Search PubMed⌕ Search

Biomedical subjects

A E Davis

Publications and source records attributed to A E Davis.

At least 109 records · Page 6Linked to original sources
PubMed1986

Human inhibitor of the first component of complement, C1: characterization of cDNA clones and localization of the gene to chromosome 11.

C1 inhibitor is a heavily glycosylated plasma protein that regulates the activity of the first component of complement (C1) by inactivation of the serine protease subcomponents, C1r and C1s. C1 inhibitor cDNA clones have been isolated, and one of these (pC1INH1, 950 base pairs) has been partially sequenced. Sequence analysis demonstrates that the C1 inhibitor is a member of the serpin "superfamily" of protease inhibitors. In the region sequenced, C1 inhibitor has 22% identity with antithrombin III, 26% with alpha 1-antitrypsin and alpha 1-antichymotrypsin, and 18% with human angiotensinogen. C1 inhibitor has a larger amino-terminal extension than do the other plasma protease inhibitors. In addition, inspection of residues that are invariant among the other protease inhibitors shows that C1 inhibitor differs at 14 of 41 of these positions. Thus, it appears that C1 inhibitor diverged from the group relatively early in evolution, although probably after the divergence of angiotensinogen. Southern blot analysis of BamHI-digested DNA from normal individuals and from rodent-human somatic cell hybrid cell lines (that contain a limited but varied human chromosome complement) was used to localize the human C1 inhibitor gene to chromosome 11.

Amino Acid Sequence↗
PubMed1986

The effect of methionine and protein deficiency in delaying expulsion of Nippostrongylus brasiliensis in the rat.

Three protein-deficient diets containing 5%, 6%, or 7% casein, with and without 0.3% methionine supplementation, were fed to Wistar rats from weaning for 6 wk. Animals were infected subcutaneously with 1500 larvae of Nippostrongylus brasiliensis and killed after 14 days when nutritionally normal animals have expelled more than 97% of the worm burden. There was a delay in worm expulsion that was related to both the protein content (p = 0.0006) and to methionine content (p less than 0.0001). Methionine supplementation significantly reduced the worm burden in animals fed the 7% protein diet from a geometric mean of 32.4 to 5.2 (p = 0.0408) and in rats fed the 6% protein diet from a mean of 162 to 8.1 (p = 0.0002) but had no effect in rats on the 5% casein diet. Thus, addition of methionine overcame the adverse effect of protein deficiency in these less severely affected groups.

Animals↗
PubMed1985

A synthetic nonapeptide corresponding to the NH2-terminal sequence of C3d-K causes leukocytosis in rabbits.

Numerous biologically active fragments have been described that are derived from the C3 molecule. Recently, a polypeptide (Mr 41,000) generated from the alpha chain of human iC3b by limited proteolysis with plasma kallikrein was shown to exhibit several biological functions. This C3-derived cleavage product, C3d-K, suppresses mitogen- and antigen-induced proliferation of human T-lymphocytes and induces leukocytosis in rabbits. We have identified and synthesized a portion of C3d-K that is associated with the leukocytosis phenomenon. A nonapeptide corresponding to the amino-terminal nine residues of C3d-K was synthesized using conventional Merrifield solid-phase peptide chemistry; the structure of this peptide is Thr-Leu-Asp-Pro-Glu-Arg-Leu-Gly-Arg (TLDPERLGR). At a final concentration of 4 X 10(-6) M, both the nonapeptide and the des-Arg octapeptide (TLDPERLG) were capable of inducing leukocytosis in rabbits. Additionally, both peptides enhance vascular permeability when injected in guinea pig skin. These activities are similar to those previously attributed to a C3 fragment identified as C3e by Ghebrehiwet and Müller-Eberhard (Ghebrehiwet, B., and Müller-Eberhard, H.J. (1979) J. Immunol. 123, 616-621). We conclude that the nonapeptide TLDPERLGR represents the active center of the C3-derived leukocytosis factors C3e and C3d-K. This active synthetic analogue of C3d-K should prove valuable in elucidating the mechanism of action for complement-dependent leukocyte mobilization in vivo.

Amino Acid Sequence↗
PubMed1985

Focus on rehabilitation in the acute care setting: the role of the neuro clinical nurse specialist.

Establishment of an early rehabilitation program for patients with neurological/neurosurgical illness or injury is the focus of this article. The Neuroscience Clinical Nurse Specialist (NCNS) is identified as having a major responsibility in initiating early rehabilitation in the acute care setting. Development of the rehabilitation program is discussed through the NCNS's roles as educator, clinician, consultant, and researcher. Implementation of the rehabilitation program emphasizes the use of the nursing process, the role of the staff nurse, active patient and family participation, and use of the interdisciplinary team approach. General concepts rather than specific practices are used in order to present an overview of the role.

Central Nervous System Diseases↗
PubMed1985

Acoustic brainstem responses for clinical use: a comparison of pure tone stimuli with wide band clicks.

The acoustic brainstem response (ABR) in clinical use is generally elicited by a wide band click stimulus. This gives a well-synchronized response detectable at low sound intensities, but requires tedious biological recalibration which could be largely eliminated by the use of pure tone pip stimuli. We have therefore assessed ABRs in response to pure tone pips at 2 KHz and 4 KHz. This has shown that these tone pips elicit a much poorer response than clicks, having thresholds which are both significantly higher, and more widely distributed. We therefore conclude that wide band clicks remain the most satisfactory stimulus for clinical use.

Acoustic Stimulation↗
PubMed1985

Acoustic brainstem responses for clinical use: the effect of attention.

The acoustic brainstem response (ABR) is generally thought to be unaffected by variation in attention; however, recent papers suggest that during visual distraction of the subject wave Nv may be delayed. We have examined the ABRs of 22 normal subjects in states of auditory attention and visual distraction, using routine clinical testing procedures. We have shown that under these conditions altered attention states have no demonstrable effect on the latency of wave Nv.

Adult↗
PubMed1984

Bovine conglutinin is a collagen-like protein.

Conglutinin is a bovine plasma protein which is relatively large and asymmetric with elevated contents of glycine and, to some extent, proline. Although its physiologic function is unknown, conglutinin is known to bind, in the presence of calcium, to yeast cell walls and to the solid-phase-inactivated third component of complement. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, isolated conglutinin appeared to consist of a single polypeptide chain (Mr 48 000). Unreduced conglutinin consisted of a single stained band with an apparent molecular weight of approximately 300 000. Cross-linking experiments with glutaraldehyde and dimethyl suberimidate suggested that this Mr 300 000 molecule consists of six of the disulfide-linked polypeptide chains. Amino acid composition revealed hydroxylysine and hydroxyproline together with elevated glycine and proline contents. Digestion of reduced, alkylated conglutinin with bacterial collagenase resulted in formation of a precipitate which consisted of an Mr 24 000 peptide which was digested to Mr 21 000 with large quantities of collagenase. These peptides contained less glycine, proline, hydroxylysine, and hydroxyproline than did the intact protein. The supernatant from this digestion mixture was, however, enriched in these four amino acids, with glycine making up nearly one-third of the total. Prolonged digestion with pepsin at 37 degrees C resulted in an Mr 20 000 peptide which was enriched in glycine, proline, hydroxyproline, and hydroxylysine. Amino-terminal sequence analysis showed that the glycine-X-Y repeating sequence begins at residue 26.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1984

Serum pancreatic isoamylase estimation by the inhibitor method as a diagnostic test for chronic pancreatitis.

The diagnosis of chronic pancreatitis is often difficult to establish and may involve invasive diagnostic procedures. Serum pancreatic isoamylase has been estimated by the inhibitor method in controls and in 38 patients with known chronic pancreatitis in order to evaluate its use as a diagnostic test. The mean pancreatic isoamylase in those with chronic pancreatitis (68 +/- 77 IU/l) was significantly lower (p less than 0.005) than in controls (113 +/- 60 IU/l). The diagnostic sensitivity of pancreatic isoamylase was 50% (compared to total amylase 9%) and had a specificity of 95%. Stimulation tests with cholecystokinin and secretin failed to increase the sensitivity of the test. A low value of pancreatic isoamylase strongly supports a diagnosis of chronic pancreatitis and may obviate the need for further investigation.

Adult↗
PubMed1984

The histopathological changes in the thymus gland in the acquired immune deficiency syndrome.

Histologic study of the thymus glands from patients who have died of AIDS reveals changes consistent with an organ-specific immune complex attack by polyclonal immunoglobulins directed against the thymic epithelial cells, Hassall's corpuscles, and certain subsets of thymocytes. This results in marked architectural alteration: there is eventual disappearance of the corpuscles, the epithelial cells become spindled with pyknotic nuclei, there is thymocyte depletion and patchy fibrosis, and there is loss of the normal corticomedullary demarcation. These changes are characteristic and are not found in the normal aging process of the thymus gland. The blood levels of thymic peptides are abnormal. There appears to be specific immunoglobulins directed against thymic epithelial cells, Hassall's corpuscles, and certain subsets of T lymphocytes. The end result appears to be both a histologic and functional thymic disorder. If this is correct, then appropriate therapy for AIDS may be thymic peptide replacement or even thymic transplantation.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Physiologic inactivation of fluid phase C3b: isolation and structural analysis of C3c, C3d,g (alpha 2D), and C3g.

The fragments that result from the inactivation of C3b have not been completely characterized. Initial inactivation is catalyzed by the protease factor I, which, in the presence of its cofactor (factor H), cleaves two peptide bonds in the alpha'-chain of C3b. This results in the release of a small peptide (C3f, Mr 3000) from iC3b, which consists of the C3 beta chain covalently bonded to two alpha'-chain-derived peptides (Mr 68,000 and Mr 43,000). Surface-bound iC3b is cleaved at a third site by factor I to produce C3c and C3d,g (or alpha 2D). The factor I cofactor for this cleavage is the C3b receptor that is present on erythrocyte and leukocyte membranes. This report describes the isolation and initial structural characterization of C3c and C3d,g generated in whole blood after complement activation with cobra venom factor. These fragments were compared with the C3 fragments isolated from the serum and plasma of a patient with complement activation in vivo. The fragments were isolated with two solid phase monoclonal antibodies, one of which recognizes a determinant on C3g (clone 9) and one of which recognizes a determinant on C3c (clone 4). C3c isolated from normal blood showed three polypeptides that had apparent m.w. of 75,000, 43,000, and 27,000. The C3d,g consisted of a single polypeptide chain with a m.w. of 40,000. Amino terminal sequence analysis showed that the Mr 27,000 peptide from C3c is derived from the amino terminal portion of the alpha'-chain of C3b, whereas the Mr 43,000 peptide is derived from the carboxy terminus of the same chain. Amino terminal sequence analysis showed also that C3g is derived from the amino terminus of C3d,g. The C3 fragments isolated from a patient with partial lipodystrophy, nephritic factor activity, low serum C3 levels, and circulating C3 cleavage products showed a more complicated pattern on SDS-PAGE. The fragment isolated with clone 9 had an apparent m.w. of 40,000, identical to C3d,g generated in vitro, and it had the same amino terminal sequence as C3d,g generated in vitro. The eluate from insolubilized clone 4, however, showed prominent bands with Mr of 75,000, 56,000, 43,000, and 27,000, together with a triple-banded pattern at 68,000 and a minor band at 80,000. This eluate thus appears to contain C3c, and iC3b or an iC3b-like product. The origin of the Mr 56,000 and Mr 80,000 peptides have not yet been determined. These studies, with previous data, definitively order the C3c and C3d,g peptides in the alpha-chain of C3.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1982

Cooperative interaction of factor B and other complement components with mononuclear cells in the antibody-independent lysis of xenogeneic erythrocytes.

Synergistic cytotoxicity is a term used to describe a cytotoxic system in which xenogeneic erythrocyte target cells are lysed in the presence of nonimmune human mononuclear effector cells and antibody-depleted normal human serum. Neither the mononuclear cells nor the serum alone are cytolytic to the target erythrocytes. Previous studies have shown that the serum activity is not immunoglobulin and is heat-labile, suggesting a similarity to serum complement. In this report, sera deficient in various complement components as well as highly purified single complement components were tested with whole mononuclear cell populations and purified monocytes and lymphocytes to further characterize this cytotoxicity system. Whole mononuclear cell populations failed to mediate target cell lysis in sera deficient in C5 or factor B. However, C3-deficient serum, even in the presence of anti-C3 antibody, supported synergistic cytotoxicity normally. Purified lymphocytes were also normally cytotoxic in C3-deficient serum but failed to lyse targets in sera deficient in C5, C7, C8, or depleted of factor B. Purified monocytes failed to lyse the target cells only in factor B-depleted serum and could lyse the target cells in serum-free medium when purified factor B alone was added. Monocyte-mediated cytotoxicity induced by factor B was inhibited 73-100% by adding lymphocytes back to the purified monocytes. Thus, both lymphocytes and monocytes can serve as effector cells in this form of cytotoxicity but require cooperative interaction with different sets of complement components. In addition, lymphocytes can modulate the monocyte-mediated form of target cell lysis associated with factor B.

Animals↗
PubMed1982

A prospective study of persistent diarrhoea.

A prospective study was undertaken in 100 patients with diarrhoea to identify the causes and to better define the prevalence of the irritable bowel syndrome (IBS) and to determine if there was a diagnostic symptom complex evident in patients with IBS. A diagnosis of IBS was made in 28 patients and in this group the prevalence of lactase deficiency was found to be 40%. Pain in association with urgency was usual and urgency occurring in the absence of pain was more likely to be found in association with an organic colonic lesion. The two most important symptoms which distinguish IBS from other causes were blood in the motions and weight loss. Giardia lamblia were found in nine patients and 15 patients responded to an empirical course of either metronidazole or tinidazole, without a positive diagnosis of giardiasis being made. Fourteen patients had inflammatory bowel disease and a variety of drugs were responsible for diarrhoea in 10% of patients. Sigmoidoscopy and small bowel biopsy were the most valuable diagnostic investigations.

Adolescent↗