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Biomedical subjects

F Barr

Publications and source records attributed to F Barr.

18 recordsLinked to original sources
PubMed2006

The frequent observation of evidence for nonsense-mediated decay in RNA from patients with carbamyl phosphate synthetase I deficiency.

CPSI deficiency is an inborn error of metabolism caused by mutations in the first, rate-determining enzyme of the urea cycle. Our mutation detection data from this disorder suggest that a significant number of mutant alleles cause RNA instability, most likely through the nonsense-mediated decay pathway. We identified 26 non-consanguinous CPSID patients with an available RNA source (liver tissue or cell line) and screened both genomic DNA and RNA for the identification and classification of mutations. Out of 52 total alleles screened from these patients, 21 (40%) have strong evidence for RNA processing mutations demonstrated by absent/minimal heterozygosity in patient cDNA sequences despite heterozygous genomic changes. These 21 alleles are a heterogenous group primarily composed of splicing defects and frameshifts that form premature termination codons which should subsequently elicit the nonsense-mediated decay pathway. This study provides evidence for the high prevalence of RNA instability mutations in genetic disease and underscores the importance of accounting for them in mutation-screening strategies.

Alleles↗
PubMed2002

Improved version of the red fluorescent protein (drFP583/DsRed/RFP).

GFP has established itself as a highly useful tool throughout many areas of modern biology. Recently, the novel fluorescent protein drFP583, also termed DsRed or RFP, was clonedfrom a coral of the Discosoma genus. The protein is only weakly homologous to GFP and has a red emission spectrum, which makes drFP583 an attractive candidate for in vivo double labeling together with GFP variants. However, wildtype drFP583 has several drawbacks, including inefficient folding of the protein, extremely slow maturation of the chromophore, and tetramerization even in dilute solutions. Here we report on important improvements to this reporter that lead to higher levels of fluorescent drFP583 species in the cell. We further characterized our best mutant for applications in yeast and mammalian cell biology.

Base Sequence↗
PubMed2000

Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: an intergroup rhabdomyosarcoma study.

A comparative genomic hybridization (CGH) approach provides identification of genomic gains and losses in a tumor specimen in a single experiment. Only 11 embryonal rhabdomyosarcomas (E-RMS) have previously been subjected to CGH. The underlying genetic events in this histologic subtype are not well defined. In this investigation, 12 E-RMS specimens from 10 patients entered into Intergroup Rhabdomyosarcoma Study (IRS) I-IV and two local patients were analyzed by CGH and fluorescence in situ hybridization (FISH). Gains of chromosomes or chromosomal regions 2 (50%), 7 (42%), 8 (67%), 11 (42%), 12 (58%), 13q21 (33%), and 20 (33%) and losses of 1p35-36.3 (42%), 6 (33%), 9q22 (33%), 14q21-32 (25%), and 17 (25%) were most prominent. Chromosomal regions 1p35-36.3 and 9q22 represent novel regions of loss. Importantly, loss of 9q22 corresponds to the locus of a putative tumor suppressor gene (PTCH), which has been shown to play a role in rhabdomyosarcoma in a mouse model of Gorlin syndrome. Loss of 1p36 corresponds to the locus for PAX7, a paired box containing gene characteristically altered in alveolar rhabdomyosarcoma. Moreover, loss of 1p36 is prominent in another common pediatric soft tissue tumor, neuroblastoma. Gains of 2, 7, 8, 12, and 13 and loss of 14 were seen in the sole prior E-RMS CGH series; thus, these data provide important confirmatory results. In contrast to this previous study, however loss, not gain, of chromosome 17 was observed in the current study. Chromosome 17 loss correlates well with previous descriptions of frequent allelic loss of 17p (TP53) in E-RMS. In summary, CGH and FISH analyses of 12 E-RMS specimens revealed novel genomic imbalances that may be useful in directing further molecular studies for the determination of E-RMS critically involved genes.

Adolescent↗
PubMed2000

Vesicular transport.

The minimal requirements for COP I and COP II vesicle formation from liposomes are the small GTPases Arf1 and Sar1, GTP and the coat complexes themselves. Coat-nucleating factors including specific GTP-GDP exchange factors, SNAREs and other cargo molecules are likely to determine the site of vesicle formation. Tethering mediated by long rod-like coiled-coil proteins precedes docking of vesicles with their target membrane and contributes to specific recognition of this membrane. NSF/Sec18p acts prior to membrane fusion to prime specific SNARE complexes for docking of vesicles with their targets, while the SNAREs are likely to be the minimal membrane-fusion machinery.

Animals↗
PubMed1999

Localization of a candidate surfactant convertase to type II cells, macrophages, and surfactant subfractions.

Pulmonary surfactant exists in the alveolus in several distinct subtypes that differ in their morphology, composition, and surface activity. Experiments by others have implicated a serine hydrolase in the production of the inactive small vesicular subtype of surfactant (N. J. Gross and R. M. Schultz. Biochim. Biophys. Acta 1044: 222-230, 1990). Our laboratory recently identified this enzyme in the rat as the serine carboxylesterase ES-2 [F. Barr, H. Clark, and S. Hawgood. Am. J. Physiol. 274 (Lung Cell. Mol. Physiol. 18): L404-L410, 1998]. In the present study, we determined the cellular sites of expression of ES-2 in rat lung using a digoxygenin-labeled ES-2 riboprobe. ES-2 mRNA was localized to type II cells and alveolar macrophages but not to Clara cells. Using a specific ES-2 antibody, we determined the protein distribution of ES-2 in the lung by immunohistochemistry, and it was found to be consistent with the sites of mRNA expression. Most of the ES-2 in rat bronchoalveolar lavage is in the surfactant-depleted supernatant, but ES-2 was also consistently localized to the small vesicular surfactant subfraction presumed to form as a consequence of conversion activity. These results are consistent with a role for endogenous lung ES-2 in surfactant metabolism.

Animals↗
PubMed1998

Reducing iron deficiency anaemia due to heavy menstrual blood loss in Nigerian rural adolescents.

OBJECTIVE: Menstrual disorders are common in young women, and heavy menstrual blood losses (MBL) are an important cause of anaemia. Menstrual morbidity normally goes untreated in developing countries where cultural barriers also serve to mask the problems. We investigated the prevalence of menstrual morbidity, and measured MBL and its relationship to iron deficiency in a rural adolescent population. The rationale was to assess whether or not reducing heavy MBL could be part of a strategy to reduce iron deficiency anaemia. SETTING: Rural village in south-east Nigeria. DESIGN: Cross-sectional survey. SUBJECTS: The study included all non-pregnant, unmarried nulliparous girls (< 20 years) who had menstruated, and who lived in K'Dere village. METHODS: A field worker allocated to each girl completed a questionnaire, and supervised recovery and collection of soiled pads and ensured blood sampling. MBL was measured using the standard alkaline haematin method. Haemoglobin (Hb), serum iron, transferrin saturation and protoporphyrin levels (ZPP) were also measured. RESULTS: 307 girls completed MBL measurements; 11.9% refused to participate. 12.1% had menorrhagia (> 80 ml); median MBL was 33.1 ml. Menorrhagia was more frequent in girls who had menstruated for > 2 years (P = 0.048), and had longer duration of menses (P < 0.001). Iron status as measured by haematocrit, serum iron, transferrin saturation and ZPP values was inversely related to MBL. Neither height nor body mass index for age was associated with current iron status. CONCLUSIONS: The level of menorrhagia detected (12%) may be an 'expected' level for a condition which often has no underlying pathology. Heavy MBL is one of the most important factors contributing to iron deficiency anaemia. Measures are needed to alleviate menstrual disorders, and improve iron status. Oral contraceptives can be part of a strategy to reduce anaemia, particularly for adolescents at high risk of unwanted pregnancies.

Adolescent↗
PubMed1998

Identification of a putative surfactant convertase in rat lung as a secreted serine carboxylesterase.

In the alveolar lumen, pulmonary surfactant converts from the contents of secreted lamellar bodies to tubular myelin to apoprotein-depleted vesicles during respiration. Using an in vitro system, researchers have reported that the conversion of tubular myelin to vesicles is blocked by inhibitors of serine hydrolase activity and have tentatively ascribed "convertase" activity to a diisopropyl fluorophosphate (DFP)-binding protein in mouse bronchoalveolar lavage (BAL). We purified and sequenced the homologous enzyme from rat BAL fluid. Amino acid sequence from the amino terminus and an internal cyanogen bromide peptide of the purified rat DFP-binding protein perfectly match the sequence of the carboxylesterase ES-2. Although ES-2 was initially cloned from liver, we found a 1.8-kilobase mRNA for ES-2 in decreasing relative abundance in rat liver, kidney, and lung but not in heart or spleen. Although further studies are required to establish the identity between "convertase" and ES-2 or a homologous member of the carboxylesterase family, our results raise the possibility that a protein with esterase/lipase activity plays a role in extracellular surfactant metabolism.

Amino Acid Sequence↗
PubMed1997

Prevalence of retinal hemorrhages in pediatric patients after in-hospital cardiopulmonary resuscitation: a prospective study.

OBJECTIVE: Child abuse occurs in 1% of children in the United States every year; 10% of the traumatic injuries suffered by children under 5 years old are nonaccidental, and 5% to 20% of these nonaccidental injuries are lethal. Rapid characterization of the injury as nonaccidental is of considerable benefit to child protection workers and police investigators seeking to safeguard the child care environment and apprehend and prosecute those who have committed the crime of child abuse. Physically abused children present with a variety of well-described injuries that are usually easily identifiable. In some cases, however, particularly those involving children with the shaken baby syndrome, obvious signs of physical injury may not exist. Although external signs of such an injury are infrequent, the rapid acceleration-deceleration forces involved often cause subdural hematomas and retinal hemorrhages, hallmarks of the syndrome. Frequently, retinal hemorrhages may be the only presenting sign that child abuse has occurred. Complicating the interpretation of the finding of retinal hemorrhages is the belief by some physicians that retinal hemorrhages may be the result of chest compressions given during resuscitative efforts. The objective of this study is to determine the prevalence of retinal hemorrhages after inpatient cardiopulmonary resuscitation (CPR) in pediatric patients hospitalized for nontraumatic illnesses in an intensive care unit. DESIGN: Prospective clinical study. SETTING: Pediatric intensive care unit. PATIENTS: Forty-three pediatric patients receiving at least 1 minute of chest compressions as inpatients and surviving long enough for a retinal examination. Patients were excluded if they were admitted with evidence of trauma, documented retinal hemorrhages before the arrest, suspicion of child abuse, or diagnosis of near-drowning or seizures. All of the precipitating events leading to cardiopulmonary arrest occurred in our intensive care unit, eliminating the possibility of physical abuse as an etiology. INTERVENTIONS: None. MEASUREMENTS: Examination of the retina was performed by one of two pediatric ophthalmologists within 96 hours of CPR. The chart was reviewed for pertinent demographic information; the platelet count, prothrombin time, and partial thromboplastin time proximate to the CPR were recorded if they had been determined. RESULTS: A total of 43 pediatric patients hospitalized with nontraumatic illnesses survived 45 episodes of inpatient CPR. The mean age was 23 months (range, 1 month to 15.8 years), and 84% of the patients were under 2 years old. The majority of the patients (44%) were admitted to the intensive care unit after surgery for congenital heart disease, and another 21% were admitted for respiratory failure. The mean duration of chest compressions was 16.4 minutes +/- 17 minutes with 58% lasting between 1 and 10 minutes. Five patients had chest compressions lasting >40 minutes, and two patients had open chest cardiac massage. All patients survived their resuscitative efforts. Ninety-three percent of patients had an elevated prothrombin time and/or partial thromboplastin time while 49% were thrombocytopenic. Sixty-two percent of the patients had low platelet counts and an elevated prothrombin time and/or partial thromboplastin time. Small punctate retinal hemorrhages were found in only one patient. CONCLUSIONS: Retinal hemorrhages are rarely found after chest compressions in pediatric patients with nontraumatic illnesses, and those retinal hemorrhages that are found appear to be different from the hemorrhages found in the shaken baby syndrome. Despite the small number of patients in this prospective study, we believe that these data support the idea that chest compressions do not result in retinal hemorrhages in children with a normal coagulation profile and platelet count. A larger number of patients should be evaluated in a prospective multi-institutional study to achieve statistical significance

Adolescent↗
PubMed1995

Percutaneous biopsy of abdominal organs under ultrasound guidance.

Percutaneous sampling of one or more abdominal organs was performed under ultrasound guidance in 89 dogs and 16 cats. Tissue core samples were considered to be of diagnostic quality in 92 per cent of hepatic and 100 per cent of renal biopsies. Core biopsies were collected from the prostate in only three cases but each was adjudged of diagnostic quality. The technique allowed a definitive diagnosis or normal tissue to be confirmed in 65 per cent of animals undergoing hepatic biopsy, 83 per cent undergoing renal biopsy and 82 per cent undergoing prostatic biopsy or aspiration. Few complications occurred which could be ascribed with certainty to the procedure. One dog with extensive hepatic necrosis died one week after the biopsy, but necropsy examination was denied. One severely debilitated cat did not recover from general anaesthesia. One dog underwent aspiration of a sterile intraprostatic cyst, and developed prostatic abscessation one week later; prostatic carcinoma was subsequently found. Careful selection and preparation of patients for biopsy are essential. With this caveat, ultrasound-guided sampling of abdominal organs is a useful technique allowing a definitive diagnosis in a high proportion of cases. The technique is minimally invasive and the complication rate low.

Animals↗
PubMed1991

Zuclopenthixol acetate in viscoleo in acutely disturbed psychotic patients.

This report describes an open pilot study of ten acutely disturbed and agitated psychotic patients who received CPT-A zuclopenthixol injections. The dosage ranged from 50 mg to 100 mg. Sedative effects were noticed already after 2 hours, and the patients were all sleepy and sedated after 8 hours. There was a definite improvement in the CGI within 24 hours. The BPRS improved within 24 hours, having the greatest effect on activation, anxiety, depression, and hostile suspiciousness. These effects were sufficient to control these patients. The findings show a rapid onset of therapeutic effect, with no side effects, a duration of 2-3 days and a good local tolerability.

Acute Disease↗