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Biomedical subjects

P Franke

Publications and source records attributed to P Franke.

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

Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma.

Twelve of 19 patients with myeloproliferative disorders showed a decrease of absence of the largest multimers of plasma von Willebrand factor (vWF) that correlated with elevated platelet counts but not with leukocyte counts. This suggested that platelets, rather than leukocytes, may be associated with the pathogenesis of the acquired vWF abnormality seen in these patients. To examine the hypothesis further, we studied 12 patients with reactive thrombocytosis after splenectomy. Increased platelet count (> 5 x 10(11)/L) after splenectomy was associated with vWF abnormalities indistinguishable from those detected in patients with myeloproliferative disorders. Accordingly, there was an inverse correlation between proportion of large vWF multimers and platelet, but not leukocyte, number: normalization of the platelet count was accompanied by restoration of a normal vWF multimeric pattern. These findings suggest that an increase in the number of platelets circulating in blood may favor the adsorption of larger vWF multimers onto the platelet membrane, resulting in their removal from the circulation and subsequent degradation.

Adult↗
PubMed1993

Evidence for a central cholinergic effect of high-dose thiamine.

In vitro animal studies have suggested that thiamine is involved in the presynaptic release of acetylcholine. Total thiamine content in cholinergic nerve terminals is comparable with that of acetylcholine, and the phosphorylation state of thiamine changes with release of acetylcholine. Thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity. Based on these observations, we investigated the effects of pharmacological doses of thiamine on the cognitive deficits induced by the anticholinergic scopolamine in healthy young adults using a randomized, double-blind, placebo-controlled, double-crossover design. Drug effects were assessed by P3 event-related potential, quantitated electroencephalography, and free recall memory. Conditions included (1) baseline, (2) thiamine 5 gm p.o. and scopolamine 0.007 mg/kg IM, and (3) lactose PO and scopolamine 0.007 mg/kg IM. Thiamine significantly reduced adverse effects of scopolamine on P3 latency, spectral components of electroencephalography, and memory recall. The results are consistent with a cholinomimetic effect of thiamine in the central nervous system. Additional studies are needed to delineate the basic mechanisms and possible therapeutic efficacy of thiamine at pharmacological dosages.

Adult↗
PubMed1993

A controlled family study in panic disorder.

There are only a few family studies in panic disorder. Although there is some evidence that panic disorder is familial, the exact figures of the familial risk for this disorder are at variance across different studies; the impact of comorbidity and of the gender of relatives is also unclear. Family studies in panic disorder controlling for the comorbidity in probands are therefore indicated. This study presents the morbid risks in families of 40 "pure" panic disorder probands (DSM-III-R) without a history of psychotic disorders, major depression or alcoholism compared with families of 80 controls recruited in the general population. The relative frequency of panic disorder (DSM-III-R) in the first-degree relatives of panic disorder probands was 5.7% (the age corrected morbid risk is 7.9%) compared to 1.8% in relatives of healthy controls (age corrected morbid risk 2.3%). Agoraphobia segregated predominantly among female relatives of agoraphobic probands. An increased familial risk of major depression and of alcoholism was also observed. Comorbidity with alcoholism and major affective disorders was excluded in panic disorder probands by definition; therefore, these findings indicate that the etiological factors underlying panic disorder may overlap with those of alcoholism and those of unipolar major depression.

Adult↗
PubMed1993

Concordance for gender in sib pairs affected with schizophrenia and related disorders.

An excess concordance by sex among siblings affected with schizophrenia has been proposed by some previous and recent investigators. However, this hypothesis has not been supported by some recent studies having complete ascertainment of probands and relatives. The present report is based on sibships with multiple affected members derived from a family study of systematically recruited inpatients (146 probands with schizophrenia and 132 probands with other psychotic disorders). Evidence for an excess concordance rate for gender among proband-sibling pairs with both members affected is suggested under a broad definition of illness.

Adult↗
PubMed1993

Cognitive functioning and anhedonia in subjects at risk for schizophrenia.

This study investigated the performance of individuals with familiar loading of schizophrenia (healthy siblings of schizophrenic inpatients) on three neuropsychological tasks assumed to require frontal lobe functions: Trail Making Test (TMT), verbal fluency and Wisconsin Card Sorting Test (WCST). Healthy siblings of schizophrenics differed in performance from healthy controls not only on the WCST, but also on the Trail Making Test and the verbal fluency task. Furthermore, scores of physical anhedonia, assessed in a self-report rating scale (Chapman et al., 1976) were also significantly higher in the high risk group than in the control sample. However, healthy siblings of schizophrenics did not differ from controls with regard to experiences of perceptual aberrations, measured by the same method (Chapman et al., 1978). Neuropsychological performance and elevated anhedonia scores in the high risk group were interpreted under the conceptual framework of vulnerability markers: they were supposed to represent a trait shared by family members of schizophrenic probands. Amongst the neuropsychological tests, there were significant correlations between the physical anhedonia score and WCST and Trail Making test performance in the group of healthy siblings of schizophrenics, but not in the control group.

Adult↗
PubMed1993

Positive/negative symptomatology and experimental measures of attention in schizophrenic patients.

In a search for an external validation of the negative syndrome construct and the attentional impairment item on Andreasen's scale, 49 unmedicated schizophrenic patients were administered the Span of Apprehension Test and a Continuous Performance Test with two levels of difficulty. This schizophrenic sample performed significantly more poorly on the attentional tests than a comparable group of 27 healthy control subjects. Depending on the difficulty of the test we found a number of significant correlations between the SANS composite score and the pertaining attentional impairment item on the one hand and experimental indices of attentional functioning on the other hand, which might corroborate the psychopathological assumptions. The implications of these results for further attempts to validate clinical concepts of the positive/negative dichotomy by experimental means will be discussed.

Adolescent↗
PubMed1993

Assessment of frontal lobe functioning in schizophrenia and unipolar major depression.

This study has used neuropsychological tasks--Wisconsin Card Sort (WCST), Trail Making (TMT) A and B, Verbal Fluency, Digit Span--to compare acute and currently off-medication schizophrenics, patients with unipolar nonpsychotic major depression and healthy controls. Both patient groups differed significantly from healthy controls in their neuropsychological performance. Furthermore there was only little (quantitative) difference between schizophrenics and depressed patients in the frontal lobe associated tasks: WCST, TMT and Verbal Fluency. Depressed patients tended to perform worse than schizophrenics on Digit Span, a task hypothesized to involve other than frontal areas of the brain. Although the group of depressed patients was older than the schizophrenic sample, the effect of age may not totally explain the findings. The results indicate that there do exist disturbances in frontal lobe cognitive functioning in schizophrenia and depression. Symptomatology (SANS/SAPS) and cognitive functioning in the schizophrenic group revealed only a trend for negative symptoms to be associated with worse performance in the WCST, but were significantly correlated with negative as well as positive symptoms on the TMT.

Adult↗
PubMed1993

N-terminal modification and amino-acid sequence of the ribosomal protein HmaS7 from Haloarcula marismortui and homology studies to other ribosomal proteins.

The ribosomal protein HmaS7 from the 30S subunit of the extreme halophilic archaeum Haloarcula marismortui was isolated by semi-preparative RP-HPLC. The complete amino-acid sequence of this protein was determined by automated microsequence analysis of appropriate peptide fragments from several proteinase digests. The entire protein consists of 205 amino acids with a corresponding molecular mass of 22580 Da. The modification at the amino-terminal amino acid was deblocked so that the N-terminal amino acids could be sequenced and the type of the modification was identified as an acetyl group by electrospray mass spectrometry of suitable peptides. Homology studies of HmaS7 showed similarities to ribosomal proteins derived from organisms of all three urkingdoms, such as to EcoS7, HmoS7, MvaS7, SacS7 and RatS7; due to the strong sequence homologies found within the archaebacterial ribosomal proteins we conclude that the protein sequence which was determined for S7 from Methanococcus vannielii by nucleotide sequencing of the gene should be about 20 or 30 amino acids longer than previously published (Lechner, K., Heller, G. & Böck, A. (1989) J. Mol. Evol. 29, 20-27).

Amino Acid Sequence↗
PubMed1993

[The biotransformation of the anticonvulsant 4-p-chlorophenylpyrrol-3-morpholino-2-carboxylic acid methyl ester (AWD 140-076)].

4-p-Chlorphenylpyrrole-3-morpholino-2-carboxylic acid methylester (1; AWD 140-076) is a substance with anticonvulsive properties. After p.o. administration in male wistar rats many metabolites in relatively small concentration are excreted in urine and faeces, six of them could be isolated and identified as quantitative dominating compounds. Compound 1 is attacked in different sites of the molecule by the cytochrome P-450 system. At the morphine ring N- and O-dealkylation reactions take place leading to the cleavage of the ring. After that a stepwise degradation by oxidative and reductive processes occurs. Further reactions concern the N-oxidation of the morpholine nitrogen as well as the hydroxylation of the pyrrole skeleton forming the main metabolites. 5 metabolites are also present as sulfate or glucuronide conjugates. The quantity ratio of the phase I to phase II metabolites amounts to 9:1. In the in vitro test system isolated perfused rat liver and rat hepatocytes culture solely the two main metabolites are formed. Compound 1 is characterized by enzyme inducing activities. The oxidative demethylation of p-nitroanisole is increased 4-fold after pretreatment.

Animals↗
PubMed1993

[Biotransformation and excretion of Z-2-amino-5-chlorobenzophenoneamidinohydrazone].

After i.v., p.o. and i.p. administration of 14C-labeled Z-2-amino-5-chlorobenzophenoneamidinohydrazone (1) to male Wistar rats the total radioactivity is mainly excreted via faeces (80%). Within 3 to 4 d after administration 86 to 100% of the dose have been found in urine and faeces. Beside 1 and its E-isomer (2) we have detected in faeces of rats and rabbits the metabolites 3 (principal metabolite) and 4, in urine of rats additionally 5 and 6, and in urine of rabbits additionally 5 to 8. With regard to the results of high resolution mass spectrometry, UV, TLC and the hydrolyzability using beta-glucuronidase we can conclude that 3 and 4 are metabolites position isomerically hydroxylated at the unsubstituted phenyl group, 5 and 6 are the glucuronides of them, and 7 and 8 are the glucuronides of 1 and 2.

Administration, Oral↗
PubMed1992

Neuropsychological indicators of the vulnerability to schizophrenia.

Schizophrenia is associated with enduring deficits in neuropsychological functioning. It is widely undecided if the various aspects of neuropsychological impairment are a consequence of the disorder or if they are also present premorbidly and in populations at increased risk for schizophrenia (vulnerability markers). Neuropsychological deficits in healthy relatives of schizophrenic patients who are at an elevated risk for schizophrenia and who did not yet pass the period of risk would indicate that these deficits are vulnerability markers. This hypothesis was tested for three neuropsychological paradigms which have been proven to distinguish schizophrenic patients from controls. 33 siblings of drug-free schizophrenic probands revealed deficits has compared to 33 matched healthy controls in a blurred single target version of the Continuous Performance Test and in a multiple item version of the Span of Apprehension Test but not so in less difficult versions of both tests or in the time needed to react to stimuli with shifting modality.

Adult↗
PubMed1992

Wisconsin Card Sorting Test: an indicator of vulnerability to schizophrenia?

The Wisconsin Card Sorting Test (WCST) is a neuropsychological test, hypothesized to be an indicator of dorsolateral prefrontal cortex (DLPFC) functioning. The performance of schizophrenic patients in our sample (off medication) was worse than the performance of healthy controls in all variables of the WCST, including perseverative responses (PR) as well as non-perseverative responses (NPR). The rate of perseverative and non-perseverative responses was neither a function of the severity of the illness (measured by SANS/SAPS scales) nor the duration of the disease. Healthy siblings of schizophrenic probands revealed more perseverative responses than healthy controls, but did not show any difference with respect to the non-perseverative responses. This finding suggests that the difficulty to shift a cognitive set, reflected by the frequency of perseverative responses, is in favor of the WCST as a vulnerability marker for schizophrenia, whereas non-perseverative responses presumably indicate a state, but not a trait marker of the disease. However, the usefulness of this indicator may be limited by its association with age, which is worthy of being studied in closer detail.

Adult↗
PubMed1991

The reliability of the SADS-LA in a family study setting.

The joint-rater and test-retest reliability study of two translated versions of the SADS-LA (Schedule for Affective Disorders and Schizophrenia--Lifetime version--modified for the study of anxiety disorders), one in French and the other in German, have been tested in family study settings, in a sample of patients and first-degree relatives. The test-retest reliability study demonstrated that identification of major affective disorders and schizophrenia was performed with sufficient reliability; however, diagnoses of subtypes of major disorders (e.g. bipolar II disorder) and identification of minor disorders was less reliable. The implications of these findings in phenotype identification during family studies in psychiatry are discussed.

Adult↗
PubMed1990

[Biotransformation and pharmacokinetics of AWD 26-06, 8-chloro-5,10-dihydro-5-[bis(2-hydroxyethyl)aminoacetyl]-11H-dibenzo[d, c][1,4]diazepin-11-one hydrochloride in the rat].

After p.o. administration to rats AWD 26-06 (1) is rapidly but incompletely absorbed. The relatively short distribution (t1/2 alpha = 37 min) is followed by a middle-long elimination (t1/2 beta = 14 h). The volumen of distribution do not suggest an uncommon accumulation in deep compartments. About 70% of 1 were excreted unchanged with the feces. In urine and feces 18 metabolites were identified. The structure of 10 products could be elucidated. All metabolites have changed side-chains. Furthermore, the tricyclic molecule without side-chain and a N-methyl derivative were identified. The metabolites with so far unknown structure contain the unsubstituted tricyclic moiety too.

Animals↗
PubMed1990

[Biotransformation of the trapidil (rocornal) derivative AR 12463 in the rat].

After p.o. administration of 5-piperidino-7-[N-pentyl-N-(beta- hydroxyethyl)]amino-s-triazolo[1,5-a]pyrimidine (1; AR 12463) more than 15 metabolites were isolated from urine and feces of male Wistar rats. Only small amounts of unchanged 1 were observed. The structure of 12 metabolites was elucidated or proposed on the basis of UV-, 13C NMR- and mass spectra. Main metabolites are 5-piperidin-4'-olyl-7-[N-pentyl-N-(beta- hydroxyethyl)]amino-s-triazolo[1,5-a]pyrimidine and 5-piperidin-4'-olyl-7-[N-pent-4-olyl-N-(beta-hydroxyet hyl)]amino-s- triazolo[1,5-a]pyrimidine. The other metabolites are mainly hydroxy- or ketopentyl derivatives and piperidinoles or piperidinones, respectively. Conjugates of most of the metabolites were identified, but the ratio phase-I/II metabolites was about 3:1. In contrast to trapidil, 5-methyl-7-diethylamino-s- triazolo[1,5-a]pyrimidine, no hydroxy derivatives of the bicyclic system were observed. The major part of unchanged 1 and metabolites is excreted via kidneys.

Adsorption↗
PubMed1990

[Biotransformation and excretion of N,N'-bis(3-(2-ethoxyphenoxy)-2-hydroxypropyl)ethylenediamine dihydrochloride (Falirytmin) in rats].

Falirytmin (1) was metabolized in rats almost completely. Besides small amounts of 1 in urine and feces 18 metabolites could be separated. The proposed structures of 14 compounds demonstrate aromatic hydroxylation, N- and O-dealkylation, side-chain oxidation, alcohol dehydrogenation and N-acetylation. The main route of excretion of 1 and metabolites was with the feces. After p.o. or i.v. administration of 14C-O-ethyl-1 the average excretion of radioactivity in urine, feces and expired air was about 75% in 96 h. The residual activity in organs was about 2-2.5%. Whole-body autoradiography confirms these results. Only slight 14C-activity was seen in muscle, fat, liver, bone marrow and gut.

Animals↗
PubMed1989

[Biotransformation of phenolglycosides leiocarposide and salicin].

Leiocarposide (1; 3-beta-D-glucopyranosyloxy-2-methoxy-6-hydroxy-benzoic acid -2'-beta-D-glucopyranosyloxybenzyl ester) is a phenolic glycoside from Solidago virgaurea L. After oral administration to rats it will be only poorly absorbed and mostly unchanged fecaly excreted. In the urine were found less than 10% as metabolites: leiocarpic acid (3; 3,6-dihydroxy-2-methoxy-benzoic acid, 2% of the administered dose), 3-conjugates (2%), salicylic acid (5; 0.5%), 5-conjugates (0.1%) and salicyluric acid (6; 0.5%). On the other hand salicin (2), structural part of 1, is good absorbed. In the urine were excreted 15% of the unchanged drug and the following metabolites: 0.1% saligenin (4), 30% 5, 5% 5-conjugates, 0.1% 6, 2% gentisic acid (7) and 0.1% 2,3-dihydroxy-benzoic acid (8). The different metabolic rates are explicable by the high stability of the ester bond of 1. It is hydrolyzed in artificial intestinal fluid only very slowly (t1/2 = 41.7 h).

Animals↗