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Biomedical subjects

D R Davis

Publications and source records attributed to D R Davis.

At least 73 records · Page 4Linked to original sources

Ninety-seven million years of angiosperm-insect association: paleobiological insights into the meaning of coevolution.

From well preserved leaf damage of the mid-Cretaceous Dakota Flora (97 million years ago), three distinctive, insect-mediated feeding traces have been identified and assigned to two extant genera and one subfamily. These taxa are the leaf miners Stigmella and Ectoedemia of the Nepticulidae and Phyllocnistinae of the Gracillariidae. These fossils indicate that within 25 million years of early angiosperm radiation, the organs of woody dicots already were exploited in intricate and modern ways by insect herbivores. For Ectoedemia and its platanoid host, we document 97 million years of continuity for a plant-insect interaction. The early occurrence during the mid-Cretaceous of diverse and extensive herbivory on woody angiosperms may be associated with the innovation of deciduousness, in which a broadleafed angiosperm provided an efficient, but disposable, photosynthetic organ that with-stood the increased cost of additional insect herbivory. Moreover, the group represented in this study, the leaf-mining Lepidoptera, exhibits a wide range of subordinal taxonomic differentiation and includes the Gracillariidae, a member of the most derived lepidopteran suborder, the Ditrysia. Ditrysian presence during the mid-Cretaceous, in addition to lepidopteran body-fossil evidence from Early Cretaceous and Late Jurassic deposits, suggests that the radiation of major lepidopteran lineages probably occurred during the Late Jurassic on a gymnosperm-dominated flora.

Journal Article↗

Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells.

BACKGROUND: Paired helical filaments (PHFs) are a characteristic pathological feature of Alzheimer's disease; their principal component is the microtubule-associated protein tau. The tau in PHFs (PHF-tau) is hyperphosphorylated, but the cellular mechanisms responsible for this hyperphosphorylation have yet to be elucidated. A number of kinases, including mitogen-activated protein (MAP) kinase, glycogen synthase kinase (GSK)-3 alpha, GSK-3 beta and cyclin-dependent kinase-5, phosphorylate recombinant tau in vitro so that it resembles PHF-tau as judged by its reactivity with a panel of antibodies capable of discriminating between normal tau and PHF-tau, and by a reduced electrophoretic mobility that is characteristic of PHF-tau. To determine whether MAP kinase, GSK-3 alpha and GSK-3 beta can also induce Alzheimer's disease-like phosphorylation of tau in mammalian cells, we studied the phosphorylation status of tau in primary neuronal cultures and transfected COS cells following changes in the activities of MAP kinase and GSK-3. RESULTS: Activating MAP kinase in cultures of primary neurons or transfected COS cells expressing tau isoforms did not increase the level of phosphorylation for any PHF-tau epitope investigated. But elevating GSK-3 activity in the COS cells by co-transfection with GSK-3 alpha or GSK-3 beta decreased the electrophoretic mobility of tau so that it resembled that of PHF-tau, and induced reactivity with eight PHF-tau-selective monoclonal antibodies. CONCLUSIONS: Our data indicate that GSK-3 alpha and/or GSK-3 beta, but not MAP kinase, are good candidates for generating PHF-type phosphorylation of tau in Alzheimer's disease. The involvement of other kinases in the generation of PHFs cannot, however, be eliminated. Our results suggest that aberrant regulation of GSK-3 may be a pathogenic mechanism in Alzheimer's disease.

Alzheimer Disease↗

Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction.

Although erectile dysfunction is frequently seen in patients with manifestations of arteriosclerotic disease, the independent contribution of serum cholesterol in predicting erectile dysfunction is unclear. The aim of this study was to examine the relation between serum cholesterol and erectile dysfunction. Medical histories, physical examinations, and blood tests were obtained at Cooper Clinic, Dallas, Texas, from 3,250 men aged 26-83 years (mean, 51 years) without erectile dysfunction at their first visit, who had one more clinic visit, all between 1987 and 1991. These men were followed 6-48 months after the first clinic visit (mean, 22 months). Erectile dysfunction was reported in 71 men (2.2%) during follow-up. Every mmol/liter of increase in total cholesterol was associated with 1.32 times the risk of erectile dysfunction (95% confidence interval 1.04-1.68), while every mmol/liter of increase in high density lipoprotein cholesterol was associated with 0.38 times the risk (95% confidence interval 0.18-0.80). Men with a high density lipoprotein cholesterol measurement over 1.55 mmol/liter (60 mg/dl) had 0.30 times the risk (95% confidence interval 0.09-1.03) as did men with less than 0.78 mmol/liter (30 mg/dl). Men with total cholesterol over 6.21 mmol/liter (240 mg/dl) had 1.83 times the risk (95% confidence interval 1.00-3.37) as did men with less than 4.65 mmol/liter (180 mg/dl). Those differences remained essentially unchanged after adjustment for other potential confounders. The authors conclude that a high level of total cholesterol and a low level of high density lipoprotein cholesterol are important risk factors for erectile dysfunction.

Adult↗

Mutational analysis of the metal sites in an LIM domain.

Site-directed mutagenesis was carried out to map the residues that form the two Zn(II) sites within a LIM domain. The C-terminal LIM domain derived from the cysteine-rich protein was utilized for this analysis and is referred to as LIM2. Seven cysteinyl residues and a single histidyl residue in the LIM2 sequence, CX2CX17HX2CX2CX2CX17CX2C, comprise the conserved residues in the LIM consensus that are potential Zn(II) ligands. Two Zn(II) binding sites exhibiting tetrathiolate (S4) and S3N1 Zn(II) coordination are displayed by LIM2 (Kosa, J. L., Michelsen, J. W., Louis, H. A., Olsen, J. I., Davis, D. R., Beckerle, M. C., and Winge, D. R. (1994) Biochemistry 33, 468-477). Site-directed mutagenesis was employed to generate three mutant LIM2 proteins with conversions of the second conserved cysteine to histidine (C2H), the fifth conserved cysteine to histidine (C5H), and the last conserved cysteine to aspartate (C8D). Metal coordination by the mutant proteins was evaluated by atomic absorption spectroscopy, Co(II) electronic spectroscopy, and 113Cd NMR spectroscopy. The results permit discrimination between various models of metal ion binding and suggest that the LIM domain is comprised of a S3N1 site generated from the four N-terminal candidate ligands (CX2CX17HX2C) and a S4 site generated from the four C-terminal candidate ligands (CX2CX17CX2C).

Amino Acid Sequence↗

Common metal ion coordination in LIM domain proteins.

The LIM motif is a cysteine- and histidine-rich sequence that was first identified in proteins involved in control of gene expression and cell differentiation. In order to characterize structural features of the LIM domain, we have carried out biophysical studies on two polypeptides that display LIM domains: the cysteine-rich intestinal protein (CRIP) and a fragment of the cysteine-rich protein (CRP). Bacterial expression vectors were constructed for the intact CRIP molecule and the C-terminal half of CRP, designated LIM2, such that each expressed protein contained a single LIM domain. Both proteins were recovered as soluble, Zn(II)-containing proteins. The metal coordination properties of these two distinct LIM domain proteins were highly similar, suggesting that a common structural architecture may exist in LIM domain proteins. Both proteins exhibit a maximum of two tetrahedrally bound Zn(II) ions per molecule. Electronic spectroscopy of Co(II) complexes and 113Cd NMR of Cd(II) complexes of CRIP and LIM2 revealed a similar ligand field pattern with one tetrathiolate (S4) site and one S3N1 site for divalent metal ions. The nitrogen ligand was shown to arise from a histidyl imidazole by heteronuclear multiple quantum coherence NMR. The eight conserved residues within the LIM domains of CRIP and LIM2 include seven cysteines and one histidine. It is likely that these conserved residues generate the S4 and S3N1 Zn(II)-binding sites. Metal binding to the two sites within a single LIM domain is sequential, with preferential occupancy of the S4 site. Slow metal ion exchange occurs between sites within an LIM domain, and metal exchange with exogenous metal ions is observed, with exchange at the S3N1 site being kinetically more facile. In the absence of metal binding both proteins appear to be substantially unfolded. Metal binding stabilizes a tertiary fold containing appreciable secondary structural elements. The common metal ion coordination in CRIP and LIM2 suggests that the LIM motif may constitute a structural module with conserved features.

Amino Acid Sequence↗

Impact of the saponin adjuvant QS-21 and aluminium hydroxide on the immunogenicity of recombinant OspA and OspB of Borrelia burgdorferi.

The impact of the adjuvants QS-21 and aluminium hydroxide (alum) on the immunogenicity of recombinant outer surface proteins A (OspA) and B (OspB) of Borrelia burgdorferi was investigated. Both non-acylated OspA and OspB derived from strain B31 were expressed in Escherichia coli and purified by reversible citraconylation and anion-exchange chromatography. Antisera to OspA or OspB were prepared in mice with antigens formulated with QS-21 or alum, and evaluated for specific immunoglobulin G isotypes, agglutination and borreliacidal activity. QS-21 significantly enhanced IgG2a and IgG2b antibody responses to OspA and OspB, and IgG1 response to OspA when compared with the formulation containing antigen alone. In contrast, alum significantly inhibited the induction of IgG2a and IgG2b responses to OspA. Alum had no significant effect on IgG1 response to OspA, or IgG2a and IgG2b responses to OspB, but significantly enhanced IgG1 antibody response to OspB. Antisera to OspA or OspB formulated by QS-21 possessed higher titres of agglutinating antibody than antisera to OspA or OspB alone. Borreliacidal activity was eight- to 64-fold higher in antisera to OspA formulated with QS-21 than in antisera to OspA formulated with or without alum. These antisera were highly borreliacidal to New York strain B31, a California isolate CA-2-87, German isolate Fr, and Swedish isolate G25. Antisera to OspB formulated with QS-21 were highly borreliacidal to strains B31 and Fr, but not to CA-2-87 and G25. Antisera to OspB formulated with alum were borreliacidal only to B31. Thus, OspA was superior to OspB and QS-21 superior to alum at eliciting functional antibody responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Differences between chimpanzees (Pan troglodytes) and humans (Homo sapiens) in the resting state of the index finger: implications for pointing.

Pointing with the index finger is a universal human (Homo sapiens) behavior found in cultures around the world. The emergence of pointing in infancy has traditionally been linked with the early development of cognitive capacities such as perspective-taking, intersubjectivity, and empathy. In contrast to humans, chimpanzees (Pan troglodytes) do not develop a pointing gesture with the index finger and rarely point by gesturing with hands or arms. However, recent experimental data suggest that chimpanzees may develop cognitive skills related to perspective-taking and empathy. In this article we report the existence of a difference in the resting morphology of the index finger in humans and chimpanzees. We speculate on how this species difference may be related to species differences in pointing with the index finger.

Animals↗

The effects of HIV/AIDS intervention groups for high-risk women in urban clinics.

OBJECTIVE: This study reports the results of a behavior change intervention offered to women at high risk for human immunodeficiency virus (HIV) infection seen in an urban primary health care clinic. METHODS: Participants were 197 women randomly assigned to either an HIV/acquired immunodeficiency syndrome (AIDS) risk reduction group or a comparison group. Women in the HIV/AIDS intervention group attended five group sessions focusing on risk education; skills training in condom use, sexual assertiveness, problem solving, and risk trigger self-management; and peer support for change efforts. Women in the comparison group attended sessions on health topics unrelated to AIDS. RESULTS: At the 3-month follow-up, women in the HIV/AIDS intervention group had increased in sexual communication and negotiation skills. Unprotected sexual intercourse had declined significantly and condom use had increased from 26% to 56% of all intercourse occasions. Women in the comparison group showed no change. CONCLUSIONS: Socially disadvantaged women can be assisted in reducing their risk of contracting HIV infection. Risk reduction behavior change interventions should be offered routinely in primary health care clinics serving low-income and high-risk patients.

Adolescent↗

Survival of Alzheimer's disease patients with regard to pattern of care in South Carolina, 1988-1993.

The length of time from diagnosis of AD to death was compared among three groups of AD patients in South Carolina. Each group received a different pattern of care. The survival time from diagnosis to death was longest among those who lived in institutions (mean three years for men, 4.6 years for women), and shortest among those who lived alone in the community (1.7 years for men, two years for women). The longer survival time of those who receive care (either in the community or in facilities) suggests that persons with AD benefit from personal attention to health needs. Providing additional support to family members of those with AD could help patients remain in the community longer, thus maintaining quality of life. For those who have no support in the community, efforts should be made to increase access to facilities.

Aged↗

Recent military experience with malaria chemoprophylaxis.

OBJECTIVE: To assess the value of various drug regimens for malaria prophylaxis under circumstances where dapsone and pyrimethamine (combined as Maloprim) and chloroquine, followed by the 14-day primaquine eradication course, were no longer effective in protecting military personnel against falciparum and vivax malaria. DESIGN, SETTING AND PARTICIPANTS: Various drug regimens given to four groups of healthy male members of the Australian Army during training exercises in malarious countries. INTERVENTIONS: Four groups of soldiers were given different regimens for 3-12 weeks: Group 1--mefloquine (250 mg weekly); Group 2--doxycycline (100 mg daily); Group 3--doxycycline (100 mg daily) and primaquine (7.5 mg daily); and Group 4--doxycycline (50 mg daily) and chloroquine (300 mg weekly). Except in Group 3, each of these regimens was followed by a 7.5 mg dose of primaquine three times a day for two weeks. MAIN OUTCOME MEASURES: The proportion of participants in the various prophylactic drug groups who developed falciparum or vivax malaria during or after the intervention. RESULTS: Group 1: 40 men receiving mefloquine were all protected against falciparum malaria but four (10%) developed vivax malaria. These results were not statistically different from those obtained for either falciparum (P = 0.28) or vivax (P = 0.36) malaria in the control group of 64 men receiving Maloprim and chloroquine. Group 2: 60 men receiving doxycycline (no control group) were all protected against falciparum malaria but two developed vivax malaria. Group 3: 124 men, of whom 55 received doxycycline and 69 primaquine in addition to doxycycline, were all protected against falciparum malaria. However, 13 men taking only doxycycline developed vivax malaria two to three weeks after prophylaxis, whereas no vivax infections were observed in the men taking the drug combination (P = 0.0001). Group 4: no malaria infections were observed in 125 men receiving doxycycline and chloroquine for 13 weeks, probably because of the low prevalence of malaria in the training area. CONCLUSIONS: These studies confirm that doxycycline is very effective in preventing falciparum malaria and, for the first time, also suggest that doxycycline used in combination with small doses of primaquine may prevent (not only suppress) vivax malaria. If further studies confirm these findings, the use of such a drug combination would reduce the incidence of both vivax and falciparum malaria in returning travellers. For individuals with a high risk of exposure to malaria, it would also forestall the need to take the bothersome primaquine eradication course.

Antimalarials↗

Body mass and risk of hip fracture among a national cohort of postmenopausal white women: a reanalysis.

To assess the prospective relationship between body mass and rate of hip fracture, we analyzed data from 2,285 postmenopausal women, aged 50-77 years, who responded to the first National Health and Nutrition Examination Survey (NHANES I) in 1971-1974 and the 1982-84 interview of the National Health Epidemiologic Follow-up Study (NHEFS). We plan to add to the previous analysis of these same data by Farmer et al. by 1) including retrospective information on estrogen replacement therapy; 2) increasing the follow-up time by 5 years and using only hospital-verified cases of hip fracture from the 1987 Health Care Facilities Stay data tape; and 3) limiting the analysis to postmenopausal white women, ages 50-77 years. Results of the multivariable Cox regression modeling showed that women with a baseline body mass index in the highest quartile (> 37 kg/m1.5) experienced a 70% lower rate of hip fracture compared with women in the lowest quartile (< or = 28.7 kg/m1.5)(RR=0.32; 95%CI:0.12, 0.82). Age was positively related to the risk of hip fracture, with the rate over 20% higher per year of age (RR=1.21; 95%CI:1.13, 1.29). Although reported education level, smoking history, physical activity level, and estrogen replacement were significantly (p < 0.0001) associated with body mass index, these covariates were not related to hip fracture in the multivariable analysis. Our findings corroborate earlier results using this same data source, and suggest that interventions aimed at preserving lean mass and consequent bone integrity should be encouraged among women before menopause and maintained through older adulthood.

Age Factors↗

Enhanced expression, secretion, and large-scale purification of recombinant HIV-1 gp120 in insect cell using the baculovirus egt and p67 signal peptides.

The expression of glycosylated and secreted recombinant mammalian proteins in baculovirus-infected insect cells is often much less efficient than that of other foreign proteins in this system. In an effort to improve the expression and secretion of such proteins we have constructed baculovirus vectors which contain the signal peptide coding regions from two baculovirus proteins, an ecdysteroid UDPglucosyltransferase (egt) and the envelope glycoprotein gp67. We used these vectors to express HIV-1 gp120, inserting the baculovirus signal peptides in place of the HIV-1 envelope signal peptide. When Sf9 cells infected with recombinant baculoviruses made from these vectors (vegt120 and vp67120) were compared with cells infected with the normal gp120 baculovirus a 6- to 20-fold increase in expression and secretion of gp120 was observed. When the HIV-1 signal peptide was used only 40% or less of the total gp120 produced in Sf9 cells was secreted. However, using the egt or p67 signal peptides, up to 70% of the total gp120 produced was secreted. Therefore, not only was more gp120 produced from these modified viruses but secretion of gp120 was more efficient. Large-scale expression and purification of egt-gp120 from a 5-liter airlift fermenter or a 6-liter spinner flask resulted in a yield of 10 to 15 mg of purified protein per liter. Using these baculovirus-derived signal peptides in baculovirus expression vectors is thus likely to aid in increasing expression and yield of heterologous secreted proteins in insect cells.

Amino Acid Sequence↗

Effect of denture wax-pattern position on radial setting expansion.

Th dynamics of the setting expansion of gypsum-bonded investment is complicated by many variables and not well understood. The purposes of this study were to examine the fluid mechanics of the flow of investment during setting and to determine if the presence of wax patterns influences effective setting expansion. Mesial-occlusal-distal (MOD) inlay wax patterns were invested at six different radial positions and four different axial positions in plastics casting rings. Total expansion was determined by using xeroradiography. Combined results of radial expansion data at different axial and radial locations within casting rings suggest that expansion of gypsum-bonded investment may represent a variant of the laminar flow of a viscous fluid.

Dental Bonding↗

Neuroimaging of arachnoiditis induced by spinal anesthesia.

Despite the simplicity, effectiveness, and safety of spinal anesthesia, arachnoiditis can occur as a complication. The cause of this is often unknown, especially since disposable spinal kits are now normally used. It is postulated that an untoward reaction to the anesthesia or chemical contamination was the cause of arachnoiditis in our patient. We also outline the use of MRI in the diagnosis of arachnoiditis. This mode of investigation is often sufficient to establish the diagnosis. When necessary, it can be augmented by myelography and CT.

Adult↗

Reproductive abnormalities in the prepubertal jaundiced Gunn rat.

The female, jaundiced Gunn rat has been previously reported to be infertile. This study describes some abnormalities in the reproductive system of the prepubertal jaundiced female rat. Vaginal opening occurred at the time of weaning, which was approximately 7 days earlier when compared to the nonjaundiced female littermates. Following vaginal opening, the jaundiced rat showed persistent vaginal cornification. The estimated age at first ovulation in the jaundiced rat was 52 days. The uteri of jaundiced rats were significantly larger than those of nonjaundiced rats by 17 days after birth. The accelerated uterine growth and the precocious vaginal opening in the jaundiced rat suggest hyperestrogenism. Feeding activated charcoal to jaundiced rats significantly reduced the uterine weight. These results show that the reproductive abnormalities in the jaundiced female rat appear in the prepubertal life and continue during adult life resulting in infertility.

Animals↗

The association of positive and negative events with depressive symptomatology among caregivers.

A pilot study of eighty-two caregivers was conducted in South Carolina in 1991 to identify positive and negative factors associated with caregiving. Through home visits, interviewers obtained data on a variety of physical and mental health measures, including two new scales designed to measure perceived "positive" and "negative" events that had occurred in the previous month. The Center for Epidemiologic Studies Depression scale was used as a measure of depressive symptomatology. For the new scales, only items that were significantly correlated with depressive symptomatology (p < 0.01) were retained. The new "positive" event scale (8 items) and the new "negative" event scale (16 items) had alpha coefficients of 0.79 and 0.86, respectively. These scales may be useful to researchers in sorting out mediating factors related to the burden of caregiving and in providing points for intervention.

Adaptation, Psychological↗

A measure of perceived burden among caregivers.

This report describes an easily administered scale for measuring perceived burden among caregivers of family members with dementia. During home interviews conducted in 1991, 82 caregivers rated their family member with dementia on several items related to functional ability, the type of care provided, and associated stress. The resulting measure of perceived burden, based on 15 internally consistent items (alpha = 0.87), is significantly correlated with depressive symptomatology (r = 0.38, p = 0.0004). This measure is useful in assessing perceived stress associated with specific caregiving responsibilities. It can be used, along with other measures of patient functional status, to assess overall caregiver burden and to target intervention strategies.

Black or African American↗