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Biomedical subjects

J H Lynch

Publications and source records attributed to J H Lynch.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Daily variability in human serum prostate-specific antigen and prostatic acid phosphatase: a comparative evaluation.

The daily variation of serum levels of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) was investigated simultaneously in 10 patients with osseous metastatic prostatic cancer, 10 patients with benign prostatic hyperplasia, and 10 volunteers 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 (two-factor analysis of variance comparing time period to disease group) of the mean PSA and PAP levels at the four sampling times on all patient groups demonstrated no evidence of circadian rhythmic variation or any other distinct pattern for the observed sample times. Overall, the variability in PSA levels was significantly less than that observed for PAP. There was no significant difference in mean percent variation between patient groups (cancer, benign, and normal prostate glands) for both the PSA and PAP assays. Our data reveal that serum PSA measurements fluctuate unpredictably over the course of a day in patients with and without prostatic disease, but to a lesser extent than that seen for serum PAP values. These findings illustrate the potential inaccuracy of single determinations of serum PAP or PSA levels for monitoring disease recurrence and treatment response in patients with prostate cancer.

Acid Phosphatase↗

Hydroxyproline as a marker for following patients with metastatic prostate cancer.

Serial measurements of urinary hydroxyproline excretion were performed in 16 patients with stage D2 prostatic cancer to evaluate its role as a marker for following disease course. Patients were defined as having stable or progressive disease by the criteria of the National Prostatic Cancer Project. For patients with stable disease and those with disease progression excretion of hydroxyproline did not correlate with the clinical course. We did not find that hydroxyproline was a useful marker in the clinical setting to follow patients with prostatic cancer.

Bone Neoplasms↗

Renal cell carcinoma: dynamic thin-section CT assessment of vascular invasion and tumor vascularity.

Dynamic thin-section computed tomography (CT) was used to evaluate renal cell carcinoma in 80 patients. The lesion was correctly staged with CT in 90% of patients. With use of the dynamic technique, the ipsilateral renal vein was depicted in 99% of patients. Extension of the tumor to the renal vein or the inferior vena cava was correctly detected in 18 of 19 patients. Actual depiction of tumor thrombus was a far more accurate indicator of renal vein invasion than was the identification of isolated renal vein enlargement. Dynamic thin-section CT of the kidney should be considered the routine method for comparison studies with other newer cross-sectional techniques in the evaluation of renal cell carcinoma.

Carcinoma, Renal Cell↗

The acute scrotum.

Testicular torsion is characterized by the sudden onset of testicular pain associated with abdominal pain, nausea and vomiting. Fever is unusual and urinalysis is often normal. Fever, pyuria, dysuria and urethral discharge are characteristic of epididymitis. Radionuclide scanning and Doppler ultrasound are helpful in establishing the diagnosis. If the diagnosis is uncertain, the patient should be considered to have testicular torsion until it is proved otherwise. Undiagnosed torsion leads to testicular necrosis.

Acute Disease↗