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Biomedical subjects

J Briggs

Publications and source records attributed to J Briggs.

At least 37 records · Page 2Linked to original sources
PubMed1999

A convenient microscale colorimetric method for terminal galactose on immunoglobulins.

A new approach for quantitative determination of terminal galactose (Gal) residues of immunoglobulins was developed by combining exoglycosidase digestion with the classical colorimetric estimation of reducing sugars. The ferricyanide colorimetric method was modified to increase the stability of the chromophore (Prussian blue) and adapted to determine the amount of terminal Gal residues present in immunoglobulins. The method involves the release of covalently bound Gal from immunoglobulins by Diplococcus pneumoniae beta-D-galactosidase (specific for beta(1,4) linked galactose), removal of the glycoprotein and enzyme from the reaction mixture by heat denaturation or ethanol precipitation, followed by colorimetric measurement of the released sugar using the ferricyanide assay. The ferricyanide method was modified to enhance the solubility and stability of the chromophore by increasing the concentration of aqueous sulfuric acid and sodium dodecyl sulfate (SDS). The linear range of the modified method was from approximately 11 to 111 microM Gal. Typical variation in assay results was on the order of 5%. Using the modified method, the terminal Gal content of a recombinant chimeric monoclonal antibody (anti-CD20, rIgG) expressed in Chinese hamster ovary (CHO) cells was determined and evaluated for batch-to-batch consistency. The method was used to optimize pH, time, temperature, and enzyme concentration for beta-galactosidase digestion for maximal release of terminal Gal residues from rIgG.

Animals↗
PubMed1999

Nutrition in ESRD patients: rationale and plan for an initiative.

End-stage renal disease (ESRD) continues to be a major public health problem in the United States. There has been an exponential growth in the incidence rate, at an average of 5% to 8% per year over the past decade. Dialysis remains the predominant therapeutic modality. Unfortunately, however, the morbidity and mortality rates remain unacceptably high for the dialysis patient population. Malnutrition has been consistently suggested as a major contributor to the high morbidity and mortality rates. However, the exact magnitude of the problem is poorly defined. The physiological and pathophysiological mechanisms have not been adequately determined. Finally, any interventional approach and its potential beneficial effect are yet to be carefully defined and explored. This National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) initiative, with input from the ad hoc advisory committee, and strengthened with public comments, is intended to address these deficiencies, and the broad issue of nutrition and nutritional derangement and their detrimental effects on the ESRD patient population.

Congresses as Topic↗
PubMed1999

Engineering Chinese hamster ovary cells to maximize sialic acid content of recombinant glycoproteins.

We have engineered two Chinese hamster ovary cell lines secreting different recombinant glycoproteins to express high levels of human beta1,4-galactosyltransferase (GT, E.C. 2.4.1.38) and/or alpha2, 3-sialyltransferase (ST, E.C. 2.4.99.6). N-linked oligosaccharide structures synthesized by cells overexpressing the glycosyltransferases showed greater homogeneity compared with control cell lines. When GT was overexpressed, oligosaccharides terminating with GlcNAc were significantly reduced compared with controls, whereas overexpression of ST resulted in sialylation of >/=90% of available branches. As expected, GT overexpression resulted in reduction of oligosaccharides terminating with GlcNAc, whereas overexpression of ST resulted in sialylation of >/=90% of available branches. The more highly sialylated glycoproteins had a significantly longer mean residence time in a rabbit model of pharmacokinetics. These experiments demonstrate the feasibility of genetically engineering cell lines to produce therapeutics with desired glycosylation patterns.

Animals↗
PubMed1999

Transcervical recovery of fetal cells from the lower uterine pole: reliability of recovery and histological/immunocytochemical analysis of recovered cell populations.

The aim of this work was to isolate, enumerate and attempt the identification of fetal cells recovered from the lower uterine pole. Immediately before elective termination of pregnancy at 7-17 weeks gestation, samples were recovered by transcervical flushing of the lower uterine pole (n = 108) or transcervical aspiration of mucus from just above the internal os (n = 187), and their contents examined using histological, immunohistochemical and molecular techniques. Syncytiotrophoblasts were identified morphologically in 28 out of 89 (31%) and 50 out of 180 (28%) flushings and aspirates respectively (mean 29%). Immunocytochemistry with monoclonal antibodies (mAbs) recognizing trophoblast or epithelial cell antigens on a smaller number of samples (n = 69) identified putative placental cells in 13 out of 19 (68%) and 25 out of 50 (50%) flushings and aspirates respectively (mean 55%). These included groups of distinctive cells with a small, round, hyperchromatic nucleus, strongly reactive with mAbs PLAP, NDOG1 and FT1.41.1. Smaller groups of larger, amorphous cells, usually containing multiple large, pale staining nuclei, reactive with mAb 340 and to a lesser degree with mAb NDOG5 were also observed. Taking cellular morphology and immunophenotype into consideration, the smaller uninucleate cells were likely to be villous mesenchymal cells, while the larger cells were possibly degrading villous syncytiotrophoblast. There was no significant difference in the frequency of fetal cells obtained by the two recovery methods. Squamous or columnar epithelial cells, labelled strongly with antibodies to cytokeratins or human milk fat globule protein, were observed in 97% (29 out of 30) of aspirates. The use of cervagem in a small number of patients prior to termination of pregnancy did not appear to influence the subsequent recovery of placental cells. Y-specific DNA was detected by polymerase chain reaction (PCR) in 13 out of 26 (50%) flushings and (99 out of 154) 64% aspirates analysed (mean 62%). In-situ hybridization (ISH) revealed Y-specific targets in 40 out of 69 (60%) of aspirates analysed. A comparison of PCR data obtained from transcervical recovered samples and placental tissues showed a concordance of 80% (76 out of 95), with 10 false positives. Comparing the PCR data from tissues with data derived by ISH from 41 aspirates gave a concordance of 90% with two false positives. Although syncytiotrophoblasts were much more likely to be present in samples containing immunoreactive placental cells, the detection rates of fetal-derived DNA were similar regardless of the morphological and/or immunological presence of placental cells. We conclude that the transcervical recovery of fetal cells, while promising, requires considerable additional effort being expended in further research and development, particular in the sampling procedure.

Antibodies, Monoclonal↗
PubMed1997

Post-translational processing and renal expression of mouse Indian hedgehog.

The full-length mouse Indian hedgehog (Ihh) cDNA was cloned from an embryonic 17.5-day kidney library and was used to study the post-translational processing of the peptide and temporal and spatial expression of the transcript. Sequence analysis predicted two putative translation initiation sites. Ihh translation was initiated at both initiation sites when expressed in an in vitro transcription/translation system. Expression of an Ihh mutant demonstrated that the internal translation initiation site was sufficient to produce the mature forms of Ihh. Ihh post-translational processing proceeded in a fashion similar to Sonic and Drosophila hedgehog; the unprocessed form underwent signal peptide cleavage as well as internal proteolytic processing to form a 19-kDa amino-terminal peptide and a 26-kDa carboxyl-terminal peptide. This processing required His313 present in a conserved serine protease motif. Ihh transcript was detected by in situ RNA hybridization as early as 10 days postcoitum (dpc) in developing gut, as early as 14.5 dpc in the cartilage primordium, and in the developing urogenital sinus. In semiquantitative reverse transcription-polymerase chain reaction experiments, Indian hedgehog transcript was first detected in the mouse metanephros at 14.5 dpc; transcript abundance increased with gestational age, becoming maximal in adulthood. In adult kidney, Ihh transcript was detected only in the proximal convoluted tubule and proximal straight tubule.

Amino Acid Sequence↗
PubMed1997

Pityriasis rubra pilaris: an unusual cutaneous complication of AIDS.

Pityriasis rubra pilaris is an uncommon hyperkeratotic, papulosquamous disorder that has been reported in patients infected by HIV. We recount a case of pityriasis rubra pilaris in an HIV-seropositive man. A 36-year-old man with a history of ulcerative colitis and recurrent otitis externa had diffuse psoriaform erythroderma. He was treated initially with methotrexate and isoretinoin without clinical improvement. Skin examination showed large, erythematous, orange, scaly patches on the upper extremities and thickening of the nail beds. The palms and soles were hyperkeratotic. Skin biopsy revealed changes that were consistent with pityriasis rubra pilaris. Six months before the onset of symptoms, results of an enzyme-linked immunosorbent assay (ELISA) and Western Blot assay for HIV were negative. Six months after symptoms, results of repeat enzyme-linked immunosorbent assay and Western blots for HIV were positive (CD4+ T-cell count = 200 cells/ mm3). Clinical course had been complicated by episodes of Staphylococcus aureus bacteremia, mucocutaneous candidiasis, and development of localized squamous cell carcinoma of the skin. The increased severity of pityriasis rubra pilaris should prompt clinicians to consider coinfection with HIV in patients who have disease that is refractory to treatment. Clinicians also should remain vigilant for the development of squamous cell carcinoma.

AIDS-Related Opportunistic Infections↗
PubMed1997

Intravenous gentamicin and ceftazidime in penetrating ocular trauma: a swine model.

PURPOSE: A swine model of ocular trauma was used to determine the extent of penetration of systematically administered gentamicin and ceftazidime to the vitreous cavity of traumatized and normal eyes. METHODS: Forty-six pigs received a scleral laceration to the right eye and then underwent surgical repair. Thirty-six animals received intravenous gentamicin, and 10 pigs were given ceftazidime. RESULTS: The level of gentamicin in the vitreous of traumatized and nontraumatized eyes did not achieve the minimum inhibitory concentrations (MIC) for Pseudomonas and Haemophilus species despite multiple and large intravenous doses. Ceftazidime concentrations in traumatized eyes were above the minimum inhibitory concentration for these organisms. CONCLUSIONS: Ceftazidime achieves an intravitreal concentration 33 times the minimum inhibitory concentration of Haemophilus species and twice that of Pseudomonas species in traumatized eyes after systemic administration, a finding that lends support to its use as a prophylactic agent in the management of penetrating ocular trauma. Gentamicin does not appear to enter the traumatized eye at appreciable levels after systemic administration, and, therefore, it is not recommended for use as a prophylactic agent in the management of penetrating ocular trauma.

Animals↗
PubMed1997

Human subject research at Armstrong Laboratory, 1973-93: medical and musculoskeletal disqualifications.

The reasons for disqualification of human subjects from 1973-93 at Armstrong Laboratory, formerly the Harry G. Armstrong Aeromedical Research Laboratory (AAMRL), are presented for both sustained and impact acceleration panels. Evaluations for both medical and spinal anomalies were accomplished. The rationale for each disqualification is discussed, demonstrating the variability in each panel physician's clinical judgment in the context of personal bias, the ethical framework surrounding the use of human volunteers, and the existing research milieu.

Acceleration↗
PubMed1997

Comparison of acceleration subjects to other populations: spinal anomaly distribution.

Two Armstrong Laboratory (AL) human volunteer subject panels (sustained and impact acceleration) at Wright Patterson AFB, OH, were compared to each other and to other samples of different populations in terms of spinal anomalies. These sample populations were obtained from the scientific literature: French, Norwegian, Netherlands, and U.S. pilots; U.S. Air Force (AF) and Navy subjects, and from representative "normal" civilian populations, and then compared using the proportion parameters for various spinal anomalies. There were only a few common parameters between the two panels and between each panel compared with the foreign military, human subjects, and "normal" population. However, there were two to six times as many similar spinal anomaly incidence rates between the AL panels and the U.S. pilot sample. It was reassuring that the AL subject panels used in AF acceleration research have more in common with AF pilots than other populations in regards to spinal anomalies, even though the pilot sample may not be representative of the true pilot population. Recommendations are to establish a common reference point in nomenclature and description of spinal anomalies (modeled after the French) and to start collecting spinal radiographs on all U.S. pilots. These radiographs would not be for screening but for establishing a database following the occupational pathology of flying. This data would also facilitate comparisons with research acceleration panels, as well as with foreign air forces. Informed decisions can then be made regarding screening criteria for the future as aircraft and ejection seat performance envelopes continue to expand.

Acceleration↗
PubMed1997

Human subject screening: a dynamic process.

INTRODUCTION: The history of disqualified (DQ) subjects from 1973-1993 at Armstrong Laboratory, Wright Patterson AFB, is presented for both sustained and impact acceleration panels. METHODS: Candidate and subject medical records were reviewed for screening results, recommendation for panel duty, and any follow-up medical findings. The generation and interpretation of the medical screening criteria and DQ rates are discussed. MEDICAL SCREENING CRITERIA: The mechanisms for change, those factors influencing change, and the interpretation of the screening criteria for Armstrong Laboratory's acceleration panels determine the panel's composition, which is reflected in the DQ rates. RESULTS: The centrifuge had a 5% (7/132) disqualification (DQ) rate from 1973-93 with 29% (2/7) due to musculoskeletal and 71% (5/7) for medical reasons. All were DQ during 1973-88. The impact panel had a DQ rate of 18% (36/195) with 71% (24/34) DQ due to musculoskeletal and 29% (10/34) for medical reasons. Only 28% (10/36) were DQ during 1973-88, while during 1989-93, 72% (26/36) were DQ. CONCLUSIONS: The differences in DQ rates between the centrifuge and impact facility were due to the variability or conservatism of individual physicians, interpretation of the medical screening criteria, and the type of research being done. These factors effect the composition of the human subject panels. This determines to which target population the research data can be applied. If the subjects do not represent pilots due to inappropriate screening, then there is no benefit from the research and, therefore, there can be no risk incurred by the subjects.

Acceleration↗
PubMed1996

Reliability of trans-cervical recovery of placental cells from the lower uterine pole using a minimally invasive procedure. Evidence based on fetal sexing and analysis of recovered cell populations.

OBJECTIVE: Efficient recovery of placental cells (and their subsequent characterisation) from the lower uterine pole (L.U.P) by trans-cervical flushing or aspiration. SUBJECTS: Women attending for termination of pregnancy (7-17 weeks' gestation) for social reasons. All patients gave their consent to the procedures outlined below. METHODS: Trans-cervical intrauterine flushing (using 0.15 M NaCl) or mucus aspiration. Embryo transfer catheters were used in both procedures. Fetal sexing was achieved by gene amplification of Y-specific DNA sequences (Y-PCR), and by in situ hybridisation (bright-field and fluorescence) to the Y-chromosome. Data were compared with results obtained from fetal tissues recovered following termination of pregnancy. Gender-independent tests for fetal cells utilised immunocytochemistry with trophoblast-specific antibodies and dual immunocytochemistry/ISH, where appropriate. RESULTS: (1) Fetal sexing by Y-PCR: 71/122 (58%) aspirates contained Y-specific DNA. In addition, the sexing of 72/86 (84%) aspirates and their corresponding samples of placental tissue, agreed exactly. (2) Microscopic detection of fetal cells. Placentally-derived syncytiotrophoblast was detected in 17/45 (38%) flushings and 39/173 (23%) aspirates. In most other Y-PCR+ samples which were negative for syncytiotrophoblast, Y-chromosome-bearing nuclei of unknown origin, were observed by ISH and immunocytochemical evidence for cytotrophoblastic cells was also uncovered. CONCLUSIONS: Since Y-derived DNA can be detected in > 50% of flushings and aspirations, and gender-independent evidence for placental cells was obtained, regardless of fetal sex, we believe that most or all of these samples contained placental cells, including trophoblasts and naked nuclei. Trans-cervical placental cell recovery is a potentially valuable alternative to more invasive methods of aneuploid detection which require amniocentesis and CVS, provided its level of accuracy and above all, safety, can be evaluated.

Cervix Uteri↗
PubMed1996

Riding a Trojan horse: computerized psychiatric treatment planning using managed care principles.

Efforts to curtail health care costs have triggered new emphasis on resource management and accountability, entailing explicit documentation of the rationale for treatment and the resulting outcome of care. This article discusses the development of a computerized psychiatric treatment planning database that embodies principles and language of managed care, including specific admission criteria, severity ratings, and time frames for completion of interventions. The program is designed to balance goals of clinical utility, usefulness of the database as a tool for utilization review, quality improvement, and health services research, while providing an interface that is acceptable to clinicians.

Case Management↗
PubMed1995

Non-syncytial sources of fetal DNA in transcervically recovered cell populations.

We have previously shown that fetal DNA can be detected in swabs and flushings obtained from the lower uterine pole prior to the termination of pregnancy. The presence of syncytiotrophoblast vesicles in transcervically retrieved samples suggested that this distinctive placental tissue was an abundant source of fetal DNA and a valuable resource in prenatal diagnosis strategies. In a more extensive study involving 150 terminations of pregnancy between 7 and 17 weeks gestational age, 29% of transcervically retrieved samples contained visible syncytial vesicles. Flushing of the uterine pole more frequently contained syncytia than direct aspiration (39% compared with 26% of samples) but this difference was not statistically significant. No samples > 14 weeks gestational age contained syncytia. Polymerase chain reaction analysis using Y-sequence specific-nested primers indicated the presence of fetal DNA in the absence of intact syncytial vesicles. We therefore examined samples by in-situ hybridization using Y-specific DNA probes. Positive labelling was observed in syncytial vesicles where present and in clumps of unidentified fetal cells. In addition, high numbers of naked nuclei were labelled in samples devoid of syncytia. These isolated nuclei are possibly derived from disrupted syncytia, and may be an important and hitherto overlooked contributory factor in fetal material which collects at the lower uterine pole.

Cervix Uteri↗
PubMed1995

Effects of opioid antagonists naloxone and naltrexone on neuropeptide Y-induced feeding and brown fat thermogenesis in the rat. Neural site of action.

Neuropeptide Y administered intracerebroventricularly and into the paraventricular nucleus of the hypothalamus stimulates feeding and decreases brown adipose tissue thermogenesis. Although specific neuropeptide Y antagonists are not yet available, previous studies had shown that the opioid antagonist naloxone blocked neuropeptide Y-induced feeding when both drugs were injected intracerebroventricularly. We wanted to find out if naloxone injected into specific brain sites would block neuropeptide Y effects on feeding and brown fat thermogenesis. Rats were double injected in specific brain sites with neuropeptide Y and either naloxone or naltrexone (a congener of naloxone). Food intake and brown fat measures were assessed. Naloxone or naltrexone in the paraventricular nucleus weakly decreased paraventricular nucleus neuropeptide Y-induced feeding and did not affect neuropeptide Y-induced reductions in brown fat activity. Peripheral naloxone blocked intracerebroventricular neuropeptide Y-induced feeding and brown fat alterations. Fourth ventricular naloxone decreased paraventricular nucleus neuropeptide Y-induced feeding, and naltrexone given into the nucleus of the solitary tract blocked paraventricular nucleus neuropeptide Y-induced alterations in feeding and brown fat. These data indicate that neuropeptide Y in the paraventricular nucleus may act on feeding and brown fat thermogenesis through opioidergic pathways in the nucleus of the solitary tract.

Adipose Tissue, Brown↗
PubMed1995

Occlusal splint prescription in the management of temporomandibular disorders.

The case records of 159 patients who had been treated for temporomandibular disorders at the School of Clinical Dentistry Queen's University of Belfast were analysed retrospectively to determine which type of occlusal splint had been prescribed. Full maxillary occlusal coverage polycarbonate vacuum formed splints were prescribed most frequently, being used in 45% of cases, whilst lower splints were rarely constructed. After treatment 54% were asymptomatic which is slightly greater than that described by others as a placebo effect in splint therapy. This low success rate was, at least, in part attributable to a poor overall management strategy. The study highlights the need for a structured management strategy in treating patients with temporomandibular disorders and suggests a need for continuing postgraduate education in the care of these patients.

Humans↗
PubMed1994

Interferon alpha selectively affects expression of the human myeloid cell nuclear differentiation antigen in late stage cells in the monocytic but not the granulocytic lineage.

The human myeloid cell nuclear differentiation antigen (MNDA) is expressed constitutively in cells of the myeloid lineage, appearing in myeloblast cells in some cases of acute myeloid leukemia and consistently being detected in promyelocyte stage cells as well as in all later stage cells including peripheral blood monocytes and granulocytes. The human myeloid leukemia cell lines, HL-60, U937, and THP-1, express similar levels of immunochemically detectable MNDA. Although, the level of MNDA mRNA in primary monocytes is very low it was up-regulated at 6 h following the addition of interferon alpha. The effect of interferon alpha on the MNDA mRNA is also observed in the cell lines HL-60, U937, and THP-1. The MNDA mRNA level in primary granulocytes was unaffected by addition of interferon alpha and other agents including interferon gamma, endotoxin, poly (I).poly (C), and FMLP. The MNDA mRNA level in the myeloid cell lines was also unaffected by the latter four agents. Induction of differentiation in the myeloid cell lines with phorbol ester induces monocyte differentiation which was accompanied by a decrease in MNDA mRNA level. This reduced level of mRNA could then be elevated with subsequent interferon alpha treatment. The effects of phorbol ester on MNDA mRNA appeared to be associated with induced differentiation since inhibiting cell proliferation did not alter the level of MNDA mRNA and cell cycle variation in MNDA mRNA levels were not observed. The ability of interferon alpha to up-regulate MNDA mRNA in phorbol ester treated myeloid cell lines is consistent with the observations made in primary monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, Myelomonocytic↗