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Biomedical subjects

C Briggs

Publications and source records attributed to C Briggs.

At least 19 recordsLinked to original sources
PubMed2002

The position of the spine in the recovery position--an experimental comparison between the lateral recovery position and the modified HAINES position.

UNLABELLED: The lateral recovery position is widely used for the positioning of unconscious patients. Ideally, in the setting of trauma it is avoided because of concerns about spinal cord injury. However, unconscious individuals with unsuspected trauma or trauma victims attended by partially trained first-aiders may be placed in the recovery position, potentially endangering the cord. Excessive movement of the spine in the recovery position may increase the risk of spinal cord injury in these situations. A new recovery position, termed the modified HAINES position, is described and the position of the spine in this position is compared with the lateral recovery position. HYPOTHESIS: That the modified HAINES position results in less distortion of the position of the spine than the lateral recovery position. METHODS: Thirty-eight healthy volunteers were imaged in the two different positions. Measurements of rotation, flexion and lateral flexion of the cervical and thoraco-lumbar spine were made. Two tailed paired t-tests were employed to compare measurements of the two positions and a McNemar test was used to compare the subjects' subjective experiences. RESULTS: The modified HAINES position resulted in 13.0 degrees (99% CI: 7.5-18.5) less lateral flexion and 12.6 degrees (99% CI: 9.4-15.9) less extension of the cervical spine while the position of the thoraco-lumbar spine was similar in both positions. Nineteen of 28 subjects found the modified HAINES position more comfortable (not significant). CONCLUSION: The modified HAINES position results in a more neutral position of the spine making it preferable to the lateral recovery position in the management of patients when trauma may have occurred. Further research is required to ensure that the recovery positions in use today are the best possible.

Adolescent↗
PubMed2002

Photodynamic therapy for superficial bladder cancer under local anaesthetic.

OBJECTIVES: To evaluate the use of local anaesthesia (LA) in 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) for superficial transitional cell carcinoma (TCC) of the bladder, and to provide further toxicity and tolerability data on this new method within the context of a phase 1 trial. PATIENTS AND METHODS: ALA PDT was administered to 19 patients with recurrent superficial TCC (stage Ta/carcinoma in situ, grades 1-3) using escalating doses of ALA (3-6%) and 633 nm laser light (25-50 J/cm2) under various LA (lignocaine) protocols. Pain was assessed using a linear analogue scale from 0 to 10. The endpoints of tolerability and toxicity were assessed for the different LA, light and ALA doses, with lignocaine levels. RESULTS: ALA PDT is painful and requires some form of anaesthesia. The discomfort was immediate, associated with bladder spasm, and was a function of the ALA concentration rather than the total light dose given. Simple passive diffusion (PD) of 2% lignocaine instilled for 40 min before PDT gave adequate anaesthesia with 3% ALA (n=8; median pain score 1, range 0-2). With 6% ALA the pain was dramatically increased using PD (n=6; median pain score 8, range 5-10) and therefore the more potent LA technique of electromotive drug administration (EMDA) of 2% lignocaine was used, with excellent results (n=3; median pain score 1, range 0-2). All patients had transient bladder irritability that typically lasted 9-12 days, with no subjective/objective change in long-term bladder function. No other toxicity was reported. Serum lignocaine levels were minimal. CONCLUSION: Bladder ALA PDT is both safe and feasible under LA. At a dose of 3% ALA, the procedure was well-tolerated using PD of lignocaine. At higher doses (6% ALA) more effective anaesthesia is required and this can be obtained satisfactorily with EMDA of lignocaine. With refinement, ALA PDT may be feasible as an outpatient treatment for superficial bladder TCC.

Aged↗
PubMed2001

Mitochondrial phosphate transport protein. Reversions of inhibitory conservative mutations identify four helices and a nonhelix protein segment with transmembrane interactions and Asp39, Glu137, and Ser158 as nonessential for transport.

The mitochondrial phosphate transport protein (PTP) has six (A--F) transmembrane (TM) helices per subunit of functional homodimer with all mutations referring to the subunit of the homodimer. In earlier studies, conservative replacements of several residues located either at the matrix end (Asp39/helix A, Glu137/helix C, Asp236/helix E) or at the membrane center (His32/helix A, Glu136/helix C) of TM helices yielded inactive single mutation PTPs. Some of these residues were suggested to act as phosphate ligands or as part of the proton cotransport path. We now show that the mutation Ser158Thr, not part of a TM helix but located near the center of the matrix loop (Ile141--Ser171) between TM helices C and D, inactivates PTP and is thus also functionally relevant. On the other side of the membrane, the single mutation Glu192Asp at the intermembrane space end of TM helix D yields a PTP with 33% wild-type activity. We constructed double mutants by adding this mutation to the six transport-inactivating mutations. Transport was detected only in those with Asp39Asn, Glu137Gln, or Ser158Thr. We conclude that TM helix D can interact with TM helices A and C and matrix loop Ile141--Ser171 and that Asp39, Glu137, and Ser158 are not essential for phosphate transport. Since our results are consistent with residues present in all 12 functionally identified members of the mitochondrial transport protein (MTP) family, they lead to a general rule that specifies MTP residue types at 7 separate locations. The conformations of all the double mutation PTPs (except that with the matrix loop Ser158Thr) are significantly different from those of the single mutation PTPs, as indicated by their very low liposome incorporation efficiency and their requirement for less detergent (Triton X-100) to stay in solution. These dramatic conformational differences also suggest an interaction between TM helices D and E. The results are discussed in terms of TM helix movements and changes in the PTP monomer/dimer ratio.

Amino Acid Sequence↗
PubMed2001

Detection of immunomagnetically captured Escherichia coli O157:H7 by antibody-conjugated alkaline phosphatase.

A rapid and sensitive detection process for Escherichia coli O157:H7 was developed using alkaline phosphatase (APase)-labeled anti-E. coli O157 antibodies to tag the targeted bacteria. Immunomagnetic beads or antibody-labeled streptavidin-coated magnetic beads were then used to capture the APase-tagged E. coli. Immunomagnetically captured bacteria were washed and distributed into microplates or optical cuvettes. The enzyme-catalyzed hydrolysis of p-nitro-phenol phosphate in alkaline solutions was then followed. Less than 1000 cfu/ml of E. coli O157:H7 could be detected. This approach was applied to detect the bacteria artificially spiked in beef hamburgers. Less than 1 cfu/g of E. coli O157:H7 produced a significant response after cultural enrichment for 4-6 h at 37 degrees C.

Alkaline Phosphatase↗
PubMed2001

Photodynamic therapy for superficial bladder cancer.

In photodynamic therapy, a photosensitizing drug is activated by visible light and in the presence of oxygen, results in local cell death. This evolving modality is now being used to treat and palliate a very wide variety of human solid tumors and carcinoma-in-situ lesions. With regard to bladder cancer, advances in drug development and modern light delivery techniques mean that photodynamic therapy shows promise in the treatment of superficial bladder cancer resistant to conventional treatments.

Aminolevulinic Acid↗
PubMed2000

Effect of the alpha-glucosidase inhibitor acarbose on control of glycemia in dogs with naturally acquired diabetes mellitus.

OBJECTIVE: To evaluate effect of acarbose on control of glycemia in dogs with diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 5 dogs with naturally acquired diabetes mellitus. PROCEDURE: Dogs were treated with acarbose and placebo for 2 months each: in 1 of 2 randomly assigned treatment sequences. Dogs that weighed < or = 10 kg (22 lb; n = 3) or > 10 kg (2) were given 25 or 50 mg of acarbose, respectively, at each meal for 2 weeks, then 50 or 100 mg of acarbose, respectively, at each meal for 6 weeks, with a 1-month interval between treatments. Caloric intake, type of insulin, and frequency of insulin administration were kept constant, and insulin dosage was adjusted as needed to maintain control of glycemia. Serum glucose concentrations, blood glycosylated hemoglobin concentration, and serum fructosamine concentration were determined. RESULTS: Significant differences in mean body weight and daily insulin dosage among dogs treated with acarbose and placebo were not found. Mean preprandial serum glucose concentration, 8-hour mean serum glucose concentration, and blood glycosylated hemoglobin concentration were significantly lower in dogs treated with insulin and acarbose, compared with insulin and placebo. Semisoft to watery feces developed in 3 dogs treated with acarbose. CONCLUSIONS AND CLINICAL RELEVANCE: Acarbose may be useful as an adjunctive treatment in diabetic dogs in which cause for poor glycemic control cannot be identified, and insulin treatment alone is ineffective.

Acarbose↗
PubMed2000

Immunoplatelet counting: a proposed new reference procedure.

Given the high degree of interoperator error and poor precision of manual platelet counting, it has recently been proposed that an immunoplatelet counting method could become the new reference procedure. Platelets are identified immunologically with a suitable monoclonal antibody, and the platelet count is derived from the ratio of fluorescent platelet events to collected red blood cell (RBC) events that are also counted by a reliable and calibrated standard impedance counter (RBC ratio). In this study, we have set up a rapid and simple method for immunoplatelet counting and simultaneously compared the RBC ratio with the bead ratio derived from two different preparations of commercial calibration beads (Trucount and FlowCount beads). Comparison of the level of imprecision of the RBC ratio with either the manual count or bead ratios revealed a superior coefficient of variation of < 5% even in samples with a platelet count < 20 x 10(9)/l. The RBC ratio correlated extremely well with the existing manual phase reference method (r2 = 0.93) and especially well with three different commercial impedance counters and a dual-angle optical counter (r2 = 0.98-0.99). However, at < 100 x 10(9)/l, the correlation of the RBC ratio with the dual-angle optical count (ADVIA 120) (r2 = 0.96) was superior to all impedance counters. This suggests that automated optical counting methods may be more accurate at determining platelet counts in thrombocytopenic samples. As the RBC ratio is rapid, cheap and relatively easy to perform, we propose that this method could replace the manual count as a new international reference method.

Calibration↗
PubMed2000

New quantitative parameters on a recently introduced automated blood cell counter--the XE 2100.

The XE 2100 (Sysmex Corporation) is a cell counter that furthers the technology of fluorescent flow cytometry developed from the earlier range of Sysmex analysers. The new diagnostic features are a nucleated red cell count (NRBC), the ability to measure platelets by impedance as well as an 'optical' platelet count using a fluorescence dye and an immature granulocyte (IG) count. The NRBC count was highly correlated (r = 0.97) with the manual reference count. For counts below 100 x 109/l the 'optical' method and the immunocount gave good a correlation (r = 0.97) optical and impedance counts were also well correlated (r = 0.89). The use of the 'optical' platelet count significantly improves the reliability of low platelet counts. The IG count correlated with visual counts (r = 0.81) and allows the detection of immature cells at an earlier stage in the laboratory process. The introduction of fluorescent flow cytometric analysis allows extended quantification of additional cell populations and so potentially improves screening and monitoring of various pathological conditions.

Adult↗
PubMed1999

Replacements of basic and hydroxyl amino acids identify structurally and functionally sensitive regions of the mitochondrial phosphate transport protein.

The mitochondrial phosphate transport protein (PTP) from the yeast Saccharomyces cerevisiae has been expressed in Escherichia coli, purified, and reconstituted. Basic and hydroxyl residues were replaced to identify structurally and functionally important regions in the protein. Physiologically relevant unidirectional transport from extraliposomal (cytosol) pH 6.8 to intraliposomal (matrix) pH 8.0 was assayed. Replacements that affect transport most dramatically are at Lys42 (matrix end of helix A), Thr79 (helix B), Lys90 (cytosol end of helix B), Arg140 and Arg142 (matrix end of helix C), Lys179 and Lys187 (helix D), Ser232 (helix E), and Arg276 (helix F). The deleterious nature of these mutations was confirmed by the observation that the yeast PTP null mutant transformed with any one of these mutant genes cannot grow or has difficulties growing with glycerol as the primary carbon source. More than 90% of transport activity can be blocked by various mutations without affecting growth on glycerol. Alterations in the structure of the transport protein caused by the mutations were characterized by determining the fraction of PTP incorporated into liposomes during reconstitution. The incorporation of all PTPs (wild type and mutant) into liposomes is 15.5 +/- 8.4 ng of PTP/25 microL and fairly independent of the amount of PTP in the initial reconstitution mix (49-212 ng of PTP/25 microL). Arg159Ala and Lys295Gln show the smallest incorporation of 2.3 +/- 1.6 ng of PTP/25 microL and 2.6 +/- 0.2 ng of PTP/25 microL, respectively. Ser145Ala shows the largest incorporation of 37.0 ng of PTP/25 microL. These three mutants show near wild-type reconstituted transport activity. Two of these three mutations are located in the loop connecting the matrix ends of helices C and D, Ser145 at its N-terminal (the matrix end of helix C) and Arg159 near its center. Lys295 is located at the C-terminal of PTP beyond helix F. These results, together with those from other mutations, suggest that like helix A, the protein segment consisting of the loop connecting helices C and D and helix D as well as the C-terminal of PTP beyond helix F faces the subunit interface of this homodimer. The role of the replacement-sensitive residues in the phosphate or in the coupled proton transport path is discussed.

Amino Acid Sequence↗
PubMed1998

The pathogenesis of Schmorl's nodes in relation to acute trauma. An autopsy study.

STUDY DESIGN: Seventy thoracolumbar spines from cadavers of individuals killed in motor vehicle accidents were examined pathologically and radiologically, particularly for the occurrence of acute Schmorl's nodes. OBJECTIVES: To document whether Schmorl's nodes occur acutely as a result of trauma. SUMMARY OF BACKGROUND DATA: Theories proposed to explain the pathogenesis of Schmorl's nodes include developmental, degenerative, traumatic, and disease influences. Few studies show a direct causal relation between a traumatic episode and acute Schmorl's node formation. METHODS: Thoracolumbar spines were removed at autopsy, underwent radiography in the anteroposterior and lateral planes, fixed, sagittally cut, and underwent radiography a second time. Pathologic and radiographic examinations were performed. RESULTS: Nine acute Schmorl's nodes were detected, most in association with other acute injuries to the spine. Most acute Schmorl's nodes were present in spines from individuals aged 11-30 years, with a male to female ratio of 9:1, and were localized to the T8-L1 region. Spines from motorcyclists showed the highest percentage of acute Schmorl's nodes. No acute Schmorl's nodes were detected radiologically. CONCLUSION: Schmorl's nodes do occur acutely as the result of a single traumatic episode, and are almost always associated with other acute spinal injury. The frequency and occurrence of acute Schmorl's nodes in motorcyclists suggest that axial loading is an important mechanism. Their predominance in the T8-L1 region suggests that this region is particularly susceptible to stress.

Acute Disease↗
PubMed1998

Repertoire analysis of CD8+ T cell responses to minor histocompatibility antigens involved in graft-versus-host disease.

Graft-vs-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. Experimentally, lethal GVHD can be induced in MHC-matched strain combinations differing in expression of multiple minor histocompatibility Ags (miHA). Recently, the GVHD potential of C57BL/6By (B6) T cells in irradiated BALB.B (both H2b) and related CXB recombinant inbred strains of mice has been studied to determine the scope of the response to miHA in vivo and how it compared with CTL responses to immunodominant miHA in vitro. The GVHD response in these strain combinations appeared to be limited to a few Ags, yet there was no correlation of these miHA with that of in vitro CTL responses. To further investigate the role of CD8+ T cells in GVHD, we analyzed positively selected miHA-specific donor CD8+ thoracic duct lymphocytes (TDL) collected from irradiated BALB.B and CXBE mice, 5 to 6 days after transplantation of B6 T cells. Flow cytometric analysis of B6-->BALB.B TDL did not indicate expansion of any particular TCR Vbeta family, whereas Vbeta10 and Vbeta14 families were significantly expanded in the B6-->CXBE TDL. However, PCR-based complementarity-determining region 3 size spectratyping revealed overlapping involvement of donor Vbeta1, 6, 8, 9, 10, and 14 families in both BALB.B and CXBE recipients and unique utilization of the Vbeta4 family in BALB.B mice, suggesting oligoclonal T cell responses to a limited number of miHA. In addition, the injection of CD8+ Vbeta14+ B6 T cells into irradiated BALB.B and CXBE mice induced lethal GVHD, confirming the involvement of miHA-specific T cells within an individual Vbeta family.

Animals↗
PubMed1998

Molecular characterization of the putative T-cell receptor cavity of the superantigen staphylococcal enterotoxin B.

A number of investigators have utilized a variety of methods to identify the structural basis for the interaction of superantigens with the T-cell receptor beta-chain. The previous studies strongly suggest that a region of the toxin near residues N23, Y61, Y91 and D209 is important for this binding activity. Examination of crystal structure data shows that these residues line the rim of one side of a shallow cavity in the toxin. In an attempt further to define the face of the staphylococcal enterotoxin B (SEB) molecule involved in the interaction with the beta-chain, we have employed a polymerase chain reaction (PCR)-based, site-specific mutagenesis method to generate amino acid substitutions of residues on the opposite side of this putative T-cell receptor interaction cavity. Our results show that Y175 and N179 appear to be involved in the function of this superantigen, since each of several substitutions at this position exhibits a significantly reduced ability to induce T-cell proliferation. At the same time, mutation of the proximal Y186 does not alter the superantigen activity of SEB. Binding analysis of these mutants shows that class II binding activity is not significantly altered. Analysis of the responding T cells shows that the mutant toxins maintain T-cell receptor V beta selectivity. However, responses of T cells bearing the V beta 8.1 allele appear to be particularly diminished. When viewed in the context of other results reported in the literature, our results suggest that the T-cell receptor interaction site involves SEB residues which ring both the Y175/N179-side and the N23-side of a cavity on one side of the toxin molecule.

Alleles↗
PubMed1998

Decreased light intensity alters the perception of day length by male European starlings (Sturnus vulgaris).

The breeding season of wild starlings is controlled by photoperiod. Full breeding condition is attained during exposure to lengthening days in the spring, and photorefractoriness ensues. The reproductive system of starlings will not subsequently be stimulated by long day lengths until photorefractoriness is dissipated by the short day lengths experienced in the autumn and winter. Unlike most studies on avian photoperiodism, this investigation involved manipulation of light intensity of a fixed photoperiod rather than of photoperiod itself. Photosensitive starlings transferred from short days to long days of different light intensities underwent graded reproductive responses according to the light intensity they experienced. Testes size in the group in the lowest intensity (3 lux) increased faster than that in controls on short days of normal intensity, but they did not become photorefractory. Testes size increased in the groups on 13, 45, and 108 lux and subsequently became photorefractory. However, the 13- and 45-lux groups required more time to become photorefractory than did the 108-lux group. The responses observed were similar to those seen in starlings exposed to different photoperiods (e.g., 11 h light:13 h dark [11L:13D], 13L:11D, 16L:8D, 18L:6D), even though all were on the same 18L:6D photoperiod. Initially, the results appear to challenge the external coincidence model for photoperiodic time measurement, but consideration of the phase response curve of the circadian rhythm of photoinducibility in starlings and the way in which it might be affected by low light intensities refute this challenge.

Animals↗
PubMed1997

Mutations affecting the superantigen activity of staphylococcal enterotoxin B.

As a superantigen, staphylococcal enterotoxin B (SEB) possesses the ability to bind to major histocompatibility complex class II molecules and be recognized by T cells bearing certain T-cell receptor (TCR) V beta alleles. Other investigators have utilized site-specific mutagenesis to generate amino acid substitutions to identify residues that may be involved in the interaction with the TCR beta-chain. In an attempt further to define the face of the SEB molecule involved in the interaction with the beta-chain, we have employed a polymerase chain reaction (PCR)-based, site-specific mutagenesis method to generate amino acid substitutions with altered superantigen activity. Our results show that valine at position 169 appears to be involved in the function of this superantigen, since each of several substitutions at this position exhibit a significantly reduced ability to induce T-cell proliferation. Analysis of the responding T cells to the residue 169 substitution shows that the mutant toxins maintain TCR V beta selectivity. At the same time, mutation of the proximal histidine at position 166 does not alter the superantigen activity of SEB. Radiolabelled binding analysis of these H166 and V169 mutants shows that class II-binding activity is not significantly altered. When viewed in the context of other results reported in the literature, combined with the crystal structure of the toxin, our results suggest that the interaction with the TCR probably involves SEB residues which ring a cavity along one side of the toxin molecule.

Animals↗
PubMed1997

Liver torsion and associated bacterial peritonitis in a dog.

A Malamute was examined for acute abdominal pain and collapse. Radiographs of the abdomen showed a pneumoabdomen, and a lucent mass in the region of the liver. Abdominocentesis yielded an inflammatory exudate with bacteria compatible with a Bacillus or a Clostridium sp. A quadrate lobe torsion was found at postmortem.

Abdomen, Acute↗
PubMed1996

Inhibitory effect of a CD4-CDR3 peptide analog on graft-versus-host disease across a major histocompatibility complex-haploidentical barrier.

A structure-based designed peptide has been engineered to exhibit the same molecular surface as a portion of the CDR3-like region in domain 1 of the murine CD4 molecule. Earlier in vitro experiments indicated that this analog, known as rD-mPGPtide, inhibited T-cell proliferation in mixed lymphocyte reactions and blocked activation of both normal CD4+ T cells and T-cell lines after T-cell receptor triggering. In addition, rD-mPGPtide proved to be a potent inhibitor in vivo of CD4+ T-cell-mediated experimental allergic encephalomyelitis disease in the SJL mouse model. In this current report, we have evaluated the potential of rD-mPGPtide for suppressing the development of graft-versus-host disease (GVHD) in an irradiated major histocompatibility complex (MHC)-haploidentical murine bone marrow transplantation (BMT) model [(B6 x DBA/2)F1-->(B6 x CBA)F1 (950 cGy)]. Our results indicated that early administration of rD-mPGPtide was effective in the inhibition of alloreactive responses of the donor T cells against the host and thus delayed or prevented the onset of GVHD. The median survival time of animals treated with rD-mPGPtide was enhanced as much as four-fold with as little as a single dose of peptide at the time of transplant. Decreased alloreactivity was indicated by phenotypic and functional analysis of positively selected thoracic duct lymphocytes 4 days after transplant and by histopathological examination of skin and gastrointestinal tissue samples 4 weeks later. Therefore, the administration of a CD4-CDR3 peptide is an efficacious approach against the development of GVHD during allogeneic BMT.

Acute Disease↗
PubMed1996

Mitochondrial phosphate transport protein. replacements of glutamic, aspartic, and histidine residues affect transport and protein conformation and point to a coupled proton transport path.

The homodimeric mitochondrial phosphate transport protein (PTP), which has six transmembrane helices per subunit, catalyzes inorganic phosphate transport in an electroneutral and pH gradient-dependent manner across the inner membrane. We have replaced the Glu, Asp, and His residues of the yeast PTP to assess their role in the transport mechanism. Mutants with physiologically relevant transport activity were identified by their ability to rescue the PTP null mutant yeast from glycerol medium. Five residues appear critical for transport: His-32 in helix A, Glu-126 and -137 in helix C, and Asp-39 and -236 at the matrix ends of helices A and E. These mutant PTPs are expressed at near normal levels in yeast. This yeast PTP and the mutants were expressed in Escherichia coli as inclusion bodies, solubilized, purified, and reconstituted. Their transport activities correlate well with the physiological assays. None of the transport inactivating mutations appear to be due to major protein conformation changes as assayed by the efficiency of PTP incorporation into liposomes. Only the Glu95Gln (cytosolic helices B and C-connecting segment), Glu163Gln and Glu164Gln (matrix helices C and D-connecting segment), and Glu126Asp (helix C) show a near 70% decrease in liposome incorporation efficiency. In addition, mutations at either end of helix D increase phosphate transport 2-fold. We would like to suggest that Glu-126, His-32, and Glu-137 (similar to Asp-96, Lys-216, and Asp-85 of bacteriorhodopsin) form a proton cotransport pathway that is coupled in an as yet undefined manner (possibly via His-32) to a phosphate transport pathway, which may include helix D.

Amino Acid Sequence↗