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Biomedical subjects

B Davis

Publications and source records attributed to B Davis.

At least 55 records · Page 3Linked to original sources
PubMed2000

Analysis of cathepsin D in human breast cancer: usefulness of the processed 31 kDa active form of the enzyme as a prognostic indicator in node-negative and node-positive patients.

The relative amounts of the precursor (52 kDa) and processed (31,27 kDa) forms of cathepsin D have been analyzed by Western blotting in biopsied breast tissue cytosols from 134 lesions from invasive breast cancer patients, 24 lesions from patients with ductal carcinoma in situ (DCIS), 227 lesions from benign breast disease patients, and 28 lesions from normal control subjects. The mean relative percentage amount of the 31 kDa form was significantly increased (p < 0.001) in the invasive breast cancer group compared to the other three groups. In addition, the mean relative percentage amount of the 31 kDa form was significantly increased (p < 0.05) in node-positive compared to node-negative breast cancer patients. In the benign breast disease group, patients with proliferative-type disease had a significantly increased (p = 0.02) mean relative percentage amount of the 31 kDa form of cathepsin D compared to patients with nonproliferative-type disease. Invasive breast cancer patients were followed for up to 75 months to determine if the relative percentage amount of the 31 kDa form of cathepsin D was predictive of disease-free and overall survival. Although the amount of the 31 kDa form was not predictive of disease-free survival, patients in the 'high' 31 kDa group (> 18%) were significantly (p < 0.05) more likely to die than patients in the 'low' 31 kDa group (< or = 18%). The 12 patients who died were all node-positive and in the high 31 kDa group. It thus appears that the relative amount of the processed, active 31 kDa form of cathepsin D is a useful prognostic indicator, at least in node-positive breast cancer patients.

Adult↗
PubMed2000

Lack of neuropeptide Y receptor detection in human bladder and prostate.

OBJECTIVE: To investigate the presence of functional neuropeptide Y (NPY) receptors in human bladder and prostate (both richly endowed with NPY-containing nerve fibers) using peptide YY (PYY) as the agonist. Materials and methods Binding studies were conducted using [125I]PYY as the radioligand. Organ-bath studies were performed on isolated tissue strips for direct (postjunctional) contractile effects and for (prejunctional) inhibition of field stimulation effects. Any possible degradation of PYY was determined using high-performance liquid chromatography (HPLC). RESULTS: In the radioligand binding studies no quantifiable specific [125I]PYY binding was detected in human bladder or prostate, while specific high-affinity binding was readily seen in rat cerebral cortex. In organ-bath experiments, PYY (up to 1 micromol/L) caused no contraction of human prostate or bladder, whereas noradrenaline and carbachol, respectively, were effective; the potency or efficacy of noradrenaline and carbachol were not altered by PYY. Field stimulation-induced contraction was not affected by PYY in either human bladder or prostate, but was readily inhibited in rat vas deferens. HPLC detected no relevant PYY degradation by human bladder or prostate homogenates. CONCLUSION: Human bladder and prostate express only very few if any functional NPY receptors.

Animals↗
PubMed2000

Altered hormonal responsiveness of proliferation and apoptosis during myometrial maturation and the development of uterine leiomyomas in the rat.

Uterine leiomyomas are responsive to the ovarian steroids, estrogen and progesterone; however, a mechanistic understanding of the role of these hormones in the development of this common gynecologic lesion remains to be elucidated. We have used the Eker rat uterine leiomyoma model to investigate how ovarian hormones regulate or promote the growth of these tumors. Proliferative and apoptotic rates were quantitated in normal uterine tissues and leiomyomas in response to endogenous ovarian steroids. In 2- to 4-mo-old animals, cell proliferation in the normal uterus corresponded with high serum levels of steroid hormones during the estrous cycle, and apoptosis occurred in the rat uterus in all cell types following sharp, cyclical declines in serum hormone levels. It is interesting that the responsiveness of uterine mesenchymal cells changed between 4 and 6 mo of age, with significant decreases in both proliferative and apoptotic rates observed in myometrial and stromal cells of cycling animals. Leiomyomas displayed much higher levels of proliferation than did age-matched myometrium; however, their apoptotic index was significantly decreased in comparison with normal myometrium. This disregulation between proliferative and apoptotic responses, which were tightly regulated during ovarian cycling in the normal myometrium, may contribute to the disruption of tissue homeostasis and underlie neoplastic growth of these tumors.

Aging↗
PubMed2000

Efficacy of sustained-release bupropion in neuropathic pain: an open-label study.

OBJECTIVE: The purpose of this study was to assess the analgesic potential of sustained-release (SR) bupropion for neuropathic pain. DESIGN: Open-label treatment design. SETTING: Outpatient pain clinic, University of Arizona Health Sciences Center, Tucson, Arizona. PATIENTS: Twenty-two patients with a diagnosis of neuropathic pain. INTERVENTIONS: Patients with neuropathic pain received 1 week of 150 mg SR bupropion once daily followed by 7 weeks of 150 mg SR bupropion twice daily. OUTCOME MEASURES: Treatment effects were assessed by daily ratings of pain intensity, posttreatment global ratings of pain relief, depression scores (Hamilton Depression Scale), and daily ratings of side effects. RESULTS: Fifteen patients (68%) reported that their pain relief was improved or much improved with bupropion. The mean average pain score at week 1 was 6.7, which decreased at the end of week 8 to 5.3 (paired t test, t[df = 21]3.327; p = 0.003) in all patients studied and to 3.8 (paired t test, t[df = 14]3.754; p = 0.002) in the patients who improved. Pain relief was statistically significant at week 5 (paired t test, t[df = 21]3.816; p = 0.001) and continued throughout weeks 6, 7, and 8. Most patients were not depressed, and analgesia was observed to occur without change in depression ratings in most patients who responded. Side effects were rated as mild and consisted primarily of insomnia (8 patients), tremor (3 patients), and gastrointestinal upset (2 patients). These symptoms had a tendency to recede with continuation of therapy. CONCLUSIONS: This uncontrolled pilot study suggests that bupropion may be an effective and tolerated treatment for some patients with neuropathic pain. Blockade of norepinephrine reuptake may mediate this effect. The role of dopamine reuptake blockade is uncertain. A larger randomized, double-blind, placebo-controlled study is currently underway to confirm these preliminary results.

Adult↗
PubMed2000

The accuracy and precision performance of four videokeratoscopes in measuring test surfaces.

In this study we evaluated the accuracy and precision of three placido-disk videokeratoscopes (the Keratron, Medmont and TMS) and one videokeratoscope that uses the raster-stereogrammetry technique (PAR-CTS) in elevation topography with six test surfaces. The test surfaces were a sphere, an asphere, a multicurve, and three bicurve surfaces. Each instrument performed well on certain test surfaces, but none of the instruments excelled on all of the surfaces. The results showed high accuracy of the Keratron and Medmont instruments in measuring the sphere, asphere, and multicurve surfaces, but not the bicurve surfaces. The precision of the Keratron and Medmont instruments were high. The TMS and PAR-CTS instruments showed poorer accuracy than the Keratron and Medmont instruments for the multicurve test surface but showed better performance for the bicurve surfaces. The PAR-CTS had the poorest performance in precision of the four instruments. The use of the Noryl spherical test surface instead of polymethyl methacrylate (PMMA) resulted in small differences in the accuracy performance of the placido-disk videokeratoscopes only.

Cornea↗
PubMed2000

A single intramuscular injection of recombinant plasmid DNA induces protective immunity and prevents Japanese encephalitis in mice.

Plasmid vectors containing Japanese encephalitis virus (JEV) premembrane (prM) and envelope (E) genes were constructed that expressed prM and E proteins under the control of a cytomegalovirus immediate-early gene promoter. COS-1 cells transformed with this plasmid vector (JE-4B clone) secreted JEV-specific extracellular particles (EPs) into the culture media. Groups of outbred ICR mice were given one or two doses of recombinant plasmid DNA or two doses of the commercial vaccine JEVAX. All mice that received one or two doses of DNA vaccine maintained JEV-specific antibodies 18 months after initial immunization. JEVAX induced 100% seroconversion in 3-week-old mice; however, none of the 3-day-old mice had enzyme-linked immunosorbent assay titers higher than 1:400. Female mice immunized with this DNA vaccine developed plaque reduction neutralization antibody titers of between 1:20 and 1:160 and provided 45 to 100% passive protection to their progeny following intraperitoneal challenge with 5,000 PFU of virulent JEV strain SA14. Seven-week-old adult mice that had received a single dose of JEV DNA vaccine when 3 days of age were completely protected from a 50, 000-PFU JEV intraperitoneal challenge. These results demonstrate that a recombinant plasmid DNA which produced JEV EPs in vitro is an effective vaccine.

Animals↗
PubMed2000

Normal lumbar vertebrae: anatomic, age, and sex variance in subjects at proton MR spectroscopy--initial experience.

Fifty-seven subjects underwent proton magnetic resonance (MR) spectroscopy of the second lumbar vertebra to evaluate single-voxel and multivoxel techniques. Measurements included lipid-to-water ratios, lipid fractions, and line width. These data provide information about vertebral fat content. There was an age-dependent linear increase in fat content and sex dependence. A higher fat concentration was found in men. The observed spectra provide a basis for future study to determine clinical utility of vertebral proton MR spectroscopy.

Adolescent↗
PubMed2000

The consequences of anterior femoral notching in total knee arthroplasty. A biomechanical study.

BACKGROUND: Notching of the anterior femoral cortex during total knee arthroplasty has been implicated as a cause of subsequent periprosthetic supracondylar femoral fracture. However, other than observational clinical data, no reliable association between these events has been established, to our knowledge. The purpose of the present study was to investigate the biomechanical effects of notching of the anterior femoral cortex. METHODS: The femoral component of a total knee replacement was implanted in twelve matched pairs of human cadaveric femora; one specimen in each pair had preservation of the anterior femoral cortex, and the other had a full-thickness cortical defect created just proximal to the anterior flange of the femoral component. The pairs were then subjected to either bending or torsional loading to failure. Both the fracture pattern and the quantitative load to failure were analyzed. Two matched pairs were excluded from the analysis because of inadvertent fracture during placement of the component. RESULTS: Following the application of a bending load, femora with notching of the anterior femoral cortex sustained a short oblique fracture that originated at the cortical defect proximal to the femoral component and femora without notching had a midshaft fracture. In contrast, notching of the anterior femoral cortex had no effect on the fracture pattern that was observed after the application of a torsional load. The mean load to failure was significantly reduced by notching in both testing modes. Notching decreased bending strength from 11,813 to 9690 newtons (18 percent; p = 0.0034), and it decreased torsional strength from 134.7 to 81.8 newton-meters (39.2 percent; p = 0.01). CONCLUSIONS: Biomechanical testing demonstrated that notching of the anterior femoral cortex significantly lessens the load to failure following total knee arthroplasty and influences the subsequent fracture pattern. These effects are manifested in different ways under the two loading conditions: the fracture pattern is altered under bending load, and there is a greater quantitative decrease in load to failure with torsional loading. CLINICAL RELEVANCE: Weakening of the femur by notching of the anterior cortex after total knee arthroplasty may warrant alteration in the customary postoperative regimen for these patients. Manipulation of a total knee replacement with a notched anterior femoral cortex should probably be avoided.

Aged↗
PubMed1999

Diagnostic marker cooperative study for the diagnosis of myocardial infarction.

BACKGROUND: Millions of patients present annually with chest pain, but only 10% to 15% have myocardial infarction. Lack of diagnostic sensitivity and specificity of clinical and conventional markers prevents or delays treatment and leads to unnecessary costly admissions. Comparative data are lacking on the new markers, yet using all of them is inappropriate and expensive. METHODS AND RESULTS: The Diagnostic Marker Cooperative Study was a prospective, multicenter, double-blind study with consecutive enrollment of patients with chest pain presenting to the emergency department. Diagnostic sensitivity and specificity and frequency of increase in patients with unstable angina were determined for creatine kinase-MB (CK-MB) subforms, myoglobin, total CK-MB (activity and mass), and troponin T and I on the basis of frequent serial sampling for </=24 hours. Of 955 patients with chest pain, 119 (12.5%) had infarction identified by use of CK-MB mass, and 203 (21%) had unstable angina. CK-MB subforms were most sensitive and specific (91% and 89%) within 6 hours of onset, followed by myoglobin (78% and 89%). For late diagnosis, total CK-MB activity (derived from subforms) was the most sensitive and specific (96% and 98%) at 10 hours from onset, followed by troponin I (96% and 93%), but not until 18 hours, and troponin T (87% and 93% at 10 hours). In unstable angina, CK-MB subforms were increased in 29.5%, myoglobin in 23.7%, troponin I in 19.7%, and troponin T in 14.8%. All markers were increased in 99 patients. With each marker as the diagnostic standard, CK-MB subforms and myoglobin remained the most sensitive for early diagnosis. CONCLUSIONS: The CK-MB subform assay alone or in combination with a troponin reliably triages patients with chest pain and should lead to improved therapy and reduced cost.

Angina, Unstable↗
PubMed1999

Disruption of the cytochrome c gene in xylose-utilizing yeast Pichia stipitis leads to higher ethanol production.

The xylose-utilizing yeast, Pichia stipitis, has a complex respiratory system that contains cytochrome and non-cytochrome alternative electron transport chains in its mitochondria. To gain primary insights into the alternative respiratory pathway, a cytochrome c gene (PsCYC1, Accession No. AF030426) was cloned from wild-type P. stipitis CBS 6054 by cross-hybridization to CYC1 from Saccharomyces cerevisiae. The 333 bp open reading frame of PsCYC1 showed 74% and 69% identity to ScCYC1 and ScCYC7, respectively, at the DNA level. Disruption of PsCYC1 resulted in a mutant that uses the salicylhydroxamic acid (SHAM)-sensitive respiratory pathway for aerobic energy production. Cytochrome spectra revealed that cytochromes c and a.a(3) both disappeared in the cyc1-Delta mutant, so no electron flow through the cytochrome c oxidase was possible. The cyc1-Delta mutant showed 50% lower growth rates than the parent when grown on fermentable sugars. The cyc1-Delta mutant was also found to be unable to grow on glycerol. Interestingly, the mutant produced 0.46 g/g ethanol from 8% xylose, which was 21% higher in yield than the parental strain (0.38 g/g). These results suggested that the alternative pathway might play an important role in supporting xylose conversion to ethanol under oxygen-limiting conditions.

Antifungal Agents↗
PubMed1999

Trisomy 3 in gastric lymphomas of extranodal marginal zone B-cell (mucosa-associated lymphoid tissue) origin demonstrated by FISH in intact paraffin tissue sections.

Some reports have indicated that trisomy 3 represents a characteristic chromosomal abnormality found in lymphomas arising in mucosa-associated lymphoid tissues (MALT)/extranodal marginal zone B-cells (MZBC). Traditional cytogenetic analysis of metaphase preparations is cumbersome and not always possible, especially in those situations in which the diagnosis in not suspected before a biopsy. Our aim is to use a relatively simple method to evaluate trisomy 3 in paraffin-embedded, formalin-fixed tissue, using fluorescence in situ hybridization (FISH) on intact tissue sections. Formalin-fixed, paraffin-embedded archival tissues from 30 cases (27 lymphoma and 3 chronic gastritis cases) were hybridized with a chromosome 3 specific alpha-satellite probe (ONCOR, Gaithersburg, MD). Three of four cases of gastric MZBC/MALT lymphoma revealed trisomy 3. Ten cases of lymphoma of possible or probable MZBC origin were examined, and four revealed trisomy 3. Five of 13 non-MZBC lymphomas revealed trisomy 3. None of the chronic gastritis cases nor normal tonsil cases revealed trisomy 3. Our results, using a different methodological approach, confirm the findings of others that trisomy 3 is an abnormality found in a significant proportion of lymphomas of MZBC origin. Our approach also makes possible interphase cytogenetic analysis (by FISH) of routinely processed formalin-fixed, paraffin-embedded tissues, without the need to disaggregate cells. It thus may facilitate genetic analysis on specimens previously deemed unsuitable for such analysis, particularly when tissue quantity is limited.

Adult↗
PubMed1999

Selecting screening criteria for clinical trials: an example from the Systolic Hypertension in the Elderly Program.

In clinical trials that study people with a continuous measure defined categorically, even repeated measurements within a visit and over successive visits do not prevent error-free classification. We describe the design of a screening procedure for the Systolic Hypertension in the Elderly Program (SHEP), a randomized clinical trial designed to test whether regular administration of antihypertensive medication reduces the risk of stroke in elderly persons with isolated systolic hypertension. Data from a pilot study performed before the inauguration of SHEP allowed empirical study of a variety of possible screening rules for SHEP. A desirable screening rule would require only two screening visits, would lead to a randomized cohort with high mean systolic blood pressure, and would not impede recruitment. We emphasize two classes of rules, "serial" and "conditional." A serial rule uses only the values observed at a given screen to determine eligibility to proceed to the next screen. A conditional rule uses the value observed at a given screen along with values already observed to determine eligibility to proceed. For the SHEP study, we chose a conditional rule for screening because of its efficiency in identifying eligible participants. Our approach to selection of screening rules should be applicable to other clinical trials in which the measurement that defines the primary entry criterion has considerable measurement error.

Aged↗
PubMed1999

Childhood social predictors of adolescent antisocial behavior: gender differences in predictive accuracy and efficacy.

This study examined the ability of several childhood, school-based, social variables to correctly classify antisocial adolescents. Children (N = 314; 163 boys, 151 girls) in the 3rd-5th grade were assessed on academic and social variables (i.e., peer rejection, aggression, withdrawal, and low prosocial behavior) and followed forward for 6-7 years until the 9th and 10th grade. Adolescent antisocial outcomes included a consensus measure formed from diagnostic interviews, contact with juvenile authorities, adolescent self-report, and mother's report. The gender-differential predictive accuracy and efficacy of the early predictor domains to a consensus measure of antisocial behavior were compared with the same estimates found for adolescent self-report of antisocial behavior. Both gender and criterion-method differences were found. For girls, regardless of the measure of antisocial behavior, early academic problems were the strongest predictors of future problems. For boys' self-reported antisocial outcomes, peer rejection was the strongest independent predictor. For consensus-reported antisocial outcomes, both early fighting-anger and withdrawn behavior displayed equally strong predictive relations. For boys, the combination of early fighting-anger and disruptive and withdrawn behavior was the strongest set of predictors for the consensus measure of antisocial functioning. Predictive accuracy and efficacy estimates are discussed in terms of predictive strength as well as the cost-benefit of misidentification.

Adolescent↗
PubMed1999

In vitro alpha1-adrenoceptor pharmacology of Ro 70-0004 and RS-100329, novel alpha1A-adrenoceptor selective antagonists.

It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (alpha1-AR) subtype selectivities of two novel alpha1-AR antagonists, Ro 70-0004 (aka RS-100975) and a structurally-related compound RS-100329, and compares them with those of prazosin and tamsulosin. Radioligand binding and second-messenger studies in intact CHO-K1 cells expressing human cloned alpha1A-, alpha1B- and alpha1D-AR showed nanomolar affinity and significant alpha1A-AR subtype selectivity for both Ro 70-0004 (pKi 8.9: 60 and 50 fold selectivity) and RS-100329 (pKi 9.6: 126 and 50 fold selectivity) over the alpha1B- and alpha1D-AR subtypes respectively. In contrast, prazosin and tamsulosin showed little subtype selectivity. Noradrenaline-induced contractions of human lower urinary tract (LUT) tissues or rabbit bladder neck were competitively antagonized by Ro 70-0004 (pA2 8.8 and 8.9), RS-100329 (pA2 9.2 and 9.2), tamsulosin (pA2 10.4 and 9.8) and prazosin (pA2 8.7 and 8.3 respectively). Affinity estimates for tamsulosin and prazosin in antagonizing alpha1-AR-mediated contractions of human renal artery (HRA) and rat aorta (RA) were similar to those observed in LUT tissues, whereas Ro 70-0004 and RS-100329 were approximately 100 fold less potent (pA2 values of 6.8/6.8 and 7.3/7.9 in HRA/RA respectively). The alpha1A-AR subtype selectivity of Ro 70-0004 and RS-100329, demonstrated in both cloned and native systems, should allow for an evaluation of the clinical utility of a 'uroselective' agent for the treatment of symptoms associated with benign prostatic hyperplasia.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

The effects of 4-nonylphenol in rats: a multigeneration reproduction study.

The alkylphenol breakdown products of alkylphenol ethoxylates have been shown in in vitro studies to be weakly estrogenic, but few in vivo data address this issue in mammals. Because estrogens have been found to be most potent during developmental/perinatal exposures, this study maximized developmental exposure to nonylphenol (NP) by treating 3.5 generations of Sprague-Dawley rats to NP in diet at 200, 650, and 2000 ppm to determine the range and severity of any toxicity. Dose rate was higher for younger rats; calculated dose ranges were 9-35, 30-100, and 100-350 mg/kg/d for the low (200NP), middle (650NP), and high (2000NP) dose groups, respectively. There were adult (F0, F1, F2) and postnatal day (pnd) 21 (F1, F2, F3) necropsies; the oldest F3 rats were killed on pnd 55-58. Body weight gain was reduced by 8-10% in the 650NP and 2000NP groups. Vaginal opening was accelerated by approximately 2 days (650NP) and approximately 6 days (2000NP) in F1, F2, and F3 generations. Uterine weights at pnd 21 were increased in 650NP (14%) and 2000NP (50%) F1 females, but not in other generations. Testis descent, anogenital distance, and preputial separation were not consistently changed. No consistent changes were seen in pup number, weight or viability, litter indices, or other functional reproductive measures. Relative ovary weight in F2 adults was decreased at 650NP and 2000NP by 12%; relative ovary was unchanged in other generations. Follicle counts were unchanged in F2 adults. Sperm indices, including CASA measures, were unchanged in F0 and F1 males. In F2 rats, epididymal sperm density was reduced by 8% and 13% at 650NP and 2000NP, respectively. Testicular spermatid count was reduced by 13% in 2000NP F2 males; testis and epididymis weights were unchanged. Erosion of gastric and duodenal mucosa was monitored grossly and microscopically, and never found. Kidney weights were increased in 650NP and 2000NP males, and renal medullary tubular dilatation and cyst formation were noted in all generations of males, and often at the lowest dose tested. These data show that NP had limited effects on the reproductive system in the presence of measurable nephrotoxicity. The F2 sperm effects are either statistical/biological "noise," or imply heretofore unknown pharmacokinetics or toxicodynamics. These sperm data should be interpreted cautiously until the findings are repeated.

Animals↗
PubMed1999

The development of alcohol and other substance use: a gender study of family and peer context.

OBJECTIVE: This study examined early school-based academic and social variables with concurrent family conflict in predicting adolescent alcohol and other drug use. METHOD: 365 children were assessed initially in grades 2-4 on academic-related and social behavior variables using teacher ratings and rankings, peer nominations and ratings and direct observation of playground and classroom behavior. They were reassessed in grades 9-10, using interviews and questionnaires to determine the initiation and sequence of their use of alcohol, tobacco, marijuana and other hard drugs. RESULTS: In three sets of analyses, independently for males and females, lifetime abstainers were compared with adolescents who had used (1) only alcohol; (2) alcohol and tobacco; (3) alcohol, tobacco and marijuana; and (4) all three plus other hard drugs. The drug classifications represent a normative-deviant continuum of adolescent drug use. Constructs were developed for early academic and social predictors as well as concurrent family conflict. The results showed more wide-ranging academic and social difficulties during elementary school for children falling at the more deviant end of the drug use continuum. For girls, the concurrent home environment appeared to moderate the effect of early academic and social variables. CONCLUSIONS: Substance use established by ages 14-15 can be predicted by academic and social behavior displayed at ages 7-9. This suggests that prevention efforts for alcohol and other drugs may be more effective if directed at earlier antecedent behaviors rather than those that are concurrent with substance use.

Adolescent↗