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Biomedical subjects

J Wagner

Publications and source records attributed to J Wagner.

At least 379 records · Page 21Linked to original sources

Segregation patterns and phenotypes of unbalanced offspring in a large family with (10;18) chromosome translocation.

We describe a large family in whom a balanced 10;18 chromosome translocation is segregating through five generations. Six severely mentally retarded relatives and an abnormal fetus further define the phenotypic expression of dup (18q21----qter). Other segregants detected prenatally included a fetus with deletion 18q21----qter and two fetuses with dup(18pter----q21) owing to tertiary trisomy. One of the latter also had an extra X chromosome; this might be another example of possible nonhomologous pairing in man.

Chromosome Aberrations↗

Treatment of portal vein obstruction by percutaneous transhepatic angioplasty.

A case of extrahepatic portal hypertension and gastric variceal bleeding due to portal vein occlusion, most probably secondary to chronic pancreatitis, was treated by percutaneous transhepatic angioplasty. After the portal angioplasty there was marked clinical improvement, with control of the variceal bleeding and significant reduction of the pressure gradient within the portal system.

Angioplasty, Balloon↗

Listeria meningitis: report of ten recent cases and review of current therapeutic recommendations.

Ten cases of meningitis due to Listeria monocytogenes were admitted to three hospitals in Berlin between 1978 and 1983. One patient was a premature infant in whom meningitis was diagnosed as part of typical granulomatosis infantiseptica. Another presented with signs of brainstem encephalitis which was confirmed post mortem. Positive blood cultures were obtained from five of the patients. Two strains of listeria were resistant and one was only moderately sensitive to penicillin. The three most recently isolated strains were tested for sensitivity to the third generation cephalosporins. All were resistant to latamoxef, and two were resistant to cefotaxime. The implications of these findings for the empirical treatment of purulent meningitis are discussed.

Adult↗

[Diagnostic conization in clinical cervix cancer].

Various methods of tissue sampling are used to verify histologically a clinical carcinoma of the cervix. The question arises whether or not diagnostic cone biopsy has any influence on the treatment and/or the clinical course of this disease. The clinical and histological data and the follow-up of 185 patients with squamous cell carcinoma of the cervix were statistically evaluated. We found no difference between patients with or without cone biopsy in respect of complications, frequency of metastases or recurrences, and survival. However, our deliberations permit the following statement: cone biopsy is an appropriate method to diagnose cervical intraepithelial neoplasia (CIN) or microcarcinoma of the cervix and may--under certain conditions--even be the adequate therapy. However, cone biopsy lacks any advantage over other diagnostic methods if it is employed merely for the purpose of histological verification of clinical carcinoma of the cervix.

Adult↗

Inhibition of monoamine oxidase selectively in brain monoamine nerves using the bioprecursor (E)-beta-fluoromethylene-m-tyrosine (MDL 72394), a substrate for aromatic L-amino acid decarboxylase.

(E)-beta-Fluoromethylene-m-tyrosine (FMMT) is a dual-enzyme-activated inhibitor of monoamine oxidase (MAO). The compound is not an inhibitor per se but is decarboxylated by aromatic L-amino acid decarboxylase (AADC) to yield a potent enzyme-activated irreversible inhibitor of MAO, (E)-beta-fluoromethylene-m-tyramine, which shows some selectivity for inhibition of MAO type A. Decarboxylation of FMMT was demonstrated in vitro using hog kidney AADC and in vivo in rats by the ability of alpha-monofluoromethyldopa (MFMD), a potent inhibitor of AADC, to prevent MAO inhibition produced by FMMT. In isolated synaptosomes, FMMT was decarboxylated by AADC, and, furthermore, the compound was actively transported into these isolated nerve endings. An active transport into the CNS has also been demonstrated in vivo by performing competition experiments with leucine. To demonstrate that FMMT is preferentially decarboxylated within monoamine nerves of the CNS, the nigrostriatal 3,4-dihydroxyphenylethylamine (dopamine) pathway of rats was unilaterally lesioned with 6-hydroxydopamine or infused with MFMD. Under these conditions, MAO inhibition produced by orally administered FMMT in the striatum ipsilateral to the lesion or infusion was markedly attenuated. Combination of FMMT with an inhibitor of extracerebral AADC, such as carbidopa, protected peripheral organs against the MAO inhibitory effects and concomitantly enhanced MAO inhibition in the CNS. Such combinations had a greatly reduced propensity to augment the cardiovascular effects of intraduodenally administered tyramine, when compared with FMMT given alone or with clorgyline, a selective inhibitor of MAO type A. The results obtained with FMMT suggest the possibility of achieving selective inhibition of MAO within monoamine nerves of the CNS and, further, suggest that combination of FMMT with an inhibitor of extracerebral AADC will reduce the propensity of this inhibitor to produce adverse interactions with tyramine.

Animals↗

Pilot study of fluzinamide (N-methyl-3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide) in refractory partial seizures.

We conducted a pilot study of fluzinamide in 15 adults with refractory partial seizures. After a baseline period, fluzinamide was added to the existing regimen of phenytoin and carbamazepine and increased to maximum tolerated dose. Common side effects included dizziness, diplopia, ataxia, headache, nausea, and rash, resulting in patient withdrawal in six cases. Seizures became less frequent in four of the nine patients who completed the 8-week trial.

Adolescent↗

[Qualitative and quantitative detection of bacterial flora in experimental blind loop syndrome of the rat].

In the blind loop syndrome bacterial overgrowth--accompanied by an increase in bile acid deconjugation--is thought to be responsible for the observed morphological alterations of the small intestinal mucosa with its concomitant malabsorption syndrome. Since in this chain of events the bacterial overgrowth is of primary importance, we have performed a complete qualitative and quantitative evaluation of the intraluminal flora in rats with surgically created self-filling blind loops. The results show a significant increase in bacteria of the aerobic growing genera E. coli and Streptococcus (Enterococcus), and of the anaerobic growing genus Bacteroides, in one single rat also of the genera Lactobacillus/Bifidobacterium. In order to elucidate which strains of bacteria are predominantly responsible for the morphological and functional alterations observed in the stagnant loop syndrome, germ-free rats with self-filling blind loops should be contaminated selectively with bacteria of these genera.

Animals↗

High-performance liquid chromatographic analysis of S-adenosylmethionine and its metabolites in rat tissues: interrelationship with changes in biogenic catechol levels following treatment with L-dopa.

A method is described for the simultaneous analysis of S-adenosylmethionine (SAM) and its metabolites, S-adenosylhomocysteine (SAH) and decarboxylated S-adenosylmethionine along with the natural polyamines, putrescine, spermidine and spermine. The separation is obtained by a reversed-phase ion-pair liquid chromatographic procedure with gradient elution followed by dual detection. The UV absorbance at 254 nm is used for the analysis of SAM and of the SAM metabolites, whereas the polyamines and some major amino acids, e.g., methionine, tyrosine and tryptophan, are analyzed by fluorescence detection after UV-cell derivatization with o-phthalaldehyde. A separate ion-pair reversed-phase high-performance liquid chromatographic (HPLC) procedure using isocratic elution and electrochemical detection is employed to analyse in the same tissue extracts the catechols and 5-hydroxyindoles, 3,4-dihydroxyphenylalanine (DOPA), dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 4-hydroxy-3- methoxyphenylalanine , tryptophan, 5-hydroxytryptophan, serotonin and 5- hydroxyindolacetic acid. The sample preparation for the two HPLC procedures requires only homogenization of the tissues in perchloric acid and centrifugation before injection onto the column. The two chromatographic procedures have been applied to study the interrelationship, in various tissues of rats, between the SAM and SAH levels and the biogenic catechols after different treatments with L-DOPA alone or in combination with alpha- monofluoromethyl -DOPA, a potent enzyme-activated irreversible inhibitor of aromatic L-amino acid decarboxylase.

Adrenal Glands↗

A rapid high-performance liquid chromatographic procedure for the simultaneous determination of methionine, ethionine, S-adenosylmethionine, S-adenosylethionine, and the natural polyamines in rat tissues.

A method for the analysis of S-adenosyl-L-methionine (SAM) and S-adenosyl-L-ethionine (SAE) and their major metabolites by high-performance liquid chromatography is described. The procedure allows the simultaneous analysis of the natural polyamines, putrescine, spermidine, and spermine, and some of the major amino acids, methionine, tyrosine, and tryptophan. The uv absorbance at 254 nm is used for the determination of the SAM and SAE analogs, whereas the polyamines and amino acids are analyzed by fluorescence detection after postcolumn derivatization with o-phthalaldehyde. The method allows SAM and polyamine determinations by direct injection of the tissue extracts without prepurification. The procedure is applied to study the effects of DL-ethionine treatment on the SAM, SAE, methionine, and polyamine levels in various tissues of rats.

Adenosine↗

A method for measuring monoamine turnover in animals using an irreversible inhibitor of aromatic L-amino acid decarboxylase, DL-alpha-mono fluoromethyldopa.

DL-alpha-monofluoromethyldopa (MFMD) is a potent enzyme-activated irreversible inhibitor of aromatic L-amino acid decarboxylase which, when given to rats or mice at 100 and 250 mg/kg i.p., respectively, causes a linear accumulation of L-DOPA and 5HTP and an exponential decline of noradrenaline, dopamine, and 5HT concentrations in the brain. Rates of change of these parameters can be used to calculate the turnover of the three principle monoamine neurotransmitters. Experiments with haloperidol (1 mg/kg s.c.) and the central 5HT agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (0.25 mg/kg s.c.), have been performed to validate the use of MFMD to measure monoamine turnover. MFMD has several advantages over classical methods for the determination of comparative turnovers using enzyme inhibitors.

3,4-Dihydroxyphenylacetic Acid↗