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Biomedical subjects

G Davis

Publications and source records attributed to G Davis.

At least 19 recordsLinked to original sources

Renal sympathetic nerve responses to somato-sensory nerve stimulation in normotensive rats.

Blood pressure, heart rate and renal sympathetic nerve activity were recorded in groups of chloralose/urethane-anaesthetised intact, vagotomised and carotid sinus denervated Wistar rats before and during bilateral somatic afferent nerve stimulation from 0.1 to 3.2 Hz. Renal sympathetic nerve activity was subjected to power spectral and cross correlation analysis. Haemodynamic and integrated renal nerve responses to graded brachial nerve stimulation were not altered by either bilateral vagotomy or carotid sinus denervation and total power of the spectra, from 0-10 Hz, was similar in each group. The percentage power peak at heart rate in intact rats decreased with increasing stimulus frequency, from a control value of 19.2 +/- 1.9% to a minimum of 2.8 +/- 0.7% at 1.6 Hz, while coherence and phase were not altered. Conversely, the peak at the stimulus frequency rose with increasing stimulus frequency reaching 35.3 +/- 2.0% at 3.2 Hz. In the vagotomised group, power at heart rate was significantly lower at each stimulus frequency compared to intact rats although coherence was similar and the phase difference was larger. The peak power at stimulus frequency, coherence and phase difference were similar to those obtained in the intact rats. In the carotid sinus denervated rats, the percentage power at heart rate, coherence and phase difference were significantly smaller than in intact rats. The peak at the stimulus frequency and the phase difference were similar to those obtained in the intact rats whereas coherence was lower. These findings demonstrate that the pattern of renal nerve activity can be changed from one modulated by the baroreceptor to one driven by somatic afferent nerve activity. The vagus appears to play a minor role in the overall pattern of renal nerve activity with the primary controller being the carotid sinus baroreceptors. The data also show that the renal nerve response to somatic afferent nerve stimulation is independent of the afferent nerve input arising from either the atrial or the carotid sinuses.

Adrenergic Fibers

Failure of high-dose oral acyclovir to suppress CMV viruria or induce ganciclovir-resistant CMV in HIV antibody positive patients.

Ninety-three symptomatic HIV antibody positive patients were randomized to receive zidovudine (ZDV) 600 mg/day and acyclovir (ACV) 4,800 mg orally per day versus ZDV 600 mg/day plus placebo. Urine was obtained at 3-month intervals and cultured for cytomegalovirus (CMV) in diploid fibroblast cells. The percent of urine specimens positive for CMV was 7.1% in the ZDV group and 5.8% in the ZDV plus ACV group (p = 0.55); 27% of patients had at least one urine culture positive for CMV while taking ZDV, versus 20% of patients taking the combination of ZDV plus ACV (p = 0.52). We conclude that ACV at a dosage of 4,800 mg/day does not suppress CMV excretion in urine of symptomatic HIV antibody positive patients taking concurrent ZDV. Use of ACV did not appear to induce resistance of CMV to ganciclovir since the ID50 of isolates from the two treatment groups did not differ.

Acyclovir

HIV prevention beliefs among urban African-American youth.

PURPOSE: This study investigates specific beliefs related to prevention of AIDS and HIV infection among African-American teenagers. METHODS: This study administered valid and reliable measures of HIV/AIDS risk knowledge and prevention beliefs to 150 African-American teenagers. Demographic and psychosocial data were gathered. RESULTS: Black teenagers respond in socially acceptable and undesirable ways and this ambivalence can be explained within the theory of reasoned action. These teens simultaneously believed in the importance of safe sex behaviors while expressing doubt about the viability of some safe sex behaviors. Females demonstrated higher self-efficacy and self-control beliefs while males were more likely to endorse culturally loaded suspicious beliefs about AIDS contraction and transmission. CONCLUSIONS: Those teenagers who perceived themselves as highly knowledgeable scored lower on reliable AIDS Knowledge and Prevention Beliefs measures than those who claimed moderate AIDS knowledge. Some of these "Know It All" teenagers may reflect a subculture of pseudo-confidence that requires special interventions.

Adolescent

B7-1 expression decreases tumorigenicity and induces partial systemic immunity to murine neuroblastoma deficient in major histocompatibility complex and costimulatory molecules.

Neuroblastoma may escape an immune attack by virtue of its low expression of surface accessory molecules essential in the antitumor response. Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector LB7-1SN to examine the influence of B7-1 expression on the immune response directed against a low major histocompatibility class (MHC) I and class II negative, B7-2, and ICAM-1 negative tumor. Using a retroperitoneal model for implantation of neuroblastoma in its natural site, we demonstrated that expression of B7-1 by neuro-2a reduces its tumorigenicity. Coinjection of B7-1-positive and -negative cells improved survival compared with mice receiving B7-1-negative cells alone. This was dependent on the ratio of B7-1+ to B7-1- neuro-2a cells injected. CD8+ and not CD4+ T-cell depletion significantly increased tumor-induced mortality in syngeneic A/J mice, indicating that B7-1 decreases tumorigenicity primarily by direct constimulation of CD8+ T cells. Rejection of N-2a/B7-1 tumors or preimmunization with irradiated N-2a/B7-1 cells die not increase protection to challenge with unmodified neuro-2a cells over mice vaccinated with N-2a/neo. Furthermore, cytotoxic T lymphocyte (CTL) precursor frequencies were not significantly higher after in vivo priming and in vitro stimulation with irradiated N-2a/B7-1 compared with N-2a/neo, indicating that B7-1 costimulation by the tumor, in the absence of adequate antigen presentation by MHC molecules, may limit the generation of effective CTLs.

Animals

Somatosensory regulation of renal function in the stroke-prone spontaneously hypertensive rat.

1. Chloralose-urethane-anaesthetized Wistar rats and stroke-prone spontaneously hypertensive rats (SHRSP) were prepared for measuring renal function. 2. Bilateral brachial nerve stimulation for 15 min, at 1.3 Hz (15 V, 0.2 ms), increased blood pressure from 119 +/- 2 to 151 +/- 6 mmHg (P < 0.01) in Wistar rats and from 181 +/- 6 to 203 +/- 6 mmHg (P < 0.05) in SHRSP; renal perfusion pressure was mechanically regulated at prestimulus levels but renal blood flow (4.1 +/- 0.7 ml min-1 g-1 in Wistar rats and 3.4 +/- 0.3 ml min-1 g-1 in SHRSP) and glomerular filtration rate (1.18 +/- 0.09 ml min-1 g-1 in Wistar rats and 0.88 +/- 0.01 ml min-1 g-1 in SHRSP) decreased between 5 and 30% (P < 0.05-0.001). 3. During brachial nerve stimulation, urine flow (13.8 +/- 2.2 microliters min-1 g-1) and absolute and fractional sodium excretion (3.70 +/- 0.64 mumol min-1 g-1 and 2.06 +/- 0.23%) decreased by 60-70% in the Wistar rats (P < 0.01-0.001) and the responses were unaffected by vagotomy or carotid sinus denervation. In the SHRSP, urine flow rate (9.74 +/- 2.52 microliters min-1 g-1) and absolute and fractional sodium excretion (1.98 +/- 0.59 mumol min-1 g-1 and 1.41 +/- 0.28%) decreased by 15-30% (P < 0.05-0.01), decreases which were significantly (P < 0.05) smaller than those observed in the Wistar rats. Moreover, the responses were some 40-60% larger in the vagotomized and carotid sinus-denervated SHRSP. 4. The influence of vagal and carotid sinus afferent nerves on the somatosensory-induced renal responses in the Wistar rats was small, whereas in the SHRSP they appeared to exert a marked tonic inhibitory effect. It is concluded that there is excessive baroreceptor restraint on neural regulation of renal function in the SHRSP.

Animals

Parallel detection of Kanizsa subjective figures in the human visual system.

Subjective figures, seen in the absence of luminance gradients (Fig. 1), provide a phenomenal illusion that can be related to the properties of single cells in the visual cortex, offering a rare bridge between brain function and visual awareness. It remains controversial whether subjective figures arise from intelligent cognitive mechanisms, or from lower-level processes in early vision. The cognitive account implies that the perception of subjective figures may require serial attentive processing, whereas on the low-level account they should arise in parallel at earlier visual stages. Physiological evidence apparently fits a low-level account and indicates that some types of subjective contour may be detected earlier than the conventional Kanizsa type. Here we report that even Kanizsa subjective figures can be detected without focal attention at parallel stages of the human visual system.

Humans

Processing of the pre-beta-amyloid protein by cathepsin D is enhanced by a familial Alzheimer's disease mutation.

A major pre-beta-amyloid protein695 (APP695) processing activity from Alzheimer's disease brain extracts was identified and found to be indistinguishable from the activity of cathepsin D.APP695 processing activity cleaved APP695 into a series of fragments that reacted on immunoblots to a monoclonal antibody (C286.8a) against beta-amyloid-(1-7)-peptide and cleaved N-dansyl-APP-(591-601)-amide at the Glu-Val and Met-Asp bonds. Fragments of 5.5 kDa and 10-12 kDa were formed from the cleavage of APP695 by cathepsin D at the Glu593-Val594 bond, and had the same N-terminus as a minor form of beta-amyloid released by cells. The Lys595-->Asn and Met596-->Leu substitutions found in a pedigree of familial Alzheimer's disease, increased the cathepsin D-catalyzed rate of accumulation of 5.5 kDa and 10-12 kDa C286.8a-reactive fragments 5-10fold. This substitution also increased the rate of N-dansyl-APP-(591-601)-amide cleavage at the Xaa-Asp bond by up to 41-fold. These observations suggest a role of cathepsin D in beta-amyloid formation under certain circumstances.

Alzheimer Disease

Cytogenetic studies in endometriosis tissue.

We analyzed 45 pelvic endometrial implants from 42 patients between the ages of 14 and 40 years to investigate whether cytogenetic abnormalities were present in these samples. Chromosomal abnormalities have been described in benign tumors of the female genital tract, such as uterine leiomyomas and endometrial polyps. Furthermore, heritable factors have been postulated to influence a woman's susceptibility to develop endometrial tissue implants outside the uterine cavity. To study whether these factors result in or are associated with chromosomal changes, endometriosis cells were analyzed cytogenetically after short-term culture. No consistent chromosome abnormalities were observed in any of the cases analyzed.

Adult

Corneal astigmatism induced by superior versus temporal corneal incisions for extracapsular cataract extraction.

PURPOSE: We tested the hypothesis that superior corneal sections induce a shift to 'against-the-rule' astigmatism and temporal corneal sections lead to the preferred 'with-the-rule' astigmatism. METHODS: We conducted a prospective randomised trial of superior versus temporal corneal incisions in extracapsular cataract surgery in a hospital practice. Thirty nine eyes of 37 patients were included. The induced astigmatism was analysed by three methods. RESULTS: When analysed by Cravy's method of induced astigmatic cylinders, the superior incision induced a greater degree of 'with-the-rule' astigmatic cylinder prior to sutures removal on day 77 (P < 0.049). Long term, the temporal incision produced 1.44 dioptre of 'with-the-rule' astigmatism, while the superior section produced 0.08 dioptre of 'against-the-rule' astigmatism (P < 0.001). CONCLUSION: The results of this small trial indicates that the superior corneal incision produces significantly less astigmatism than the temporal incision. The temporal incision induces a moderate degree of 'with-the-rule' astigmatism.

Aged

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

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

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

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

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

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

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