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Biomedical subjects

R D Williams

Publications and source records attributed to R D Williams.

At least 145 records · Page 8Linked to original sources
PubMed1985

Activation of the parathyroid hormone receptor-adenylate cyclase system in osteosarcoma cells by a human renal carcinoma factor.

Human renal carcinoma cell line 786-0 elaborates a protein that is structurally and immunochemically distinct from parathyroid hormone (PTH) and that activates renal cortical adenylate cyclase via an interaction with the PTH receptor. Because of the high frequency of excessive bone resorption and resultant hypercalcemia in patients with malignant disease we evaluated the ability of this 786-0 cell factor to reproduce PTH action in bone-derived cells. The 786-0 factor as well as bovine PTH (BPTH) (1-34) and prostaglandin E1 produced marked increases in cyclic adenosine 3':5'-monophosphate (cAMP) accumulation in the clonal rat osteosarcoma cell line UMR-106. A competitive antagonist of PTH action, [norleucine8, norleucine18, tyrosine34] BPTH(3-34)amide, blocked the cAMP stimulation produced by 786-0 factor and BPTH(1-34) but not that produced by prostaglandin E1. In the presence of forskolin (0.1 microM) UMR-106 cells were extremely sensitive to 786-0 factor, showing significant increases in cAMP production at a concentration 10-fold less than that required to activate adenylate cyclase in renal membranes. In contrast UMR-106 cells were less sensitive to BPTH(1-34) than were renal membranes. This preferential increase in sensitivity to 786-0 factor was not seen in membranes prepared from UMR-106 cells suggesting the importance of cytosolic components. Six additional human genitourinary carcinoma cell lines were found to produce factors that increased cAMP levels in UMR-106 cells. We conclude that 786-0 factor is a potent activator of the PTH receptor-adenylate cyclase system in these bone-derived cells. These findings are consistent with the view that cancer-associated hypercalcemia may frequently be attributable to tumor secretion of proteins (such as 786-0 factor) that are distinct from PTH but are capable of activating skeletal PTH receptors.

Adenylyl Cyclases↗
PubMed1985

Magnetic resonance imaging in the evaluation of urologic malignancies.

Although MRI has been available for clinical use for only a short time it has already proven its value in the diagnosis and staging of renal malignancies and has shown promise in evaluation of malignancies of the lower urinary tract. Its excellent tissue contrast discrimination, ease of evaluation of vascular structures and perivascular lymph nodes and its capability for multiplanar imaging contribute to this promise. Its dependence on multiple tissue and imaging parameters allows manipulation of images to permit evaluation of a variety of structures for anatomic and physiologic abnormalities. Its lack of ionizing radiation and the absence of requirement for intravenous contrast agents are attractive features in evaluation of genitourinary structures. Clinical experience with MRI in diagnosis and staging of urologic malignancies is growing in a number of academic centers, and MRI units are being installed in many private hospitals. It is anticipated that the importance of MRI in the evaluation of the genitourinary tract will increase rapidly as this technology becomes widely available.

Adenocarcinoma↗
PubMed1985

Activities of serine palmitoyltransferase (3-ketosphinganine synthase) in microsomes from different rat tissues.

Serine palmitoyltransferase [EC 2.3.1.50] catalyzes the first unique reaction of sphingolipid biosynthesis. To determine whether or not different rat tissues are capable of initiating this pathway, its activity was determined for microsomes from rat liver, lung, brain, kidney, intestine, spleen, muscle, heart, pancreas, testes, ovary, and stomach. Serine palmitoyltransferase was found in every tissue, and, when compared to the microsomal glycerol 3-phosphate acyltransferase, the activities correlated directly with their sphingomyelin levels as a percentage of total phospholipids. This suggests that the activities were comparable to expected cellular needs for long-chain bases, if the initial enzymes of glycerolipid and sphingolipid biosynthesis influence the phospholipid composition of cells by determining the relative partitioning of fatty acyl-CoA's toward these two lipid classes. Serine palmitoyltransferase activities were also determined using different fatty acyl-CoA's and were consistently greatest with CoA thioesters of saturated fatty acids with 16 +/- 1 carbon atoms. This suggests that the predominance of 18-carbon long-chain bases in vivo is due to the higher activity of this enzyme with palmitoyl-CoA. Together, these findings indicate a role for serine palmitoyltransferase in regulating both the type and amount of long-chain bases found in tissues.

Acyl Coenzyme A↗
PubMed1985

Sexual potency before and after radical prostatectomy.

A TRIAD OF FACTORS CAN FAVORABLY INFLUENCE THE MAINTENANCE OF SEXUAL POTENCY AFTER RADICAL PROSTATECTOMY: the surgical avoidance of cavernous neurovascular bundles, the preoperative interest of the surgeon in broaching the subject with the patient and the continued encouragement given the patient by his attending physician as to probable preservation of sexual competency following the surgical procedure.

Erectile Dysfunction↗
PubMed1984

Enzymology of long-chain base synthesis by liver: characterization of serine palmitoyltransferase in rat liver microsomes.

Serine palmitoyltransferase [palmitoyl-CoA:L-serine C-palmitoyltransferase (decarboxylating) EC 2.3.1.50] catalyzes the initial and committed step in the biosynthesis of the long-chain bases of sphingolipids. A simple assay, based upon the incorporation of [3H]serine into the chloroform-soluble product 3-ketosphinganine, has been developed and demonstrated to be valid for analyzing this enzyme in rat liver microsomes. More than 75% of the serine palmitoyltransferase of rat liver was associated with the microsomal subfraction. The dependencies of activity on the incubation time, pH, temperature, other assay components (e.g., dithiothreitol, EDTA, and pyridoxal 5'-phosphate), and the concentrations of microsomal protein, L-serine, and palmitoyl-CoA were investigated. The requirement of pyridoxal 5'-phosphate for activity was established by formation of the apoenzyme by dialysis against cysteine, and recovery of full activity upon reconstitution with the coenzyme. Activities with fatty acyl-CoA's of varying alkyl chain length were distributed nearly symmetrically around a maximum at 16 carbons (palmitoyl-CoA) for the fully saturated substrates. Less activity was obtained with the CoA thioesters of cis-unsaturated fatty acids, but trans-9-hexadecenoyl-CoA yielded essentially the same activity as palmitoyl-CoA. Hence, this enzyme is capable of initiating the synthesis of the major long-chain bases, as well as compounds that may constitute the unidentified bases reported in analyses of mammalian sphingolipids.

Acyl Coenzyme A↗
PubMed1984

Primary transitional cell carcinoma of prostate.

Primary transitional cell carcinoma of the prostate (TCC-P) is a rare tumor for which definitive therapy remains undefined. To establish a basis for therapy, we analyzed 3 new cases and reviewed the literature. The following points were observed: (1) the true diagnosis is often missed at initial pathologic examination; (2) the tumor has a propensity for extensive local invasion; and (3) it commonly presents with obstructive symptoms in relatively young patients. Treatment recommendations based on our review include: maintenance of a high index of suspicion, especially for fifty to sixty-year-old men with prostate tumors or for suspected prostatic adenocarcinoma that is rapidly progressive and/or unresponsive to hormonal therapy; preoperative pelvic irradiation followed by radical cystoprostatourethrectomy is the treatment of choice in low-stage disease, and combined radiation therapy and chemotherapy should be used for disease beyond the prostate.

Adenocarcinoma↗
PubMed1984

Mitomycin C reused: an in vitro cost-effectiveness study.

The use of mitomycin C, an effective agent in the intravesical treatment of superficial bladder cancer, is limited by its high cost. An in vitro study was done to determine whether mitomycin C could be recovered after intravesical administration and reused in the same patient. Cultured human transitional carcinoma cells from line 253-J were exposed to: medium alone; fresh mitomycin C (1 mg./ml.); mitomycin C stored for 1, 2 and 4 weeks; and mitomycin C recovered from patients after intravesical use, tested immediately and stored and tested after serial dilution after 1, 2, and 3 weeks. Results were assessed by cell counts 2 and 5 days after 2-hour exposure to the test solutions. With fresh mitomycin C and that stored up to 4 weeks, cell growth was less than 1 per cent of control (medium alone) at 2 and 5 days. Mitomycin C was also effective when recovered after intravesical use for up to 2 weeks, at which time cell growth was 9.7 and 3.1 per cent of control at 2 and 5 days, respectively. However, at 3 weeks, cell counts were 11.5 and 18.3 per cent of control at 2 and 5 days, suggesting that mitomycin C loses potency with dilution. We conclude that mitomycin C might be recovered, stored and reused for at least 2 weeks in individual patients, a practice that could result in a substantial reduction of treatment cost.

Antibiotics, Antineoplastic↗
PubMed1984

The extent of surgery after chemotherapy for advanced germ cell tumors.

The histopathological findings of tissue removed from 40 patients with a residual mass after completion of induction chemotherapy with cis-platinum, vinblastine and bleomycin are reviewed. These patients with advanced testicular cancer were treated with chemotherapy until normalization of tumor markers and until there was no further decrease in the size of palpable or radiologically evident masses for 2 successive cycles of chemotherapy. The mean number of chemotherapy cycles preoperatively was 5.2. Residual carcinoma was found in only 1 patient (3 per cent), teratoma in 18 (45 per cent), and fibrotic and/or necrotic masses in 21 (52 per cent). With this tailored treatment regimen in which an operation is performed after maximal chemotherapeutic response, the number of patients with viable residual tumor at operation can be minimized. Complete retroperitoneal lymph node dissection concomitant with resection of the residual mass was performed in 22 of 32 patients with residual masses in the retroperitoneum. The 1 patient with carcinoma in the mass also had carcinoma in several of the lymph nodes, and 4 of the 11 with teratoma in the mass had teratoma in the lymph nodes. Since the histopathological findings of the mass often parallel those of the lymph nodes, and since masses containing only fibrosis and/or necrosis cannot be ascertained with accuracy at operation, a complete retroperitoneal lymph node dissection is recommended in patients with a residual retroperitoneal mass.

Adolescent↗
PubMed1984

Malignant urachal lesions.

Urachal cancers are uncommon malignancies with a location that often permits considerable local extension before they are discovered. The most common histological type is adenocarcinoma, which may produce mucus that is a valuable aid in diagnosis. The presence of stippled calcification in a midline abdominal wall mass is almost pathognomonic for urachal carcinoma. More commonly, however, the symptoms are less specific, such as hematuria and an abdominal mass. Many lesions are visible endoscopically and, thus, the diagnosis can be made preoperatively from a biopsy. Most treatment failures occur because the tumor is not controlled locally by the initial operation and, therefore, we recommend en bloc cystectomy with umbilectomy and pelvic lymphadenectomy unless the tumor is known to be a sarcoma or early stage (I) carcinoma. If these patients are undertreated and there is a local recurrence then the patient usually is not salvageable. Because of the difficulty in identifying the origin of a bladder adenocarcinoma, any tumor on the dome or anterior wall should be approached initially as if it were a urachal tumor.

Adult↗
PubMed1984

Magnetic resonance imaging and its application in urology.

Magnetic resonance imaging (MRI) adds an additional dimension to radiologic diagnostic technique. In addition to topographic anatomic display, this new nonionizing modality is capable of providing functional information as well as data about the chemical composition of a given organ and blood flow velocity. In a short period of time in clinical experience its application in urology already includes evaluation of adrenal pathology regarding adrenal hyperplasia and adrenal tumors, diagnosis and staging of renal cell carcinoma, evaluation of retroperitoneal lymphadenopathy, and retroperitoneal fibrosis. In the pelvis, MRI promises to improve our diagnosis and staging of malignancy in the urinary bladder and prostate gland. This is only the beginning of clinical evaluation and the true potential of magnetic resonance, and further clinical indications are constantly evolving.

Adrenal Gland Neoplasms↗
PubMed1984

High-resolution sonography of scrotal contents in asymptomatic subjects.

Forty male volunteers with no known intrascrotal pathology by history and physical examination were scanned with a 10-MHz dedicated superficial-parts scanner. Sonographic features of intrascrotal anatomy were reviewed. The testes appeared homogeneous in texture and occasionally contained cysts (8%). The echogenic head of the epididymis, although variable in size and shape, was consistently imaged. Epididymal cystic structures (29%) and calcifications (3%) were occasionally seen. The amount of peritesticular fluid, presence of variococeles , and range of scrotal skin thickness were also noted. An understanding of intrascrotal anatomy in asymptomatic subjects can provide a baseline for the evaluation of the symptomatic scrotum.

Adult↗
PubMed1984

Utilization of different fatty acyl-CoA thioesters by serine palmitoyltransferase from rat brain.

Serine palmitoyltransferase (EC 2.3.1.50) catalyzes the first unique reaction of sphingolipid biosynthesis. Activities were determined with different fatty acyl-CoA substrates to describe the range of long-chain bases that could be made by rat brain microsomes. The activities were greatest with palmitoyl-CoA and palmitelaidoyl-CoA, followed by fully saturated homologs differing from these by only one carbon atom, and diminished considerably as the alkyl-chain length increased or decreased, or with the presence of a cis-double bond. These characteristics explain the predominance of long-chain bases with 18 carbon atoms in brain sphingolipids, and account for the minor variants such as the C17- and C20-long chain bases.

Acyl Coenzyme A↗
PubMed1984

Comparison of serine palmitoyltransferase in Morris hepatoma 7777 and rat liver.

Serine palmitoyltransferase (EC 2.3.1.50) catalyzes an initial and regulatory reaction of sphingolipid biosynthesis, the formation of a homologue of 3-ketosphinganine from L-serine and a fatty acyl coenzyme A thioester. We have demonstrated that this enzyme exists in microsomes from Morris hepatoma 7777 and, moreover, found that its specific activity was 199 +/- 23 pmol/min/mg of microsomal protein, which was significantly higher than that for microsomes from host (69 +/- 4.2 pmol/min/mg; S.D.) or control (43 +/- 4.1 pmol/min/mg) rat livers when assayed under optimal conditions. The activities varied with tumor weight. For comparison, the activities of microsomes from regenerating liver were also higher; whereas fetal and neonatal rat livers had substantially lower activities. Assays conducted without added pyridoxal 5'-phosphate revealed that the enzyme in microsomes isolated from the tumor was more readily depleted of this cofactor than was that in control microsomes; this phenomenon was most pronounced with the larger tumors. The other properties of the enzyme resembled those for liver. On the basis of these experiments, we propose that the elevated proportions of sphingomyelin and other sphingolipids found in hepatomas and regenerating rat liver are related to increases in long-chain base synthesis by serine palmitoyltransferase. Since the activity is apparently more sensitive to the availability of pyridoxal 5'-phosphate in the hepatoma, this reaction could become limiting under more severe vitamin B6 deficiencies.

Acyltransferases↗
PubMed1983

Radioimmunoassay of serum prostatic acid phosphatase after prostatic massage.

The effect of prostatic massage on the concentration of prostatic acid phosphatase (PAP) in blood serum as determined by radioimmunoassay (RIA) was compared with that determined by a standard enzymatic assay (EA). Serum was drawn from 24 men before prostatic massage and after--at specified intervals, up to twenty-four hours. Three of these men were young, normal controls; 10 had biopsy-proved prostate cancer (CA); 11 had histologically confirmed benign prostatic hyperplasia (BPH). After prostatic massage, 3 of the 10 CA patients (30%) had elevation of PAP as determined by EA and 4 of the 11 BPH patients (36%) as determined by RIA. None of the controls showed elevated levels of PAP by either assay. In all patients elevated levels of PAP by both assays had returned to normal twenty-four hours after massage. It was concluded that serum for PAP testing by either assay method should be drawn before or twenty-four hours after rectal examination to prevent false positive results and the need for retesting.

Acid Phosphatase↗
PubMed1983

Zeranol: a review of the metabolism, toxicology, and analytical methods for detection of tissue residues.

Zeranol, an anabolic agent produced commercially for use in cattle and sheep intended for human consumption, is noncarcinogenic, nonteratogenic, and nonmutagenic. Toxicity testing (acute, subacute, and chronic) in several species by various routes of administration reveals an extremely low toxicity, the oral rat LD50 exceeding 40 g/kg. Postmortem abnormalities of high-dose animals are attributed to the effects of the compound on the endocrine system. Both zeranol itself and zearalanone, the major Phase I metabolite in the seven species studied, are excreted in the feces and in the urine, either free or as sulfates/glucuronides. A minor urinary metabolite has been identified as taleranol, an epimer of zeranol. Both metabolites exhibit a very low order of toxicity (oral rat LD50 exceeding 10 g/kg in both cases), and both exhibit less biological activity than the parent compound. The four types of analytical methods which have been employed for the specific detection and quantitation of residues of zeranol in edible tissues are: (1) gas chromatography (detection limit = 20 ppb), (2) high-performance liquid chromatography (detection limit = 5 ppb), (3) thin-layer chromatography (detection limit = 1-3 ppb), and (4) radioimmunoassay methods (detection limit to be published). The following residue levels were determined radiometrically in tissue samples taken 45 days after implantation of cattle with 36 mg tritiated zeranol: less than or equal to 2 ppb in liver, less than or equal to 1 ppb in kidney and fat, and less than or equal to 0.2 ppb in muscle and plasma. A no-effect level (NEL) of 0.225 mg/kg was determined as the highest oral dosage of zeranol which produced no estrogenic effects in female monkeys. Based on the NEL, a tolerance level for tissue residues of zeranol was calculated as 315 ppb.

Abnormalities, Drug-Induced↗