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Biomedical subjects

G Davis

Publications and source records attributed to G Davis.

At least 127 records · Page 7Linked to original sources
PubMed1993

Role of haematocrit in mediating the actions of chronic erythropoietin treatment on blood pressure and renal haemodynamics in the rat.

1. This investigation aimed to study the effect of chronic administration of human recombinant erythropoietin on haematocrit, blood pressure, renal cortical and papillary resistances and vascular responsiveness to vasoconstrictor agents. 2. Rats were treated with placebo or 25, 50 or 100 units/kg erythropoietin subcutaneously, every other day for 3 weeks. Animals were then anaesthetized with sodium pentobarbitone and were prepared for laser-Doppler flowmetry measurement in the renal cortex and papilla. 3. Haematocrit in the placebo-treated group was 48.0 +/- 0.5% and was raised to 52.5 +/- 0.7, 55.9 +/- 0.8 and 62.4 +/- 1.1% (all P < 0.05) by the chronic administration of 25, 50 and 100 units/kg doses of the hormone, respectively. Blood pressure was 107 +/- 1 mmHg in the placebo-treated group and was elevated to 116 +/- 2 and 130 +/- 1 mmHg (both P < 0.05), respectively, by the two highest doses of erythropoietin. Cortical and papillary perfusions were reduced at the highest dose of erythropoietin, but calculated resistances were increased by 15 and 40% (P < 0.05) at 50 and 100 units/kg doses of the hormone, respectively. 4. Infusion of the vasopressor hormones vasopressin and phenylephrine caused increases in blood pressure and decreases in renal cortical and papillary perfusion, the magnitudes of which were only marginally changed by the highest dose of the erythropoietin. Angiotensin II increased blood pressure and decreased cortical perfusion, and the magnitudes of these responses were unchanged by the chronic treatment with erythropoietin. 5. Acute graded increases in haematocrit resulted in significantly (P < 0.05) raised blood pressure above a value of 58%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Seizure severity and the quality of life.

The efficacy of an antiepileptic drug (AED) is determined at present by the drug-elicited reduction in seizure frequency. Reduction of seizure frequency as the sole measure of efficacy does not account for treatment-induced reductions in seizure severity and positive psychological effects experienced by the patient. A clinical trial was undertaken in which seizure frequency was the primary and seizure severity and psychological well-being were the secondary measures of efficacy. Psychological assessment and seizure frequency were monitored in patients whose epilepsy was treated with lamotrigine (LTG) or placebo. The results indicate that LTG is an effective AED, causing reductions in seizure frequency and severity and improvements in mood and mastery. In addition, the study demonstrated that the use of seizure severity scales, especially the ictal subscale, may enhance the sensitivity of assessment of trials of AED treatments.

Anticonvulsants↗
PubMed1993

Semi-quantitative SPECT scanning in acute ischaemic stroke.

We performed semi-quantitative SPECT scans using 99mTcm-HMPAO on 34 elderly subjects 10-15 days after ischaemic stroke. Each cerebral hemisphere was divided into five regions of interest. Asymmetry scores were determined for ten slices in each region using activity ratios to the other hemisphere and to the ipsilateral cerebellum. Outcome was assessed by maximal Barthel ADL score during the first two months after stroke. Asymmetry scores in the hemisphere involved by the stroke event were much higher than those in the opposite hemisphere. Subjects with poor outcome (maximal Barthel 0-12) had significantly higher asymmetry scores than those with good outcome (Barthel 13-20). The total asymmetry score (both hemispheres) and the score of the involved hemisphere predicted Barthel ADL score in a general linear model. Total asymmetry score remained a significant predictor of maximal Barthel score in multivariate models. Thus semi-quantitative SPECT scanning is of value in predicting functional recovery after stroke.

Activities of Daily Living↗
PubMed1993

Laparoscopic oophorectomy.

Oophorectomies were performed on 312 women as part of an operative laparoscopic procedure over an eight-year period. The average age of the women was 40.4 +/- 0.6 (SEM) years; 36.5% had previously undergone a hysterectomy. The median operating time was 120 minutes. The length of hospitalization was less than 24 hours in 77.6% of women, between 24 and 48 hours in 15.1% and over 48 hours in 7.4%. Intraoperative and/or postoperative complications occurred in 12 women (3.8%). Estimated blood loss greater than 300 mL occurred in two women. The most frequent diagnoses were endometriosis/endometrioma, functional cysts and normal ovarian tissue (usually from ovaries enmeshed in adhesions); two ovaries demonstrated borderline malignant potential. Laparoscopic oophorectomy is acceptable under appropriate conditions. Further studies are necessary to provide criteria for accurate differentiation of benign from malignant ovarian enlargement.

Adult↗
PubMed1993

Specific cleavage of the alpha 4 integrin associated with activation of peripheral T lymphocytes.

The heterodimeric VLA-4 integrin has been implicated in lymphocyte migration to inflamed peripheral tissues, lympho-haemopoiesis and autoimmune disease. To determine the structure and function of VLA-4 in physiological processes, molecular forms of the VLA-4 alpha-chain were analysed during T-cell activation. The results showed that prolonged activation of human peripheral T cells was associated with increased cleavage of the 150,000 MW alpha 4 chain into 80,000 and 66,000 MW fragments. Similar-sized alpha 4 fragments could also be generated from 150,000 MW alpha 4 on intact resting T cells by brief trypsinization, whereas trypsin treatment of isolated 150,000 MW alpha 4 resulted in nearly complete protein degradation. Native 80,000 and 66,000 MW alpha 4 chains on activated T cells could not be digested further by trypsin. These results indicated that specific cleavage of 150,000 MW alpha 4 was largely dependent on the tertiary structure of native alpha 4 chains. To determine the specific cleavage site in alpha 4 on peripheral T cells, VLA-4 was isolated and purified from in vitro-activated T cells and the N-terminus of the 66,000 MW fragment was partially sequenced. The sequence SKR/STE was identified as the specific alpha 4 cleavage site on T cells. These results indicate that T cells, upon activation, acquire an enhanced dipeptidase processing activity, which cleaves alpha 4 at a specific site.

Amino Acid Sequence↗
PubMed1993

Prenatal diagnosis in twin gestations: a comparison between second-trimester amniocentesis and first-trimester chorionic villus sampling.

OBJECTIVE: To evaluate prospectively the relative risks and accuracy of first-trimester chorionic villus sampling (CVS) and second-trimester amniocentesis in the genetic evaluation of twin gestations. METHODS: Between March 1984 and August 1990, patients presenting for prenatal diagnosis of a twin gestation of less than 12 weeks were offered sampling by either first-trimester CVS or amniocentesis at 16-18 weeks' gestation. Selection was based solely on patient preference and was obtained before ultrasound identification of placental position. Women presenting beyond 12 weeks' gestation were sampled by amniocentesis. Clinical and laboratory outcomes were evaluated. RESULTS: Eighty-one women had amniocentesis (nine of whom also had CVS), and 161 women had CVS. All fetuses in both groups were successfully sampled and karyotyped; 85.3% of the amniocentesis patients and 75.8% of the CVS patients were sampled in two or fewer passes (P = not significant). There were three cases of twin-twin villus contamination following CVS; one of these led to incorrect gender assignment because of erroneous laboratory interpretation. Loss of the entire pregnancy from the time of sampling until the 28th week of gestation followed amniocentesis in 2.9% of the cass and CVS in 3.2%. The total fetal loss rates were 9.3% for amniocentesis and 4.9% for CVS (P = not significant). When pregnancies having mosaic or abnormal karyotype results are excluded, the total amniocentesis loss rate remained 9.3% and the CVS loss rate became 3.9% (P < .05). CONCLUSION: In the hands of experienced operators, CVS is at least as safe and effective as amniocentesis for the prenatal diagnosis of twin gestations.

Abortion, Eugenic↗
PubMed1992

N-terminal sequence of proteoglycan fragments isolated from medium of interleukin-1-treated articular-cartilage cultures. Putative site(s) of enzymic cleavage.

Bovine articular cartilage was cultured both in the presence and in the absence of human recombinant interleukin-1 alpha (IL-1) (100 units/ml). Addition of this cytokine stimulated matrix degradation approx. 3-fold. This increased degradation permitted characterization of the large chondroitin sulphate proteoglycan (aggrecan) fragments accumulating in the media. When compared with controls, the proteoglycans isolated from the medium of cultures treated with IL-1 exhibited a decrease in the Kav. (control 0.25; IL-1-treated 0.37), determined by Sepharose CL-2B chromatography. This decrease in proteoglycan size was accompanied by a decreased ability of these monomers to associate with hyaluronic acid. Thus only 20% of the proteoglycans isolated from the medium of IL-1-treated cultures, compared with 39% for control cultures, had the capacity to form high-M(r) aggregates with hyaluronic acid. SDS/PAGE analysis of the proteoglycans from the media of IL-1-treated cultures demonstrated several large proteoglycan protein-core bands (M(r) 144,000-380,000). The protein-core bands with M(r) 144,000-266,000 exhibited a significantly decreased reactivity with monoclonal antibody 1-C-6 (specific for domains G1 and G2). The N-terminal amino acid sequence of four of these protein-core bands (M(r) 144,000, 173,000, 214,000 and 266,000) yielded sequences LGQRPPV-Y-PQLF(E), AGEGP(S)GILEL-GAP(S)-AP(D)M, GLG-VEL-LPGE and (A)RGSVIL-AKPDFEV-P-A. A comparison of these N-terminal amino acid sequences with the published proteoglycan sequence for bovine nasal cartilage [Oldberg, Antonsson & Heinegård (1987) Biochem. J. 243, 255-259], rat chondrosarcoma [Doege, Sasaki, Horigan, Hassell & Yamada (1987) J. Biol. Chem. 262, 17757-17769] and human articular cartilage [Doege, Sasaki, Kimura & Yamada (1991) J. Biol. Chem. 266, 894-902] permitted assignment of their relative positions on the core protein. Furthermore, on the basis of this similarity to published sequence, putative sites of enzymic cleavage were constructed. These theoretical cleavage sites revealed a glutamic acid residue in the P1 position and an uncharged polar or non-polar residue in the P1' position.

Aggrecans↗
PubMed1992

Study of the actions of human recombinant erythropoietin on rat renal haemodynamics.

1. Studies were undertaken to examine the effect of acute and chronic administration of human recombinant erythropoietin on kidney cortical and papillary perfusion in the anaesthetized rat using laser-Doppler flowmetry. 2. Thirty minutes after erythropoietin (50 and 150 units/kg intravenously), blood pressure, cortical perfusion and papillary perfusion were unchanged. 3. In animals treated chronically with erythropoietin over 7 days (three doses of 150 units/kg subcutaneously) blood pressure was similar to that of vehicle-treated animals, whereas cortical perfusion and papillary perfusion were reduced by 23% and 20%, respectively (both P < 0.05), and the packed cell volume (51.1 +/- 0.7%) was significantly (P < 0.01) greater than in vehicle-treated animals (46.2 +/- 0.6%). 4. Bolus doses of vasopressin and phenylephrine increased blood pressure (by between 10% and 40%) and decreased cortical and papillary perfusion (by between 10% and 20%), while angiotensin II caused similar increases in blood pressure and decreases in cortical perfusion but not papillary perfusion. The magnitude and pattern of these responses were comparable after both acute and chronic administration of erythropoietin. 5. Erythropoietin given acutely at therapeutic levels has a marginal effect on cortical and papillary perfusion. However, the chronic treatment indicated that there was a sustained reduction in both cortical and papillary perfusion, reflecting a vasoconstriction. This reduction in renal haemodynamics could contribute to the increase in blood pressure observed when this hormone is administered in man.

Animals↗
PubMed1992

Interactions between extracellular Borrelia burgdorferi proteins and non-Borrelia-directed immunoglobulin M antibodies.

Previous work showed that outer surface protein A (OspA) and OspB of Borrelia burgdorferi may occur within an extracellular multiprotein complex, which was resolved by electrophoresis as an 83-kDa major extracellular protein band. To characterize the 83-kDa band, we sequenced the N terminus of the predominant peptide in the band and examined the interaction between the associated proteins. Peptide sequence and amino acid composition comparisons showed identity with the heavy chain of immunoglobulin M (IgM). Reduction sensitivity experiments and the recognition of the band by antibodies specific for rabbit mu chain indicated that the multiprotein complex contained pentameric IgM. Immunoelectron microscopy showed that anti-mu chain antibodies and monoclonal antibodies to OspA and OspB bound to extracellular amorphous material surrounding cells. Furthermore, the Osps coprecipitated with either nonspecific polyclonal rabbit IgM antibodies or with murine monoclonal anti-human serum albumin IgM antibodies, using insoluble anti-mu chain antibody conjugates. Although the apparent 83-kDa complex was stable under conditions of chelation and concentrated salts, it was disrupted by treatment with neuraminidase. These results indicate that extracellular B. burgdorferi proteins, including OspA and OspB, interact with IgM. The association is apparently not a classic antibody-antigen interaction but may result from other mechanisms.

Amino Acid Sequence↗
PubMed1992

Determinants of failure in superficial femoral artery angioplasty.

Although results of iliac artery balloon angioplasty have been shown to be good, there are much less data regarding initial success and durability of superficial femoral artery (SFA) dilation. The authors retrospectively reviewed the results of 22 patients treated for 27 SFA lesions between 1981 and 1986. Mean age was 64.5 years (fifty-five to seventy-six). Results were analyzed with respect to initial, early (< twelve months), and late (> twelve months) angiographic and clinical success. Indications were claudication (22), nonhealing ulcer (3), and rest pain (2). Mean follow-up was 30.9 months; 100% at one year and 92% at two years. Initial failure occurred in 9 (33%) lesions. There were 2 early and 2 late failures for a cumulative patency rate of 90.3% and 78% at one and two years, respectively. Predictors of clinical failure were: (1) initial--age, SFA occlusion, and angioplasty rating; (2) early--age, SFA occlusion, degree of atherosclerosis, and angioplasty rating; (3) late--angioplasty rating. There were 3 complications (11%). The authors conclude that: (1) 33% of attempted SFA angioplasties were initially unsuccessful and that the cumulative patency rate was 78% at two years. (2) Age is predictive of initial and early failure; SFA occlusion, of initial and early failure; degree of atherosclerosis, of early failure; and angioplasty appearance, of initial, early, and late failures. (3) Complications did not result in limb loss or require surgery.

Age Factors↗
PubMed1992

What Pediatricians Should Know About Adolescent Psychiatry.

The authors review the most common psychiatric disorders in adolescents in order to familiarize pediatricians with techniques for recognizing, treating, and, when necessary, referring adolescents with a psychiatric disorder.

Journal Article↗
PubMed1991

Sequential NMR resonance assignment and structure determination of the Kunitz-type inhibitor domain of the Alzheimer's beta-amyloid precursor protein.

Certain precursor proteins (APP751 and APP770) of the amyloid beta-protein (AP) present in Alzheimer's disease contain a Kunitz-type serine protease inhibitor domain (APPI). In this study, the domain is obtained as a functional inhibitor through both recombinant (APPIr) and synthetic (APPIs) methodologies, and the solution structure of APPI is determined by 1H 2D NMR techniques. Complete sequence-specific resonance assignments (except for P13 and G37 NH) for both APPIr and APPIs are achieved using standard procedures. Ambiguities arising from degeneracies in the NMR resonances are resolved by varying sample conditions. Qualitative interpretation of short- and long-range NOEs reveals secondary structural features similar to those extensively documented by NMR for bovine pancreatic trypsin inhibitor (BPTI). A more rigorous interpretation of the NOESY spectra yields NOE-derived interresidue distance restraints which are used in conjunction with dynamic simulated annealing to generate a family of APPI structures. Within this family, the beta-sheet and helical regions are in good agreement with the crystal structure of BPTI, whereas portions of the protease-binding loops deviate from those in BPTI. These deviations are consistent with those recently described in the crystal structure of APPI (Hynes et al., 1990). Also supported in the NMR study is the hydrophobic patch in the protease-binding domain created by side chain-side chain NOE contacts between M17 and F34. In addition, the NMR spectra indicate that the rotation of the W21 ring in APPI is hindered, unlike Y21 in BPTI, showing a greater than 90% preference for one orientation in the hydrophobic groove.

Amino Acid Sequence↗
PubMed1991

Flow injection analysis of lactose using covalently immobilized beta-galactosidase, mutarotase, and glucose oxidase/peroxidase on a 2-fluoro-1-methylpyridinium salt-activated Fractogel support.

Milk samples were analyzed for their lactose content using flow injection analysis and incorporating immobilized beta-galactosidase or beta-galactosidase/mutarotase and glucose oxidase/peroxidase bioreactors. These enzymes were immobilized, under mild conditions, on to a 2-fluoro-1-methylpyridinium salt-activated Fractogel support. The use of a phosphate buffer (0.15 M) was found to facilitate the rapid mutarotation of alpha-D-glucose and hence could obviate the need for the more expensive mutarotase. The chromogenic agents of choice for monitoring the reaction were 3-methyl-2-benzothiazolinone hydrazone and 3-dimethylaminobenzoic acid. Linearity was observed over the concentration range 16-160 micrograms/ml using lactose standards (r = 0.996). Between 30 and 40 milk samples/h can be analyzed. Comparisons are made with existing HPLC and alkaline methylamine methods for a range of milk matrices. The FIA method consistently gives the lowest standard deviations and coefficient of variation for the various milk matrices analyzed.

Animals↗
PubMed1991

Enhancement of CD2-mediated T cell activation by the interaction of VLA-4 with fibronectin.

Human fibroblasts were shown to enhance the proliferation of peripheral T cells in the presence of suboptimal concentrations of anti-CD2 antibodies (anti-T112 and anti-T113) and agonistic anti-VLA-4 antibody. Evidence is provided that the interaction of VLA-4 with immobilized fibronectin can enhance the proliferation of T cells subjected to suboptimal stimulation via CD2. Our results suggest that the fibroblast-stimulated T cell proliferative response to low doses of anti-T112 and T113 antibodies is due to the interaction of VLA-4 with fibroblast fibronectin. These findings also suggest a role for the fibronectin/VLA-4 interaction in the inflammatory process.

Antibodies, Monoclonal↗
PubMed1991

Effect of Macerase, Oxalic Acid, and EGTA on Deep Supercooling and Pit Membrane Structure of Xylem Parenchyma of Peach.

The object of this study was to determine if calcium cross-linking of pectin in the pit membrane of xylem parenchyma restricts water movement which results in deep supercooling. Current year shoots of ;Loring' peach (Prunus persica) were infiltrated with oxalic acid or EGTA solutions for 24 or 48 hours and then either prepared for ultrastructural analysis or subjected to differential thermal analysis. The effect of 0.25 to 1.0% pectinase (weight/volume) on deep supercooling was also investigated. The use of 5 to 50 millimolar oxalic acid and pectinase resulted in a significant reduction (flattening) of the low temperature exotherm and a distinct swelling and partial degradation of the pit membrane. EGTA (10 millimolar) for 24 or 48 hours shifted the low temperature exotherm to warmer temperatures and effected the outermost layer of the pit membrane. A hypothesis is presented on pectin-mediated regulation of deep supercooling of xylem parenchyma.

Journal Article↗
PubMed1991

An investigation into the influence of vasopressin on perfusion of the cortex and papilla of the rat kidney.

An investigation was undertaken to examine the effects of vasopressin on blood pressure and perfusion of the cortical and papillary regions of the kidney, and to determine the receptor subtype involved. Pentobarbitone-anaesthetized rats were used and laser-Doppler flowmetry applied to measure regional renal haemodynamics. Infusion of vasopressin at 10, 20 and 40 mU kg-1 min-1 caused dose-related increases in blood pressure and reductions in cortical and papillary perfusion of approximately 21, 35 and 41%, respectively at the highest dose. Administration of the V1-receptor antagonist, [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(o-methyl)tyrosine]-Arg8-vasopressin, at 1 microgram kg-1 plus 5 micrograms kg-1 h-1 or four times this dose had no effect on the basal levels of any variable. Vasopressin administration during the low dose of antagonist increased blood pressure and reduced papillary perfusion, the magnitudes of which were only slightly less than those obtained in the absence of the drug, whereas there was a significant attenuation of the response in cortical perfusion. During infusion of the V1 antagonist at 4 micrograms kg-1 plus 20 micrograms kg-1 h-1, vasopressin had no effect on either blood pressure or renal haemodynamics. Infusion of the V2 antagonist, [d(CH2)5, D-Phe2, Ile4, Arg8, Ala9-NH2]-vasopressin at 1 microgram kg-1 plus 5 micrograms kg-1 h-1, and twice this dose had no effect on the basal value of any variable and had no effect on the ability of vasopressin to induce an increase in blood pressure or cause reductions in renal cortical and papillary perfusions. However, the administration of the V2 antagonist at 4 micrograms kg-1 plus 20 micrograms kg-1 h-1 significantly attenuated blood pressure, cortical and papillary perfusion responses to the vasopressin. These studies have shown that vasopressin, given at doses which increased blood pressure, caused dose-related decreases in perfusion of renal cortex as well as the papilla. The data further show that these systemic and renal actions were mediated primarily by V1-receptors and that the contribution of V2-receptors at these vascular beds was very small.

Angiotensin Receptor Antagonists↗