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D Davis

Publications and source records attributed to D Davis.

At least 19 recordsLinked to original sources
PubMed1992

Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids.

Cerebral deposition of the beta-amyloid peptide (A beta) is an invariant feature of Alzheimer's disease. Since the original isolation and characterization of A beta (ref. 1) and the subsequent cloning of its precursor protein, no direct evidence for the actual production of discrete A beta has been reported. Here we investigate whether A beta is present in human biological fluids using antibodies specific for an epitope within A beta that spans the site of normal constitutive cleavage. These antibodies were used to construct a sandwich-type enzyme-linked immunosorbent assay that detects A beta in cerebrospinal fluid, plasma and conditioned medium of human mixed-brain cells grown in vitro (see also ref. 14). By affinity chromatography, we have purified and sequenced A beta and a novel A beta fragment from human cerebrospinal fluid and conditioned medium of human mixed-brain cell cultures. These findings demonstrate that A beta is produced and released both in vivo and in vitro. These observations offer new opportunities for developing diagnostic tests for Alzheimer's disease and therapeutic strategies aimed at reducing the cerebral deposition of A beta.

Alzheimer Disease↗
PubMed1992

Analysis of the p21 ras system during development of meiotic competence in Xenopus laevis oocytes.

The ability of Xenopus oocytes to undergo insulin- or insulin-like growth factor 1-induced meiotic maturation develops during oogenesis, with cells 1.0 mm in diameter or larger responding in a size-dependent manner. Since insulin-induced oocyte maturation was shown previously to be p21 ras-dependent, experiments were performed to test whether a deficiency in the p21 ras system might account for meiotic incompetence in small oocytes (less than or equal to 0.9 mm diameter). Both small and large oocytes were found to contain comparable levels of membrane-associated p21, as determined by protein immunoblotting. Treatment of both small and large oocytes with 2 microM insulin for 2 hr increased endogenous levels of membrane-associated p21 by approximately 70%. Stimulation of microinjected p21-membrane association by insulin was observed to be both time- and concentration-dependent in large oocytes with an EC50 of 50 nM. In addition, comparable levels of GTPase activating protein were measured in extracts prepared from oocytes ranging from 0.8 to 1.3 mm in diameter. Therefore, the p21 system is apparently not limiting during oogenesis, and expression of some other cellular component must account for development of meiotic competence in Xenopus oocytes.

Animals↗
PubMed1992

H-1, C-13, and F-19 nuclear magnetic resonance assignments of 3,3-difluoro-5 alpha-androstane-17 beta-ol acetate.

The molecular structure of 3,3-difluoro-5 alpha-androstane-17 beta-ol acetate was analyzed by 1H, 13C, and 19F nuclear magnetic resonance (NMR) techniques; two-dimensional NMR was used to assigned 1H and 13C resonances. The 1H NMR spectrum in deuterated chloroform shows three sharp singlets (delta = 0.74, 0.79, and 2.00 ppm) integrating for three protons each, an isolated triplet at 4.55 ppm integrating for one proton, and overlapping multiplets between 0.72 and 2.12 ppm integrating for 31 protons. The 13C spectrum shows 18 resonances between 10 and 55 ppm, and three additional resonances at 82.9, 124.0, and 171.5 ppm. The 19F[1H] spectrum shows two sets of doublets (observed 2J = 150 Hz) at 5.00 and -4.80 ppm. Multiplets arising from 19F-13C J-coupling provide the starting assignment for all resonances by means of 1H homonuclear correlation (COSY) and 1H-13C heteronuclear correlation spectroscopy.

Androstanols↗
PubMed1992

Regulation of tissue noradrenaline in the rat myocardial infarction model of chronic heart failure.

OBJECTIVE: The aim was to evaluate mechanisms regulating tissue noradrenaline in congestive heart failure. METHODS: Tissue noradrenaline was measured in the conscious post myocardial infarction rat model of congestive heart failure and in sham operated rats (1) under control conditions, (2) 6 h after inhibition of tyrosine hydroxylase by the intraperitoneal administration of alpha-methyl-para-tyrosine (AMPT) (100 mg.kg-1 every 2 h), (3) 6 h after AMPT with desipramine pretreatment (0.3 mg.kg-1), and (4) following exhaustive exercise after AMPT. Tissue noradrenaline was extracted with perchloric acid and measured by high performance liquid chromatography with electrochemical detection. RESULTS: In control animals without drug, tissue noradrenaline concentration was lower in the following tissues in the rats with myocardial infarction compared with the sham operated group: left and right ventricles, spleen, soleus and white gastrocnemius muscles, kidney cortex, and tail artery. After AMPT, tissue noradrenaline concentration in the sham operated group was significantly lower than control; in the myocardial infarction group the fall in noradrenaline was only significant in the kidney, and group differences were no longer present. In the sham operated animals, coadministration of desipramine with AMPT attenuated the fall in tissue noradrenaline caused by AMPT in the heart and spleen. With exercise to exhaustion, cardiac noradrenaline was lower in rats with myocardial infarction than in sham operated rats, but higher in the soleus muscle. CONCLUSIONS: These data suggest that tissue noradrenaline depletion in congestive heart failure is not isolated to the heart, and it occurs despite activation of mechanisms that might be operating to conserve neuronal noradrenaline. One mechanism may be reduced organ blood flow to retard diffusion of noradrenaline into the circulation. If this increases interstitial noradrenaline concentration, it would facilitate prejunctional alpha 2 receptor restraint on noradrenaline release. Metabolic coronary vasodilatation during exercise reverses this process, and makes the heart most susceptible to noradrenaline depletion in congestive heart failure.

Animals↗
PubMed1992

Phase II trial of indicine N-oxide in relapsed acute leukemia of childhood. A report from the Childrens Cancer Study Group.

We treated 31 children with acute lymphoblastic leukemia (ALL), 14 children with acute nonlymphoblastic leukemia (ANLL) in relapse, and 1 child with chronic myelogenous leukemia (CML) in blast crisis (CALLA negative) with indicine N-oxide in a Phase II study. The efficacy and toxicity of the drug were assessed at two dose levels: 2,000 mg/m2/day for 5 consecutive days (14 patients) and 2,500 mg/m2/day for 5 consecutive days (17 patients). One patient with ALL at each dose level achieved a complete response (CR) lasting 6 months and 1 month, respectively. The patient with CML achieved a partial response lasting 4 months. None of the patients with ANLL achieved a CR. Hepatotoxicity was mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of patients; 3 patients (9%) experienced severe hepatotoxicity. Although indicine N-oxide has some antileukemic activity in ALL and is safe at the doses used in this study, the antileukemic activity is significantly less at these two doses than at greater than or equal to 3,000 mg/m2/days for 5 consecutive days. Unfortunately, when the higher doses are administered to children, they are associated with an unacceptably high incidence of severe, irreversible hepatotoxicity.

Acute Disease↗
PubMed1992

Antibodies are produced to the variable regions of the external envelope glycoprotein of human immunodeficiency virus type 1 in chimpanzees infected with the virus and baboons immunized with a candidate recombinant vaccine.

Chimpanzees infected with human immunodeficiency virus type 1 produce antibodies against the variable regions of the external envelope glycoprotein gp120. All five variable regions contain an epitope which is recognized by at least one of five chimpanzee sera. Each of the sera recognized a different pattern of epitopes. It is suggested that this varying response contributes to the emergence of variant viruses in the host. In contrast with the variability of the chimpanzees' response to replicating virus, that of baboons to a candidate recombinant vaccine is more uniform. Baboons injected with recombinant gp120 produced high levels of antibodies to epitopes within both the variable and conserved regions which coincided with epitopes previously shown to induce neutralizing antibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Predictors of two-year post-hospitalization mortality among elderly veterans in a study evaluating a geriatric consultation team.

OBJECTIVE: To determine predictors of 2-year post-hospitalization mortality in a cohort of elderly hospitalized patients originally assembled to assess the impact of a Geriatric Consultation Team (GCT). DESIGN: Two-year follow-up of an inception cohort. SETTING: University-affiliated tertiary care VA Medical Center. PATIENTS: One hundred sixty-seven veterans age 75 or older discharged following hospitalization on medical, surgical, or psychiatry services but not intensive care units. INTERVENTION: None specifically studied here though cohort was previously part of randomized control trial of a Geriatric Consultation Team. MEASUREMENT: Mortality during 2 years of post-hospitalization follow-up. RESULTS: Two-year post-hospitalization mortality was 28 percent with no difference between the original GCT and control groups. For the entire sample, age, mental status, admission or discharge ADLs (but not change in ADL status), number of admission problems, number of discharge diagnoses, and discharge site were significant predictors of mortality in univariate analysis. Only discharge ADLs and discharge site remained significant in multivariate analysis. CONCLUSION: Measures of ADLs during hospitalization are stronger predictors of mortality following hospitalization than disease diagnoses. Impaired ADLs and placement other than at home are significant predictors of mortality, suggesting that the decision for nursing home placement contains other independently predictive information within it and/or that the subsequent nursing home period produces excess mortality. As had been indicated in short-term follow-up, there was no survival advantage for the Geriatric Consultation Group.

Activities of Daily Living↗
PubMed1992

Comparison of norepinephrine and isoproterenol clearance in congestive heart failure.

Congestive heart failure (CHF) is accompanied by increased sympathetic nervous activity. Previous studies have demonstrated that plasma norepinephrine (NE), a marker of sympathetic nervous activity, is elevated in CHF due to increased NE spillover into the circulation and decreased NE clearance. In this study we compared the clearance of NE and isoproterenol (ISO) in eight CHF subjects (plasma NE 601 +/- 133 pg/ml), and in nine controls (plasma NE 285 +/- 53 pg/ml) by using steady-state infusions of tritiated NE ([3H]NE) and tritiated ISO ([3H]ISO). Because ISO is not a substrate of neuronal reuptake but is removed from the circulation in a way that is similar to NE after neuronal reuptake blockade with desipramine, ISO clearance may permit a gross estimation of non-neuronal uptake of circulating NE. The NE clearance was lower in CHF than in the control group (CHF 1.25 +/- 0.13, controls 2.04 +/- 0.22 l.min-1.m-2; P = 0.009). The ISO clearance was reduced similarly in CHF (CHF 0.90 +/- 0.09, controls 1.59 +/- 0.12 l.min-1.m-2; P less than 0.001). Because the ratio of ISO to NE clearance was similar in both groups, our findings suggest that a low cardiac output in CHF decreases the availability of circulating catecholamines to tissue elimination sites.

Aged↗
PubMed1992

Effect of short-term fasting/refeeding on epidermal growth factor content in the gastrointestinal tract of suckling rats.

Epidermal growth factor (EGF) is trophic for varying regions of the developing gastrointestinal tract (GIT) of suckling rats. The presence of large amounts of EGF in milk from various species, combined with low production of EGF by suckling animals, led to speculation that milk is a major source of EGF for suckling rats. We report that short-term fasting (8 hr) of 12-day-old suckling rats resulted in a significant decrease in the levels of immunoreactive EGF (irEGF) in the GIT. Pups refed by lactating mothers for 1 to 4 hr exhibited an increase in irEGF to original levels, whereas pups fed a rat milk substitute by gastric gavage did not have an increase in irEGF content. The irEGF levels in the GIT of pups that were manually fed normal rat milk, or rat milk substitute supplemented with EGF, returned to the prefasted levels. Fasted suckling rats refed 2 ml of rat milk in 2 h exhibited significantly higher level of irEGF in the GIT than did those refed with 0.5 ml in 45 min. Since rat milk irEGF exists in three distinct forms (A, B, and C; C is equal to authentic submandibular gland EGF, the irEGF forms in the GIT were characterized by native polyacrylamide gel electrophoresis. In the stomach luminal contents of the fed suckling rats, only the larger form, Peak B, was observed. Both the luminal content and the mucosa scrapings of all other segments of all groups contained only Form D (comigrating with desarginyl EGF), a metabolic derivative of EGF. All forms were immunoreactive, exhibited receptor binding, and stimulated DNA synthesis in growth-arrested fibroblasts. The rapid changes in EGF within the GIT of suckling rats suggest the EGF can acutely modify some GIT functions of suckling rats.

Animals↗
PubMed1992

beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity.

In Alzheimer's disease (AD), abnormal accumulations of beta-amyloid are present in the brain and degenerating neurons exhibit cytoskeletal aberrations (neurofibrillary tangles). Roles for beta-amyloid in the neuronal degeneration of AD have been suggested based on recent data obtained in rodent studies demonstrating neurotoxic actions of beta-amyloid. However, the cellular mechanism of action of beta-amyloid is unknown, and there is no direct information concerning the biological activity of beta-amyloid in human neurons. We now report on experiments in human cerebral cortical cell cultures that tested the hypothesis that beta-amyloid can destabilize neuronal calcium regulation and render neurons more vulnerable to environmental stimuli that elevate intracellular calcium levels. Synthetic beta-amyloid peptides (beta APs) corresponding to amino acids 1-38 or 25-35 of the beta-amyloid protein enhanced glutamate neurotoxicity in cortical cultures, while a peptide with a scrambled sequence was without effect. beta APs alone had no effect on neuronal survival during a 4 d exposure period. beta APs enhanced both kainate and NMDA neurotoxicity, indicating that the effect was not specific for a particular subtype of glutamate receptor. The effects of beta APs on excitatory amino acid (EAA)-induced neuronal degeneration were concentration dependent and required prolonged (days) exposures. The beta APs also rendered neurons more vulnerable to calcium ionophore neurotoxicity, indicating that beta APs compromised the ability of the neurons to reduce intracellular calcium levels to normal limits. Direct measurements of intracellular calcium levels demonstrated that beta APs elevated rest levels of calcium and enhanced calcium responses to EAAs and calcium ionophore. The neurotoxicity caused by EAAs and potentiated by beta APs was dependent upon calcium influx since it did not occur in calcium-deficient culture medium. Finally, the beta APs made neurons more vulnerable to neurofibrillary tangle-like antigenic changes induced by EAAs or calcium ionophore (i.e., increased staining with tau and ubiquitin antibodies). Taken together, these data suggest that beta-amyloid destabilizes neuronal calcium homeostasis and thereby renders neurons more vulnerable to environmental insults.

Amino Acid Sequence↗
PubMed1991

Phase II trial of indicine N-oxide in relapsed pediatric solid tumors. A report from the Childrens Cancer Study Group.

We used indicine N-oxide to treat 46 children with malignant solid tumors: 17 with osteosarcoma, 12 with neuroblastoma, 13 with a brain tumor, and 4 with other miscellaneous tumors. The efficacy and toxicity of the drug was assessed at the dose of 2000 mg/m2/day for five consecutive days. None of the 39 patients evaluable for response achieved a complete or partial response. Hepatotoxicity was experienced by 13 patients: 11 patients developed asymptomatic elevations of transaminases, 1 patient developed hyperbilirubinemia, and 1 developed ascites. Indicine N-oxide appears to be ineffective in the treatment of osteosarcoma, neuroblastoma, and pediatric brain tumors at this dose and schedule. Because higher doses are associated with an unacceptably high incidence of severe, irreversible hepatotoxicity, we do not recommend further study of this agent in pediatric solid tumors.

Adolescent↗
PubMed1991

Time-constant adaptations in heart failure.

The circulatory compensatory mechanisms designed to cope quickly with physiological stress (e.g. sympathetic nervous system and the Frank-Starling mechanism) are less effective when there is chronic pathological stress, such as congestive heart failure (CHF). Other mechanisms come into play that operate over a longer time (e.g. activation of the renin-angiotensin-aldosterone system, myocardial hypertrophy and physiological deconditioning). Changes in blood vessels and skeletal muscle metabolism that result from inadequate delivery of oxygenated blood to working muscles belong to the group of mechanisms that develop slowly. When CHF therapy is successful, the abnormalities produced by this latter group of mechanisms will improve, but slowly. The concept that compensatory mechanisms have either short or long time constants for activation and reversal may explain why exercise tolerance improves much later than haemodynamics, which can be reversed acutely with vasodilator therapy.

Adaptation, Physiological↗
PubMed1991

Transbronchial needle aspiration.

Transbronchial needle aspiration biopsy is an endoscopic pulmonary procedure used to diagnose a variety of pulmonary conditions including staging patients with lung cancer and identifying nodules, masses, and benign disorders such as sarcoidosis. Transbronchial needle aspiration biopsy is a safe procedure, performed primarily with local anesthesia combined with intravenous sedation. With the anticipation of this procedure being widely used, more endoscopy nurses will be exposed to this technique. This article is intended to educate nurses and technicians about the procedure of transbronchial needle aspiration and its instruments.

Biopsy, Needle↗
PubMed1991

A controlled trial of colchicine to reduce the elastase load in the lungs of ex-cigarette smokers with chronic obstructive pulmonary disease.

A great deal of experimental evidence suggests that emphysema in smokers is caused by the action of neutrophil elastase on lung elastin. In order to test this hypothesis, it is necessary to find a drug that reduces the load of neutrophil elastase in the lungs of patients with emphysema. In a previous study we treated smokers with emphysema with colchicine, a drug that prevents neutrophil elastase secretion, to determine if it would reduce the elastase burden in the lungs. Colchicine was unable to reduce the elastase load while the stimulus of smoking continued. In this study we treated ex-smokers with emphysema to determine if colchicine could reduce the elastase burden in the lungs. The objective of the study was to determine if colchicine can reduce the elastase load and putative indicators of elastase load in the lungs of patients with chronic obstructive pulmonary disease. The study was a prospective, double-blind, randomized, and placebo-controlled clinical trial. The subjects were outpatients seeking treatment at the University of Texas Health Center at Tyler. We studied 16 ex-cigarette smokers between 45 and 75 yr of age with lung disease defined by FEV1 less than 70% of predicted but greater than 1.2 L whose airflow obstruction was less than 20% reversible with bronchodilators. Colchicine or placebo was taken by mouth in disguised capsules, 0.6 mg three times per day. Volunteers were placed on a baseline bronchodilator regimen of theodur by mouth and albuterol by inhalation. Blood, urine, and bronchoalveolar lavage fluids were obtained after 1 wk of stabilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Modulation of immunoreactive epidermal growth factor levels in the submandibular gland, pancreas, liver, kidney and gastrointestinal tract of suckling rats by cortisone and tri-iodothyronine.

Suckling rats exhibit age-dependent differences in epidermal growth factor (EGF) levels in several organs. The present studies evaluated the effects of two hormones known for their maturative effect on suckling rats, cortisone and tri-iodothyronine (T3), on immunoreactive EGF levels in specific organs. Suckling rats were administered cortisone (5 mg/100 g body weight per day) or T3 (50 micrograms/100 g body weight per day) on days 8, 9, 10 and 11 after birth, and killed on day 12. Submandibular glands, kidneys, pancreas, liver and gastrointestinal tract mucosa and lumen were assayed for immunoreactive EGF by a species-specific radioimmunoassay. Low levels of EGF in the submandibular glands were increased slightly by both T3 and cortisone treatment. Cortisone evoked a tenfold increase in EGF in the pancreas, but had no effect on levels in the kidney or liver. In contrast, T3 evoked a sixfold increase in the EGF level in the kidney, but had no effect on levels in the pancreas or liver. Hormonal administration had no effect on EGF levels in the stomach. Within the intestinal tract, cortisone had no effect on the luminal EGF content of the duodenum, jejunum or ileum, but caused a decrease in the midjejunum. T3 evoked a decrease in the luminal EGF content of the ileum. The effect of cortisone on mucosal EGF content varied between regions; an increase was seen in the duodenum with a decrease in the midjejunum and ileum. T3 administration resulted in a significant decrease in EGF only in the mucosa of the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗