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Biomedical subjects

S Fuchs

Publications and source records attributed to S Fuchs.

At least 37 records · Page 2Linked to original sources

Advances in pediatric emergency medical service systems.

Only recently has attention turned to the needs of children in the EMS system, and it has been shown that there is work to be done if these needs are to be met. The founders of EMS systems were trained in adult specialties and worked without input from the pediatric community. It is not surprising that the special needs of children within an adult-oriented EMS system were underemphasized. Children make up less than 10% of prehospital runs and less than 5% of the critically ill patients. Numerous EMS systems nationwide are undertaking this work and federal support is evident through the Maternal and Child Health EMSC program. Vital issues include the need for experts in emergency medical services to work together with experts in pediatric emergency care and for sound program evaluations to be performed to demonstrate the efficacy of these new programs.

Child

Phosphorylation of membrane-bound acetylcholine receptor by protein kinase C: characterization and subunit specificity.

Acetylcholine receptor (AChR) from Torpedo electric organ in its membrane-bound or solubilized form is phosphorylated by the Ca2+/phospholipid-dependent protein kinase (PKC). The subunit specificity for PKC is different from that observed for cAMP-dependent protein kinase (PKA). Whereas PKC phosphorylates predominantly the delta subunit and the phosphorylation of the gamma subunit by this enzyme is very low, PKA phosphorylates both subunits to a similar high extent. We have extended our phosphorylation studies to a synthetic peptide from the gamma subunit, corresponding to residues 346-359, which contains a consensus PKA phosphorylation site. This synthetic peptide is phosphorylated by both PKA and PKC, suggesting that in the intact receptor both kinases may phosphorylate the gamma subunit at a similar site, as has been previously demonstrated by us for the delta subunit [Safran, A., et al. (1987) J. Biol. Chem. 262, 10506-10510]. The diverse pattern of phosphorylation of AChR by PKA and PKC may play a role in the regulation of its function.

Amino Acid Sequence

Acetylcholine receptor gene expression in experimental autoimmune myasthenia gravis.

Acetylcholine receptor (AChR) gene expression was analyzed in experimental autoimmune myasthenia gravis (EAMG) in rabbits, rats and mice. An increase in AChR transcripts was demonstrated to be exclusively associated with myasthenic symptoms and with a severe loss in membrane AChR. An increase of alpha-, beta-, epsilon-, and delta-subunit specific mRNAs (5.2-, 1.6-, 3.2- and 3.7-fold, respectively), which code for the adult type of AChR (alpha 2 beta epsilon delta) was observed in EAMG in rats. The gamma-subunit transcript was not detectable in myasthenic or healthy rats. It appears that the regulatory control of AChR gene expression in EAMG is different from that observed upon denervation.

Animals

Inhibition by brefeldin A of presentation of exogenous protein antigens to MHC class II-restricted T cells.

Peptides bound to class I or class II major histocompatibility complex (MHC)-encoded molecules are ligands for the antigen-specific T-cell receptor of T-cells carrying the CD8 and CD4 antigens, respectively. MHC class I-restricted T cells generally recognize peptides derived from processing of endogenously synthesized cellular antigens, whereas class II-restricted T cells usually recognize peptides derived from exogenous antigens entering antigen presenting cells. Accordingly, two separate pathways of antigen processing and presentation have been proposed. The fungal metabolite brefeldin A (BFA), an inhibitor of protein transport from the endoplasmic reticulum, inhibits presentation of endogenous antigens for MHC-restricted T-cell recognition. The selectivity of BFA activity has been inferred to reflect presentation of a given antigen processed through the cytosolic or the endocytic route. Here we show that BFA also greatly inhibits the presentation of exogenous protein antigens by MHC class II molecules to T cells, indicating a broader effect of this drug on antigen presentation and an additional similarity between the two processing pathways. As cycloheximide, a protein synthesis inhibitor, also inhibits presentation of protein antigens to class II-restricted T cells, the data indicate that peptides generated by processing of exogenous proteins binds to newly synthesized class II molecules for presentation to T cells.

Animals

Townes-Brocks syndrome.

A 2-week-old male is presented with the clinical findings of the autosomal dominant Townes-Brocks syndrome in an otherwise unaffected family. The patient showed the full spectrum of anomalies including imperforate anus, perineal fistula, triphalangeal thumb, preaxial polydactyly, pre-auricular tags, and microtia. As there is considerable overlap with the VACTERL association, careful examination of the parents is necessary with regard to the genetic counselling risk.

Anus, Imperforate

Vomiting.

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Child

The autoimmune response of different mouse strains to T-cell epitopes of the human acetylcholine receptor alpha subunit.

The specific recognition of the acetylcholine receptor and its alpha-subunit by T cells derived from patients with myasthenia gravis or mice with experimental autoimmune myasthenia gravis raises the question of the role of autoreactive T cells in the myasthenic process. Sequences of the acetylcholine receptor alpha-subunit previously shown to be immunogenic in myasthenic patients were tested for their immunogenicity in various inbred mouse strains. High, intermediate and low T-cell proliferative responses could be observed to peptides representing sequences 195-212 and 259-271 of the human acetylcholine receptor alpha-subunit. Following immunization with the Torpedo acetylcholine receptor, lymphocytes of SJL mice proliferated efficiently to p 195-212 but not to p259-271. On the other hand, lymph node cells of BALB/c mice responded well to p259-271 but not to p195-212. Thus, the influence of the genetic make-up of the examined mice on the immune response to the two peptides could be clearly demonstrated by the existence of strain-dependent immunodominant and cryptic regions on the autoantigen. The differences between the strains were less pronounced when antibody responses were measured to these two T-cell epitopes, although a partial correlation with the proliferative responses could be observed. It can be concluded that epitopes specifically recognized by T lymphocytes of patients with myasthenia gravis also represent specific T-cell epitopes in the autoreactivity to the acetylcholine receptor in mice and that immune responsiveness to these peptides is influenced by the genetic make-up of the responding mouse strains.

Animals

Association of two pertussis toxin-sensitive G-proteins with the D2-dopamine receptor from bovine striatum.

The solubilized D2-dopamine receptor from bovine striatum exhibits high and low affinity states for dopaminergic agonists. Guanine nucleotides and pertussis toxin convert the solubilized receptor from a high affinity state to a low one. A D2-receptor preparation partially purified by affinity chromatography on a haloperidol adsorbent, exhibited agonist-stimulated GTPase activity. [32P]ADP-ribosylation by pertussis toxin of this receptor preparation resulted in the specific labeling of two protein bands corresponding to mol. wts of 39 and 41 kd, in SDS-PAGE. Association of these G-proteins with the receptor was specifically inhibited by Gpp(NH)p. Immunoblot analysis of these G-proteins indicated that the 41- and 39-kd protein bands are analogous to brain Gi and Go respectively. These experiments demonstrate that two distinct pertussis toxin-sensitive G-proteins are functionally associated with bovine striatum D2-dopamine receptor.

Adenosine Diphosphate

Snake acetylcholine receptor: cloning of the domain containing the four extracellular cysteines of the alpha subunit.

The acetylcholine receptor (AcChoR) at the neuromuscular junction of elapid snakes binds cholinergic ligands but unlike other muscle AcChoRs does not bind alpha-bungarotoxin. Numerous studies indicate that the ligand-binding site of the AcChoR includes cysteine residues at positions 192 and 193 of the alpha subunit. We have previously shown that a synthetic dodecapeptide corresponding to residues 185-196 of the Torpedo AcChoR alpha subunit contains the essential elements of the ligand-binding site. In an attempt to elucidate the structural basis for the precise binding properties of snake AcChoR, we sequenced a portion of the snake AcChoR alpha subunit. First, a mouse AcChoR alpha-subunit cDNA probe was used to screen a size-selected snake (Natrix tessellata) genomic library. A genomic clone was isolated and was found to contain sequences homologous to the exon including the first two cysteines (Cys-128 and -142) of AcChoR alpha subunit. The domain of the alpha subunit from Natrix and cobra AcChoR (amino acid residues 119-222), which contains the four extracellular cysteines (128, 142, 192, and 193), was amplified by reverse transcription of mRNA and the polymerase chain reaction and then sequenced. The deduced amino acid sequence showed that the snake alpha subunit contains the two tandem cysteines at positions 192 and 193, resembling all other AcChoR alpha subunits. Sequence comparison revealed that the cloned region of the snake alpha subunit is highly homologous (75-80%) to other muscle AcChoRs and not to neuronal AcChoR, which also does not bind alpha-bungarotoxin. In the presumed ligand-binding site, in the vicinity of Cys-192 and Cys-193, four major substitutions occur in the snake sequence--at positions 184 (Trp----Phe), 185 (Lys----Trp), 187 (Trp----Ser), and 194 (Pro----Leu). In addition, Asn-189 is a putative N-glycosylation site, present only in the snake. These changes, or part of them, may explain the lack of alpha-bungarotoxin-binding to snake AcChoR.

Amino Acid Sequence

[Congenital cholesteatoma of the petrous bone. Etiopathogenic discussions apropos of 11 cases].

The authors report on 11 cases of congenital cholesteatomas, treated between 1979 and 1988. In all cases, there was a long-standing history of deafness. The diagnosis revealed 6 cophoses, 5 cases of mixed deafness, 9 cases of impairment of the facial nerve (7 cases of paralysis including 4 with sudden onset and 2 hemispasms), 2 facial neuralgias with facial hypesthesia, one Gradenigo-Lannois syndrome, 2 leaks of the C.S.F. (1 nasal, 1 very abundant auricular leak). In 6 cases, the surgical approach route was trans-cochlear, and in 5 cases surpa-petrosal, two of which were extended to a petrectomy. Of the 5 cases of partial deafness, only one was preserved. In 5 cases, the facial nerve was destroyed at the level of the ganglion of the facial nerve, a region where a frankly epidermal tissue is always found. In 4 cases the facial nerve was repaired (three hypo-glosso-facial anastomoses and one end-to-end suture, after re-routing). The authors share the opinion of Fisch that the origin of the intra-petrosal congenital cholesteatoma always occurs at the level of the ganglion of the facial nerve.

Adolescent

Pediatric emergencies in office practices: prevalence and office preparedness.

Because of a nationally apparent increased interest in emergency medical services for children and the need for a greater understanding of the relationship between office pediatric and emergency department care of children, a questionnaire was mailed to practitioners to (1) describe office physician involvement with emergent conditions, and (2) evaluate physician office preparedness for pediatric emergencies. Responses were received from 280 pediatricians and family practitioners, including information regarding the availability of equipment and medication, physician training, and practice characteristics. Of the responding physicians, 62% reported that they assessed in their offices more than one child each week who required hospitalization or urgent treatment. A preparedness score was developed and multiple regression analysis was used to investigate the relationship between this score and physician and practice characteristics. The mean overall preparedness score was 53.7 of a possible 156 (range 5 to 136, SD = 31.3). Characteristics related to this score were type of practice and advanced cardiac life support certification. Large multispecialty practices and practices with physicians trained in advanced cardiac life support tended to have better preparedness scores. Family practitioners tended to have more complete stock of medications than pediatricians. The data presented suggested that critically ill children who enter the medical system via the office setting may have a better than even chance of finding the office unprepared to treat the emergency: in fewer than one third of the offices in which it was reported that at least one patient was seen weekly with asthma, anaphylaxis, sickle cell vasoocclusive crisis, status epilepticus, and sepsis were they fully equipped to treat emergencies related to these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Chicago

Cervical spine fractures sustained by young children in forward-facing car seats.

Child passenger safety restraint laws have reduced the number of children killed or injured in motor vehicle accidents in the past few years. However, the increased used of child safety seats has brought with it an increase in the misuse of these devices. High cervical spine injuries sustained by five children less than 2 years of age while in forward-facing car seats are described. In the cases of three children, the care safety seat use was correct. Misuse of car seats and anatomic and biomechanical factors in the cervical spines of infants and young children appear to have contributed to the occurrence of these previously rare injuries. Like seat belts, car safety seats are now a factor in child passenger injury characteristics, and therefore, car safety seat design merits reevaluation. In light of this development, public and parent education by health care professionals concerning the correct use of car safety seats is necessary.

Accidents, Traffic

[Choice of surgical technic for correcting the nose tip].

The surgical approach should be adapted to the type of correction needed. There is no room of standard technics. The various selection criteria that have to be considered are: the structure of the alar cartilages and the infra-and suprastructural characteristics thereof, determining the upper triangle of the lobule; the relative incidence of the abnormalities encountered in rhinoplastic practice; an analysis of the failures leading to secondary rhinoplastic operations, among which the most frequent are lobule and/or irregularities and drooping apex or insufficient projection thereof. Currently, the authors' conclusions are that: Most of the times, the upper triangle of the lobule is overdeveloped: reduction is carried out by resecting a superior strip laterally, while additionally trimming the cupulae, if necessary. Much more rarely, a globally hypertrophied lobule will be found that requires management by section-reconstruction of the cupulae. In case of a "normal", excessively projected lobule, the technic of choice is apex retraction. Primary apex projection defects should be recognized and treated with molding grafts. The nose tip should be prevented from drooping by means of columellar supporting grafts.

Humans

Purification of the D-2 dopamine receptor from bovine striatum.

The D-2 dopamine receptor has been purified 21500 fold from bovine striatal membranes. Solubilized receptor preparation was partially purified by affinity chromatography on a haloperidol adsorbent followed by gel filtration on a Sephacryl S-300 column. The fractions eluted from this column which contained the ligand binding activity were further chromatographed on wheat germ agglutinin conjugated to Sepharose. The resulting receptor preparation displays a major polypeptide band of an apparent molecular weight of 92 kDa, and exhibits a specific binding activity of 2490 pmol spiperone per mg protein. This purified receptor preparation can reabsorb specifically to the haloperidol affinity column indicating that the 92 kDa polypeptide represents the ligand binding unit of the D-2 dopamine receptor.

Animals

Immuno-photoaffinity labeling of the D2-dopamine receptor.

Azido-haloperidol was synthesized and applied as a photoaffinity ligand for the D2-dopamine receptor. In bovine striatal membranes, azido-haloperidol bound reversibly to the receptor (KD = 15 nM), and when exposed to light, it bound to the receptor irreversibly. This irreversible inactivation was prevented by the dopaminergic agonist N-propylnorapomorphine or the dopaminergic antagonists haloperidol and (+)-butaclamol. The photoaffinity labeled D2-receptor was probed with anti-haloperidol antibodies following gel electrophoresis and transfer to nitrocellulose. A major polypeptide of 94 kDa reacted with the anti-haloperidol antibodies. This polypeptide band was not observed when the photoaffinity labeling was performed in the presence of (+)-butaclamol or spiperone.

Affinity Labels