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Biomedical subjects

A J Davis

Publications and source records attributed to A J Davis.

At least 19 recordsLinked to original sources
PubMed2006

Vif-deficient HIV reverse transcription complexes (RTCs) are subject to structural changes and mutation of RTC-associated reverse transcription products.

Reverse transcription (RTn) in HIV-infected cells occurs in a nucleoprotein complex termed the reverse transcription complex (RTC). RTCs containing RT activity and integrase (IN) were shown to be heterogeneous in size and density on sucrose velocity and equilibrium gradients. WT and Vif-deficient (Deltavif) RTCs produced by infection with virus from permissive cells displayed similar sedimentation characteristics, while RTCs from Deltavif virus produced in non-permissive cells demonstrated a reduction in the major RTC form and more of the RTn products in rapidly sedimenting structures. APOBEC3G derived from virions did not co-sediment with RTCs, but RTCs from Deltavif infections showed elevated levels of mutations in RTn products, consistent with APOBEC3G and other mutational mechanisms. The most mutated transcripts were present within rapidly sedimenting RTCs. Thus, virus without functional vif, produced from non-permissive cells, forms abnormal RTCs that contain increased mutation of RTC-associated RTn products in newly infected target cells.

APOBEC-3G Deaminase↗
PubMed2006

The role of glucagon in regulating chicken hepatic malic enzyme and histidase messenger ribonucleic acid expression in response to an increase in dietary protein intake.

Increased dietary protein intake rapidly (3 h) decreases hepatic malic enzyme and increases hepatic histidase mRNA expression in broiler chicks. A series of experiments was conducted to determine the role that glucagon or a specific mixture of dietary amino acids might have in regulating the rapid changes in mRNA expression of these enzymes, when dietary protein intake is increased. Three hours after the injection of glucagon (240 microg/kg of BW) into the brachial vein of broiler chicks, hepatic malic enzyme mRNA expression was significantly lower and hepatic histidase mRNA expression was significantly greater than the level detected in saline-injected chicks. In addition, broiler chicks fed a high (40 g/ 100 g of diet) protein diet had significantly higher plasma glucagon levels at 1 and 3 h after initial access to this diet than broiler chicks fed a basal (22 g/100 g of diet) protein diet. The plasma glucagon concentration, however, was not different between the chicks fed the 2 dietary protein levels at 2 h after the initial access to the 2 diets. When a mixture of indispensable or dispensable amino acids was added to the basal diet to equal the concentrations of the individual indispensable or dispensable amino acids in the high protein diet, hepatic mRNA expression of malic enzyme and histidase were intermediate to the expression found in chicks fed the basal and high protein diet. The results indicate that glucagon may mediate the changes in the mRNA expression of malic enzyme and histidase in response to dietary protein intake and that total amino acid intake rather than the ingestion of specific amino acids regulates the mRNA expression of malic enzyme and histidase in chicks.

Animals↗
PubMed2006

Cellular interactions of virion infectivity factor (Vif) as potential therapeutic targets: APOBEC3G and more?

Vif is an HIV accessory protein whose primary function is to negate the action of APOBEC3G, a naturally occurring cellular inhibitor of HIV replication. Vif acts by binding to APOBEC3G, inducing its protein degradation within infected cells and reducing its levels in progeny virions. Interventions that interfere with the Vif-APOBEC3G interaction, raise intracellular or virion associated levels of APOBEC3G, or reduce intracellular levels of Vif, all could hold promise as potential therapeutic approaches aimed at enhancing the cells innate antiviral activity. Levels of APOBEC3G might be increased or Vif levels decreased, by strategies targeting protein synthesis, protein degradation or cellular localisation and function, and properties of APOBEC3G and Vif relevant to these strategies are discussed. Recent data have suggested that Vif may have other mechanisms of action apart from the above activities against APOBEC3G, including effects against other anti-viral mechanisms independent of APOBEC3G cytidine deaminase activity. In addition to interaction with APOBEC3G, Vif may have other accessory functions, which are discussed in relation to potential therapies that may affect multiple stages of the HIV life cycle. Future development of strategies that combine enhancement of APBOEC3G functional with inhibition of multiple Vif functions may become useful tools for HIV therapy.

APOBEC-3G Deaminase↗
PubMed2005

Pattern of secretion of immunoreactive inhibin/activin subunits by avian granulosa cells.

The messenger RNA expression for the inhibin/activin subunits in the granulosa layer of avian follicles of different developmental stages has previously been reported. In the present study, we examined the pattern of secretion of these protein subunits from cultured granulosa cells (GC) of avian follicles of defined maturity. Laying hens were euthanized and the F1, F2, F3, F4, small yellow follicles (SYF; 6-10 mm) and large white follicles (LWF; 3-5 mm) were removed. GC were isolated from the follicles, plated by size at a density of 6.25 x 10(5)cells per well (3 wells per follicle size) and cultured for 48 h in medium 199 with 5% FBS, antibiotics, and 1.0 microg/ml bovine insulin. After 48 h, the cultures were terminated and the media were saved (n = 6 replications). Proteins were precipitated from media, reconstituted for electrophoresis (SDS-PAGE), and analyzed by Western blot. Progesterone was also measured in the medium. For detection of the inhibin alpha-subunit, a rabbit antibody against the chicken inhibin alpha-subunit (1-26 aa) was used. The betaA-subunit was detected with rabbit anti-betaA-subunit (81-113 aa) and the betaB-subunit was detected with rabbit anti-betaB-subunit (80-112 aa). Under reduced conditions, GC from the larger follicle sizes (F1-F4) secreted the most (p < 0.05) immunoreactive inhibin alpha-subunit compared to smaller follicle sizes. Under non-reduced conditions, a band at approximately 32 kDa was detected by both the alpha-subunit antibody and by the betaA-subunit antibody in media from GC of the F1-F4 follicles, suggesting secretion of intact inhibin A. Immunoreactive alpha-subunit and betaB-subunit were detected under reduced conditions in media from the GC of the SYF, suggesting that this follicle population may secrete intact inhibin B. In addition, under non-reduced conditions, cells from the SYF secreted the greatest amount of intact inhibin B (p < 0.05) at a size of approximately 32 kDa. Cells from the LWF expressed low levels of all inhibin subunits. Progesterone concentration in the media from the F1 follicle was greatest and was decreased in media from smaller follicles. It is suggested that the largest follicles in the hierarchy are the source of most circulating intact inhibin A while the small follicles are the source of intact inhibin B.

Activins↗
PubMed2005

Relative toxicity of gossypol enantiomers in broilers.

Use of cottonseed meal in poultry diets has been avoided in large part because of fear of gossypol toxicity. Gossypol exists naturally as a mixture of 2 enantiomers that exhibit different biological activities. Two experiments were conducted to determine the relative toxicity of gossypol enantiomers on broilers. In the first experiment, 3-d-old broilers were fed a standard diet containing 0, 100, 200, 300, or 400 mg of gossypol from gossypol acetic acid per kilogram of diet from 3 to 42 d of age. This form of gossypol contains both enantiomers in an equimolar ratio. Each dietary treatment consisted of 6 replicate pens of 4 birds. In the second experiment, 3-d-old broilers were divided into 15 pens of 4 birds each and fed a standard diet supplemented with either no gossypol or one of the gossypol enantiomers at 200 or 400 mg/kg of diet from 3 to 21 d of age. In both experiments, feed intake and BW gain were measured. In addition, several organ and tissue samples were collected at 21 d (experiments 1 and 2) and 42 d (experiment 1) of age and analyzed for gossypol. In experiment 1, feed consumption and BW gain were reduced (P < 0.05) at 21 and 42 d for the birds fed the highest level of gossypol. The concentration of gossypol in the heart, kidney, and plasma were equivalent at 21 and 42 d of age. In experiment 2, total feed consumption was reduced only in birds consuming (-)-gossypol, but BW gains were lower for birds fed either enantiomer. However, (-)-gossypol was more detrimental to growth than (+)-gossypol. The liver had the highest tissue concentration of both enantiomers, and accumulation of (+)-gossypol was higher than (-)-gossypol in all tissues examined. No racemization of the enantiomers was apparent in the tissues analyzed. Our results indicated that both gossypol enantiomers were toxic to broilers but that (-)-gossypol was more harmful to efficient broiler production than (+)-gossypol.

Animals↗
PubMed2004

Responses of broilers to dietary zinc concentrations and sources in relation to environmental implications.

1. Since high concentrations of zinc are associated with reduced crop yields, environmental concerns are emerging regarding zinc accumulation in areas where poultry production is prevalent. This study investigates growth performance and zinc utilisation during the life cycle of broilers when diets were supplemented with various concentrations of zinc from two different sources. 2. A total of 740 Cobb 500 1-d-old male broiler chicks was randomly distributed into 88 battery cages. Excreta were collected over a 48-h period on d 10, 17, 24, 31, 38, and 45 to measure zinc excretion on a dry matter basis. 3. During the 45-d experimental period, broilers were given a maize-soybean meal basal diet (30 mg/kg zinc) supplemented with 0, 20, 40, and 80 mg/kg of zinc from zinc sulphate, Availa Zn amino acid complex, or an equal combination of zinc sulphate and Availa Zn amino acid complex. 4. Progressive additions of zinc to the basal diet significantly increased body weight gain of broilers, but did not affect feed conversion or mortality. Optimum body weight gain was achieved at 80 mg/kg supplemental zinc, which exceeds the NRC recommendations of 40 mg/kg. 5. During each excreta collection period, increased supplemental zinc concentrations significantly increased zinc excretion. However, the zinc source did not influence zinc utilisation. 6. As compared with zinc sulphate supplementation, the cumulative zinc excretion data indicate that adding zinc to the basal diet in the form of Availa Zn amino acid complex decreased zinc excretion.

Animal Feed↗
PubMed2003

Phase I study of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours.

This phase I study was conducted to determine the recommended phase II doses, safety profile, and antitumour activity of a combination regimen of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours. Cisplatin and epirubicin were given at fixed doses of 50 and 60 mg m(-2), respectively. The irinotecan dose was escalated at 10 mg m(-2) increments from a starting dose level of 70 mg m(-2). Epirubicin, irinotecan, and their metabolites were measured with HPLC methods. In all, 35 patients received 141 courses of treatment. Irinotecan dose was escalated in seven cohorts up to 130 mg m(-2), and then finally de-escalated to 110 mg m(-2). The dose-limiting toxicity was neutropenic fever. Nonhaematologic toxicities included mild to moderate nausea/vomiting, diarrhoea and fatigue. Of 34 patients with evaluable disease, one patient had a complete response and nine patients had partial response, yielding an overall response rate of 29.4%. Pharmacokinetic parameters of epirubicin were not affected by the sequence of drug administration. However, the AUCs of irinotecan and its metabolites were increased significantly when irinotecan and epirubicin were administered concurrently. This combination regimen has promising broad antitumour activity, and will be further evaluated in phase II studies in multiple tumour types.

Adult↗
PubMed2003

Assessment of tumor cell repopulation after chemotherapy for advanced ovarian cancer: pilot study.

BACKGROUND: Repopulation of clonogenic tumor cells appears to increase during fractionated radiation treatment and is recognized as an important factor affecting local control. Given the longer intervals between cycles and longer total duration of treatment, the impact of repopulation is likely to be greater after chemotherapy. METHODS: We assessed tumor cell repopulation with the proliferative marker Ki-67 in 21 patients with ovarian carcinoma who received initial chemotherapy. Paraffin slides were evaluated from the diagnostic biopsy and from tumor obtained at debulking surgery after chemotherapy. Immunohistochemistry using the MIB-1 antibody was performed on the paired samples and analyzed with a digital imaging device linked to a color camera mounted on a transmitted-light microscope. The ratio of Ki-67 positive to all nuclei was used as a proliferative index and compared for pre- and postchemotherapy specimens. RESULTS: All patients received platinum-based chemotherapy and most showed a response to treatment. The median duration between last chemotherapy and debulking surgery was 33 days (range, 22-50 days). Four (19%) of 21 patients showed an increased proliferative index after chemotherapy, and the remainder showed a decrease (n = 12) or no significant change (n = 5). CONCLUSIONS: Our results did not suggest an increase in proliferation of tumor cells after this type of chemotherapy in the majority of patients with ovarian cancer.

Antineoplastic Agents↗
PubMed2003

Growth in a context of cultural marginality: North American nurse educators in Japan.

BACKGROUND: Concepts of marginality and partnership emerged from a questionnaire completed by 12 North American nurse educators working long term in Japan. METHODS: To study individual perceptions regarding current professional and personal experiences, including language competency, roles and responsibilities in a different culture, contributions made, and management of daily living. Respondents also made recommendations to others who accepted similar assignments. RESULTS: The data revealed growth accomplished and challenges encountered as a result of marginal status in the Japanese context with varying levels of socio-cultural adaptation.

Adult↗
PubMed2003

Early growth and environmental implications of dietary zinc and copper concentrations and sources of broiler chicks.

1. Environmental accumulation of zinc and copper is becoming a concern in areas having intensive animal production. This study examined performance and excretion of broiler chicks given diets supplemented with graded concentrations of zinc and copper from three different sources. 2. Two experiments were conducted, each utilising 570 1-d-old chicks. In Experiment 1, chicks were given diets containing supplemental zinc concentrations from 40 to 120 mg/kg supplied as zinc sulphate, a zinc amino acid complex (Availa Zn), or a combination of zinc sulphate and Availa Zn with each contributing one-half of the total supplemental zinc. In Experiment 2, broiler chicks were given diets with graded concentrations of supplemental copper ranging from 4 to 12 mg/kg from copper sulphate, a copper amino acid complex (Availa Cu), or a combination of copper sulphate and Availa Cu with each contributing one-half of the total supplemental copper. 3. During the 17-d experimental period, mineral concentration or source did not influence body weight, feed conversion, or the incidence of mortality from 1 to 17 d. 4. Decreasing dietary zinc concentration from 120 to 40 mg/kg reduced zinc excretion by 50%. 5. Copper excretion was decreased by 35% as supplemental copper was reduced from 12 to 4 mg/kg. 6. Reducing dietary zinc and copper concentrations can potentially decrease the accumulation of heavy metals in the environment without compromising bird performance.

Animals↗
PubMed2003

Attributes of broiler breeder males characterized by low and high sperm mobility.

The attributes of broiler breeder males characterized by sperm mobility phenotype were studied in replicate experiments. Low and high phenotypes were observed in the first experiment over a 10-wk interval. Average straight line velocity differed between phenotypes (P < or = 0.05) as evidenced by computer-assisted sperm motion analysis. The second experiment compared low and high phenotypes from the same broiler breeder strain over a 29-wk interval. Body weight and fertility were measured in this experiment. Body weight data approximated parallel lines. The low phenotype averaged 227 g more than the high phenotype over the course of the experiment. Individual males were used as semen donors at 50, 54, 58, 62, and 65 wk of age. Eggs were collected for 2 wk after a single insemination at each age. Mean overall fertility (+/- SEM) was 44 +/- 4 and 69 +/- 2% for low and high sperm mobility phenotypes, respectively (P < or = 0.0001). As determined by transmission electron microscopy, the percentage of sperm with aberrant mitochondria was greater for the low sperm mobility phenotype (P < or = 0.0001). Neither blood plasma testosterone concentration nor testis weight differed between phenotypes. Sperm mobility is a biologically significant predictor of broiler breeder semen quality. The relationship between sperm mobility phenotype and body weight warrants further investigation.

Aging↗
PubMed2003

The expression of calbindin in chicks that are divergently selected for low or high incidence of tibial dyschondroplasia.

Three experiments were conducted with broiler chicks that were divergently selected for low or high incidence of tibial dyschondroplasia (LTD and HTD, respectively) to determine if the expression of intestinal calbindin-28 kD mRNA and protein differed between the 2 strains. In addition, levels of intestinal vitamin D receptor mRNA and plasma thyroid hormone concentrations were also examined. In experiment 1, LTD and HTD chicks were fed a corn-soybean meal diet that was adequate in all nutrients except cholecalciferol (D3), which was titrated to 5 or 40 microg/kg diet in a completely randomized 2 x 2 factorial arrangement. At 4 and 8 d of age, HTD chicks fed 5 microg of D3/kg of diet had a lower (P < 0.05) expression level of calbindin-28 kD mRNA than the LTD chicks fed the same diet. At 4 and 8 d of age, HTD chicks fed 5 microg of D3 had the lowest intestinal expression of calbindin-28 kD protein. Expression of vitamin D receptor mRNA did not differ for broiler strains at either level of D3 supplementation. In experiment 2, there was no significant difference in the expression of calbindin-28 kD mRNA or vitamin D receptor mRNA between day-of-hatch LTD, HTD, and commercial broiler chicks. Experiment 3 was similar in design to the first experiment except that the birds were fed for 18 d. Calbindin-28 kD and vitamin D receptor mRNA expression levels at 18 d were similar to those observed in experiment 1. Plasma triiodothyronine and free-triiodothyronine concentrations were greater for LTD chicks, regardless of dietary D3 supplementation levels. These results suggest that divergent selection of broilers for LTD or HTD alters the physiological response to nutritionally inadequate levels of dietary D3.

Animals↗
PubMed2003

Expression pattern of messenger ribonucleic acid for the activin type II receptors and the inhibin/activin subunits during follicular development in broiler breeder hens.

The expression of mRNA for the activin type II receptors (ActRII and ActRIIB), follistatin, and the inhibin/activin subunits was investigated in the follicles of broiler breeder hens. Total RNA was isolated from individual granulosa and theca layers of the F1 through F5 follicles, a pool of the F6 and F7 follicles, the small yellow follicles, and from the combined granulosa and theca layers of the large white follicles from six birds. Northern blot analysis was performed, and two ActRII mRNA transcripts of 6.5 and 3.7 kb were detected in granulosa and theca samples. Both ActRII transcripts were equally expressed in the granulosa samples, but in the theca samples expression of the 3.7-kb transcript was greater than the 6.5-kb transcript. ActRIIB was not detected by Northern analysis in any of the samples. Expression of the mRNA for the activin/inhibin binding protein, follistatin, was detected in theca and granulosa samples with the greatest expression found in small yellow follicle samples for both cell layers. Expression of the inhibin alpha-subunit was detected in the granulosa layer of all the follicles, but expression was greatest in the F6 and F7 follicles. Granulosa from the large hierarchical follicles expressed the most inhibin/activin betaA-subunit, whereas expression of the inhibin/activin betaB-subunit was greatest in the granulosa of small yellow and F6 and F7 follicles. This report is the first, to our knowledge, on detection of activin type II receptor mRNA in the hen ovary and characterization of the expression pattern of the inhibin family in both the theca and granulosa layers throughout follicular development. The presence of activin receptor and follistatin mRNA in the theca and granulosa layers of the small developing follicles suggests that locally produced activin may be highly regulated and have a vital role in early follicular development.

Activin Receptors, Type II↗
PubMed2002

A 5.9-kb tandem repeat at the euchromatin-heterochromatin boundary of the X chromosome of Drosophila melanogaster.

We present an analysis of a chromosomal walk in the region of the euchromatin-heterochromatin transition at the base of the X chromosome of Drosophila melanogaster. This region is difficult to analyse because of the presence of repeated sequences, and we have used cosmids to walk from the last euchromatic gene, suppressor of forked, towards the pericentric heterochromatin. The proximal 30-kb sequence we have isolated consists of repetitive DNA, including four tandem copies of a 5.9-kb sequence. This tandem repeat is itself a mosaic of other, mostly repeated, sequences, including part of a retrotransposon without long terminal repeats, a simple-sequence region of TAA repeats and part of a retrotransposon with long terminal repeats that has not been previously described. Although sequences homologous to these components are found elsewhere in the genome, this arrangement of repeated sequences is only found at the base of the X chromosome. It is conserved in D. melanogaster strains of different geographic origin, but is not conserved in even closely related species.

Animals↗
PubMed2002

The telling and knowing of dying: philosophical bases for hospice care in Japan.

This article describes the historical and cultural factors that led to the modern definition of hospice in the United States and Japan. It also raises questions about the import of western hospice philosophy into Japan by examining some traditional values and cultural norms of behaviour surrounding dying in that country. The ethics of disclosure and open discussion, as a prerequisite to and foundational value in western hospice care, differs in Japan. If traditional Japanese values remain strong, expectations regarding hospice care based on this western ethics may be misplaced. This report ends with a suggestion of replacing the western imported hospice philosophy with an (as yet not explicated) Japanese philosophical ethic of the good.

Bioethics↗
PubMed2001

Role for anti-Müllerian hormone in congenital absence of the uterus and vagina.

Molecular genetic techniques were used to determine if mutations in the genes encoding anti-Müllerian hormone (AMH) (also known as Müllerian inhibiting substance (MIS)) and its receptor (AMHR) are commonly present in patients with congenital absence of the uterus and vagina (CAUV). Twenty-two CAUV patients and 96 control subjects from diverse ethnic groups were studied after obtaining informed consent. Genomic DNA samples prepared from leukocytes were digested separately with several different restriction enzymes, and the resultant fragments were analyzed for restriction fragment melting polymorphisms (RFMPs) by denaturing gradient gel electrophoresis (DGGE). Electrophoretic mobility of DNA fragments which were 200-700 base pairs in length was compared using polyacrylamide gels that included linear gradients of denaturing solvents designed to separate DNA fragments according to sequence-dependent variation in thermal stability. Two RFMPs were found in the AMH gene in both patients and normal control subjects. One RFMP in the AMHR gene was present at low frequencies in both patients and normal control subjects. No RFMPs specific to CAUV patients were found in either gene. Because no mutations or rare DNA sequence polymorphisms were detected in the AMH and the AMHR genes in this group of CAUV patients, it is unlikely that either gene commonly has an etiologic role in CAUV.

Anti-Mullerian Hormone↗
PubMed2001

The X element, a novel LINE transposable element from Drosophila melanogaster.

Whilst analysing the nature of repeated DNA sequences in the transition zone between euchromatin and heterochromatin at the base of the X chromosome of Drosophila melanogaster, we discovered a novel transposable element of the LINE class that we have named the X element. Several apparently complete elements have been cloned and analysed, and one has been sequenced. It is 4740 bp long, with a polyadenylation sequence and a run of A residues at one end. It contains two ORFs: the 5' ORF is related to the retroviral gag gene and encodes a protein with cysteine-rich motifs that are thought to form a "zinc-knuckle" in a nucleic-acid binding protein; the 3' ORF encodes a putative reverse transcriptase that includes the conserved domains found in reverse transcriptases from other LINEs and retroviruses. The DNA sequence and the sequences of the predicted gene products are most similar to other LINEs from D. melanogaster, such as the F, jockey, Doc and BS elements. Southern analysis suggests that there are at least 30 copies in the genome and that some elements are polymorphic between different strains. Analysis of the DNA sequence of the euchromatic arms of the Drosophila genome identified five full-length elements and a similar number of elements that were intact at the 3' end but had variable 5' truncations. Sequences flanking two different insertion sites were used to design PCR primers to assess the occupancy of sites in wild-type flies of different geographical origins. Flies that lacked each of the insertions were found, suggesting that the element is an active transposon.

Animals↗