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Biomedical subjects

J B Nelson

Publications and source records attributed to J B Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Perioperative plasma endothelin-1 and Big endothelin-1 concentrations in elderly patients undergoing major surgical procedures.

UNLABELLED: Plasma concentrations of the vasoconstrictor endothelin-1 (ET-1) increase during acute physiologic stress, but the role of ET-1 in the pathophysiology of stress remains largely undefined. Whether ET-1 mediates thermoregulatory changes in vasomotor tone is unknown. ET-1 and its more stable precursor, Big ET-1, were measured in plasma obtained at several perioperative time points from 95 consecutive elderly patients (mean age 70 +/- 1 yr) randomized to receive either normothermic or hypothermic perioperative care while undergoing major surgical procedures. In the postoperative period, there were no significant changes in plasma ET-1 concentrations, but Big ET-1 concentrations increased considerably (P < 0.0001). There were no significant differences in mean ET-1 or Big ET-1 levels in normothermic and hypothermic patients. Preoperative and postoperative ET-1 concentrations were significantly higher in patients with a history of hypertension (P < 0.002) and in those requiring treatment for postoperative hypertension (P < 0.003). Patients with cancer and those undergoing abdominal surgery had significantly higher Big ET-1 concentrations (P < 0.0001 and P < 0.003, respectively). These data support the hypothesis that Big ET-1 is a more sensitive measure of endothelin system activation after major surgery. Premorbid conditions and location and type of surgery influence perioperative ET-1/Big ET-1 concentrations. IMPLICATIONS: The endothelin response seems to be significantly associated with perioperative hemodynamic aberrations. The endothelin-1 (ET-1) precursor Big ET-1 is a more sensitive measure of the endothelin system activation in response to surgical stress than ET-1 alone. Thermoregulatory vasoconstriction in response to mild perioperative hypothermia occurs independently of the endothelin system.

Abdomen↗
PubMed1998

Laparoscopic nephrectomy for renal cell cancer: evaluation of efficacy and safety: a multicenter experience.

OBJECTIVES: Although laparoscopic radical nephrectomy is a safe and minimally invasive alternative to open surgery, the long-term disease-free outcome of this procedure has not been reported. We evaluated our experience with the laparoscopic management of renal cell carcinoma to assess the clinical efficacy of this surgical modality. METHODS: Between February 1991 and June 1997, 157 patients at five institutions were retrospectively identified who had clinically localized, pathologically confirmed, renal cell carcinoma and had undergone laparoscopic radical nephrectomy. Operative and clinical records were reviewed to determine morbidity, disease-free status, and cancer-specific survival. Of the patients followed up for at least 12 months (n = 101), 75% had an abdominal computed tomography scan at their last visit. RESULTS: The mean age at surgery was 61 years (range 27 to 92) and all patients were clinical Stage T1-2,NO,MO. Fifteen patients (9.6%) had perioperative complications. During a mean follow-up of 19.2 months (range 1 to 72; 51 patients with 2 years or more of follow-up), no patient developed a laparoscopic port site or renal fossa tumor recurrence. Four patients developed metastatic disease, and 1 patient developed a local recurrence. The 5-year actuarial disease-free rate was 91%+/-4.8 (SE). At last follow-up, there were no cancer-specific mortalities. CONCLUSIONS: The laparoscopic surgical management of localized renal cell carcinoma is feasible. Short-term results indicate that laparoscopic radical nephrectomy is not associated with an increased risk of port site or retroperitoneal recurrence. Longer follow-up is necessary to compare long-term survival and disease-free rates with those of open surgery.

Adult↗
PubMed1997

Methylation of the 5' CpG island of the endothelin B receptor gene is common in human prostate cancer.

Production of the potent vasoconstrictor endothelin-1 (ET-1) by human prostate cancer cells accompanies prostate cancer progression in vivo. The predominant endothelin receptor expressed by normal prostate epithelium, ETB, is not expressed by any of the established human prostate cancer cell lines, and ETB binding is decreased on prostate cancer tissues. ETB, which may mediate ET-1 clearance and may inhibit ET-1 secretion, is encoded by a gene that contains a 5' CpG island encompassing the transcriptional regulatory region. We examined this regulatory region of the ETB receptor gene (EDNRB) to determine whether hypermethylation of cytidine nucleotides accompanies decreased ETB expression in human prostate cancer. We found somatic methylation of CpG island sequences in EDNRB in 5 of 5 human prostate cancer cell lines, 15 of 21 primary prostate cancer tissues, and 8 of 14 prostate cancer metastases (70% of samples overall). Normal tissues contained only unmethylated EDNRB. Treatment of human prostatic carcinoma cell line cultures with 5-azacytidine induced ETB mRNA expression, suggesting that CpG island methylation changes might accompany the apparent transcriptional silencing of EDNRB in vivo.

Dinucleoside Phosphates↗
PubMed1997

Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue.

In previous studies, we have demonstrated that androgen ablation-induced growth inhibition of androgen-responsive PC-82 and A-2 human prostate cancer xenografts involves not only direct activation of programmed (apoptotic) death of these cells but also indirect activation of this death process via a decrease in tumor angiogenesis secondary to a reduction in tumor vascular endothelial growth factor (VEGF) levels. To determine whether androgens consistently regulate angiogenesis via control of VEGF levels, an additional human (i.e., LnCaP) and two rodent (i.e., Dunning G and H) androgen-sensitive prostate cancer sublines were tested. Androgen ablation causes a decrease in the subsequent growth rate of each of these three additional prostate cancer sublines, and this growth inhibition is consistently associated with a >60% reduction in tumor VEGF levels. To examine whether androgens regulate VEGF levels not only in malignant but also in normal prostatic tissue, male rats were castrated, and the temporal changes in the VEGF content of ventral prostate tissue were determined. One week after castration, VEGF content decreased to <20% within the ventral prostate. Subsequent replacement with exogenous androgen to long-term castrated rats stimulated an 8-fold rise in ventral prostate VEGF content within 1 week. To evaluate whether androgen regulation of VEGF is due to a direct effect of androgen on prostatic cells, the dose-response ability of androgens to increase VEGF levels in media of LnCaP cells grown in vitro was tested. These studies demonstrate that androgens directly stimulate VEGF secretion in these cells. The presence of 4-5-fold higher levels of VEGF in prostatic fluid versus seminal vesicle fluid obtained from benign prostatic hyperplasia and clinically localized prostate cancer patients suggests that elevated levels of VEGF may contribute to the progression of these prostatic conditions by promoting angiogenesis. In summary, one of the mechanisms for androgen sensitivity for the control of the growth of both normal and malignant prostatic tissue is via its stimulation of VEGF levels.

Androgens↗
PubMed1996

Secretagogue-induced proteolysis of cAMP-dependent protein kinase in intact rat alveolar epithelial type II cells.

Stimulation of secretion from rat alveolar epithelial type II cells by the beta-adrenergic agonist terbutaline activates cAMP-dependent protein kinase (PKA). The same secretagogue also activates endogenous protease calpain in type II cells. In this study, we investigated the effect of calpain activation on PKA and its phosphorylation activity in stimulated type II cells. Type II cells were either pretreated with cell-permeable calpain specific inhibitor (N-acetyl-leucyl-leucyl-methioninal) or untreated, and subsequently stimulated with terbutaline. Stimulus-induced phosphorylation activity was assayed using the PKA-specific substrate Kemptide. Maximum PKA activity was observed within 1-3 min of stimulation. Peak activity of the untreated cells was 20-25% higher and longer than that of the inhibitor-treated cells. The stimulus-induced phosphorylation activity of both cell groups was suppressable by PKA-specific inhibitor. Concomitant photoaffinity labeling with radioactive 8-azido-cAMP revealed that a 39 kDa proteolytic fragment was generated in response to stimulation by terbutaline. Stimulus-induced activation of PKA resulted in the phosphorylation of two endogenous proteins, p112 and p47. Phosphorylation of p112 and p47 was modulated in cells pretreated with calpain inhibitor or in the presence of PKA inhibitor. Aggregate results indicate that stimulus-induced proteolysis of pKA occurs in type II cells, suggesting that limited proteolysis of PKA by endogenous calpain may convert an initial transient signal to sustained and augumented phosphorylation activity for secretion.

Adrenergic beta-Agonists↗
PubMed1996

Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer.

The potent vasoconstrictor endothelin-1 (ET-1) is at its highest concentration in the normal human ejaculate and is associated with the progression of metastatic prostate cancer. ET-1 protein expression is detected in situ in 14 of 14 primary cancers and 14 of 16 metastatic sites of human prostatic carcinoma. Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. The ETA-selective receptor antagonist A-127722 inhibits ET-1-stimulated growth, but the ETB-selective receptor antagonist BQ-788 does not. ET-3, an ETB-selective agonist, also had no effect on prostate cancer growth. No specific ETB-binding sites could be demonstrated in any established human prostate cancer cell line tested, and ETB mRNA, detected by reverse transcription PCR, was reduced. The predominance of ETB binding on human benign prostatic epithelial tissue is not present in metastatic prostate cancer by autoradiography. In human prostate cancer progression to metastases, ET-1 and ETA expression are retained, whereas ETB receptor expression is reduced.

Apoptosis↗
PubMed1996

Phenylbutyrate induces apoptosis in human prostate cancer and is more potent than phenylacetate.

Phenylbutyrate (PB), a novel lead compound for prostate cancer therapy, has molecular activities distinct from its metabolite, phenylacetate (PA). Both PB and PA promote differentiation in human prostate cancer cell lines, yet little data exist comparing the cytotoxic effects of each drug. We found that PB is more potent than PA in vitro; PB is 1.5-2.5 times more active at inhibiting growth and inducing programmed cell death than PA at clinically achievable doses against each human prostate cancer line studied. PB is equipotent to sodium butyrate, which induces apoptosis and differentiation through multiple mechanisms. Exposure of prostate cancer cell lines to PB reduces their DNA synthesis, leads to fragmentation of genomic DNA, and causes 50-60% of cells to undergo apoptosis. These PB-induced effects are 2-10 times greater than those of the control or PA. The stereotypical changes of apoptosis can be seen with sodium butyrate at similar concentrations, but not with PA. Prostate cancer cell lines overexpressing P-glycoprotein or possessing heterogeneous molecular alterations, including p53 mutations, are also sensitive to the effects of PB. In vivo, Copenhagen rats treated with oral PB had delayed growth of the androgen refractory Dunning R-3327 MAT-LyLu prostate cancer subline by 30-45% in a dose-dependent manner. These results demonstrate that PB induces cytotoxicity via apoptosis in human prostate cancer, in addition to its differentiating properties.

Animals↗
PubMed1995

Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate.

Prostate cancer is the second most common cause of death from cancer in U.S. men, and advanced, hormone-refractory disease is characterized by painful osteoblastic bone metastases. Endothelin-1, more commonly known as a potent vasoconstrictor, is a normal ejaculate protein that also stimulates osteoblasts. We show here that plasma immunoreactive endothelin concentrations are significantly elevated in men with metastatic prostate cancer and that every human prostate cancer cell line tested produces endothelin-1 messenger RNA and secretes immunoreactive endothelin. Exogenous endothelin-1 is a prostate cancer mitogen in vitro and increases alkaline phosphatase activity in new bone formation, indicating that ectopic endothelin-1 may be a mediator of the osteoblastic response of bone to metastatic prostate cancer.

Adenocarcinoma↗
PubMed1995

An ergonomic evaluation of dexterity and tactility with increase in examination/surgical glove thickness.

Latex gloves of five different thicknesses (0.21 mm, 0.51 mm, 0.65 mm, 0.76 mm, and 0.83 mm) were manufactured in-house and tested for dexterity and tactility; dexterity and tactility measures with the bare hand were used as control values. Fifteen adult males (mean age = 22.8 years, mean stature = 179 cm, mean body weight = 75.4 kg, mean palm width = 9.9 cm, mean palm depth = 10.9 cm, and mean middle finger length = 9 cm) and five adult females (mean age = 21.2 years, mean stature = 168 cm, mean body weight = 53.6 kg, mean palm width = 8 cm, mean palm depth = 8 cm, and mean middle finger length = 8.3 cm) voluntarily participated. The gloves also were tested for punctures resulting from impact forces encountered during routine hand movements. The results indicated that the latex glove with 0.83 mm thickness successfully resisted routine impact forces and at the same time provided dexterity and tactility comparable to the bare hand. Thinner gloves failed the impact test and punctured. This indicates that it is possible to greatly reduce the incidence of exposure to contaminated body fluids through accidental needlesticks without compromising the preferred hand's capabilities.

Blood-Borne Pathogens↗
PubMed1995

Unusual presentation of an unusual type of choledochal cyst.

Type II choledochal cysts are rare congenital malformations of the biliary ductal system. We report a case in which a type II choledochal cyst presented as a mass in the porta hepatis without any demonstrable connection with the biliary tree. In the English literature, this is the first described case of this type in the absence of biliary tract malignancy. We hypothesize that the connection to the biliary tree was lost by either torsion of the cyst or fibrosis due to chronic inflammation.

Adult↗
PubMed1994

The clinical and pathological manifestations of renal tumors in von Hippel-Lindau disease.

The protean nature of renal lesions in von Hippel-Lindau disease has made surgical management difficult. To develop a sensible surgical approach the pathological and clinical manifestations of renal involvement in von Hippel-Lindau disease patients were defined. A total of 87 lesions in 9 kidneys from 6 patients with von Hippel-Lindau disease was examined for size, presence of renal cell carcinoma, cystic or solid qualities and local invasion. There was no correlation between the size of the lesion and renal cell carcinoma. All 44 benign lesions were cystic, while 35% (15 of 43) of malignant lesions were cystic and 65% (28 of 43) were solid. All 9 locally invasive tumors were solid. The distribution of lesions in our patients was compared to the findings in 138 cases we collected from the literature. The 3 patterns of clinical presentation recognized were solitary, multiple and diffuse. We recommended that all lesions, cystic or solid, be excised at the time of nephron sparing surgery, with a wider margin for solid lesions, and that nephron sparing surgery should be reserved for patients with cystic and small solid lesions, with radical nephrectomy being preferred for patients with diffuse disease.

Adult↗
PubMed1994

Retroperitoneal pulmonary sequestration: a rare congenital anomaly in a 71-year-old man.

The suprarenal fossa is a clinically silent area of the body where nonfunctioning, indolent lesions may pass unnoticed. We report on a 71-year-old man with muscle invasive transitional cell carcinoma of the bladder who was found on staging abdominopelvic computerized tomography to have a 5 x 6 cm. left periaortic suprarenal mass. Serum analysis for a hormonally or vasoactive tumor was unrevealing. Fine needle aspiration was also nondiagnostic. An extrathoracic pulmonary sequestration was found at surgical exploration. Pulmonary sequestration rarely occurs in an extrathoracic location, is usually diagnosed in the first decade of life and to our knowledge has never been reported in this location in a patient of this age.

Aged↗
PubMed1994

Lithotripsy of urinary calculi by tunable pulsed dye lasers: a randomized in vitro study.

Pulsed dye laser lithotripsy has been used in the treatment of urinary calculi. We compared the efficacy of 2 pulsed dye lasers with different pulse durations in lithotripsy. A total of 20 pairs of human kidney stones was matched by size and composition, and randomized for laser lithotripsy under identical in vitro conditions. Each stone received 150 shocks at sequential energy settings between 40 and 140 mJ. while in a laser fiber compatible stone basket until complete fragmentation occurred. Stone fragments were separated by size and weight. We found that the laser with the shorter pulse duration fragmented stones with less total energy and produced fewer fragments greater than 3.35 mm. The differences were statistically significant.

Humans↗
PubMed1994

Context-specificity of target versus feature inhibition in a feature-negative discrimination.

Four experiments with rats examined the effects of a context switch on inhibition that was acquired during a feature-negative discrimination. A target conditioned stimulus was paired with food when it was presented alone but occurred without food when it was combined with a feature stimulus. A context switch following training did not disrupt inhibition conditioned to the feature. However, responding to the target was more difficult to inhibit when it was tested in a different context. It is suggested that both the target and the feature acquired inhibition and that the target's inhibition was especially sensitive to the context. The feature may inhibit responding to the target (a) by directly suppressing the representation of the food and (b) by activating the target's own inhibitory association with food, which is at least partly context-specific. Implications for theories of inhibition and negative occasion-setting are discussed.

Animals↗