Biomedical subjects
Publications and source records attributed to R K Lawson.
Juxtaglomerular cell tumor of the kidney is an uncommon neoplastic cause of surgically curable hypertension. We report a case of erythrocytosis due to elevated serum erythropoietin with a renin secreting juxtaglomerular cell tumor.
Homogenates of human testes, epididymides and prostate, and calf testes and epididymides are mitogenic for cultured human foreskin fibroblasts. The growth factors appear similar in that they are inactivated by boiling and acid, but not by treatment with reducing agent. The growth factor in human and bovine testes was partially purified from tissue homogenates, prepared in high ionic strength buffer (pH 7.6) containing protease inhibitors, by ammonium sulfate precipitation and two cycles of heparin-Sepharose chromatography. The growth factor in calf testes was also partially purified from tissue extracted in ammonium sulfate without protease inhibitors, acidified to pH 4.5, and precipitated by ammonium sulfate followed by two cycles of heparin-affinity chromatography. A predominant 17,500 molecular weight (MW) growth factor was identified from alkaline homogenates of human and calf testes by its reactivity with antisera prepared against synthetic peptides whose sequences corresponded to residues 1-12 (amino-terminal), 33-43 (internal) and 136-145 (carboxy-terminal) of bovine basic fibroblast growth factor (bFGF). A slightly smaller 16,600 MW peptide from acidic extracts of calf testes also reacted with antisera to the three synthetic peptides. A 15,500 MW peptide, lacking immunoreactivity with antiserum to the amino-terminal synthetic peptide, was also seen. These findings suggest that a growth factor is present in human and calf testes that is structurally related to bFGF. The structure of the growth factors appears to be altered during the isolation procedure.
Tissue homogenates of rat ventral prostate were examined for growth factor activity using a fibroblast mitogenesis assay. G-75 Sephadex gel filtration separated the growth factor activity into two peaks. A broad first peak contained 98% of the protein and several growth factor moieties. A smaller second peak (MW 6,000) contained epidermal growth factor (EGF) as determined by binding in both a competitive receptor binding assay and a radioimmunoassay using anti-mouse epidermal growth factor (anti-mEGF). The broad first peak also contained substantial amounts of EGF-like activity as higher MW forms of EGF. The broad first peak was further fractionated by heparin-Sepharose affinity chromatography. A major fraction with growth factor activity eluted at 1.5 M NaCl and this fraction was shown to contain bFGF by immunostaining with antisera prepared against synthetic peptides corresponding to amino acid sequences 1-12 (amino terminal), 33-43 (internal), and 136-145 (carboxy terminal) of basic fibroblast growth factor (bFGF). EGF-like and bFGF-like molecules account for the major growth factor activity in the rat ventral prostate.
A 3F electrohydraulic electrode was used with flexible ureteroscopy to treat upper urinary tract calculi in 18 patients. Of 21 procedures performed 10 involved retrograde passage of the ureteroscope and 11 consisted of antegrade procedures with percutaneous nephrostomy access. Complete fragmentation was achieved in 19 of the 21 procedures. In 1 patient bilateral renal caliceal diverticular calculi were treated with the electrohydraulic electrode used to open initially the diverticular orifice. Minor complications included retained stone fragments and small ureteral perforations. No serious complications resulted from the lithotripsy and no patient required an open operation. Flexible ureteroscopy, retrograde or antegrade, appears to offer access to upper tract stones not treated reliably with rigid ureteroscopy. Electrohydraulic lithotripsy with this small 3F probe appears to be a safe and effective means to treat upper urinary tract stones.
Prostatic growth factor (PrGF) was purified from alkaline homogenates of human benign prostatic hyperplastic tissue by a combination of ammonium sulfate precipitation, heparin affinity chromatography, and cation-exchange chromatography. The 17,600-dalton, basic (pI 10.2) PrGF is related to basic fibroblast growth factor (bFGF) since antisera raised against synthetic peptides with sequence homologies corresponding to an internal peptide and amino- and carboxyl-terminal peptides of bFGF react with the growth factor. The growth factor appears larger than bFGF, suggesting that additional amino-terminal sequences may be present as a result of alkaline extraction in the presence of protease inhibitors.
Homogenization of human benign prostatic hyperplastic tissue in high ionic strength alkaline buffer containing protease inhibitors resulted in the isolation of a 17,400 molecular weight growth factor. When tissue was homogenized in ammonium sulfate at pH 4.5 without protease inhibitors a smaller, 16,600 dalton, growth factor was isolated. Both growth factors reacted with antisera against synthetic peptides whose sequences corresponded to the amino-terminal (1-12), Internal (33-43) and carboxyl-terminal (135-145) portions of basic fibroblast growth factor (bFGF). This suggested that the smaller growth factor was not a truncated form of (1-146) bFGF and that the larger growth factor may contain additional sequences. Amino-terminal sequencing showed the larger growth factor to have the sequence: Ala-Ala-Gly-Ser-Ile-Thr-Thr-Leu-Pro-Ala-Leu-Pro-Glu-Asp-Gly-Gly-Ser-Gly- Ala-Phe-Pro-. These results show that the larger growth factor is an 8 amino acid extended from of (1-146) bFGF and it is likely that the smaller growth factor is a proteolytic cleavage product of the larger growth factor produced during the extraction procedure.
A consecutive series of 52 living related renal donors were evaluated preoperatively by angiography. The preoperative angiographic interpretation was compared with the anatomy found at donor nephrectomy. Standard selective renal arteriography was found to be 100 per cent accurate in defining single (25) or multiple (1) renal arteries. Digital subtraction angiography (DSA) alone performed with an intra-arterial injection of contrast material was found to be 82 per cent accurate in determining the number of renal arteries. In five kidneys with multiple renal arteries, only two had the correct number of vessels identified. The errors are inherent in the DSA technology. DSA at the present time is not accurate enough to replace the standard arteriogram in the evaluation of the donor nephrectomy patient.
The prostate gland from a 32-year-old gorilla was examined. The prostate weighed 15 g and was composed primarily of dilated cystic acinar areas with only modest stromal thickening. The acini were lined by a low cuboidal epithelium. A second minor population of smaller glands with extensive papillary projections was also present. The epithelial cells stained densely for acid phosphatase and prostatic-specific antigen. Human prostatic acid phosphatase content of the gland as determined by radioimmunoassay was 2.3 mg/g protein. This is the first published histologic description of a gorilla prostate. The animal was in late middle age but did not display predominant prostatic stromal hyperplasia. Prostatic acid phosphatase from the gorilla cross-reacts immunologically, or is identical to human prostatic acid phosphatase.
Colovesical fistulas were identified in 42 patients. Diverticulitis was the underlying cause in 40 per cent of the patients. Carcinoma of the colon or cervix caused 33 per cent of the fistulas. Cystoscopy was the most effective procedure in diagnosing the fistulas. Surgical therapy had to be individualized to the patient's condition. Fistulas secondary to radiation were associated with a high complication rate.
We have assembled a computer hardware system and have written software programs that convert analogue urodynamic input to digital data. This has allowed for 1) extremely accurate recording of urodynamic events with a higher frequency response than existing units, 2) data storage of urodynamic events in digital form on floppy disks, 3) retrieval and plotting of urodynamic studies during and at times remote from the study performance, and 4) manipulation of the parameters in the urodynamic study for patient care and research purposes. Software is now available for the performance of cystometrograms (volume, total pressure, intravesical pressure and dP/dt), electromyograms, flow studies and dynamic renal pelvic pressure testing. Programs are in the development phase for computer analysis of urodynamic studies.
A 5-step fractionation procedure was used to isolate a prostatic growth factor from a tissue homogenate of human benign prostatic hyperplasia. The procedure made use of the property of prostatic growth factor to occur predominately as a large molecule (greater than 67,000) in low ionic strength solution (Tris with 0.05 M NaCl) but as a smaller molecule (less than 33,000) in high salt buffer (Tris with 1.55 M NaCl). The fractionation scheme consisted of ammonium sulfate precipitation, gel filtration (low ionic strength) and DEAE chromatography. The growth factor activity was eluted from DEAE with high ionic strength buffer followed by 2 gel filtration steps in high ionic strength buffer. The fractionation scheme produced greater than a 200-fold increase in prostatic growth factor activity and 10 per cent recovery. Additional separation steps will be required to purify prostatic growth factor to homogeneity.
A total of 6 patients with bulky pelvic bladder cancer underwent combination cis-diamminedichloroplatinum II (cisplatin) hypogastric artery infusion and local bladder hyperthermia as a preoperative adjunct to radical cystectomy. Pathological examination showed extensive tumor necrosis on the luminal side, with a gradient of tumor destruction to viable tumor on the serosal surface in 4 of the 6 bladders, while 2 specimens showed no tumor. Uninvolved portions of the bladders showed minor changes in the urothelium, submucosal edema and no effect on detrusor muscle or perivesical fat. Analysis of tissue for platinum revealed uptake by the tumors and normal tissues. Systemic effects of spillover cisplatin were not seen. Adjunctive preoperative hypogastric artery infusion of cisplatin is safe and well tolerated. Further study is required to determine the upper limits of safety of the regimen.
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Although priapism secondary to hematologic malignancies has been well described, review of the literature reveals 75 case reports of priapism due to local corporeal involvement by solid tumors. Our recent experience with 6 cases of local invasion of the corporeal bodies is reviewed. Three transitional cell carcinomas, one prostatic adenocarcinoma, one rectal carcinoma, and one sarcoma comprise the series. Three patients presented with priapism as their chief complaint, and 3 patients presented with priapism as their first sign of recurrence. Therapy included corporeal curettage, surgery, radiotherapy, or chemotherapy. None of the modalities was entirely effective, although chemotherapy seemed to offer the best palliation.
A technique is described for gaining percutaneous access to the kidney by puncturing from inside out using a retrograde catheter and a sharpened stainless steel stylet. The method allows precise placement of a percutaneous tract in the nondilated upper urinary tract.
Extracts of benign prostatic hyperplasia (BPH) contain a factor which is mitogenic for human foreskin fibroblasts in culture. Because of the similarity of BPH extract and epidermal growth factor (EGF) in stimulating quiescent fibroblasts to divide, it was of interest to determine if the prostate-associated growth factor competes for EGF receptor binding. BPH extract was found to compete poorly for 125I-EGF-receptor binding, did not influence the dissociation of cell-bound 125I-EGF and caused only a slight down-regulation of the EGF receptor. These findings indicate that EGF and BPH extract do not recognize the same receptor and that the major growth stimulating activity of BPH extract is not due to EGF.
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