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Biomedical subjects

A Fritz

Publications and source records attributed to A Fritz.

At least 19 recordsLinked to original sources

The axonally secreted cell adhesion molecule, axonin-1. Primary structure, immunoglobulin-like and fibronectin-type-III-like domains and glycosyl-phosphatidylinositol anchorage.

Axonin-1 is an axon-associated cell adhesion molecule (AxCAM) of the chicken, which promotes neurite outgrowth by interaction with the AxCAM L1(G4) of the neuritic membrane. Here we report the cloning and sequence determination of a cDNA encoding axonin-1. Peptides generated by enzymatic cleavage showed similarity to the AxCAM F11. Degenerated polymerase chain reaction (PCR) primers were designed and an axonin-1 fragment was amplified from mRNA of embryonic retina. Screening of a cDNA library from embryonic brain resulted in the isolation of a 4.0-kb cDNA insert with an open reading frame of 3108 nucleotides. The deduced polypeptide of 1036 amino acids includes a putative hydrophobic N-terminal signal sequence of 23 or 25 amino acids and a C-terminal hydrophobic sequence of 29 amino acids which is suggestive of sequences serving as signal for the attachment of a glycosyl-phosphatidylinositol (glycosyl-PtdIns) anchor. The putative mature form of axonin-1 comprises six immunoglobulin-like repeats, followed by four fibronectin-type III repeats. Axonin-1 exhibits 75% amino acid identity with the AxCAM TAG-1 of the rat, suggesting that it is the chicken homologue of TAG-1. Like TAG-1, axonin-1 is glycosyl-PtdIns-anchored to the neuronal membrane; in contrast to TAG-1, it does not exhibit an Arg-Gly-Asp sequence.

Amino Acid Sequence

Identification of two families of satellite-like repetitive DNA sequences from the zebrafish (Brachydanio rerio).

To further our understanding of the structure and organization of the zebrafish genome, we have undertaken the analysis of highly and middle-repetitive DNA sequences. We have cloned and sequenced two families of tandemly repeated DNA fragments. The monomer units of the Type I satellite-like sequence are 186 bp long, A+T-rich (65%), and exhibit a high degree of sequence conservation. The Type I satellite-like sequence constitutes 8% of the zebrafish genome, or approximately 8 x 10(5) copies per haploid genome. Southern analysis of genomic DNA, digested with several restriction endonucleases, shows a ladder of hybridizing bands, consistent with a tandem array, and suggests longer range periodic variations in the sequence of the tandem repeats. The Type II satellite has a monomer length of 165 bp, is also A+T-rich (68%), and constitutes 0.2% of the zebrafish genome (22,000 copies per haploid genome). Southern analysis reveals a complex pattern rather than a ladder of regularly spaced hybridizing bands.

Animals

[Prevalence and follow-up of psychiatric disorders in childhood and adolescence. Results of a prospective epidemiologic longitudinal study from ages 8-18 years].

In a prospective longitudinal epidemiological study with assessments at age 8, 13 and 18 the prevalence rate for psychiatric disorders remained constant at about 16%. The sex ratio for severe disorders was male dominated even in adolescence, which was a consequence of the high rate of unsocialized disturbances of conduct in boys. Persistence of psychiatric disorders between age 13 and 18 was about 50%, as had previously been the case between age 8 and 13. One child in four suffered from a psychiatric disorder for at least 10 years. In childhood, conduct disorders had a very poor prognosis and emotional disorders a very good one. In adolescence, the course of disorders depended on an interaction between diagnosis and gender. Boys with unsocialized disturbances and girls with emotional problems had a poor prognosis.

Adaptation, Psychological

[The growth modifying effect of wound ointments on cell cultures].

Ointments are often used for the treatment of wounds with impaired healing or for patients with severe burning. Therefore, some information about their pharmacological effects is necessary. This paper presents an in vitro model for testing the effects of ointments on an isolated cell type with the possibility of quantification. In this study fibroblasts of the human gums and 12 ointments available without prescription were used. To investigate the toxic effects, we examined the morphological changes and autoradiography. The results and their clinical implications are discussed.

Anti-Infective Agents, Local

[Problems of long-term therapy with anticoagulants].

Oral anticoagulants are highly effective for the prevention of recurrence of venous thromboembolism and of thromboembolic complications in rheumatic and non-rheumatic atrial fibrillation, dilated cardiomyopathy and in patients with prosthetic heart valves, but less effective for prevention of arterial thrombosis. Bleeding is the main side effect, the risk of fatal bleeding is 0.2 to 0.4% per year, depending on the intensity of treatment. The problem of the standardization of the prothrombin time determination has been solved by the introduction of the international normalized ratio. Recent studies have shown that a lesser degree of anticoagulation (INR 2.0 to 3.0) is sufficient to prevent venous thromboembolism and cardiac emboli. The measurement of activation markers of coagulation will probably allow a more rational monitoring in the near future.

Administration, Oral

[Coronary reperfusion by anistreplase (Eminase) used intravenously during the acute phase of myocardial infarction].

Coronary recanalisation rate is one of the parameters utilized to evaluate the effectiveness of a thrombolytic agent. This parameter can only be measured when the occlusion and reopening of the coronary artery involved are demonstrated by angiography. Moreover, this type of study enables the kinetics of drug activity to be accurately determined. When injected intravenously in doses of 30 units less than four hours after the onset of chest pain and when studied by this method, Eminase produces recanalisation in more than 60 per 100 of the cases. The time elapsed between injection and action is 45 minutes on average. The risk of early reocclusion is low (about 5%). The recanalisation rate obtained with Eminase is similar to that obtained with intracoronary streptokinase.

Anistreplase

Xenopus homeobox-containing cDNAs expressed in early development.

We report the isolation of six different homeobox-containing genes in Xenopus laevis which are expressed during early embryogenesis. cDNA clones of all of them were partially sequenced including two from previously isolated Xenopus genomic loci and found to contain homeodomains which share a high degree of homology with the Antennapedia protein (50 to 59 out of 60 amino acids). We find a short region of homology (consensus Ile Tyr Pro Trp Met) in four of the cDNAs, which is also present in Antennapedia and that may correspond to a bend region preceding the homeodomain. Northern blots have been performed to show the transcriptional pattern through early frog embryogenesis. Three of the genes are expressed only during a very narrow period of embryogenesis, reinforcing the view that homeobox genes are developmentally regulated.

Amino Acid Sequence

Differential utilization of the same reading frame in a Xenopus homeobox gene encodes two related proteins sharing the same DNA-binding specificity.

Xenopus XlHbox 1 produces two transcripts during early development. One encodes a long open reading frame (ORF) and the other a short ORF sharing the same homeodomain, but differing by an 82 amino acid domain at the amino terminus. The long protein amino terminus is conserved with many other homeodomain proteins, and its absence from the short protein could have functional consequences. Some viral genes also utilize a single ORF to encode transcription factors of antagonistic functions. The overall organization of the homologous genes in frog and man is similar, supporting the notion that both transcripts are of functional significance. Studies on XlHbox 1 function show that the region common to the long and short proteins has a sequence-specific DNA-binding activity, and that microinjection of specific antibodies into embryos results in the loss of structures derived from cells normally expressing XlHbox 1.

Amino Acid Sequence

A Xenopus laevis gene encodes both homeobox-containing and homeobox-less transcripts.

A cDNA clone (p52) that contains all the protein-coding region from the maternally expressed XlHbox 2 locus of the frog Xenopus laevis has been isolated and sequenced. A probe containing the exon preceding the homeobox detected transcripts which arise from a splicing event in which the homeobox-containing exon is replaced by another exon lying 5' to it in the genome. Both the homeobox-containing and homeobox-less splicing event occur in the same tissues, with the homeobox-less RNA representing the minority of mRNA from this gene. There may therefore be a function for two types of transcript, and hence protein, from this locus. This phenomenon may not be exclusive to the XlHbox 2 gene of Xenopus, but might occur more generally in other homeobox-containing genes. The protein deduced from the homeobox-containing cDNA is significantly similar to the yeast mating type factor a1 (MAT-a1) gene product. In addition to the previously described homology of the homeodomains, the amino-terminal domains of XlHbox 2 and MAT-a1 are similar to each other; thus essentially all of the MAT-a1 protein corresponds to some part of the XlHbox 2 protein. In the case of XlHbox 2, the protein coded for by the homeoboxless mRNA would contain all of the non-homeobox homology to yeast MAT-a1.

Amino Acid Sequence

A homeobox-containing marker of posterior neural differentiation shows the importance of predetermination in neural induction.

A homeobox sequence has been used to isolate a new Xenopus cDNA, named XIHbox6. A short probe from this gene serves as an early marker of posterior neural differentiation in the Xenopus nervous system. The gene recognized by this cDNA sequence is first transcribed at the late gastrula stage and solely in the posterior neural cells. The gene is expressed when ectodermal and mesodermal tissues of an early gastrula are placed in contact, but not by either tissue cultured on its own. However, gene expression is most easily inducible in ectoderm from the dorsal region, i.e., in ectoderm normally destined to form neural structures. This establishes the principle, in contrast to previous belief, that the induction of the embryonic nervous system involves a predisposition of the ectoderm and does not depend entirely on an interaction with inducing mesoderm.

Animals

Efficacy and safety of fezolamine in depressed patients.

Forty-two outpatients with major depressive disorder were treated with oral fezolamine in a 6-week, three-center open-label study. Therapy was initiated at 100 mg/day; thereafter dosage was increased based on the response of the patient. Maintenance dosage usually ranged between 100 and 450 mg/day. Clinically significant improvement relative to the patient's prestudy state was observed after 2 weeks in both patient and physician-rating scales. Fifty-five percent of patients improved their Hamilton Psychiatric Rating Scale for Depression (HAM-D) scores by more than 50%. The median dose associated with a clinically significant response was 245 mg/day. Five of the 6 patients who dropped out did so because of gastrointestinal adverse effects. The most common adverse effects were nausea (36%), headache (29%), constipation (26%), and dry mouth (24%).

Adult

[Diastolic coronary prolapse in partial left pericardial agenesis].

A few rare cases of coronary artery stenosis and occlusion have been reported in partial left pericardial agenesis. The authors report a privileged observation of partial left pericardial agenesis associated with an atrial septal defect in which diastolic collapse of the left marginal artery was demonstrated; this chronology was confirmed by synchronous analysis. The peroperative findings may explain the pathogenesis of the coronary disease encountered in this type of malformation, providing a new diagnostic sign of partial left pericardial agenesis.

Adult

[Eye movements of children with cerebral function disorders diagnosed by different methods].

Saccadic eye movements were recorded in 31 children with cerebral dysfunction as evidenced on different levels (neurophysiological or neuropsychological deficits or specific learning disabilities, see Schmidt et al. 1984), 20 restless underachievers with concentration problems but without cerebral dysfunction and 28 normal third graders while the children followed a jumping spot of light. The recorded data were analyzed off-line. Measures of performance and activation were calculated and the values plotted as functions of stimulus jumping frequency (0.1 to 1.2 Hz). All three subgroups with cerebral dysfunction first showed a normal tendency to anticipatory responses, but the neurophysiology and learning disabled subgroups did not perform as well as the other groups above 0.5 Hz. The compensatory increase in activation (effort effect) usually associated with an increase in task difficulty was seen only in the learning-disabled subgroup and the two control groups. The results show that the children in the neurophysiology and neuropsychology subgroups did not have optimal adaptation of activation to task difficulty. This deficit was coupled with a performance deficit in the neuropsychology subgroup only, however. The children in the neurophysiology subgroup performed almost as well as those in the control groups in spite of this inadequate regulation. Even though the learning-disabled children showed no abnormalities in activation behavior, they still performed poorly. The conclusion was therefore drawn that their poor performance was the result of deficits in cognitive abilities prerequisite to the task.

Attention Deficit Disorder with Hyperactivity