Search PubMed⌕ Search

Biomedical subjects

J Hirschberg

Publications and source records attributed to J Hirschberg.

At least 19 recordsLinked to original sources
PubMed2001

[Functional consequences of cleft palate and its management].

On the basis of the experience with 5200 various types of orofacial cleft operations performed during 42 years (1959-2000) and of the 60-70 cases with velopharyngeal insufficiency without cleft examined yearly author stresses that the surgical closure of the cleft is not enough in the care: the functional consequences (respiratory, sucking, swallowing, speech, hearing and maxillofacial developmental disorders) should also be managed. The first symptom of Robin sequent (cleft palate associated with dysgnathia) is respiratory disorder improving mostly spontaneously but worsening sometimes after palatoplasty. Polysomnography has been performed by the author routinely before all primary palatoplasties for establishing the possible surgical risks and for choice of the optimal time for surgery. On the basis of the results in 61 infants, the surgery was contraindicated and postponed in 6 cases. The various orofacial clefts may cause swallowing problems in different phase of swallowing and different types of dysphagia: the cleft lip cause sucking problems in the preparatory phase, the cleft palate in the oral transitory phase and the velopharyngeal insufficiency in the pharyngeal phase, but the sensomotor function is more decisive in the swallowing process than the cleft itself. Use of an obturator is not necessary, long-term catheter feeding is inappropriate, early closure of the soft palate (in the age of 8-10 months) is recommended. The liquid or food reflux through the nose can be established by cinefluoroscopy with contrast material and with nasoendoscopy following the way of coloured boluses. Retarded speech development, hyperrhinophony, nasal escape, facial grimacing, articulation disorders and dysphonia are the most frequent voice and speech disorders; speech therapy is in 70%, velopharyngoplasty in 20% of the cases indicated. Anatomical result was good in 98% of 1107 flap surgeries operated on by the author, hyperrhinophony ceased in 90%. The results are assessed by a 5-grade perceptual scale. Among the instrumental procedures videofluoroscopy, videoendoscopy, and nasometry seems to be the most informative. The cause of the frequent hearing disorders is mostly the eustachian tube dysfunction. Author found pathological tympanograms in 64% of their cases. The hearing slightly improves after staphylorraphy and often after flap surgery. Adenoidectomy and grommet insertion are alternative procedures in the therapy. The surgeries have an effect on the maxillofacial growth but this is not significant. Multidisciplinary co-operation in the management of cleft patients is indispensable.

Adolescent↗
PubMed2001

Carotenoid biosynthesis in flowering plants.

The general scheme of carotenoid biosynthesis has been known for more than three decades. However, molecular description of the pathway in plants began only in the 1990s after the genes for the carotenogenic enzymes were cloned. Recent data on the biochemistry of carotenogenesis and its regulation in vivo present the possibility of genetically manipulating this pathway in crop plants.

Carotenoids↗
PubMed2000

Ketocarotenoid biosynthesis outside of plastids in the unicellular green alga Haematococcus pluvialis.

The carotenoid biosynthetic pathway in algae and plants takes place within plastids. In these organelles, carotenoids occur either in a free form or bound to proteins. Under stress, the unicellular green alga Haematococcus pluvialis accumulates secondary carotenoids, mainly astaxanthin esters, in cytoplasmic lipid vesicles up to 4% of its dry mass. It is therefore one of the favored organisms for the biotechnological production of these antioxidative compounds. We have studied the cellular localization and regulation of the enzyme beta-carotene oxygenase in H. pluvialis that catalyzes the introduction of keto functions at position C-4 of the beta-ionone ring of beta-carotene and zeaxanthin. Using immunogold labeling of ultrathin sections and Western blot analysis of cell fractions, we discovered that under inductive conditions, beta-carotene oxygenase was localized both in the chloroplast and in the cytoplasmic lipid vesicles, which are (according to their lipid composition) derived from cytoplasmic membranes. However, beta-carotene oxygenase activity was confined to the lipid vesicle compartment. Because an early carotenogenic enzyme in the pathway, phytoene desaturase, was found only in the chloroplast (Grünewald, K., Eckert, M., Hirschberg, J., and Hagen, C. (2000) Plant Physiol. 122, 1261-1268), a transport of intermediates from the site of early biosynthetic steps in the chloroplast to the site of oxygenation and accumulation in cytoplasmic lipid vesicles is proposed.

Antioxidants↗
PubMed2000

An alternative pathway to beta -carotene formation in plant chromoplasts discovered by map-based cloning of beta and old-gold color mutations in tomato.

Carotenoid pigments in plants fulfill indispensable functions in photosynthesis. Carotenoids that accumulate as secondary metabolites in chromoplasts provide distinct coloration to flowers and fruits. In this work we investigated the genetic mechanisms that regulate accumulation of carotenoids as secondary metabolites during ripening of tomato fruits. We analyzed two mutations that affect fruit pigmentation in tomato (Lycopersicon esculentum): Beta (B), a single dominant gene that increases beta-carotene in the fruit, and old-gold (og), a recessive mutation that abolishes beta-carotene and increases lycopene. Using a map-based cloning approach we cloned the genes B and og. Molecular analysis revealed that B encodes a novel type of lycopene beta-cyclase, an enzyme that converts lycopene to beta-carotene. The amino acid sequence of B is similar to capsanthin-capsorubin synthase, an enzyme that produces red xanthophylls in fruits of pepper (Capsicum annum). Our results prove that beta-carotene is synthesized de novo during tomato fruit development by the B lycopene cyclase. In wild-type tomatoes B is expressed at low levels during the breaker stage of ripening, whereas in the Beta mutant its transcription is dramatically increased. Null mutations in the gene B are responsible for the phenotype in og, indicating that og is an allele of B. These results confirm that developmentally regulated transcription is the major mechanism that governs lycopene accumulation in ripening fruits. The cloned B genes can be used in various genetic manipulations toward altering pigmentation and enhancing nutritional value of plant foods.

Chloroplasts↗
PubMed2000

The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons.

APP-BP1 binds to the amyloid precursor protein (APP) carboxyl-terminal domain. Recent work suggests that APP-BP1 participates in a novel ubiquitinylation-related pathway involving the ubiquitin-like molecule NEDD8. We show here that, in vivo in mammalian cells, APP-BP1 interacts with hUba3, its presumptive partner in the NEDD8 activation pathway, and that the APP-BP1 binding site for hUba3 is within amino acids 443-479. We also provide evidence that the human APP-BP1 molecule can rescue the ts41 mutation in Chinese hamster cells. This mutation previously has been shown to lead to successive S phases of the cell cycle without intervening G(2), M, and G(1), suggesting that the product of this gene negatively regulates entry into the S phase and positively regulates entry into mitosis. We show that expression of APP-BP1 in ts41 cells drives the cell cycle through the S-M checkpoint and that this function requires both hUba3 and hUbc12. Overexpression of APP-BP1 in primary neurons causes apoptosis via the same pathway. A specific caspase-6 inhibitor blocks this apoptosis. These findings are discussed in the context of abnormalities in the cell cycle that have been observed in Alzheimer's disease.

Animals↗
PubMed2000

Metabolic engineering of astaxanthin production in tobacco flowers.

Using metabolic engineering, we have modified the carotenoid biosynthesis pathway in tobacco (Nicotiana tabacum) to produce astaxanthin, a red pigment of considerable economic value. To alter the carotenoid pathway in chromoplasts of higher plants, the cDNA of the gene CrtO from the alga Haematococcus pluvialis, encoding beta-carotene ketolase, was transferred to tobacco under the regulation of the tomato Pds (phytoene desaturase) promoter. The transit peptide of PDS from tomato was used to target the CRTO polypeptide to the plastids. Chromoplasts in the nectary tissue of transgenic plants accumulated (3S,3'S) astaxanthin and other ketocarotenoids, changing the color of the nectary from yellow to red. This accomplishment demonstrates that plants can be used as a source of novel carotenoid pigments such as astaxanthin. The procedures described in this work can serve as a platform technology for future genetic manipulations of pigmentation of fruits and flowers of horticultural and floricultural importance.

Bacterial Proteins↗
PubMed2000

Phytoene desaturase is localized exclusively in the chloroplast and up-regulated at the mRNA level during accumulation of secondary carotenoids in Haematococcus pluvialis (Volvocales, chlorophyceae).

The unicellular green alga Haematococcus pluvialis Flotow is known for its massive accumulation of ketocarotenoids under various stress conditions. Therefore, this microalga is one of the favored organisms for biotechnological production of these antioxidative compounds. Astaxanthin makes up the main part of the secondary carotenoids and is accumulated mostly in an esterified form in extraplastidic lipid vesicles. We have studied phytoene desaturase, an early enzyme of the carotenoid biosynthetic pathway. The increase in the phytoene desaturase protein levels that occurs following induction is accompanied by a corresponding increase of its mRNA during the accumulation period, indicating that phytoene desaturase is regulated at the mRNA level. We also investigated the localization of the enzyme by western-blot analysis of cell fractions and by immunogold labeling of ultrathin sections for electron microscopy. In spite of the fact that secondary carotenoids accumulate outside the chloroplast, no extra pathway specific for secondary carotenoid biosynthesis in H. pluvialis was found, at least at this early stage in the biosynthesis. A transport process of carotenoids from the site of biosynthesis (chloroplast) to the site of accumulation (cytoplasmatic located lipid vesicles) is implicated.

Base Sequence↗
PubMed1999

Dysphonia in infants.

The definition of infant dysphonia is difficult because the physiological phonation itself may be extremely variable in newborns. In a wider sense, all voice utterings can be interpreted as dysphonia which deviate continuously in any of the parameters (timbre, pitch, intensity, or noise) from the normal. We differentiated 20 types of such pathological phonation. The most characteristic are: the hoarse (caused by inflammation or tumor of the vocal cords); the hollow (indicative of tracheal stenosis); the shrill (suggesting a CNS damage); the bleating (pathognostic of Down syndrome); the faint (a result of myogenic diseases); and the mewing cry (etiology: cri-du-chat syndrome). In a narrower sense dysphonia in infants is a kind of pathological phonation without evidence of neurological alteration or chromosomal aberration and without a verified laryngeal lesion. These infants utter pressed, harsh, or very high voice (hyperfunctional form) or a weak, inert cry (hypofunctional form). The dysphonic voice may be characterized also by sudden change in melody or in pitch (glide, shift, break, bitonality) and by turbulent noises. This type of newborn dysphonia is a result of the immature innervation of the larynx, it gradually improves and lateron spontaneously disappears. Perceptual evaluation, endoscopy, and acoustic analysis yield useful diagnostic information.

Crying↗
PubMed1999

Production of high-value compounds: carotenoids and vitamin E.

The unraveling in recent years of the pathways and genes that are responsible for biosynthesis of vitamins and carotenoids in plants has provided new molecular tools that can be utilized to genetically modify the content and composition of these compounds in vivo. There have been recent examples of successful manipulation of carotenoid composition and vitamin E activity in plants using gene-transfer technology.

Carotenoids↗
PubMed1999

Photosystem II activity and turnover of the D1 protein are impaired in the psbA Y112L mutant of Synechocystis PCC6803 sp.

Site-directed psbA mutants at the tyrosine Y112 position have been generated in Synechocystis PCC6803 cells. The mutation Y112F does not affect photosystem II (PSII) activity as compared with control 4 delta 1K cells. However, the Y112L mutant exhibits a photosynthetically impaired phenotype. PSII activity is not detectable in this mutant when grown at 30 mumol photons m-2 s-1, while low levels of the D1 and D2 proteins and oxygen evolution activity are present in the mutant cells grown at a low light intensity (0.5-1 mumol m-2 s-1). The recombination of the QB-/S2,3 states of PSII in the Y112L mutant cells as detected by thermoluminescence (TL) is altered. The TL signal emission maximum of these cells due to charge recombination of the S2,3/QB- occurs at 20 degrees C as compared to 35-40 degrees C for the wild-type cells, indicating a possible change in the S2,3/Yz equilibrium. The Y112L mutant cells are rapidly photoinactivated and impaired in the recovery of the PSII activity. These results suggest that replacement of the aromatic residue at position Y112 by a hydrophobic amino acid may alter the function of the donor-side activity and affects the degradation and replacement of the PSII core proteins.

Cyanobacteria↗
PubMed1999

Regulation of carotenoid biosynthesis during tomato fruit development: expression of the gene for lycopene epsilon-cyclase is down-regulated during ripening and is elevated in the mutant Delta.

The red colour of tomato (Lycopersicon esculentum) fruits is provided by the carotenoid pigment lycopene whose concentration increases dramatically during the ripening process. A single dominant gene, Del, in the tomato mutant Delta changes the fruit colour to orange as a result of accumulation of delta-carotene at the expense of lycopene. The cDNA for lycopene epsilon-cyclase (CrtL-e), which converts lycopene to delta-carotene, was cloned from tomato. The primary structure of CRTL-E is 71% identical to the homologous polypeptide from Arabidopsis and 36% identical to the tomato lycopene beta-cyclase, CRTL-B. The CrtL-e gene was mapped to a single locus on chromosome 12 of the tomato linkage map. This locus co-segregated with the Del gene. In the wild-type tomato, the transcript level of CrtL-e decreases at the 'breaker' stage of ripening to a non-detectable level in the ripe fruit. In contrast, it increases approximately 30-fold during fruit ripening in the Delta plants. The Delta mutation does not affect carotenoid composition nor the mRNA level of CrtL-e in leaves and flowers. These results strongly suggest that the mutation Del is an allele of the gene for epsilon-cyclase. Together with previous data, our results indicate that the primary mechanism that controls lycopene accumulation in tomato fruits is based on the differential regulation of expression of carotenoid biosynthesis genes. During fruit development, the mRNA levels for the lycopene-producing enzymes phytoene synthase (PSY) and phytoene desaturase (PDS) increase, while the mRNA levels of the genes for the lycopene beta- and epsilon-cyclases, which convert lycopene to either beta- or delta-carotene, respectively, decline and completely disappear.

Amino Acid Sequence↗
PubMed1998

Paracoccus marcusii sp. nov., an orange gram-negative coccus.

Phenotypic, chemotaxonomic and 16S rDNA sequence analysis of an orange Gram-negative coccus that appeared as a contaminant on a nutrient agar plate delineated a new species of the genus Paracoccus. Phenotypic features of the strain that differ from all or most of the previously described Paracoccus species include its bright orange colour, caused by the synthesis of large amounts of carotenoids (mainly astaxanthin), and its inability to use nitrate as an electron acceptor in respiration. The name Paracoccus marcusii is proposed for this organism. The type strain is DSM 11574T.

Azo Compounds↗
PubMed1998

A software sensor using neural networks for detection of patient workload.

The morphology of intracardiac electrograms (IEGMs) was used for pacemaker patient workload estimation. The body posture also was studied as another characteristic. The IEGMs were obtained and recorded via temporary transcutaneous leads connected to the implanted pacemaker. IEGMs were recorded during exercise and at rest. Recordings at rest were performed in different body positions. The morphology was analyzed visually in order to observe changes due to workload and posture. The recordings were digitized and processed by a computer-simulated neural network. The network was used as an automatic IEGM classifier based on the morphology. Our results show that the morphology of the IEGM may be used as an indicator of patient workload and body posture. The necessary information is found mainly in the ST segment. We conclude that neural networks seem to be useful in an active cardiac device.

Aged↗
PubMed1997

Biosynthesis of ketocarotenoids in transgenic cyanobacteria expressing the algal gene for beta-C-4-oxygenase, crtO.

The ketocarotenoid astaxanthin is produced by a number of marine bacteria and microalgae. It is synthesized from beta-carotene by the addition of two keto groups to carbons C4 and C4' and two hydroxyl groups to C3 and C3'. The gene, crtO, encoding beta-C-4-oxygenase which converts beta-carotene to canthaxanthin was cloned from the green alga Haematococcus plurialis. We transferred crtO to the cyanobacterium Synechococcus PCC7942, which contains a beta-carotene hydroxylase gene and normally accumulates beta-carotene and zeaxanthin. The genetically engineered cyanobacterium produced astaxanthin as well as other ketocarotenoids. The results confirm that crtO can function in cyanobacteria in conjunction with the intrinsic carotenoid enzymes to produce astaxanthin. Specifically, this finding indicates that beta-carotene hydroxylase, which normally converts beta-carotene to zeaxanthin, can also function in the biosynthesis of astaxanthin. These results provide the first evidence of genetic manipulation of a plant-type carotenoid biosynthesis pathway toward the production of novel carotenoids.

Bacterial Proteins↗
PubMed1997

Orofacial clefts in Hungary. Epidemiological and genetic data, primary prevention.

The occurrences (birth prevalences) of different types of isolated and multiple orofacial clefts are known in Hungary. The empiric risk figures in the first-degree relatives of probands with cleft lip +/- cleft palate, cleft palate, Robin sequence and multiple congenital abnormalities including orofacial clefts as component defects were also determined. Finally the recent controversial data concerning the primary prevention of isolated orofacial clefts by periconceptional folic acid-containing multivitamins are summarized.

Cleft Lip↗
PubMed1997

A proposal for standardization of speech and hearing evaluations to assess velopharyngeal function.

The article comprises the proposal made by the Cleft Palate Committee of IALP to standardize the parameters of the speech and hearing evaluation in individuals with cleft palate/velopharyngeal incompetence (CP/VPI). The suggested parameters are the following: nasal resonance, nasal escape, articulation and its disorders, facial grimacing, speech intelligibility, patient teachability, expressive language and voice. The authors recommend a five-point scale description system, which can be used also for assessment of hearing, velopharyngeal competence and other attributes of the CP/VPI individual. The most important diagnostic procedures are: X-ray (video/cinefluoroscopy), nasopharyngoscopy, nasometry; in dubious cases it is also fundamental to clarify the etiology with electrophysiological methods. The utilization of this proposal might contribute to a more accurate diagnosis and a more effective treatment on an international basis.

Articulation Disorders↗
PubMed1997

Flap surgery: experience with 1,030 operations and cephalometric investigation.

The authors report 1,030 (velo)pharyngoplasties performed in 40 years. The anatomical result was good in 98%, hyperrhinophony ceased or became minimal in 90% after surgery. The surgical indication and technique, the operative complications and the factors influencing the functional effect are discussed. In the present investigation cephalograms of 53 unilateral cleft lip and palate (UCLP) patients with inferiorly based pharyngeal flap were compared with the cephalograms of 38 UCLP patients without pharyngeal flap operation. Pharyngeal flap surgery has an adverse effect on the growing face both in the sagittal and vertical dimensions, but the changes do not reach a degree that would justify the abandonment of the good functional effect of velopharyngoplasty.

Articulation Disorders↗