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Biomedical subjects

L McBride

Publications and source records attributed to L McBride.

35 records · Page 2Linked to original sources
PubMed1996

Androgen-regulated proliferation and gene transcription in a prostate smooth muscle cell line (PS-1).

Androgens play a key role in directing stromal-epithelial interactions in prostate gland development, in maintenance of adult phenotype, and in disease progression. To address the molecular mechanisms of androgen action in prostate stromal cells and the genes regulated by androgens in this cell type, a stromal cell line (PS-1) was developed from rat ventral prostate. The PS-1 cell line was adapted to chemically defined media and characterized as smooth muscle based on expression of desmin, smooth muscle alpha-actin, and nuclear androgen receptor, markers for prostate smooth muscle. To examine steroid hormone regulation, PS-1 cells were analyzed for response to a panel of steroid hormones in serum-free, chemically defined media. PS-1 cells were significantly growth stimulated by physiological concentrations of androgens (10nM) relative to other steroids tested. To ascertain whether this cell line could be used to examine androgen-regulated gene expression, differential display PCR was used to demonstrate the presence of androgen-regulated transcripts and provide the initial steps in cloning these genes. Replicate differential display PCR analyses showed consistent androgen stimulation of 16 messenger RNA species. Northern analysis confirmed androgen regulation of 6 species. Sequence analysis of each indicated no regions of significant homology or direct matches to existing sequences. Further study of the PS-1 stromal cell line and androgen-regulated genes identified here will provide a novel in vitro system for defining molecular mechanisms of androgen action in prostate stromal cells and the significance of stromal androgen-regulated genes to stromal-epithelial interactions.

Androgens↗
PubMed1995

Purification of a novel protein (ps20) from urogenital sinus mesenchymal cells with growth inhibitory properties in vitro.

Our previous studies have characterized mesenchyme-derived proteins to identify biologically active proteins and novel markers for stromal cell paracrine action relative to stromal-epithelial interactions. Previous reports have characterized properties of a growth inhibitory activity (to bladder and prostatic epithelial cells), secreted by U4F fetal rat urogenital sinus mesenchymal cells, not cross-reactive with antibodies to known cytokines, and provisionally termed UGIF. The present study reports the characterization, purification, and biological properties of a 20-21-kDa protein responsible for UGIF activity. The 20-21-kDa protein (termed ps20) was purified to near homogeneity, the amino-terminal sequence was determined, and biological properties were characterized in vitro. Amino-terminal sequence analysis indicated no direct matches or regions of homology with known proteins. Purified ps20 induced a linear and saturable inhibition of [3H]thymidine incorporation in PC-3 prostatic carcinoma cells (half-maximal activity at 2.6 nM), inhibited cell proliferation (increased population doubling time from 19.8 to 25.8 h), and induced a 210% stimulation in the synthesis of secreted proteins. These data suggest that ps20 may be a candidate paracrine effector protein and may play a role in stromal-epithelial cell interaction in the prostate gland.

Animals↗
PubMed1995

Beta-2 microglobulin is mitogenic to PC-3 prostatic carcinoma cells and antagonistic to transforming growth factor beta 1 action.

Previous studies have identified a M(r) 12,000 protein in rat prostatic stromal cell-conditioned medium with growth stimulatory activity to human prostatic carcinoma cells as a direct match with beta 2-microglobulin (beta 2-m). The present study was conducted to characterize the activities of human beta 2-m directly, using commercially available, purified human beta 2-m. Beta 2-m was assayed for growth stimulatory activity to human PC-3 prostatic carcinoma cells and rat PS-1 prostatic stromal cells and for antagonistic activity to transforming growth factor beta 1 (TGF-beta 1)-induced growth inhibitory actions. Beta 2-m acted to stimulate [3H]thymidine incorporation in PC-3 cells in a linear, concentration-dependent and saturable manner in serum-free medium. Beta 2-m stimulated cell proliferation and significantly decreased population doubling times in both PC-3 and PS-1 cell lines. At half-maximal concentrations of TGF-beta 1 and lower, beta 2-m acted in a concentration-dependent, antagonistic manner, acting to stimulate growth-inhibited PC-3 cells to fully neutralize TGF-B1 activity. In contrast, cells exposed to maximum activity TGF-beta 1 concentrations were refractory to beta 2-m action, regardless of the concentration tested. This represents the first report to demonstrate a growth-stimulatory activity of B2-m with carcinoma/epithelial cells and to show beta 2-m antagonistic activity to TGF-B1 growth-induced inhibition. Beta 2-m has been shown previously to associate with hormone/growth factor receptors. Together, these data suggest that beta 2-m may play a role in modulating cell proliferation, possibly through modification of ligand/receptor kinetics. Owing to the elevation of both beta 2-m and TGF-beta 1 in many dysplastic-neoplastic conditions, beta 2-m may be relevant to mechanisms of abnormal proliferation disorders and in modulating TGF-beta 1 mechanisms of actions.

Cell Division↗
PubMed1994

Reinfusion potassium blood cardioplegia versus cold blood reinfusion alone in elective revascularization.

The purpose of this study was to determine if the addition of potassium to reinfusion cold blood cardioplegia (CBC) offers an advantage over cold blood alone. Forty patients matched for age, left ventricular function, extent of coronary disease and number of vessels bypassed were prospectively randomized. Each patient received an initial dose of CBC (10 cc/kg) with potassium. Group I patients (n = 23) received subsequent infusions of CBC (5 cc/kg) containing potassium while Group II patients (n = 17) received cold blood only. The cross-clamp time, mean infusate volume and temperature were not significantly different in the two groups. Following reperfusion, the cardiac index and the CPK isoenzyme release at 0.5, 1, 8, and 12 h after cross-clamp release were not significantly different between the groups. The postoperative appearance of new Q-waves, inotropic agent requirement, and reversal of the lactate dehydrogenase (LDH) isoenzyme ratio were also not significantly different in the two groups. The study demonstrated that following initial arrest with potassium, cold blood is equally as effective as potassium blood cardioplegia in protecting the ischemic myocardium.

Aged↗
PubMed1989

A high-resolution, fluorescence-based, semiautomated method for DNA fingerprinting.

We describe a fluorescence-based method for the automated analysis of DNA fragments on polyacrylamide gels. A single-stranded oligonucleotide primer (18-mer) with a fluorochrome covalently bound to its 5'-end is annealed to a synthetic oligonucleotide to create a double-stranded oligonucleotide linker with a 5'-overhang complementary to a restriction enzyme site. Cosmid or plasmid DNA is digested with the appropriate restriction enzyme and then ligated to the fluorochrome-labeled linker. The labeled restriction fragments are loaded on a denaturing polyacrylamide gel in a commercially available DNA sequencer. As the restriction fragments migrate through the gel, they intersect a laser beam which excites the fluorochrome-labeled fragment. Fluorescence emission data are captured on a computer in real time and analyzed after the completion of electrophoresis. Fragment length is nearly linearly related to migration time. This method offers very near single-base resolution up to 400 bases and the ability to quantitate fragment size up to 2000 bases. The fluorochrome-labeling chemistry relies on straightforward enzymatic reactions and can be performed in a single reaction tube. Because four different fluorochromes can be used, each of 16 lanes on the gel can be used to analyze four different digest reactions, one in each color. One of the fluorochromes can be used to label size standards in each lane, eliminating interlane variability and allowing more precise estimates of fragment size. We apply the method to the analysis of overlapping cosmids.

Animals↗
PubMed1987

Multiple aortic tears treated by primary suture repair.

Blunt trauma to the chest with aortic tear is not an unusual sequela of rapid deceleration. Multiple aortic tears in a viable patient are unusual. A case is reported where multiple aortic lacerations were repaired without the use of prosthetic material. The use of a primary suture repair of aortic injuries is advocated for simple aortic tears not extending proximally to the arch whether they be single or multiple.

Aorta, Thoracic↗
PubMed1982

Fluorometric coupled-enzyme assay for delta-aminolevulinate synthase.

The rapid and specific determination of picomole quantities of gamma-aminolevulinate has been accomplished by its enzymatic conversion to uroporphyrinogen I and subsequent fluorometric detection of the oxidized uroporphyrin I. The coupled-enzyme assay was linear with time and protein concentration and required less than 3 h for 25 individual determinations. Under the standard assay conditions, 5-100 pmol of uroporphyrin I was reliably quantitated; these values corresponded to a range of gamma-aminolevulinate synthase activities from 0.2 to 15 nmol/h/ml enzyme. The sensitivity of this method was comparable to the more time-consuming radiochemical determinations of gamma-aminolevulinate synthase activity. The gamma-aminolevulinate synthase activity of liver homogenates from uninduced rats was 8.6 U/g liver (37 degrees C).

5-Aminolevulinate Synthetase↗
PubMed1979

Esophageal atresia and tracheoesophageal fistula: preoperative assessment and reduced mortality.

One hundred twenty-nine infants with esophageal atresia and tracheoesophageal fistula were reviewed from 1955 to 1978. The overall mortality was 38%. Factors associated with the increased mortality include prematurity, pneumonia, and congenital defects other than this anomaly. A classification based on these factors in introduced, which provides the clinician with a prognostic survival rate greater than 90% with only physical examination, chest and abdominal roentgenography, and intravenous pyelography. Postoperative mortality was reduced to 11% in the last five years of the study; this is attributed to the exclusive use of the retropleural approach to the esophagus, more intensive postoperative ventilatory support, and routine use of parenteral nutrition.

Esophageal Atresia↗
PubMedDate not supplied

Balancing the 'heart' of patient care.

Home health nurses are in a unique position to facilitate understanding of the patient's psychosocial context. As opposed to the practice of minimizing or separating this aspect of care, this article emphasizes the importance of a collaborative and integrative treatment model.

Community Health Nursing↗
PubMedDate not supplied

Importance of ventricular arrhythmias in bridge patients with ventricular assist devices.

To evaluate whether bridge to transplant patients with ventricular arrhythmias (VA; fibrillation or tachycardia) are at risk of death before or during ventricular assist device (VAD) support, the records of 28 patients who were supported with VADs for periods of 0.1 to 370 days (mean, 35.3 days) were retrospectively reviewed. VADs were effective in reducing the incidence of VA by 36%; however, patients with ischemic heart disease had a high incidence of VA (44%) during VAD. Only one patient with non-ischemic heart disease (8%) had VA during VAD. All five patients supported with left ventricular assist devices who had VA during support survived. Overall, the occurrence of VA during VAD was not a mortality risk. Since VAs are not predictors of survival, the presence of VA should not influence patient selection. While biventricular assist devices may be necessary in patients with the most severe VA, an LVAD provides excellent support in many patients.

Adolescent↗
PubMedDate not supplied

Heart transplantation in patients over age fifty-five years.

The age limit for heart transplantation remains undefined. The shortage of available donors coupled with fears of increased morbidity and mortality in older patients has until recently resulted in a limited application of heart transplantation in patients over age 50 years. In 1986, however, data from the International Heart Transplant Registry demonstrated that 25% of all patients undergoing this procedure were over age 55 years. This study reviews our experience with 30 consecutive patients who underwent heart transplantation over a 15-month period. There were eight patients over age 55 years (group 1) and 22 patients under age 55 years (group 2). We compared the hospital course and incidence of infection and rejection and other complications after heart transplantation between the two groups. Carefully selected patients between ages 55 and 60 years can undergo transplantation with similar expectations to younger patients for survival, complications, and rehabilitation, including employability. Caution is warranted in extrapolating these optimistic data to patients older than age 50 years.

Age Factors↗
PubMedDate not supplied

Analgesia following major gynecological laparoscopic surgery--PCA versus intermittent intramuscular injection.

BACKGROUND AND OBJECTIVES: To compare the use of patient-controlled analgesia to intermittent intramuscular injections of morphine following major gynecological laparoscopic procedures in order to assess differences in level of pain, sedation, episodes of nausea and/or vomiting, hospitalization time and patient satisfaction with their postoperative analgesia. METHODS: Seventy-two patients undergoing major gynecological laparoscopic surgery were randomized to receive either postoperative analgesia via intermittent intramuscular injection of morphine (Group 1) or patient controlled analgesia (PCA-Group 2). All patients received anesthesia via a standardized protocol. Postoperative pain levels were recorded via a 10 cm visual analogue scale, and sedation scores were recorded on a standard PCA form. Episodes of nausea and vomiting were also recorded on the same form. RESULTS: There were no statistically significant differences between intramuscular analgesia and PCA for any of the factors studied. Most significantly it was found that most patients ceased to require either form of parenteral analgesia within 24 hours of their procedure, regardless of the operating time. CONCLUSION: It is important for the surgeon to be aware of the effects of postoperative analgesia on his or her patients' level of satisfaction. We do not recommend the use of PCA analgesia following major laparoscopic gynecological surgery.

Adult↗