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Biomedical subjects

H Bader

Publications and source records attributed to H Bader.

At least 37 records · Page 2Linked to original sources
PubMed1994

Role of human chorionic gonadotropin in patients with pure seminoma.

Human chorionic gonadotropin (beta-hCG) and alpha-fetoprotein (AFP) are widely established specific and sensitive tumor markers for nonseminomatous testicular cancer. In 106 patients with pure seminoma, a highly sensitive method detected beta-hCG both before and repeatedly during therapy. The low detection limit of the test (0.3 IU/l) coincided with the 95 percentile of a group of 60 healthy blood donors. Its 100 percentile of < 1.0 IU/l was applied as the upper limit of the normal range. In 30.2% of our patients with pure seminoma, elevated beta-hCG levels were noted prior to orchiectomy. The levels returned to normal in 76% of these patients thereafter, and in 34% after additional irradiation or chemotherapy. During an observation period of 2-84 months, all beta-hCG-positive patients were in complete remission. Prior to semicastration, 1 patient showed extremely high beta-hCG levels, while in another patient, beta-hCG and AFP were elevated simultaneously. In both cases, tumor marker levels did not seem to agree with the histology of 'pure seminoma' and rather suggested the presence of nonseminomatous tumor cells. Increased AFP levels contradict the presence of a pure seminoma and indicate a nonseminomatous testicular tumor. The same holds true for strongly elevated beta-hCG levels, whereas levels of up to 200 IU/l correlate with the diagnosis of pure seminoma.

Adult↗
PubMed1994

Characterization of bile ducts in primary biliary cirrhosis and other liver diseases by immunohistochemical demonstration of Lewis(a) or b antigen.

We investigated Lewis(a) and Lewis(b) expression of bile ducts in 68 specimens from various kinds of liver disease. In addition, the number of IgM and IgG synthesizing plasma cells in the hepatic inflammatory reactions were immunostained and counted. We found a statistically significant decrease in the number of bile ducts in PBC (primary biliary cirrhosis) in comparison with either chronic active or persistent hepatitis (CAH/CPH). Bile ducts could be detected easily and constantly by their Lewis antigen expression. Isolated bile duct epithelial cells not apparent in H&E sections could be identified by Lewis(a) and b immunostaining. The number of plasma cells in PBC was significantly different than in (CAH/CPH). A large number of IgM plasma cells was a characteristic feature of PBC. However, neither counting of Lewis(a) and b positive bile ducts nor counting of IgM plasma cells was of definite diagnostic significance in the individual clinical case, since no cut-off value could be determined above or below which a PBC was ruled out or proven.

Bile Ducts↗
PubMed1993

Intra- and perivesical tumor growth in preoperative staging of bladder cancer: the role of transrectal ultrasonography and high resolution magnetic resonance imaging.

Bladder tumors were staged preoperatively before and/or after M-VEC poly-chemotherapy using transrectal ultrasonography and magnetic resonance imaging in 46 patients. The resultant findings were each compared with histomorphologic results. The sensitivity of both methods compared with pathohistology was 88%. Using this technique, the degree of tumor invasion of the bladder wall could be evaluated and the appropriate therapy selected. Further applications included the monitoring of transurethral resection determine its adequacy as a treatment modality.

Adenocarcinoma↗
PubMed1993

Computer-assisted analysis of motility, velocity and linearity of dog spermatozoa.

Two different computer systems were tested for the analysis of motility parameters of dog semen. First, the Cellsoft computer videomicrography system was adapted to the morphological and motility traits of dog semen. The computer-calculated motility (percentage of progressively motile spermatozoa) was significantly correlated with the estimated motility (r = 0.97, P < 0.001), as was the sperm concentration determined by counting chamber and by computer (r = 0.62, P < 0.001). Mean velocity varied from 61.1 to 102.0 microns s-1. Irrespective of a low or high motility, the linearity varied from 5.9 +/- 3.5 to 7.6 +/- 0.9. Second, in an investigation into suitability of different concentrations (4, 6 and 8%) of glycerol for freezing dog semen diluted with a Tris-egg-yolk extender, the Strömberg-Mika Cell Motion Analyser was used. Particles identified as spermatozoa ranged in size from 35 to 350 pixels. The mean computer-calculated motility was 93.1 +/- 2.9% in the diluted semen without glycerol; 10 min after adding glycerol it was 88.0 +/- 3.8% with 4% glycerol, 83.7 +/- 4.9% with 6% glycerol, and 78.6 +/- 6.3% with 8% glycerol. Significant correlations were found between the estimated and the computer-analysed motility for the fresh diluted semen (P < 0.01) and for the thawed semen, irrespective of the glycerol concentration (P < 0.001). The mean velocity was 159.3 +/- 13.8 microns s-1 before adding glycerol, showing a decreasing tendency thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Intracerebral gliofibroma].

A 14-month-old girl had three epileptiform attacks in the course of 6 months, each consisting of rhythmic movements of the right arm and right hand of 5 minutes' duration, followed by a 15-minute period of weakness. There were otherwise no abnormal neurological signs. Prenatal and perinatal development had been uneventful and the mother was healthy. Computed tomography showed a tumour in the left frontoparietal region. Surgery revealed an intracerebral tumour 7 cm in diameter with two large cysts; it was not sharply demarcated from the brain parenchyma, had no connection with the dura and was not infiltrating the ventricular system. The tumour was completely removed and at follow-up 18 months later there was no evidence of recurrence. Histological and immunohistochemical investigations showed that the tumour consisted of closely interwoven astrocytes and fibroblasts, two different cell types the latter of which does not normally occur in the brain. Exact immunohistochemical analysis of the components of a tumour is important because, unlike pure glial tumours, gliofibromas have a good prognosis after complete resections.

Brain↗
PubMed1992

Biochemical and biological studies on 2-desamino-2-methylaminopterin, an antifolate the polyglutamates of which are more potent than the monoglutamate against three key enzymes of folate metabolism.

Biochemical and biological studies have been carried out with 2-desamino-2-methylaminopterin (dmAMT), which inhibits tumor cell growth in culture but is only a weak inhibitor of dihydrofolate reductase (DHFR). Since it was possible that the species responsible for growth inhibition are polyglutamylated metabolites, the di-, tri-, and tetraglutamates of dmAMT were synthesized and tested as inhibitors of purified recombinant human DHFR, murine L1210 leukemia thymidylate synthase (TS), chicken liver glycinamide ribonucleotide formyltransferase (GARFT), and murine L1210 leukemia aminoimidazolecarboxamide ribonucleotide formyltransferase (AICARFT). The compounds with three and four gamma-glutamyl residues were found to bind two orders of magnitude better than dmAMT itself to DHFR, TS, and AICARFT, with 50% inhibitory concentration values in the 200 to 300 nM range against all three enzymes. In contrast, at a concentration of 10 microM, dmAMT polyglutamates had no appreciable effect on GARFT activity. These findings support the hypothesis that dmAMT requires intracellular polyglutamylation for activity and indicate that replacement of the 2-amino group by 2-methyl is as acceptable a structural modification in antifolates targeted against DHFR as it is in antifolates targeted against TS. In growth assays against methotrexate (MTX)-sensitive H35 rat hepatoma cells and MTX-resistant H35 sublines with a transport defect, dmAMT was highly cross-resistant with MTX, but not with the TS inhibitors N10-propargyl-5,8-dideazafolic acid and N-(5-[N-(3,4-dihydro-2-methyl-4-ox-oquinazolin-6-yl)-N- methylamino]thenoyl)-L-glutamic acid, implicating DHFR rather than TS as the principal target for dmAMT polyglutamates in intact cells. On the other hand, an H35 subline resistant to 2'-deoxy-5-fluorouridine by virtue of increased TS activity was highly cross-resistant to N10-propargyl-5,8-dideazafolic acid and not cross-resistant to MTX, but showed partial cross-resistance to dmAMT. Both thymidine and hypoxanthine were required to protect H35 cells treated with concentrations of dmAMT and MTX that inhibited growth by greater than 90% relative to unprotected controls. In contrast, N10-propargyl-5,8-dideazafolic acid and N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-yl)-N-methylamino] thenoyl)- L-glutamic acid required only thymidine for protection. Like MTX, therefore, dmAMT appears to inhibit purine as well as pyrimidine de novo synthesis, and its effect on cell growth probably reflects the ability of dmAMT polyglutamates to not only block dihydrofolate reduction but also interfere with other steps of folate metabolism, either directly or indirectly via alteration of reduced folate pools.(ABSTRACT TRUNCATED AT 400 WORDS)

Acyltransferases↗
PubMed1992

[Herpes simplex-associated exacerbation of Crohn's disease. Successful treatment with acyclovir].

Seven years ago, a now 25-year-old man was found to have Crohn's disease of the terminal ileum as well as of the transverse and sigmoid colon. Despite treatment with both corticosteroids and mesalazine the disease progressed and led to almost complete stenosis of the lumen of the sigmoid colon so that surgical intervention was planned. But because immunohistological examination of the small and large intestinal mucosa had demonstrated herpes simplex virus (HSV I + II) DNA, additional treatment with acyclovir appeared worth-while. The morphological and clinical findings indeed changed decisively, obviating surgery. If a virus infection is found to be a pathogenetic co-factor in a case of Crohn's disease, a therapeutic trial with a suitable antiviral agent seems reasonable.

Acyclovir↗
PubMed1991

Analogues of methotrexate and aminopterin with gamma-methylene and gamma-cyano substitution of the glutamate side chain: synthesis and in vitro biological activity.

Analogues of methotrexate (MTX) and aminopterin (AMT) modified at the gamma-position of the glutamate side chain were synthesized and evaluated as dihydrofolate reductase (DHFR) inhibitors and tumor cell growth inhibitors. Condesations of 4-amino-4-deoxy-N10-methylpteroic acid (mAPA) with dimethyl DL-4-methyleneglutamate in the presence of diethyl phosphorocyanidate (DEPC) followed by alkaline hydrolysis yielded N-(4-amino-4-deoxy-N10-methylpteroyl)-DL-4-methyleneglutamic acid (gamma-methyleneMTX). Condensation of 4-amino-4-deoxy-N10-formylpteroic acid (fAPA) with dimethyl-DL-4-methyleneglutamate by the mixed carboxylic-carbonic anhydride method yielded N-4-amino-4-deoxypteroyl)-DL-4-methyleneglutamic acid (gamma-methyleneAMT). Also prepared via DEPC coupling was a mixture of the four possible diastereomers of N-(4-amino-4-deoxy-N10-methylpteroyl)-4-cyanoglutamic acid (gamma-cyanoMTX). The requisite intermediate gamma-tert-butyl alpha-methyl 4-cyanoglutamate, as a DL-threo/DL-erythro mixture, was prepared from methyl N alpha-Boc-O-tosyl-L-serinate by reaction with sodium tert-butyl cyanoacetate followed by mild trifluoroacetic treatment to selectively remove the Boc group. The gamma-methylene derivatives of MTX and AMT are attractive because of their potential to act as Michael acceptors within the DHFR active site. gamma-CyanoMTX may be viewed as a congener of the nonpolyglutamated MTX analogue gamma-fluoroMTX. In vitro bioassay data for the gamma-methylene and gamma-cyano compounds support the idea that the active site of DHFR, already known for its ability to tolerate modification of the gamma-carboxyl group of MTX and AMT, can likewise accommodate substitution on the gamma-carbon itself.

Aminopterin↗
PubMed1991

Synthesis and biological activity of methotrexate analogues with two acid groups and a hydrophobic aromatic ring in the side chain.

The heretofore unknown gamma-(m-carboxyanilide) and gamma-(m-boronoanillide) derivatives of methotrexate (MTX) and the gamma-(m-carboxyanilide) derivatives of aminopterin (AMT) were prepared and tested as inhibitors of dihydrofolate reductase (DHFR) and as inhibitors of cell growth in culture with the aim of comparing their activity with that of N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine, a potent antifolate whose side chain likewise contains a hydrophobic aromatic ring with an acid group on the ring. All three anilides were potent DHFR inhibitors, with activity comparable to MTX and AMT. The gamma-(m-boronoanilide) displayed growth inhibitory potency similar to that of the hemiphthaloylornithine analogue, with an IC50 of only 0.7 nM. This compound, which is the most potent of the gamma-amides of MTX tested to date, is also the first reported example of an antifolate with a B(OH)2 group in the side chain and is especially novel because of its potential to form a stable tetrahedral boronate complex by reaction with electron rich OH or NH2 groups in the active site of DHFR or other folate enzymes. In antitumor assays against L1210 leukemia in mice, N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine gave a T/C of greater than 263% at 20 mg/kg (qdx9) and 300% at 16 mg/kg (bidx10), whereas maximally tolerated doses of MTX of 8 mg/kg (qdx9) and 1 mg/kg (bidx10) gave T/C values of 213 and 188%, respectively. MTX gamma-(m-boronoanilide) was also active, with a T/C of 175% at 32 mg/kg (qdx9), the highest dose tested.

Aminopterin↗
PubMed1991

Synthesis and in vitro biological activity of new deaza analogues of folic acid, aminopterin, and methotrexate with an L-ornithine side chain.

The 5-deaza and 5,8-dideaza analogues of N alpha-pteroyl-L-ornithine (Pter-Orn), the 5-deaza, 8-deaza, and 5,8-dideaza analogues of N alpha-(4-amino-4-deoxypteroyl)-L-ornithine (APA-Orn), and the N delta-carboxymethyl derivative of N alpha-(4-amino-4-deoxy-N10-methylpteroyl)-L-ornithine (mAPA-Orn) were synthesized and tested as inhibitors of dihydrofolate reductase (DHFR) and as inhibitors of tumor cell growth in culture. Reductive amination of 2-acetamido-6-formylpyrido[2,3-d]pyrimidine-4(3H)-one with methyl N alpha-(4-aminobenzoyl)-N delta-(benzyloxycarbonyl)-L-ornithinate followed by removal of the blocking groups afforded the 5-deaza analogue of Pter-Orn, whereas N-alkylation of methyl N alpha-(4-aminobenzoyl)-N delta-(benzyloxycarbonyl)-L-ornithinate with 2-amino-6-(bromomethyl)quinazolin-4(3H)-one and deprotection gave the corresponding 5,8-dideaza analogue. Reductive coupling of 2,4-diaminopyrido[2,3-d]pyrimidine-6-carbonitrile and 4-aminobenzoic acid followed by reaction with 95-97% formic acid yielded 4-amino-4-deoxy-5-deaza-N10-formylpteroic acid, which on condensation with methyl N delta-(benzyloxycarbonyl)-L-ornithinate and deprotection gave the 5-deaza analogue of APA-Orn. A similar sequence starting from 2,4-diamino-quinazoline-6-carbonitrile led to the corresponding 5,8-dideaza compound, whereas treatment of 2,4-diamino-pyrido[3,2-d]pyrimidine-6-methanol with phosphorus tribromide followed by condensation with methyl N alpha-(4-aminobenzoyl)-N delta-(benzyloxycarbonyl)-L-ornithinate and deprotection afforded the 8-deaza analogue. For the preparation of the N delta-carboxymethyl derivative of mAPA-Orn, N alpha-(benzyloxycarbonyl)-L-ornithine was subjected to N delta-monoalkylation with glyoxylic acid and sodium cyanoborohydride, followed by N delta-acylation with ethyl trifluoroacetate, N alpha-deprotection by hydrogenolysis, condensation with 4-amino-4-deoxy-N10-methylpteroic acid, and N delta-deprotection by gentle treatment with ammonia. The 2,4-diamino derivatives all inhibited the growth of tumor cells in culture, with IC50 values of 0.2-2 microM, and inhibited purified DHFR with IC50 values of 0.02-0.08 microM. Deletion of ring nitrogens and N delta-carboxymethylation both increased potency in the cell growth assay; however, the ornithine derivatives were less potent than aminopterin or methotrexate.

Aminopterin↗
PubMed1990

[Thymus hyperplasia in patients with malignant testicular tumors].

Follow-up serial computed tomographic scans of 124 patients treated for testicular cancer with either radiotherapy or retroperitoneal lymphadenectomy alone or in combination with chemotherapy were evaluated. Thymic enlargement occurred three to 20 months after initiation of treatment in 15 of the 124 patients. Thymic enlargement could histopathologically be demonstrated in seven patients as true hyperplasia. One of these seven patients however had evidence of metastatic disease with thymic infiltration by a malignant teratoma. Thus it may be impossible to distinguish benign thymus hyperplasia from tumor-infiltration on the basis of ct information alone and sternotomy may be required. No severe defect of cellular immunity could be found. There is no specific constellation of lymphocytic markers in peripheral blood which could indicate true thymic hyperplasia.

Adult↗
PubMed1990

[Effects of a metabolic endurance test developed for the constitution examination of young bulls on spermatologic and endocrine parameters].

The purpose of this study was to examine the influence of an eight day starvation period on semen characteristics and some endocrine parameters of young bulls. The experiments were performed with 18 bulls in two trials showing the following set-up: pre-treatment period (7 or 20 days), starvation period (8 days), realimentation period (3 days) and control period (64 days). During the pre-treatment period and the control period the bulls obtained a well-balanced food-ration, during the period of starvation only 2 kg straw daily. During the starvation period the bulls lost 6% of their bodyweight. No influence on general health could be noticed. The concentrations of testosterone, LH, bovine growth hormone, insulin and insulin-like growth factor decreased significantly during or after the period of starvation. There was no clear influence in volume, sperm density and total number of sperm due to the metabolic stress during the hunger period. The initial progressive motility of sperm was not affected. The percentage of morphological abnormal spermatozoa increased 45-55 days after the hunger period. Simultaneously the semen freezability was decreased. An influence on the acrosomal morphology of frozen/thawed spermatozoa could not be obtained. The concentration of fructose, citric acid and glycerylphosphorylcholine (GPC) of the seminal plasma was insignificantly influenced during the period of starvation. The realimentation caused a stimulating effect on the secretion mainly of GPC.

Animals↗
PubMed1989

The role of membrane bound sialic acid of rat mast cells in histamine release induced by compound 48/80 and derivatives as well as calcium.

Histamine release induced by compound 48/80 from rat mast cells is not dependent on extracellular Ca2+. Preincubation of mast cells with trypsin has only little effects on histamine release induced by this polycation. This work also demonstrates that histamine release induced by compound 48/80 and its analogues in the absence of extracellular Ca2+ depends on membrane bound sialic acid of the mast cell. Neuraminidase treatment of the cells in the presence of extracellular Ca2+ leads to histamine liberation. These findings suggest that sialic acid residues of the mast cell membrane constitute the site at which polycations exert their stimulatory actions of histamine liberation.

Animals↗