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Biomedical subjects

J H Lynch

Publications and source records attributed to J H Lynch.

At least 19 recordsLinked to original sources
PubMed1993

Transurethral microwave thermotherapy for management of benign prostatic hyperplasia: results of the United States Prostatron Cooperative Study.

The primary objective of the study was to determine the safety and efficacy of transurethral microwave thermotherapy for the treatment of symptomatic benign prostatic hyperplasia. From March to August 1991, 150 patients were entered into a multi-site study and treated with transurethral microwave thermotherapy under a Food and Drug Administration approved protocol. Only patients with symmetrical trilobar or bilobar prostatic hypertrophy, peak flow rate of less than 15 cc per second (on 2 voided volumes of 150 cc or greater) and a total Madsen symptom score of more than 8 were treated. Transurethral microwave thermotherapy was performed with a 20F catheter and 1,296 MHz. microwave antenna for 60 minutes. The mean power achieved for this single session was 32.1 watts, with a mean power at maximum urethral temperature of 41.1 watts. Mean urethral temperature was 44.3C and the mean rectal temperature was 42.2C. The rectal and urethral temperatures were continuously monitored. Mean peak urinary flow rates, Madsen symptom score, post-void residual volume and improvement in motivating symptom to seek treatment were measured at 6 weeks, and 3, 6 and 12 months. Mean peak urinary flow rates improved 33% at 12 months (p < 0.0001). Overall, the mean Madsen symptom score improved 61% (p < 0.0001). The obstructive score and the irritative score improved 67% and 43%, respectively. Of 17 patients 12 (71%) reported improvement in weak stream when that was the motivating symptom to seek treatment. Of 28 men 18 (64%) reported improvement in nocturia, while 11 of 30 (37%) reported improvement in daytime frequency and 12 of 17 (71%) reported improvement in urgency. There was no statistically significant difference in post-void residual volume at 12 months from baseline. The treatment was well tolerated by all patients, and side effects were considered mild and transitory. Our study demonstrates the safety, effectiveness, patient tolerability and durability of transurethral microwave thermotherapy.

Adult↗
PubMed1993

Treatment of advanced prostate cancer.

Many patients with prostate cancer present with advanced disease (stage C or D). For these patients, treatment is palliative and is aimed at reducing serum testosterone levels. Since the growth of prostate cancer is testosterone-dependent (approximately 95% of testosterone is produced by the testes, with the remainder coming from the adrenals), hormonal manipulation has been the mainstay of palliative treatment. Bilateral orchiectomy has been the traditional approach, but most patients prefer equally effective drug therapies that include the administration of estrogens, luteinizing hormone-releasing hormone (LHRH) agonists, and anti-androgens.

Androgen Antagonists↗
PubMed1992

Reduced expression of the low affinity nerve growth factor receptor in benign and malignant human prostate tissue and loss of expression in four human metastatic prostate tumor cell lines.

In the human prostate, a low affinity (p75) nerve growth factor (NGF) receptor (NGF-R) localizes to the epithelia while a NGF-like protein localizes to the stroma. This NGF-like ligand, derived from prostate stromal cell cultures, has been shown to participate in paracrine mediated growth of a human tumor epithelial cell line (TSU-prl) in vitro. In order to investigate the role of the NGF-R in neoplastic growth we have examined the expression of the NGF-R in normal prostate tissues, benign prostatic hyperplasia tissues, adenocarcinoma tissues, and four metastatic tumor cell lines of the human prostate. In primary epithelial cell cultures of normal human prostate the p75 NGF-R was localized by immunocytochemistry to cytoplasmic vesicles. Furthermore, Western blot analysis of the NGF-R in subcellular fractions of normal prostate tissue identified an M(r) 75,000 immunoreactive protein in the microsomal fraction under nonreducing conditions of sodium dodecyl sulfatepolyacrylamide gel electrophoresis. However, microsomal preparations of five prostatic adenocarcinoma and five benign prostatic hyperplasia specimens showed varying immunoreactivity among samples, all of which expressed less of the p75 NGF-R than the normal tissue. Interestingly, microsomal preparations of the human prostatic epithelial cell lines, TSU-prl, DU-145, PC-3, and LNCaP did not show NGF-R expression by immunoblot analysis. Hence, expression of the p75 NGF-R in normal prostate tissue, partial loss of NGF-R expression in benign and malignant prostate tissue, and complete loss of NGF-R expression in the four metastatic tumor cell lines, suggests an inverse association of p75 NGF-R expression with the neoplastic progression of the human prostate.

Adenocarcinoma↗
PubMed1992

Density dependent polarized secretion of a prostatic epithelial cell line.

The polarized secretions (apical/basal) of newly synthesized total protein and proteases from prostatic epithelial sheets of PA-III cells grown in dual compartment chambers were investigated at various cell densities and culture conditions. PA-III cells grown in a serum free defined medium (SFDM) form morphologically polarized monolayers of epithelial cells. These cells secreted their 35S-methionine labeled total protein in a predominantly apical direction (apical/basal ratio, 4-8 fold), with a lesser proportion of protein secreted apically at lower cell densities of the PA-III cell monolayer. PA-III cells grown in 5% fetal calf serum (FCS) are morphologically squamous, comparable to the anaplastic phenotype, and exhibited an inversion of polarized total protein secretion (apical/basal ratio, 0.4-0.9 fold), with an increased proportion of total protein secreted in a basal direction at lower cell densities. Since the culture of PA-III cells in FCS may approximate the anaplastic phenotype we investigated the polarized secretion of proteases from these cells at various cell densities, and compared them with the secretory pattern of protease secretion from polarized PA-III cells cultured in SFDM. At lower cell densities of the PA-III cells grown in FCS the polarity of protease secretion was inverted such that metalloproteinases, tissue type plasminogen activator, and a 72 kD gelatinase were secreted in a predominantly basal direction, as well as urokinase and a gelatinase of 26 kD that were secreted more or less equally into the apical and basal compartments of the chambers. On the other hand, for cultures of PA-III cells grown in SFDM the aforementioned proteases exhibited predominantly an apically directed polarity of secretion. These results suggest that the anaplastic phenotype characterized by a loss of polarized structure may also be characterized by a functional loss or inversion of polarized secretion. The consequences of such a loss or inversion of polarized secretion would be to increase the localized concentrations of proteases along the basal domain of cells thereby facilitating degradation of the basement membrane and interstitial tissue in vivo.

Adenocarcinoma↗
PubMed1992

The effect of pH on the in vitro colony forming ability of transitional cell carcinoma cells treated with various chemotherapeutic agents: implications for in vivo therapy.

Extracellular pH may affect the sensitivity of cancer cells to chemotherapy agents. In an attempt to maximize the conditions for chemotherapy treatment of transitional cell carcinoma we tested the effect of pH on sensitivity of MGH-U3 transitional cell carcinoma cell line to thiotepa, doxorubicin, and mitomycin c in vitro. The toxicity of each agent tested varied with pH. There was no variation in cell growth in response to pH alone. The cytotoxic activity of thiotepa was markedly enhanced when cells were treated with a diluent pH of 5.5. Significant differences were also observed after treatment with doxorubicin and mitomycin c with a diluent pH of 7.0. This in vitro assay may be useful for clinical application of pH modulation during intravesical chemotherapy.

Adult↗
PubMed1992

Distribution of nerve growth factor-like protein and nerve growth factor receptor in human benign prostatic hyperplasia and prostatic adenocarcinoma.

Recent observations from our laboratory have identified a nerve growth factor (NGF)-like protein in conditioned media of stromal cells and neoplastic epithelial cells of the human prostate which mediates paracrine interactive growth of both cell types in vitro. In order to investigate the location of this NGF-like protein in the human prostate in vivo, and whether a nerve growth factor receptor (NGF-R) could be identified, we have carried out immunocytochemical studies on frozen tissue sections of human benign prostatic hyperplasia (BPH), prostatic adenocarcinoma and normal prostatic tissue. The NGF-like protein localized predominantly to the stromal component of BPH, adenocarcinoma and normal (non-cancerous) prostatic tissue. Conversely, the NGF-R localized predominantly to the epithelial cells of these tissues. Renal tissue provided negative controls for both the NGF-like protein and the NGF-R. The testis provided positive controls for both the NGF-like protein and the NGF-R. These results provide corroborative evidence for a NGF-like protein produced by stromal cells which interacts with a NGF-R on the adjacent epithelial cells thereby mediating paracrine interactive growth regulation of the human prostate.

Adenocarcinoma↗
PubMed1992

Management of stage C adenocarcinoma of the prostate.

A review of numerous clinical series dealing with the treatment of patients with clinical stage C prostate cancer failed to find the treatment or a combination of treatments that is superior to any other. Accurate staging, which was difficult in older studies, and stage migration, which complicates the comparison of recent to older studies, may contribute to this lack of identification. The majority of patients ultimately experience disease progression and are therefore treated with hormonal therapy, the use of which obscures survival data for initial modes of treatment. These observations point to the need for control of randomised clinical trials to identify effective treatments in the future.

Adenocarcinoma↗
PubMed1991

Penile cancer: curable with early detection.

When this malignancy is recognized and treated early, cure rates are high. No one approach to the treatment of penile cancer is acceptable to all surgeons, however. Diagnosis and treatment guidelines are reviewed.

Biopsy↗
PubMed1991

Regulation of growth by a nerve growth factor-like protein which modulates paracrine interactions between a neoplastic epithelial cell line and stromal cells of the human prostate.

Nerve growth factor-like substance(s) were identified in both conditioned media of a human prostatic tumor epithelial cell line (TSU-pr1) and a human prostatic stromal cell line (HPS) by Western blot analysis and bioassay of neurite outgrowth of PC12 cells. Nerve growth factor-beta (NGF) immunofluorescence was also localized to secretory vesicles in the cytoplasm of both the TSU-pr1 and HPS cells. Western blot of the TSU-pr1 and HPS cell-secreted protein identified an Mr 65,000 major protein which immunoreacted with murine NGF antibody. NGF Western blot of HPS cell-secreted protein also identified an Mr 42,000 minor band under reduced and nonreduced conditions and an Mr 61,000 minor band under reduced conditions. The secreted protein from the TSU-pr1 cells (50 micrograms/ml) and HPS (50 micrograms/ml), as well as murine NGF (50 ng/ml) or human recombinant NGF (50 ng/ml), stimulated neurite outgrowth from PC12 cells. This neurite outgrowth activity was partially inhibited by treatment with NGF antibody. Neither the serum containing growth medium nor bovine serum albumin (50 micrograms/ml) stimulated neurite outgrowth. The NGF-like secretory protein appeared to play a role in the paracrine regulation of prostatic growth between TSU-pr1 cells and HPS cells. The relative growth of TSU-pr1 cells, as indicated by [3H]thymidine incorporation, in response to HPS secretory protein was stimulated 2.8-fold in a dose-dependent manner. In the converse interaction, the relative growth of HPS cells in response to TSU-pr1 secretory protein was stimulated 1.8-fold in a dose-dependent manner. Immunoneutralization of TSU-pr1 and HPS secretory protein was performed with antibody against NGF, acidic fibroblast growth factor, and basic fibroblast growth factor. Removal of the NGF-like protein from the maximal stimulatory dose of TSU-pr1 secretory protein (100 micrograms/ml) with NGF antibody reduced HPS proliferation to 52% of maximal levels, and immunoneutralization of the NGF-like protein in the maximal stimulatory dose of HPS secretory protein (20 micrograms/ml) also reduced TSU-pr1 proliferation to 16% of maximal levels. Addition of normal rabbit serum or prior immunoprecipitation of either TSU-pr1 or HPS secretory protein with antibody against acidic fibroblast growth factor and basic fibroblast growth factor did not inhibit the proliferation of either cell type. These results suggest that TSU-pr1 tumor cells and HPS cells secrete NGF-like protein(s) which modulate their paracrine interactive growth in vitro.

Adrenal Gland Neoplasms↗
PubMed1991

Primary leiomyosarcoma of adrenal gland. Case report with immunohistochemical and ultrastructural study.

A primary leiomyosarcoma of the right adrenal gland is reported in a 49-year-old male who presented with progressive flank pain. This is the second case in the English language literature and the first to have documentation of malignant behavior. The tumor measured 11 cm in diameter and showed marked necrosis with prominent mitotic activity (average 15 per 10 high-power fields). Smooth muscle differentiation was apparent ultrastructurally and confirmed by positive immunostaining for muscle-specific and alpha-smooth muscle actin. Bony metastases developed; following palliative treatment with radiation and chemotherapy, the patient is alive with tumor 9 months later. Origin from smooth muscle associated with the central adrenal vein or its tributaries is proposed.

Adrenal Gland Neoplasms↗
PubMed1990

Paracrine stimulation of polarized secretion from monolayers of a neoplastic prostatic epithelial cell line by prostatic stromal cell proteins.

The paracrine influence of prostatic stromal cell proteins on a neoplastic prostate cell line (PA-III) was investigated. We have utilized an in vitro experimental model whereby confluent epithelial sheets of PA-III cells are grown on Matrigel-coated filters in bicameral chambers (Millicell-HA). Confluence of the epithelial sheet was confirmed morphologically by electrical resistance measurements and by impedence of [3H]inulin permeability across paracellular channels. Stromal cells were isolated from the ventral prostate of 50-day-old rats by isopyknic Percoll centrifugation. Purity (92%) of the isolated stromal cells was confirmed by indirect immunofluorescence of vimentin intermediate filaments. Prostatic epithelial cells were negative for vimentin immunofluorescence. Prostatic stromal cell secretory proteins with molecular weights greater than 10,000 were placed in the basal reservoir of the bicameral chambers underneath the confluent epithelial sheets of PA-III in a manner that mimics the relationship between stroma and epithelia in vivo. After 24 h incubation the stromal cell proteins increased the [35S]methionine-labeled protein secretion from the epithelial sheet of cells. Trypsinization of the stromal cell secretory proteins eliminated the stimulatory effect on epithelial protein secretion. In addition, conditioned media from Swiss 3T3 fibroblasts, A431 cells, or bovine serum albumin did not stimulate epithelial protein secretion. Two-dimensional gel electrophoresis of the [35S]methionine-labeled epithelial protein secretion showed that the stromal cell proteins induced the secretion of a novel peptide (SE-1) from the basal domain of the epithelial sheet of cells within the first hour of metabolic labeling. These results indicate that stromal cell secretory proteins contain a stimulatory protein that can induce overall protein secretion as well as the vectorial secretion of a novel peptide from the basal domain of PA-III epithelial cells. These results are consistent with a paracrine interaction between epithelial and stromal cells in the regulation of prostatic secretion.

Adenocarcinoma↗
PubMed1989

Prognostic significance of DNA ploidy in carcinoma of prostate.

Flow cytometry was used to measure the DNA content in archived paraffin-embedded human prostatic cancer tissue for 69 patients with known outcomes that presented between 1975 and 1982. Of these, 51 patients had clinically localized lesions and were surgically staged prior to radical prostatectomy, while 18 patients presented with advanced Stage D2 disease. Thirty-six of 37 (97.3%) pathologic Stage B lesions were diploid. In contrast, the majority (72.2%) of patients with metastatic disease had aneuploid tumors. The average Gleason grade for aneuploid tumors was 8.2 +/- 1.98 versus 5.5 +/- 1.89 for diploid tumors (p less than 0.01). For 51 patients with clinically localized tumors, 13.9 percent of diploid tumors with a low Gleason sum (2 to 6) had extracapsular spread of tumor or regional lymph node involvement compared with 83.3 percent of aneuploid tumors with high Gleason scores (7 to 10). The addition of DNA ploidy to degree of glandular differentiation may enhance the prognostic evaluation of prostatic tumors and eventually improve our ability to select patients who are likely to benefit from radical prostatectomy.

Aged↗
PubMed1989

Priapism: current concepts.

The treatment options for the management of the patient with priapism have changed markedly within the past several years. When possible, the underlying cause of the priapism should be identified. Therapy should be guided by the results of aspiration of the blood-filled corpora cavernosa of the erect penis. Early intervention through pharmacologic manipulation or surgical shunting should not be delayed while trying conservative measures.

Adrenergic alpha-Agonists↗
PubMed1989

Emotional autonomy versus detachment: revisiting the vicissitudes of adolescence and young adulthood.

3 studies reexamine Steinberg and Silverberg's construct of "emotional autonomy" (EA) in adolescent and young adult samples. We argue that rather than measuring either autonomy or independence, EA represents emotional detachment from parents. In Study 1, EA is shown to be negatively associated with early adolescents' (n = 148) reported quality of attachment to parents, but not to friends. In Study 2, EA is shown to be positively related to experienced parental rejection but largely unrelated to perceived independence-support in a high school sample (n = 193). In Study 3, EA in young adults (n = 104) is inversely related to measures of family cohesion, parental acceptance, independence support, and self-perceived lovability. Finally, a projective measure of parental nurturance taken by a subsample of subjects (n = 58) was associated negatively with EA but positively with perceived lovability. Discussion concerns the conceptualization of attachment versus detachment, dependence, and autonomy in theories of adolescence.

Adolescent↗
PubMed1988

Characterization of secretion pattern of human prostatic acid phosphatase: a reassessment.

The daily variation of serum levels of prostatic acid phosphatase (PAP) determined by the Roy enzymatic method was investigated in 10 patients with metastatic prostatic cancer and in 10 patients without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis of the mean PAP levels at the four sampling times in both groups of patients demonstrated no evidence of circadian or diurnal rhythmic variation. Prostate cancer patients did show significantly greater variability in daily PAP than patients without prostatic disease, although a distinct pattern of secretion was not observed in either group. These results underscore the potential inaccuracy of the use of single determination of serum PAP as a parameter of response in patients with metastatic prostatic cancer and in the staging of patients with clinically localized prostatic malignancy. Evaluation of trends of PAP levels over time, however, continues to play a major role in the assessment and management of patients with prostatic carcinoma.

Acid Phosphatase↗