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Biomedical subjects

R Clements

Publications and source records attributed to R Clements.

At least 19 recordsLinked to original sources
PubMed2000

Protein kinase C-alpha mediates endothelial barrier dysfunction induced by TNF-alpha.

We tested the hypothesis that protein kinase C-alpha (PKC-alpha) mediates tumor necrosis factor-alpha (TNF-alpha)-induced alterations in permeability of pulmonary microvessel endothelial monolayers (PEM). The permeability of PEM was assessed by the clearance rate of Evans blue-labeled albumin. PEM lysates were analyzed for PKC-alpha mRNA (Northern cDNA blot), protein (Western immunoblot), and activity (translocation and phosphorylation of myristoylated arginine-rich C kinase substrate). Incubation of PEM with TNF-alpha (1,000 U/ml) for 4 h resulted in increases in 1) PKC-alpha protein, 2) cytoskeletal-associated PKC-alpha, 3) PKC-alpha activity, and 4) permeability to albumin. The TNF-alpha-induced increase in PKC-alpha protein, PKC-alpha activity, and permeability was prevented by a 4-h pretreatment with PKC-alpha antisense oligonucleotide but not by the scrambled nonsense oligonucleotide. The TNF-alpha-induced increase in permeability to albumin was prevented by myristoylated protein kinase C inhibitor (an inhibitor of PKC-alpha/beta, 100 microM) and calphostin (an inhibitor of the classic and novel PKC isotypes, 200 nM). The treatment with calphostin from 0.5 to 3.0 h after TNF-alpha still prevented barrier dysfunction induced by 4 h of TNF-alpha treatment. The data indicate that prolonged activation of PKC-alpha, maintained by a translation-dependent pool of PKC-alpha protein, mediates TNF-alpha-induced increases in endothelial permeability in PEM.

Animals↗
PubMed2000

Tumor necrosis factor-alpha-induced activating protein-1 activity is modulated by nitric oxide-mediated protein kinase G activation.

We tested the hypothesis that protein kinase (PK)G activation in response to nitric oxide ((*)NO) mediates tumor necrosis factor (TNF)-alpha-induced activation of the transcription factor activating protein-1 (AP-1) in pulmonary microvessel endothelial monolayers (PEM). The DNA-binding activity of AP-1 was assessed using the electrophoretic mobility shift assay. TNF treatment (1,000 U/ml) for 4 h induced a significant increase in DNA binding of AP-1. The effects of TNF were prevented by the superoxide radical scavenger superoxide dismutase (SOD) (100 U/ml), the (*)NO synthase inhibitor aminoguanidine (100 microM), the guanylate cyclase inhibitor ODQ (100 microM), and the PKG inhibitors KT5823 (1 microM) and 8-bromo-cyclic guanosine monophosphate (cGMP)-thioate (100 microM). Spermine-NO (1 microM) and L-arginine (400 microM) prevented the aminoguanidine-induced ablation of AP-1 activation in response to TNF. Phosphorylation of H-Arg-Lys-Ile-Ser-Ala-Ser-Glu-Phe-Asp-Arg-Pro-Leu-Arg-OH (BPDEtide), a specific substrate for PKG, measured the activity of cGMP-dependent protein kinase (PKG). TNF for 0.5 h induced an increase in PKG activity that was prevented by aminoguanidine, ODQ, KT5823, and 8-bromo-cGMP-thioate; however, SOD had no effect. The PKG agonist 8-bromo-cGMP (100 microM), when given alone, increased PKG activity but induced significant DNA-binding activity of AP-1 only when given in the ODQ + TNF Group. SIN-1 (1 mM, a peroxynitrite agonist) increased DNA-binding activity of AP-1. SOD prevented SIN-1-induced AP-1 activation, a response similar to that of the SOD + TNF Group. PEM were transfected with the chloramphenicol acetyltransferase (CAT) reporter plasmid pBLCAT2, which contains a regulation sequence responsive to AP-1. The pharmacologic profile of TNF-induced CAT activity was identical to TNF-induced DNA binding by AP-1. Thus, TNF-induced AP-1-dependent gene transcription is modulated by (*)NO-dependent mediated activation of PKG.

Animals↗
PubMed1999

Prostate specific antigen: an opinion on its value to the radiologist.

Screening for prostate cancer is controversial. There is currently enormous pressure from the public and media to test men for early prostate cancer, in a manner similar to the screening of women for breast cancer. Unfortunately, however, the two cancers do not behave in a similar biological manner; breast cancer screening has been shown to reduce mortality, but prostate cancer screening has not yet been proven to reduce mortality. Prostate-specific antigen (PSA) is currently the best single test for prostate cancer diagnosis, but it cannot identify whether the detected cancer will cause clinically significant disease. PSA can be used as an aid to the diagnosis, staging, prognosis and follow-up of patients with prostate cancer, and its use has transformed the diagnosis of cancer and has markedly improved the detection of organ-confined prostate cancer in Europe and North America. PSA is, however, an imperfect diagnostic marker, and a variety of approaches have been investigated in recent years to improve its specificity in the diagnosis of prostate cancer. These new approaches have been developed by urologists, radiologists and biochemists, and can be confusing for the clinician without special knowledge in this field. This article aims to review current knowledge of PSA from the viewpoint of the radiologist.

Antigens, Neoplasm↗
PubMed1999

Prevalence of alcohol-use disorders and alcohol-related problems in a college student sample.

Most studies of alcohol consumption patterns and alcohol-related problems among college students have failed to include a diagnostic measure based on Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. Applying the DSM-IV standards would facilitate an analysis of the prevalence of alcohol-use disorders and individual symptoms of those disorders. A structured diagnostic interview based on DSM-IV criteria (the alcohol section of the Substance Abuse Module) and several alcohol screening instruments were administered to 306 undergraduate students at an urban commuter campus. The prevalence of current and lifetime alcohol-use disorders, individual symptoms of those disorders, and other alcohol-related problems are reported, as well as data regarding alcohol consumption patterns and binge drinking. The data are analyzed in terms of demographic variables, including sex, ethnicity, year in school, age, and marital status of those in the sample.

Adolescent↗
PubMed1998

A critical evaluation of several alcohol screening instruments using the CIDI-SAM as a criterion measure.

Four alcohol screening instruments (the AUDIT, CAGE, MAST, and Svanum's scale) were administered to a sample of 306 undergraduate students at a Midwestern university and were compared with regard to several test characteristics, using the alcohol section of the CIDI-SAM (DSM-IV version) as the criterion measure. The performance of these instruments was evaluated using two subsets of subjects: (1) students who currently met diagnostic criteria for alcohol dependence (n = 35); and (2) students who met diagnostic criteria for alcohol dependence in the past and/or at present (i.e., lifetime diagnosis; n = 50). The AUDIT performed significantly better than the other three instruments in identifying students who were currently alcohol dependent, providing a moderate degree of clinical utility with this group. The four instruments did not differ significantly in their ability to identify students with a lifetime diagnosis; each measure provided only a modest degree of clinical utility with this group.

Adolescent↗
PubMed1997

Has ultrasonography a role in screening for prostatic cancer?

Prostate specific antigen (PSA) is widely used as the first line test for the diagnosis of prostate cancer in asymptomatic men. The role of transrectal ultrasound is now predominantly accepted as a means of accurate biopsy of the prostate, but there is confusion about the best biopsy protocols for the diagnosis of prostate cancer. Optimum diagnosis of prostate cancer is obtained using a combination of digital palpation of the prostate, serum PSA measurements and transrectal sonography. The role of colour Doppler imaging in the diagnosis of prostate cancer is still under assessment.

Biopsy, Needle↗
PubMed1996

How complete is a transurethral resection of the prostate?

OBJECTIVE: To determine the completeness of transurethral resection of the prostate (TURP). PATIENTS AND METHODS: The prostate volume of 432 patients was measured by transrectal ultrasonography (TRUS) before they underwent a TURP performed by one of three consultant urological surgeons. The prostate tissue collected at resection was weighed, multiplied by 1.2 to compensate for 'shrinkage', and the amount of tissue removed expressed as a percentage of the pre-operative prostate volume determined by TRUS (resection ratio). The patients were categorized into groups based on pre-operative prostate size. RESULTS: The mean weight of prostate tissue resected was 25.6 g. Resection ratios increased with prostate size, with the largest occurring in prostates of 71-110 g. The surgeon did not resect more than 50% of the gland volume in any group. CONCLUSION: This study counters the theory that a complete resection of the prostate is routinely achieved. The endoscopic appearances probably imply a complete resection of the adenoma but a considerable volume of the gland remains. This has important implications for the detection of prostate carcinoma at TURP and for the staging of the disease.

Endoscopy↗
PubMed1993

Transrectal ultrasound appearances of granulomatous prostatitis.

Granulomatous prostatitis is an unusual, but well-recognized entity frequently mistaken for carcinoma on both digital rectal examination and transrectal ultrasound. The ultrasonographic findings of 11 patients with histologically-proven granulomatous prostatitis are reviewed.

Adult↗
PubMed1993

Side effects and patient acceptability of transrectal biopsy of the prostate.

The side effects and patient acceptability of 230 ultrasound guided prostatic needle biopsies performed by the transrectal route in an out-patient setting were reviewed retrospectively. Most of the side effects were transient and mild; one patient required hospitalization for urinary retention. Patient acceptability was good; over 70% of patients reported no significant pain from the biopsy procedure.

Biopsy, Needle↗
PubMed1992

Volume of normal prostate, of prostate cancer, and of benign prostatic hyperplasia: are correlations with prostate specific antigen clinically useful?

This retrospective study correlated prostate volume, determined by transrectal ultrasonography, with serum prostate specific antigen (PSA), by Deming regression analysis, in patients with confirmed benign prostatic hyperplasia (BPH) and patients with non-metastatic (M0) or metastatic (M1) prostate cancer. In BPH, a highly significant correlation was found between log10[PSA] and prostate volume. When this PSA/volume regression pattern for BPH was used as a reference standard, all 17 patients with M1 prostate cancer and 83% of the 23 patients with M0 disease were discriminated from BPH.

Aged↗
PubMed1992

Complete resolution of a large seminal vesicle cyst--evidence for an obstructive aetiology.

Seminal vesicle cysts may arise from inflammation or obstruction of the seminal vesicle or from embryological remnants such as the müllerian duct. Surgical removal has been proposed as the treatment of choice. A 19-year-old boy presented with abdominal pain and constipation. Investigations revealed a 14-cm multiloculated cyst arising from the right seminal vesicle and a small stone lodged at the orifice of the ipsilateral ejaculatory duct. Following endoscopic removal of the stone the mass decreased in size considerably and 2 months later transrectal ultrasound and magnetic resonance imaging showed normal seminal vesicles and no evidence of the cyst. This case strongly supports an obstructive aetiology for this cyst and we would suggest that, in similar cases, full assessment of the ejaculatory apparatus should be carried out to exclude an obstructive cause before embarking on major surgery.

Adult↗
PubMed1992

Inter-relation between measurement of serum prostatic specific antigen and transrectal ultrasound in the diagnosis of benign prostatic hyperplasia and prostatic cancer.

Serum prostatic specific antigen (PSA) and ultrasound-determined prostatic volume (UPV) were measured in 50 patients with histologically proven benign prostatic hyperplasia (BPH) and in 40 patients with histologically proven prostatic cancer of whom 17 had evidence of distant metastases (M1) and 23 did not (M0). A good correlation between log PSA and UPV was demonstrated in the BPH group and rearrangement of the linear regression equation allowed calculation of a single variable--the log PSA corrected to a standard prostate volume for any given individual. A volume-corrected PSA correctly identified all patients with M1 disease and greatly improved but did not eliminate overlap of M0 disease with BPH. Reduction of serum PSA to a single volume-corrected variable will allow the introduction of practical and optimum protocols for the management of patients with prostatic enlargement.

Aged↗
PubMed1992

Can serum prostate-specific antigen replace bone scintigraphy in the follow-up of metastatic prostatic cancer?

Bone scintigraphy is the most sensitive imaging technique for the initial detection of bone metastases and is widely used in the staging of prostatic cancer. This study was performed to assess whether the development of further bone metastases can be detected by serial measurements of the serum glycoprotein prostate-specific antigen (PSA) as an alternative to follow-up scintigraphy. The bone scintigrams and PSA levels of 101 patients with metastatic prostate cancer entered into two therapeutic trials have been reviewed. Serial results of both investigations were available in 59 cases. In three cases new bone deposits were observed without a corresponding rise in PSA. In two other cases the scintigrams were considered to be suspicious of progression with no change in PSA levels; however, further follow-up indicated that these changes were not due to metastases. In 13 cases PSA levels were rising in advance of new deposits on the scintigrams. In the remaining 41 cases the PSA levels and scintigraphic findings paralleled each other. We conclude that serial estimation of PSA levels is a simpler marker for disease progression than bone scintigraphy in metastatic prostatic cancer, but that neither technique in isolation gives complete accuracy.

Aged↗
PubMed1991

Transrectal ultrasound of the ejaculatory apparatus.

Most interest in transrectal ultrasound (US) of the prostate has concentrated on its role in the diagnosis and management of prostatic cancer. The increasingly detailed investigation of male patients with infertility has recently led to interest in the use of US in investigating the structure and function of the ejaculatory ducts and seminal vesicles. The anatomy and pathology of the ejaculatory ducts and seminal vesicles as demonstrated by transrectal US are discussed and illustrated.

Ejaculatory Ducts↗