell replication mainly in the periportal areas. However, upon one NAF application almost all of the preneoplastic foci showed a considerably weaker immunoreaction for peroxisomal acyl-CoA oxidase than the surrounding tissue. Concomitantly NAF elevated replicative DNA synthesis index in foci up to approximately 40%, while replication of hepatocytes in the unaltered portion of the livers increased only slightly to moderately. In conclusion, NAF-induced peroxisomal acyl-CoA oxidase and replicative DNA synthesis seem not to be necessarily coupled within the same liver cell. Furthermore, preneoplastic foci responded rather to the cell replicative than to the peroxisomal effects of NAF, suggesting that the PP-induced growth stimulus is of particular significance for the carcinogenic action of this class of compounds.

Acyl-CoA Oxidase↗
PubMed1993

Enhancement of peroxisomal enzymes, cytochrome P-452 and DNA synthesis in putative preneoplastic foci of rat liver treated with the peroxisome proliferator nafenopin.

The peroxisome proliferator (PP) nafenopin (NAF) enhanced tumor development in rat liver through promotion of a subtype of putative preneoplastic cell foci, characterized by weak cytoplasmic basophilia. In order to elucidate the selective growth advantage of these weakly basophilic foci (WBF) we investigated the effects of NAF on their metabolic phenotype and DNA synthesis. In WBF, as well as in other foci subpopulations and in hepatocellular carcinomas the occurrence of five NAF-inducible enzymes, i.e. of peroxisomal beta-oxidation (acyl-CoA oxidase, bifunctional protein and thiolase), catalase and cytochrome P-452 was studied by immunohistochemical methods. In untreated livers almost all foci were stained with the same intensity as the surrounding tissue. When NAF was applied, most of the liver foci showed considerably less staining than the non-focal parenchyma in which pronounced enzyme induction had occurred. However, the subpopulation of WBF showed a more heterogeneous pattern of enzyme expression varying from less to even more than in the adjacent tissue. A similarly broad range of expression of peroxisomal enzymes was found in hepatocellular carcinomas. On average, however, the tumors exhibited less staining and lower activity of peroxisomal beta-oxidation than the surrounding parenchyma. WBF always showed higher rates of DNA synthesis than other foci subtypes and unaltered liver. In approximately one-third of these foci DNA synthesis was found to be enhanced concomitantly with elevated expression of peroxisomal beta-oxidation enzymes. In conclusion, WBF may have a selective growth advantage as they 'overrespond' to the inducing effects of NAF on DNA synthesis and peroxisomal enzymes.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1993

Leukotriene B4 and C4 production in isolated rat gastric mucosal cells.

Dispersed rat gastric mucosal cells (F0) were separated into five fractions (F1-F5) by counterflow elutriation, with F1 representing the smallest and F5 the largest cell diameters. In F0-F5, leukotriene B4 (LTB4) release in response to 10(-5) M calcium ionophore A-23187 was 7.68 +/- 1.26, 51.6 +/- 10.8, 72.4 +/- 10.4, 7.1 +/- 0.7, 5.7 +/- 0.6, and 11.6 +/- 3.4 pg.10(6) cells-1 x 30 min-1. In the identical fractions, sulfidopeptide release in response to A-23187 was 200.6 +/- 20.5, 1,116.0 +/- 166.6, 1,309.4 +/- 163.2, 189.8 +/- 25.8, 108.0 +/- 18.0, and 158.4 +/- 54.0 pg.10(6) cells-1 x 30 min-1. High-pressure liquid chromatography verified the radioimmunologically determined LTB4 and identified LTC4 as the only sulfidopeptide LT released. LT release from F2 cells in response to A-23187 was time and dose dependent, reaching maximal stimulation at 10(-5) M A-23187. This response was blocked by the dual inhibitor of cyclooxygenase and lipoxygenases, BW755C (2 x 10(-5)-2 x 10(-4) M), by the selective 5-lipoxygenase inhibitor L-651,392 (10(-7)-10(-5) M), and by MK-886 (10(-9)-10(-7) M), which blocks translocation of 5-lipoxygenase. The postreceptor stimuli dibutyryl adenosine 3',5'-cyclic monophosphate, forskolin, 12-O-tetradecanoyl-phorbol-13-acetate, and oleyl-acetyl-glycerol failed to induce LT release. However, 10(-4) M arachidonic acid increased basal LT release up to eightfold and increased A-23187-stimulated LT release by an additional 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1992

Abnormal eye movement behaviour during text reading in neglect syndrome: a case study.

The eye movement behaviour of a patient suffering from a right basal ganglia infarction with a left-sided hemineglect but without any visual field defects was investigated during reading. The eye movements were registered by means of an i.r. light technique (pupil-corneal reflection method). The main findings were abnormal return sweeps. Whereas in normal readers the end of one line of text is linked to the beginning of the new line by a long leftward saccade, the return sweeps of the hemineglect patient stereotypically ended in the middle of the next line. They were followed by sequences of short saccades indicating silent backward reading until a linguistically plausible continuation of sentences from the previous line was found, irrespective of the actual beginning of text. The shortened return sweeps could not be attributed to a general oculomotor disturbance. The spatial border for the occurrence of the patient's abnormal scanning pattern (left half of texts) clearly did not depend on a retinal coordinate frame of reference but rather has to be attributed to a different body-centred reference system.

Attention↗
PubMed1992

Organ-specific distribution of genotoxic effects in mice exposed to cooked food mutagens.

The induction of organ-specific genotoxic effects of five cooked food mutagens in Swiss albino mice was investigated in microbial animal-mediated assays. The indicator of the induction of DNA damage was a pair of Escherichia coli K12 strains, differing vastly in repair capacity (uvrB/recA versus uvr+/rec+). All compounds gave positive results in the tested dose range between 2.5 and 40 mg/kg body weight (i.p. administration, exposure time 120 min). 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) were slightly more genotoxic than 2-amino-3,8-dimethylimidazo[4,5-f]quinoline (MeIQx), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) which caused similar effects. When the compounds were administered orally, higher doses were required to induce repairable DNA damage. The pattern of organ-specific effects was essentially similar for all compounds; genotoxicity was most pronounced in livers and lungs, whereas in kidneys, spleen and testes comparatively lower effects were measured. The activity of PhIP, MeIQ and IQ in the blood was similar to that observed in the liver. The results obtained in vivo were compared with data gained in vitro with subcellular organ fractions. Our findings indicate the following. (i) The concentrations required to induce repairable DNA damage in microbial animal-mediated assays are substantially higher than might be expected on the basis of the liquid suspension tests. (ii) The ranking order of the genotoxicity of the various compounds in vitro is similar to that measured in vivo, but the differences in genotoxic potencies are less pronounced in the living animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[The Aachen Aphasia Bedside Test--criteria for validity of psychologic tests].

The Aachen Aphasia Bedside Test (AABT) has been developed in order to examine aphasic patients within the first 4 to 6 weeks after onset of illness. The psychometric properties of the AABT were established by repeated examination of 82 acute stroke patients, ratings by 20 raters on the basis of 10 videotapes, repeated examination of 28 chronic aphasics three times with an interval of 2 days, and parallel examination of 47 chronic aphasic patients with the AABT and the Aachen Aphasia Test (AAT), administered on the same day. Objectivity, reliability and validity of the AABT were highly rated, indicating its usefulness in acute stroke cases. Data on the 82 acute stroke patients showed that an initial prognosis can be made as early as the fourth day after the stroke.

Adult↗
PubMed1991

Role of oxidative stress in age dependent hepatocarcinogenesis by the peroxisome proliferator nafenopin in the rat.

Recently old rats were found to be much more susceptible than young rats to the hepatocarcinogenic effect of a 55-59-week treatment with the peroxisome proliferator nafenopin (NAF) (B. Kraupp-Grasl, W. Huber, H. Taper, and R. Schulte-Hermann, Cancer Res., 51: 666-671, 1991). In the present study indicators of oxidative stress were measured in the livers of the same animals (male Wistar). NAF enhanced peroxisomal beta-oxidation 10-12-fold and reduced glutathione peroxidase activity by 40-50%. Indicators of lipid peroxidation like thiobarbituric acid reactive substances and malondialdehyde were both decreased by one-third and two-thirds, respectively. Of the oxidation-sensitive polyunsaturated fatty acids linoleic acid and docosahexaenoic acid were decreased by 40% and two-thirds, respectively, but the particularly sensitive arachidonic acid remained unchanged. Taken together these data suggest that NAF did not significantly enhance lipid peroxidation in the present experiment. All NAF effects were of the same magnitude in the old and young animals. Therefore, the considerably stronger induction of hepatocarcinoma by NAF in the old animals was not associated with evidence of enhanced oxidative stress. These findings are consistent with the hypothesis that NAF acts hepatocarcinogenically by promotion of tumor development from preneoplastic lesions occurring spontaneously with age.

Age Factors↗
PubMed1991

Increased susceptibility of aged rats to hepatocarcinogenesis by the peroxisome proliferator nafenopin and the possible involvement of altered liver foci occurring spontaneously.

We investigated the mechanism of the hepatocarcinogenic action of nafenopin (NAF), a nongenotoxic peroxisome proliferator. Groups of male rats aged 13 wk (designated "young") or 57 wk (designated "old") were fed NAF for 13 mo; additional groups received a basal diet or a phenobarbital (PB)-containing diet as positive control. The following results were obtained. (a) NAF produced numerous hepatocellular adenomas and carcinomas in old animals but very few in young animals. A similar result, although less pronounced, was seen with PB. Adenomas of PB-treated groups mostly consisted of eosinophilic and glycogen-storing cells. However, adenomas and carcinomas of NAF-treated livers were composed of weakly basophilic cells. (b) Phenotypically altered foci, evaluated in hematoxylin:eosin-stained sections, appeared spontaneously in untreated livers. The majority of these foci was either of the eosinophilic-clear cell or the tigroid cell type. In addition, we identified foci which are characterized by weak, diffuse cytoplasmatic basophilia. Their phenotype was similar to that of adenomas and carcinomas in NAF-treated rats. The number and size of eosinophilic-clear cell and of tigroid cell foci increased considerably with the age of the animals. At the end of the experiment, approximately 2.4% of liver tissue was occupied by focal cells. NAF, but not PB, treatment led to a selective increase in number and size of weakly basophilic foci. This subtype has previously been described as a likely precursor lesion for liver tumors induced by an aflatoxin B1-NAF initiation-promotion regimen (B. Kraupp-Grasl et al., Cancer Res., 50:3701-3708, 1990). These findings suggest that the peroxisome proliferator NAF leads to tumor development in aging rat liver by promotion of spontaneously occurring preneoplastic lesions. The type of lesion appears to be different from that promotable by PB.

Aging↗
PubMed1991

[Change in acylneuraminic acid content of T-lymphocytes and in plasma in breast cancer].

Increased sialic acid levels reflecting tumor burden are found on the surface of T-lymphocytes and in the plasma of patients with carcinoma of the mammary gland. The data of the determinations of sialic acid content and distribution on T-cells, using microanalytical methods such as HPLC and a colorimetric test, show that the total sialic acid content is increased by about 60% and that nearly 80-90% of the sialic acids consist of N-acetyl-9-O-acetyl-neuraminic acid, in comparison to the healthy controls (not containing O-acetylated neuraminic acid). Investigations on lymphocytes of malignant melanoma patients show similar changes of sialic acid content and distribution on the cell surface. Increased sialic acid levels are also found in the plasma of patients with cancer but no O-acetylated derivative can be found. Furthermore the examinations show that the separation of the T-lymphocytes from the total lymphocyte fraction is not required. Determination of sialic acids in the total lymphocyte fraction can be a simplification in carrying out further diagnostic investigations. A high level of sialic acids as "antirecognition factor" seems to be not only a marker of tumor cells but also an attribute of T-lymphocytes, involved in the defence against the malignoma (malignant melanoma, breast cancer). Considering the possible contribution of sialic acid to the immunoregulatory protective mechanism during the first stage of pregnancy, sialic acid content and distribution on T-cells of pregnant women are investigated. Both an increase and a change in the distribution of sialic acids can be excluded.

B-Lymphocytes↗
PubMed1991

Eye movement behaviour of patients with cerebral microangiopathy and macroangiopathy in simple visual detection tasks.

Patients with cerebral microangiopathy (n = 17), acute and chronic left hemisphere (LH) stroke (n = 18, n = 21) and normal controls (n = 41) were studied in 2 simple visual detection tasks, one with predictable, the other with unpredictable targets. Eye movements were registered by means of infrared light reflections (pupil-corneal reflection method); the points of visual fixation were continuously calculated by a microprocessor system. Patients with cerebral microangiopathy showed primarily difficulties in holding attention, as reflected by pathologically short durations of gaze on target, frequent unsuccessful anticipations and a high overall number of fixations. In contrast, acute LH stroke patients were characterized by a deficit in shifting attention, as reflected by prolonged latencies and long search durations due to many intervening search fixations. By means of a nonparametric discriminant analysis procedure, about 90% of patients with microangiopathy and about 80% of acute LH stroke patients were reliably distinguished from normal controls. The differences between these two patient groups were most pronounced in the simpler task with predictable targets. Among those patients discriminated from normals, about 96% were correctly reclassified as belonging either to the microangiopathy or to the acute LH stroke group on the basis of their abnormal eye movement variables alone.

Adult↗
PubMed1991

[A test for the detection of speech and language disorders in the acute phase after stroke. Development and clinical application].

No standardized assessment of aphasic symptoms for stroke patients in the acute phase has as yet been published in the German language. Current test batteries such as the AAT are too time-consuming and cannot be performed on severely impaired patients. A short test for the examination of aphasic and dysarthric symptoms has been developed which contains 7 subtests in three main areas: spontaneous speech, comprehension and planning of movements, speech and language abilities. Since abilities in acute cases may only be functionally impaired and often only detectable after stimulation, standardized stimulation is applied in most of the subtests. In this way it is possible to test acute stroke patients for aphasic and dysarthric symptoms. The course of recovery in a typical case is described.

Aged↗
PubMed1991

[Euphylong in standard dosage: comparison with an international retard preparation for twice-daily administration in recommended dosage].

24 patients with COPD and delta FEV1 greater than 15% were included in a double-blind crossover study. 7 dropouts due to deterioration of findings and incomplete data reduced the number of assessable patients to 17. Most of the patients had been pretreated with a slightly higher theophylline dosage before initiation of the study. In the preliminary period a 24-hour profile of the peak flow was set up with a morning and evening theophylline level. During the 5-day treatment intervals a 24-hour profile of the serum theophylline levels and of the peak flow was recorded at two-hour intervals. A complete lung function test was performed in each phase. The pharmacokinetic data of both preparations are comparable. Euphylong showed a bioavailability of 83%, the maximum of the serum level was attained at night. Serum level variations were only slightly higher than those of the reference drug. Euphylong had a night level of 24% above the daily average (reference drug 3%). This was associated in a part of the group, about one-third of the total number of patients, with an improvement of the "morning dip" compared with the preliminary period or the reference drug. Over the entire group of patients there were no differences between both drugs or the preliminary period that could be ascribed to the theophylline premedication. An advantage shown by Euphylong was the better predictability of the serum levels. During the time period of the clinical routine the deviation of the serum level from the actual serum maximum was less than 15%.

Adult↗
PubMed1990

Tumor promotion by the peroxisome proliferator nafenopin involving a specific subtype of altered foci in rat liver.

The involvement of tumor promotion in the hepatocarcinogenic action of peroxisome proliferators has not been generally accepted. We studied the effect of nafenopin (NAF) as a model compound in a two-stage initiation-promotion protocol. Carcinogenesis was initiated by a single dose of aflatoxin B1 (AFB1) in female (AFB1, 5 mg/kg) and male (AFB1, 2 mg/kg) Wistar rats. After recovery NAF was fed via the diet, providing a daily dose of 100 mg/kg body weight. Phenobarbital (PB) (50 mg/kg body weight) was fed to female rats as a positive control. The following results were obtained. (a) At weeks 40, 55, 59, and 70, significantly more and larger liver tumors were present in AFB1-NAF-treated rats than in rats receiving either compound alone, and the effect of the combined treatment was clearly more than additive, in three independent experiments including both sexes. This suggests tumor promotion by NAF. Male rats responded more strongly than females. Similarly, PB enhanced the yield of liver tumors. Histologically, tumors were hepatocellular adenoma or carcinoma. In group AFB1-PB the majority consisted of eosinophilic and glycogenstoring cells. However, adenoma and carcinoma of groups AFB1-NAF and O-NAF consisted of weakly basophilic cells. (b) Phenotypically altered foci were evaluated in hematoxylin- and eosin-stained liver sections from the female rats. NAF treatment after AFB1 had little effect on number and size of eosinophilic-clear cell foci and decreased the number of trigroid foci. However, it led to a dramatic increase (20-fold after 70 weeks of NAF treatment) in number and size of foci of a special phenotype that was extremely rare after AFB1 alone and virtually absent in group AFB1-PB. Hepatocytes in these foci are characterized by weak diffuse basophilia and some eosinophilia, similar to the phenotype in adenoma and carcinoma, and by absence of gamma-glutamyltranspeptidase (GGT) expression. Based on these findings, we propose the hypothesis that NAF promotes the development of liver tumors via a mechanism involving amplification of a specific subtype of altered hepatic foci.

Aflatoxin B1↗