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Biomedical subjects

G Davis

Publications and source records attributed to G Davis.

At least 73 records · Page 4Linked to original sources

Gibberellin Biosynthesis in Maize. Metabolic Studies with GA(15), GA(24), GA(25), GA(7), and 2,3-Dehydro-GA(9).

[17-(14)C]-Labeled GA(15), GA(24), GA(25), GA(7), and 2,3-dehydro-GA(9) were separately injected into normal, dwarf-1 (d1), and dwarf-5 (d5) seedlings of maize (Zea mays L.). Purified radioactive metabolites from the plant tissues were identified by full-scan gas chromatography-mass spectrometry and Kovats retention index data. The metabolites from GA(15) were GA(44), GA(19), GA(20), GA(113), and GA(15)-15,16-ene (artifact?). GA(24) was metabolized to GA(19), GA(20), and GA(17). The metabolites from GA(25) were GA(17), GA(25) 16alpha,17-H(2)-17-OH, and HO-GA(25) (hydroxyl position not determined). GA(7) was metabolized to GA(30), GA(3), isoGA(3) (artifact?), and trace amounts of GA(7)-diene-diacid (artifact?). 2,3-Dehydro-GA(9) was metabolized to GA(5), GA(7) (trace amounts), 2,3-dehydro-GA(10) (artifact?), GA(31), and GA(62). Our results provide additional in vivo evidence of a metabolic grid in maize (i.e. pathway convergence). The grid connects members of a putative, non-early 3,13-hydroxylation branch pathway to the corresponding members of the previously documented early 13-hydroxylation branch pathway. The inability to detect the sequence GA(12) --> GA(15) --> GA(24) --> GA(9) indicates that the non-early 3,13-hydroxylation pathway probably plays a minor role in the origin of bioactive gibberellins in maize.

Journal Article↗

Summary report of the TD-3 workshop: characterization of 83 antibodies against prostate-specific antigen.

Twelve research groups participated in the ISOBM TD-3 Workshop in which the reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety of techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays and immunohistochemistry, the antibodies were categorized into six major groups which formed the basis for mapping onto two- and three-dimensional (2-D and 3-D) models of PSA. The overall findings of the TD-3 Workshop are summarized in this report. In agreement with all participating groups, three main antigenic domains were identified: free PSA-specific epitopes located in or close to amino acids 86-91; discontinuous epitopes specific for PSA without human kallikrein (hK2) cross-reactivity located at or close to amino acids 158-163; and continuous or linear epitopes shared between PSA and hK2 located close to amino acids 3-11. In addition, several minor and partly overlapping domains were also identified. Clearly, the characterization of antibodies from this workshop and the location of their epitopes on the 3-D model of PSA illustrate the importance of selecting appropriate antibody pairs for use in immunoassays. It is hoped that these findings and the epitope nomenclature described in this TD-3 Workshop are used as a standard for future evaluation of anti-PSA antibodies.

Antibodies, Monoclonal↗

Analysis of monoclonal antibodies to prostate-specific antigen: reactivity with native and recombinant prostate-specific antigen.

Epitope mapping analysis was performed on 53 antibodies submitted to the ISOBM TD-3 PSA Workshop. Western blotting and N-terminal amino acid sequencing, using both native and recombinant human prostate-specific antigen (rPSA), identified four different epitope groups for native PSA. Under reducing conditions native PSA was not recognized by 18/53 antibodies suggesting they reacted with conformation-dependent epitopes. Nine other antibodies reacted with a rPSA polypeptide doublet of 34-35 kD corresponding to different rPSA glycoforms. From sequence mapping studies 22/53 antibodies bound epitopes within amino acid residues 25-85, 3/53 antibodies bound to epitopes within residues 86-220, while 10/53 antibodies bound epitopes within residues 221-261. These results indicate that there are multiple immunogenic epitopes localized on the PSA molecule.

Antibodies, Monoclonal↗

Urinary incontinence among female soldiers.

A self-administered questionnaire was developed to assess the prevalence of urinary incontinence among active duty female soldiers. The questionnaire also addressed basic demographic information, including height, age, weight, and the subjects' present and past military activities. Adaptive measures that the soldiers commonly used to continue exercising and perform their duties were also explored. Seven hundred thirteen questionnaires were handed out to female soldiers at Fort Lewis (Washington), Fort Benning (Georgia), and Fitzsimons Army Medical Center (Colorado) during preparation for physical fitness tests. Of the 563 soldiers (79%) who returned completed questionnaires, 31% indicated that they commonly experienced urinary incontinence during duty and/or training to the extent that it interfered with job performance, hygiene, or was socially embarrassing. Thus, urinary incontinence is a pervasive problem among female soldiers.

Activities of Daily Living↗

The female athlete triad: prevalence in military women.

The objective of this study was to define the prevalence of the female athlete triad, i.e., the simultaneous occurrence of disordered eating, amenorrhea, and osteoporosis, in military women. A total of 423 active duty female soldiers participated in a three-part prospective, cross-sectional study. Part 1 entailed completing the Eating Disorder Inventory and a clinical interview with those women "at risk" for an eating disorder. Part 2 consisted of a clinical evaluation and laboratory studies of any woman with menstrual irregularities. Part 3 evaluated the bone mineral density of all women meeting the inclusion criteria for parts 1 and 2 using dual-energy X-ray absorptiometry. Of the 423 active duty women who participated in the study, no subject exhibited the full female athlete triad. Thirty-three women (8%) had an eating disorder and 109 women (26%) were at risk for an eating disorder. Our results suggest that the female athlete triad is not a clinically significant problem for the Army.

Adolescent↗

Female circumcision: the prevalence and nature of the ritual in Eritrea.

This study evaluates the prevalence, complications, and attitudes concerning the practice of female circumcision among the women of Eritrea. Four hundred thirty-six Eritrean women from rural and urban environments were questioned about their perceptions and beliefs concerning female circumcision. Eighty-eight percent of those interviewed had undergone some form of female circumcision. Those who favored the continuation of the practice were more likely to be rural dwellers with little formal education, and they did so primarily out of tradition or cultural conformity. The direct and indirect consequences of this practice to the health of women and infants are considerable and as complex as the social, religious, and traditional factors that have led to its preservation.

Adult↗

Randomised trial of management of hypertensive pregnancies by Korotkoff phase IV or phase V.

BACKGROUND: There is debate about whether diastolic blood pressure should be recorded as the fourth (muffling, K4) or fifth (disappearance, K5) Korotkoff sound in pregnancy. We compared maternal and fetal outcomes and the likelihood that episodes of severe hypertension would be recorded when hypertensive pregnancies were managed according to either K4 or K5. METHODS: 220 pregnant women with diastolic hypertension (K4 > or =90 mm Hg) after the 20th week of gestation were enrolled in a prospective randomised study at two obstetric units in Australia; they were randomly assigned management with K4 (n=103) or K5 (n=117) for the remainder of the pregnancy. Clinical management was according to a uniform department protocol. Analysis was by intention to treat. All the women completed the trial. FINDINGS: An episode of severe hypertension (systolic > or =170 mm Hg, diastolic > or =110 mm Hg, or both) was more likely to be recorded with use of K4 than with use of K5 (39 [38%] vs 30 [26%] women, p=0.051), mainly because of a greater likelihood that severe diastolic hypertension would be recorded (34 [33%] vs 20 [17%], p=0.006). The frequency of severe systolic hypertension and simultaneous severe systolic and diastolic hypertension did not differ between groups. Pregnancy was prolonged by an average of 2 weeks in both groups, and there were no significant differences between the groups in laboratory data, requirements for antihypertensive treatment, birthweight, fetal growth retardation, or perinatal mortality. There was no eclampsia or significant maternal morbidity in either group. INTERPRETATION: A change from use of K4 to K5 would mean that one fewer case of severe diastolic hypertension would be recorded for every six hypertensive pregnancies, but all other episodes of severe hypertension would be recorded with similar frequency. Since the K4/K5 difference is smaller in hypertensive than in normotensive pregnant women and since K5 is closer to the actual intra-arterial pressure and more reliably detected, universal adoption of K5 to record diastolic blood pressure in hypertensive pregnancy should be considered.

Blood Pressure Determination↗

Can a multimedia educational computer-based program on genital herpes teach patients about their disease?

Objective: Education of patients with genital herpes about their disease is time consuming. To evaluate the effectiveness of an educational computer program, we developed a multimedia interactive presentation to teach patients about genital herpes. Such programs can supplement clinician visits for patients with genital herpes, or those at risk for HSV acquisition.Methods: Patients seeking care for genital herpes, or those at risk for HSV acquisition, were asked to participate in the program during routine clinic visits at 5 physician's offices nationwide. A self-administered 7 item herpes knowledge questionnaire was given before and after participation. An additional questionnaire evaluating the satisfaction with the program was also self-administered at completion.Results: 428 patients were enrolled and completed the pre- and post-knowledge questionnaire and 332 patients completed the satisfaction survey. On the pre-test, 20.1% of patients answered all questions correctly, 65.4% answered correctly 4 to 6 questions, and 14.5% 3 or less. On the post-test, 32.9% of patients answered all questions correctly, 61.5% answered correctly 4 to 6 questions, and 5.6% 3 or less (P <.001 for pre- and post-test comparison). A positive change in knowledge between pre- and post-test was seen on 6 of 7 items (P <.001 for all 6). The overall satisfaction with the program was high: the mean rating was 6.2 on a scale 1 (poor) to 7 (excellent).Conclusion: Computer-based education programs about genital herpes may provide a useful adjunct to teaching in physician offices and result in knowledge gain about the disease, at least short-term. Such programs may assist in management of chronic sexually transmitted infections.

Journal Article↗

Microlaparoscopic tubal ligation under local anesthesia.

Local anesthesia to perform laparoscopic tubal ligation is of increased interest due to potential safety and cost benefits. We performed tubal ligation using microlaparoscopic techniques with local anesthesia and continuous intravenous sedation in 16 women desiring sterilization. Operating and recovery times and patient satisfaction were recorded and compared with values for 30 similar women undergoing microlaparoscopic tubal ligation under general anesthesia. Mean +/- SD operating and recovery times for local and general anesthesia were 29.3+/- 8.1 versus 33.6 +/- 11.1 minutes, and 83.9 +/- 59.4 versus 114.5 +/- 69.8 minutes, respectively. Patient satisfaction was high. The potential for cost savings when performed in an outpatient or clinic setting is significant.

Adult↗

Evaluation of technician supervised treadmill exercise testing in a cardiac chest pain clinic.

OBJECTIVE: To determine the efficacy and safety of trained cardiac technicians independently performing treadmill exercise stress tests as part of the assessment of patients with suspected angina pectoris. DESIGN: Retrospective comparison of 250 exercise tests performed by cardiac technicians and 225 tests performed by experienced cardiology clinical assistants (general practitioners who perform regular NHS cardiology duties), and consultant cardiologists over the same time period. SETTING: Regional cardiac centre with a dedicated cardiac chest pain clinic. PATIENTS: All patients were referred by their general practitioners with a history of recent onset of chest pain, which was suspected to be angina pectoris. OUTCOME MEASURES: Peak workload achieved, symptoms, indications for termination, complications. RESULTS: The diagnostic yield of technician supervised tests (percentage positive or negative) was similar to that of medically supervised tests (76% v 69%, NS). The average peak workload achieved by patients was less by 1.2 mets (p < 0.005). This was probably due to more tests being terminated earlier due to chest pain and ST segment depression in the technician group compared with doctors (10% and 16% v 5% and 11% respectively, p = 0.06 and 0.07). One patient in the technician supervised group developed a supraventricular tachycardia during the recovery phase of the exercise test. CONCLUSIONS: Technician supervised stress testing is associated with a high diagnostic rate and low complication rate in patients with suspected ischaemic heart disease. Its efficacy is comparable to tests supervised by experienced doctors and its use should be encouraged.

Aged↗

Effect of desialylation on binding, affinity, and specificity of 56 monoclonal antibodies against MUC1 mucin.

We evaluated 56 monoclonal antibodies (MAbs), submitted to the ISOBM TD-4 Workshop, for changes in binding following desialylation of the MUC1 molecule and for epitope specificity. Antibody binding of MAbs was assayed by an ELISA method using microtiter plates coated with the MUC1 mucin obtained from supernatants of the ZR75-1 cell line. The MUC1 mucin was desialylated directly on the plate by treatment with neuraminidase. For each MAb, binding to untreated mucin was compared over a range of antibody concentrations. The concentration at which binding was half-maximal (K50) was determined for all antibodies whose binding reached saturation in the assay. Results showed that K50 values for MAb binding to untreated MUC1 mucin varied from 10(-10) to 10(-6) M. These data suggest that MAbs to MUC1 mucin bind with a broad range of intrinsic affinities. Desialylation was found to have variable effects on antibody binding, in that binding was either increased, decreased, or unchanged. No relationship was found between the apparent affinities for untreated mucin and changes in binding following desialylation. Among the 56 Workshop MAbs, 33 were found reactive with synthetic peptides which mimic the MUC1 tandem repeat. We determined the epitope specificity of the 33 MAbs by competitive binding using 10 amino acid peptides corresponding to various regions of the 20-amino acid tandem repeat domain of MUC1. All antibodies which recognized epitopes in the 1-10 amino acid region of the tandem repeat showed increased binding to desialylated mucin. Antibodies to other peptide epitopes showed no consistent pattern of change in binding following desialylation. Our results suggest that sialic acid residues on the MUC1 mucin may contribute either positively or negatively to antibody binding. In addition, our results suggest that improved antibody selection methods could provide MAbs with improved selectivity for cancer-derived mucin compared with mucin from normal tissues. This could form the basis of improved biomarker assays for breast cancer.

Amino Acid Sequence↗

Ambulatory urodynamics of female soldiers.

The purpose of this study was to assess the accuracy of ambulatory urodynamic monitoring compared with conventional urodynamic studies for the detection of exercise-induced urinary incontinence in the female soldier. Fifty active duty female soldiers with exercise-induced urinary incontinence and 10 asymptomatic control soldiers underwent conventional multichannel cystometry and then ambulatory monitoring during work or exercise. Ambulatory monitoring detected a greater number of abnormalities than conventional multichannel urodynamic studies in exercise-induced urinary incontinence. This greater sensitivity is valuable in formulating more effective treatment. Behavioral interventions were effective in treating exercise-induced urinary incontinence in this population. Test results normalized after behavioral intervention. It is neither cost-effective nor efficacious to require sophisticated urodynamic testing before instituting behavioral interventions.

Adult↗

Identification and cloning of human placental bikunin, a novel serine protease inhibitor containing two Kunitz domains.

Interrogation of the public expressed sequence tag (EST) data base with the sequence of preproaprotinin identified ESTs encoding two potential new members of the Kunitz family of serine protease inhibitors. Through reiterative interrogation, an EST contig was obtained, the consensus sequence from which encoded both of the novel Kunitz domains in a single open reading frame. This consensus sequence was used to direct the isolation of a full-length cDNA clone from a placental library. The resulting cDNA sequence predicted a 252-residue protein containing a putative NH2-terminal signal peptide followed sequentially by each of the two Kunitz domains within a 170-residue ectodomain, a putative transmembrane domain, and a 31-residue hydrophilic COOH terminus. The gene for this putative novel protein was mapped by use of a radiation hybrid panel to chromosome 19q13, and Northern analysis showed that the corresponding mRNA was expressed at high levels in human placenta and pancreas and at lower levels in brain, lung, and kidney. An endogenous soluble form of this protein, which was designated as placental bikunin, was highly purified from human placenta by sequential kallikrein-Sepharose affinity, gel filtration, and C18 reverse-phase chromatography. The natural protein exhibited the same NH2 terminus as predicted from the cloned cDNA and inhibited trypsin, plasma kallikrein, and plasmin with IC50 values in the nanomolar range.

Amino Acid Sequence↗

Frequent genital herpes simplex virus 2 shedding in immunocompetent women. Effect of acyclovir treatment.

Reactivation of herpes simplex virus type 2 (HSV-2) occurs intermittently as perceived clinically and by viral culture. We performed a series of studies to evaluate the frequency and pattern of HSV-2 reactivation using both viral isolation and HSV PCR assay. Daily samples of genital secretions were obtained from 27 HSV-2 seropositive women; a subset of subjects obtained samples while receiving oral acyclovir 400 mg PO twice a day. HSV DNA was detected in genital swab specimens on 28% of 1,410 d compared with 8.1% of days by viral isolation. 11 of 20 women had HSV DNA detected on > 20% of days, 4 on > 50%, and 2 on > 75% of days; in contrast, none of the women shed on > 21% of days by viral isolation. The daily administration of oral acyclovir promptly reduced the frequency of HSV DNA detection by a median of 80%. Within 3-4 d of discontinuing daily acyclovir, HSV DNA again appeared in the genital area. HSV-2 shedding in the genital mucosa occurs much more frequently than previously appreciated. This frequent reactivation likely plays a role in the epidemic spread of genital herpes worldwide.

Acyclovir↗

B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors.

The B7 family of costimulatory molecules provides the second signal necessary for activation of T cells. In the absence of the second signal, responding T cells become anergic. Although predominantly expressed on professional APCs, recent evidence shows that the B7 molecules are also expressed on T cells. To study the functions of B7 molecules on T cells, we transfected murine B7.1 (CD80) and B7.2 (CD86) cDNAs into the EL4 T cell thymoma cell line and examined the transfectants for their ability to costimulate T cell proliferation in vitro and to induce antitumor immunity in vivo. Here we show that although EL4-B7.1 cells costimulate T cells and induce tumor regression, EL4-B7.2 transfectants failed to costimulate T cell proliferation or induce tumor regression. To understand the cellular basis for this difference, we examined the binding of EL4-B7.1 and EL4-B7.2 to CTLA4 and CD28. Whereas EL4-B7.1 cells bound both CTLA4-Ig and CD28-Ig, EL4-B7.2 transfectants preferentially bound CTLA4-Ig, but not CD28-Ig. Similar binding data were obtained with freshly isolated murine T cells, which have been shown to constitutively express B7.2. Our data suggest, therefore, that B7.2 expressed on T cells may not costimulate but instead inhibit the T cell response by preferential binding to CTLA4.

Abatacept↗

Reduced cytochrome oxidase and memory dysfunction after chronic brain ischemia in aged rats.

The effects of chronic cerebrovascular ischemia on memory function and cytochrome oxidase (CO) activity were investigated. Cerebrovascular insufficiency was induced by permanent bilateral carotid artery ligation (2-VO) in 19 month old rats. Sham surgery in no-vessel occlusion (no-VO) rats were used for controls. Memory function was tested 1 week prior to surgery and then weekly for 21 days using the Morris water maze. Regional brain activity of CO was measured 4 weeks after surgery by quantitative histochemistry. Histologic examination of brain slices was used to evaluate any neuropathology present. Results showed that 2-VO rats were significantly impaired in the water maze task at each testing period with respect to no-VO controls. In addition, CO activity in 2-VO rats was markedly reduced only in the dorsal CA1 region of the hippocampus and in the posterior parietal cortex. These brain regions are involved in visuo-spatial memory mechanisms. Analysis of other brain regions in 2-VO rats did not reveal further CO activity changes. There were no damaged or loss of neurons in 2-VO or no-VO groups in any region examined, including CA1 and posterior parietal cortex. The CA1 region however, is known to undergo neuronal loss 25 weeks after chronic 2-VO suggesting that this vascular insult can induce a slowly-evolving cascade consisting of neuronal damage, atrophy and death. The present findings indicate that reduced CO activity in CA1 and posterior parietal regions can predict neural damage and atrophy prior to structural perikaryal pathology following chronic brain ischemia. In addition, the data shows that neuronal energy metabolic deficiency may initiate visuo-spatial memory impairment in this aging rat model.

Aging↗