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Biomedical subjects

A Robinson

Publications and source records attributed to A Robinson.

At least 361 records · Page 20Linked to original sources
PubMed1987

GTP-dependent ADP-ribosylation of a 22 kDa protein in the endoplasmic reticulum membrane.

Treatment of salt-stripped rough microsomal membranes from pancreas or liver with NAD and cholera toxin in the presence of GTP yields an ADP-ribosylated non-ribosomal 22 kDa protein. Membranes containing the modified protein are less active in the co-translational processing of secretory preproteins translated from isolated mRNA in a reticulocyte translation system, but signal peptidase activity is unchanged, suggesting that the 22 kDa protein is involved in the targetting or translocation of secretory proteins at the membrane of the endoplasmic reticulum.

Adenosine Diphosphate Ribose↗
PubMed1987

Current problems in antimicrobial therapy for bacterial enteric infection.

Trimethoprim/sulfamethoxazole is currently considered the treatment of choice for shigellosis and severe travelers' diarrhea. The problem with this combination regimen is inactivity against Campylobacter jejuni strains and other bacterial enteropathogens showing in vitro resistance to the drug. Resistance to trimethoprim/sulfamethoxazole among enteric pathogens has occurred frequently in certain areas of the world. A study of the in vitro susceptibility of enteric bacterial pathogens isolated from multiple countries was recently performed. The minimal inhibitory concentration of ciprofloxacin required to inhibit 90 percent of the 210 bacterial enteropathogens ranged from 0.25 micrograms/ml for C. jejuni to 0.016 micrograms/ml for enterotoxigenic Escherichia coli, Salmonella, and Shigella. In a clinical trial carried out in a United States student population that acquired diarrhea while in Mexico, it was shown that ciprofloxacin was as effective as trimethoprim/sulfamethoxazole and both were significantly (p less than 0.001) more effective than placebo. The average duration of diarrhea was 29 or 20 hours after initiation of treatment with ciprofloxacin or trimethoprim/sulfamethoxazole, respectively, compared with 81 hours in the placebo group. The antimicrobial agents were more efficacious than placebo in treating diarrhea caused by enterotoxigenic E. coli, invasive enteropathogens, and unknown pathogens. Ciprofloxacin and the quinolone derivatives are uniquely suited to the therapy of acute bacterial diarrhea in areas where C. jejuni is commonly found and where trimethoprim/sulfamethoxazole-resistant strains regularly occur.

Anti-Bacterial Agents↗
PubMed1987

Identification of signal sequence binding proteins integrated into the rough endoplasmic reticulum membrane.

An azidophenacyl derivative of a chemically synthesized consensus signal peptide has been prepared. The peptide, when photoactivated in the presence of rough or high-salt-stripped microsomes from pancreas, leads to inhibition of their activity in cotranslational processing of secretory pre-proteins translated from their mRNA in vitro. The peptide binds specifically with high affinity to components in the microsomal membranes from pancreas and liver, and photoreaction of a radioactive form of the azidophenacyl derivative leads to covalent linkage to yield two closely related radiolabelled proteins of Mr about 45,000. These proteins are integrated into the membrane, with large 30,000-Mr domains embedded into the phospholipid bilayer to which the signal peptide binds. A smaller, endopeptidase-sensitive, domain is exposed on the cytoplasmic surface of the microsomal vesicles. The specificity and selectivity of the binding of azidophenacyl-derivatized consensus signal peptide was demonstrated by concentration-dependent inhibition of photolabelling by the 'cold' synthetic consensus signal peptide and by a natural internal signal sequence cleaved and isolated from ovalbumin. The properties of the labelled 45,000-Mr protein-signal peptide complexes, i.e. mass, pI, ease of dissociation from the membrane by detergent or salts and immunological properties, distinguish them from other proteins, e.g. subunits of signal recognition particle, docking protein and signal peptidase, already known to be involved in targetting and processing of nascent secretory proteins at the rough endoplasmic reticulum membrane. Although the 45,000-Mr signal peptide binding protein displays properties similar to those of the signal peptidase, a component of the endoplasmic reticulum, the azido-derivatized consensus signal peptide does not interact with it. It is proposed that the endoplasmic reticulum proteins with which the azidophenacyl-derivatized consensus signal peptide interacts to yield the 45,000-Mr adducts may act as receptors for signals in nascent secretory pre-proteins in transduction of changes in the endoplasmic reticulum which bring about translocation of secretory protein across the membrane.

Affinity Labels↗
PubMed1987

Interaction of cimetidine with oral melphalan. A pharmacokinetic study.

The effects of pretreatment with cimetidine (200 mg three times daily, 400 mg at night) on the pharmacokinetics of oral melphalan (10 mg) have been investigated in patients with multiple myeloma. Cimetidine pretreatment reduced the bioavailability of oral melphalan by approximately 30% (P less than 0.05). The elimination rate of melphalan from plasma was significantly increased by cimetidine (P less than 0.05), the half-life being reduced from 1.94 +/- 0.55 h to 1.57 +/- 0.53 h. Cimetidine appeared to reduce the interindividual variability in melphalan absorption, but at the cost of reduced bioavailability.

Administration, Oral↗
PubMed1987

Abnormalities of copper in Gilles de la Tourette syndrome.

The Gilles de la Tourette syndrome is a disorder whose etiology and pathogenesis are little understood. The number of biochemical abnormalities described in this disorder is minimal. Ten of a total of 80 patients were found to have an abnormally low serum copper. A report is presented on two patients who consented to further detailed investigation and in whom copper radioisotope studies were carried out. Both exhibited abnormalities of copper handling, in that we observed an abnormally fast disappearance of copper from the plasma and an abnormally slow uptake by the liver. The rates of intestinal absorption and urinary excretion were normal. We did not identify an abnormal site of sequestration of the metal in the body.

Adult↗
PubMed1987

Methodology of premature chromosome condensation and its potential for relapse prediction in acute leukemia of children and adolescents.

Premature chromosome condensation has been examined as a method for measuring the proliferative potential of bone marrow cells derived from children with acute leukemia with the intention of finding a predictor of relapse. A proliferative potential index (PPI) has been determined for patients with active disease at diagnosis and relapse, as well as at onset of remission and at extramedullary relapse. A modification of the technique established by Hittelman is described, which can be easily performed by the leukemia cytogeneticist. A PPI of 35% or greater is usually obtained for patients at diagnosis or in relapse. At the onset of remission, the PPI declines to values significantly below 35% and during extramedullary relapse the value of the PPI is near normal (12%). The method for the determination of the PPI is given in detail.

Acute Disease↗
PubMed1987

Premature chromosome condensation as a predictive indicator of relapse in children and adolescents with acute leukemia: initial observations.

Premature chromosome condensation has been used to determine a proliferative potential index (PPI) in a study of children in leukemia remission at varying times during the disease. Values 35% and greater were considered predictive of relapse. Such values preceded relapse with a mean of 5 months in acute lymphoblastic leukemia (ALL) patients who had previously relapsed and in myeloid leukemia patients. ALL patients followed from diagnosis and children off therapy had fluctuating and false predictive PPI values preceding long courses of continued remission. This study suggests that the PPI as a predictive indicator for relapse may be useful for patients with ALL who have previously relapsed and for patients with myeloid leukemias. Future exploration to further evaluate this mechanism of prediction is to be attempted by investigating the ability to obtain similar and more detailed information through the use of peripheral blood rather than bone marrow samples.

Acute Disease↗
PubMed1987

Susceptibility testing of fastidious organisms in the API microdilution panel.

It has become increasingly important to perform routine susceptibility tests on certain anaerobic bacteria, Haemophilus influenzae and Streptococcus pneumoniae, as a result of the decreasing predictability of their antimicrobial susceptibility patterns. The antimicrobial susceptibilities of 49 anaerobic isolates, 25 H. influenzae isolates, and 25 S. pneumoniae isolates were determined concurrently by API Uniscept MIC trays and a conventional broth microdilution method using Wilkins-Chalgren broth, 5% Fildes in Schaedler broth, or 5% lysed horse blood in Mueller-Hinton broth, respectively. Analysis of 490 anaerobic organism-antibiotic combinations, 144 H. influenzae-antibiotic combinations, and 125 S. pneumoniae-antibiotic combinations showed that 98.9%, 100%, and 99.2%, respectively, of the API results were within +/- 1 log2 dilution of the reference system. The API Uniscept MIC panel would be acceptable for use as a routine susceptibility system for anaerobic organisms in a clinical microbiology laboratory. To eliminate trailing endpoints, however, further studies need to be performed to evaluate additional broth media for the susceptibility testing of H. influenzae and S. pneumoniae in the API panels.

Anti-Bacterial Agents↗
PubMed1987

The activity of purified Bordetella pertussis components in murine encephalopathy.

A murine encephalopathic syndrome can be induced by the administration of BSA and whole-cell pertussis vaccine. The present paper reports studies of the capacity of purified individual pertussis components to induce this effect. Pertussis toxin and endotoxin together with a highly immunogenic sensitizer protein were required to induce the effect. The strength of the antibody response to the sensitizer appeared to be more important than the H-2 type of the recipient in determining the susceptibility of different mouse strains. The relevance of this syndrome to the study of possible vaccine-induced encephalopathy in man is uncertain and requires further investigation.

Animals↗
PubMed1987

Clinical interpretation of beta-lactamase-producing strains of Branhamella catarrhalis in sputum Gram's stain and culture.

Branhamella catarrhalis has been implicated previously as a cause of bronchopulmonary infections. Sputum Gram's stain and culture results suggesting significant infection with beta-lactamase-producing strains of B. catarrhalis were correlated with a retrospective chart review of eight pediatric and ten adult patients. Preexisting pulmonary disease was observed in 12 patients; 5 had a history of aspiration; and 13 were intubated. Clinically, ten patients had pneumonia, five had bronchitis, and three manifested no disease. Only three sputum specimens grew a pure culture of B. catarrhalis, and six specimens yielded B. catarrhalis in the presence of normal upper respiratory flora. Analysis of broth microdilution susceptibility test results showed that 90% of the strains were inhibited at the following minimum inhibitory concentrations (MICs90): ampicillin, 8 micrograms/mL; cefotaxime, 0.5 microgram/mL; cefoxitin, 0.5 microgram/mL; cephalexin, 4 micrograms/mL; cephalothin, 8 micrograms/mL; chloramphenicol, 1 microgram/mL; clindamycin, 4 micrograms/mL; erythromycin, 0.25 microgram/mL; methicillin, 16 micrograms/mL; mezlocillin, 16 micrograms/mL; moxalactam less than or equal to 0.6 microgram/mL; penicillin, 16 micrograms/mL; piperacillin, 8 micrograms/mL; tetracycline, less than or equal to 0.3 microgram/mL; and trimethoprim/sulfamethoxazole, 1.6/30 micrograms/mL. Therapy may have been adequate in only eight (44%) of the cases. However, all but four of the patients, who died of unrelated causes, exhibited resolution of disease. The data indicate that Gram's stain and culture results of sputum specimens suggesting B. catarrhalis bronchopulmonary infection should be interpreted with caution by clinicians.

Adolescent↗
PubMed1987

Cloning and nucleotide sequence analysis of the serotype 2 fimbrial subunit gene of Bordetella pertussis.

An oligonucleotide probe complementary to the beginning of the gene encoding the serotype 2(ST2) fimbrial subunit of Bordetella pertussis was synthesized and a cloned DNA fragment hybridizing with the probe identified and sequenced. Several lines of evidence indicate that an open reading frame with coding information for a polypeptide of 207 amino acids, including a 26-amino-acid signal sequence, is the ST2 gene. The protein deduced from the nucleotide sequence shows good agreement with the NH2-terminal amino acid sequence, amino acid composition and molecular weight of the purified fimbrial subunit. In addition, the proposed ST2 subunit is shown to have homology with other fimbrial subunits.

Amino Acid Sequence↗
PubMed1987

Gross and fine motor development in 47,XXY and 47,XYY males.

Neuromuscular deficits described in early childhood as motor awkwardness or slow movements are still clinically present in school-aged boys with XXY and XYY sex chromosome aneuploidy. A control group of 14 boys (6 to 19 years of age) and 14 XXY and four XYY boys (6 to 15 years of age), identified by newborn screening, were blindly evaluated by a physical therapist. The Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) was administered and a clinical rating of neurologic status and sensory-motor integration was assigned. On the motor proficiency test, the XXY boys had significantly lower mean scores for upper limb coordination, speed and dexterity, and on gross motor and battery composites. The neuromuscular status of the aneuploid boys was deficient, with hypotonia, apraxia, primitive reflex retention, and problems with bilateral coordination and visual-perceptual-motor integration. This mild to moderate dysfunctional sensory-motor integration, as well as previously described auditory-processing deficits and dyslexia, contributed to school performance below that expected from their cognitive potential.

Adolescent↗
PubMed1987

Genetic risk for recombinant 8 syndrome and the transmission rate of balanced inversion 8 in the Hispanic population of the southwestern United States.

A rec(8) dup(q) syndrome, secondary to a pericentric inversion--inv(8)(p23q22)--has been identified in 26 probands from Hispanic kindreds in the southwestern United States. The clinical phenotype of the Hispanic rec(8) syndrome includes a dysmorphic facies, cardiovascular and urinary-tract malformations, and mental retardation. Segregation analysis utilizing pedigree and cytogenetic data from 31 kindreds including five additional kindreds from additional sources has provided computation of genetic risks for counseling. An inv(8) carrier parent has a 6.2% risk of having a rec(8) child. The transmission rate of the inv(8) was significantly higher for inv(8) carrier mothers (59%) than for carrier fathers (42%). The combined transmission rate for both sexes was 53%. Risk for spontaneous abortion or stillbirth (11.3%) was not higher than the general population frequency of 13%-15%. It is significant that all kindreds identified to date are of Hispanic background with ancestors traced to the southern Colorado/northern New Mexico region. By means of extended pedigree information, three independently ascertained kindreds have been linked through common ancestry 4 generations in ascendance. The Hispanic background, geographic localization, and common ancestry in three kindreds suggest a single founder of the Hispanic inv(8) in the Southwest.

Chromosome Inversion↗
PubMed1986

Isolation and properties of the signal region from ovalbumin.

A tryptic fragment (residues 21-47) containing the signal peptide of ovalbumin has been isolated by reverse-phase chromatography. The peptide is more active at inhibiting the processing of pre-prolactin in an in vitro translation system than fragments of ovalbumin isolated previously, and is similar in properties to synthetic signal peptides. The ovalbumin signal fragment is shown to bind to a protein component of salt-stripped pancreatic microsomal membranes, which is cross-linked under UV irradiation by a radioactive synthetic photoaffinity signal peptide probe to yield a radiolabelled 45 kDa protein.

Amino Acid Sequence↗