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Biomedical subjects

R H Williams

Publications and source records attributed to R H Williams.

At least 37 records · Page 2Linked to original sources

Reduced levels of transforming growth factor beta receptor type II in human prostate cancer: an immunohistochemical study.

In previous studies we demonstrated that the growth of human prostatic adenocarcinoma is associated with aberrant accumulation of transforming growth factor (TGF) beta1, a growth factor that has been shown to be a potent inhibitor of epithelial cell proliferation. We investigated the expression of TGF-beta receptor II (TGFbetaR-II) in benign prostate tissue and in prostate cancer using standard immunohistochemical techniques. Quantitation of immunopositivity for TGFbetaR-II was assessed on a visual analogue scale ranging from 0 (absence of staining) to 4+ (intensely positive staining). All of the benign glandular epithelia stained intensely, either 3+ or 4+, representative of the ubiquitous nature of TGFbetaR-II in normal tissue. Overall, staining was reduced in prostate cancer sections, and there was progressively diminished staining as the histological grade of the cancer increased (P < 0.01, Kruskal-Wallis test). This immunohistochemical study indicates that a decline in the levels of TGFbetaR-II is correlated with advancing histological aggressiveness of the cancer and suggests that aberrant TGFbetaR-II function may play a role in human prostate carcinogenesis.

Aged↗

The reversibility of anabolic steroid-induced azoospermia.

Anabolic steroid associated male infertility is a little known but potentially treatable form of drug related infertility. We report on a bodybuilder with a 5-year history of steroid use who was azoospermic. He underwent successful gonadotropin replacement and conception was achieved 3 months after therapy was initiated. Important diagnostic and therapeutic considerations in steroid-induced infertility are discussed.

Adult↗

Evaluation of a community staff preparation strategy for the teaching, assessing and mentorship of Project 2000 diploma students.

This article presents findings of a study which investigated effectiveness of an educational strategy for community nurses in relationship to their teaching, assessing and mentorship roles with Project 2000 diploma student nurses. The research was conducted in the North Staffordshire Health District when the College of Nursing and Midwifery's first cohort of Project 2000 diploma students were in their third year of studies. Data were collected using a postal questionnaire and face-to-face interviews. The findings reveal that just over half the sample felt they had adequate preparation for their role of teachers and assessors of Project 2000 diploma students. Analysis of the data showed that there had been a need initially for more information to be disseminated regarding the college curriculum and assessment criteria. Chi square analysis revealed a significant result in relationship to those in the sample who felt they were adequately prepared for their teaching and assessment role and those who had undertaken a formal teaching and assessing course. The findings have implications for the desirability of community nurses to undertake formal teaching and assessing courses. Conclusions can also be drawn regarding future ventures in curriculum innovation and the need for adequate clinical staff preparation for changed needs of a curriculum.

Community Health Nursing↗

Use of zinc protoporphyrin measured by the Protofluor-Z hematofluorometer in screening children for elevated blood lead levels.

OBJECTIVE: To determine the usefulness of zinc protoporphyrin, as measured by the Helena Protofluor-Z hematofluorometer, for detecting elevated lead levels. DESIGN: Observational, descriptive review of laboratory records from a university toxicology laboratory. SETTING: Inner-city university pediatric clinic and two affiliated community clinics in Chicago, Ill. PATIENTS: Seven hundred seventy-five children younger than 7 years with paired lead-zinc protoporphyrin results. MEASUREMENTS/RESULTS: Fifty-six percent had lead levels of at least 0.48 mumol/L and 8% had lead levels of at least 1.21 mumol/L. The sensitivity, positive predictive value, and negative predictive value of a zinc protoporphyrin level of 70 mumol/mol of hemoglobin for detecting a lead level of 0.48 mumol/L were 42%, 66%, and 50%, respectively, and for a lead level of 1.21 mumol/L were 74%, 18%, and 97%, respectively. Receiver operating characteristic curves demonstrated that for detecting lead levels of 0.48 mumol/L with zinc protoporphyrin, the probability of a true-positive result is close to that of a false-positive one. CONCLUSION: Zinc protoporphyrin is not a reliable screening test for detecting low blood lead levels.

Chicago↗

Alkali absorption and citrate excretion in calcium nephrolithiasis.

The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

Acidosis, Renal Tubular↗

A study of xanthopterin in chronic renal failure.

Xanthopterin, a metabolic end product of the nonconjugated pterins dihydrobiopterin and tetrahydrobiopterin, is present in many organs and is known to inhibit the proliferation and growth of conconavalin-stimulated lymphocytes. We have developed a simple fluorometric method to measure xanthopterin in the blood and have validated the method by high pressure liquid chromatography (HPLC). Serum levels were 14 +/- 7 nmol/l in normal subjects and 141 +/- 51 nmol/l in hemodialysis patients (p < 0.02). Intermediate levels from patients with renal insufficiency not on dialysis correlated with serum creatinine levels (p < 0.001). Xanthopterin (MW 179) was cleared by hemodialysis at a slightly lower rate than creatinine. It is bound to protein, but the binding, 90 +/- 5% in normal subjects, is decreased in uremia to 60 +/- 15%, p < 0.01. Red cell levels of xanthopterin were five times higher than those of plasma in normal subjects (69 +/- 15 vs. 14 +/- 7 nmol/l, p < 0.001), but uremic patients had lower levels in red cells than in plasma (101 +/- 24 vs. 141 +/- 51 nmol/l, p < 0.05). Slight or moderate hemolysis induced by mechanical stress increased plasma xanthopterin levels by 35%, the effect being more pronounced when hemolysis was severe. We conclude that xanthopterin is increased and its binding to protein is decreased in chronic renal failure. The altered ratio of red cell/plasma xanthopterin levels may reflect an abnormality of the red cell membrane in uremia. We are conducting further studies to amplify our preliminary findings that xanthopterin inhibits cellular growth in vitro.

Chromatography, High Pressure Liquid↗

Purification and biochemical characterization of xanthopterin from patients with chronic renal failure. I. Isolation, purification and preliminary characterization.

We describe the purification and initial characterization of a hitherto unrecognized fluorescence (excitation/emission maxima at 380/440 nm and 400/460 nm) reported from this laboratory in patients with chronic renal failure (Clin Chem 31: 1988, 1985). Purification was achieved using Sephadex G-10 gel chromatography combined with reverse phase and ion exchange high-performance liquid chromatography (HPLC). Purity of the "blue-green" fluorescent compound was determined to be greater than 99% by HPLC, and two-dimensional thin layer chromatography using an acidic and basic solvent system. The excitation/emission maxima were shown to be 390 nm/456 nm, and ultraviolet scans, at pH 1.0, 7.0, and 13.0, gave absorbance optima at 261 nm/356 nm, 278 nm/390 nm, and 255 nm/394 nm, respectively. The isoelectric point of 4.05 in conjunction with the fluorescent and ultraviolet spectra suggests that the fluorophore belongs to the class of compounds known as pteridines.

Chromatography, High Pressure Liquid↗

Purification and biochemical characterization of xanthopterin from patients with chronic renal failure. II. Biochemical elucidation and structural analysis.

We have identified the primary endogenous fluorescent substance, which has characteristic excitation/emission maxima at 380/440 nm and 400/460 nm, found in the sera of patients with chronic renal failure (Clin Chem 32: 1276, 1988). Preliminary studies, using thin layer chromatography (with cellulose) in conjunction with pteridine standards, indicated that the compound is an unconjugated pteridine. Characterization by gas chromatography-mass spectrometry (electron impact), direct probe-mass spectrometry (electron impact/chemical ionization), and Fourier Transform Infrared analysis showed this compound to be xanthopterin (2-amino 4,6 pteridinedione), an unconjugated pteridine known to be present in man in trace quantities. An authentic sample of this compound had a retention time with high-performance liquid chromatography (HPLC) identical to that of the purified fluorophore. The physiological role of xanthopterin in the pathogenesis of uremia has yet to be elucidated.

Chromatography, Thin Layer↗

Schistosoma mansoni: immuno-localization of the calcium binding protein Sm20.

The 20 kDa calcium binding protein of Schistosoma mansoni, Sm20, is expressed in all stages of the life cycle from the cercaria to the adult worm and in the egg, with equal levels of Sm20 present in adult male and female worms. Localization of Sm20 by immuno-electron microscopy using Sm20-specific antisera and the protein A gold technique demonstrated that the majority of Sm20 is expressed in muscle but that it may also be expressed at low levels in the tegument. These results suggest that Sm20 plays a role in the calcium mediated regulation of muscle contraction. However, it is not clear whether Sm20 acts as a reservoir for calcium in muscle or is directly involved in the regulatory mechanisms of contraction.

Animals↗

Underestimation of cardiac output by thermodilution in patients with tricuspid regurgitation.

INTRODUCTION: This study was done to assess the accuracy and reliability of the thermodilution technique in measuring cardiac output in patients with tricuspid regurgitation. PATIENTS AND METHODS: In 30 subjects (17 men, 13 women, aged 50 +/- 14 [mean +/- SD] years), cardiac output was measured in close temporal proximity by thermodilution as well as Fick or indocyanine green dye, after which the presence and severity of tricuspid regurgitation were assessed by contrast right ventriculography or pulsed Doppler echocardiography. RESULTS: In the 13 patients without tricuspid regurgitation, there was excellent agreement between the results of thermodilution and Fick or indocyanine green dye cardiac output determinations (4.95 +/- 1.19 liters/minute by thermodilution, 4.90 +/- 1.11 liters/minute by Fick or indocyanine green dye; NS). In contrast, in the 17 patients with tricuspid regurgitation, the results of thermodilution were consistently lower than those of Fick or indocyanine green dye (4.22 +/- 1.45 liters/minute by thermodilution, 4.99 +/- 1.67 liters/minute by Fick or indocyanine green dye; p less than 0.001). CONCLUSION: Thus, the thermodilution technique of measuring cardiac output is inaccurate in patients with tricuspid regurgitation, yielding results that are consistently lower than the actual outputs.

Adult↗

Dosing of contrast material to prevent contrast nephropathy in patients with renal disease.

PURPOSE: Contrast-induced renal dysfunction has been reported to occur in 15% to 42% of patients with underlying azotemia, but there is disagreement as to whether its incidence is reduced by limiting the amount of contrast material. To adjust the amount of contrast material to the severity of azotemia, we have utilized the following formula to calculate a contrast material "limit" in patients with renal disease: Contrast material limit = (formula; see text) PATIENTS AND METHODS: Over a 10-year period, 115 patients (53 men, 62 women, aged 61 +/- 11 [mean +/- SD] years) with renal dysfunction (baseline serum creatinine level greater than or equal to 1.8 mg/dL) underwent cardiac catheterization and angiography, after which the level of serum creatinine was measured daily for five days. The amount of contrast material that was given adhered to the limit in 86 patients (Group I) and exceeded it in 29 (Group II). RESULTS: Contrast-induced renal dysfunction (an increase in serum creatinine greater than or equal to 1.0 mg/dL) occurred in two (2%) patients in Group I and in six (21%) patients in Group II (p less than 0.001). Of the 48 patients with concomitant diabetes mellitus, the contrast limit was surpassed in 16, six (38%) of whom had contrast nephropathy. Only two of the 32 (6%) diabetic patients in whom the contrast limit was not exceeded had contrast nephropathy (p less than 0.001). CONCLUSIONS: Thus, contrast-induced renal dysfunction occurs infrequently if the amount of contrast material is limited in accordance with the degree of azotemia. Diabetic patients have a high incidence of contrast nephropathy, particularly when they receive an excessive amount of contrast. In patients with diabetes and renal impairment, it may be preferable to perform angiography as a staged procedure or to utilize alternative (non-contrast) techniques to obtain the desired information rather than to exceed the prescribed contrast limit.

Acute Kidney Injury↗

Amino acid composition of uremic middle and low molecular weight retention products.

In order to characterize the spectrum of small peptides retained in chronic renal failure, we carried out high pressure liquid chromatography (HPLC) of serum ultrafiltrates from patients with chronic renal failure (CRF), acute renal failure (ARF), and normal subjects. HPLC patterns in CRF resolved into more than twenty peaks; those in ARF contained fewer peaks and resembled that of normals. We carried out amino acid analysis of HPLC fractions after hydrolysis with 6N HC1 of four patients with CRF, one patient with ARF, and one normal subject. Following hydrolysis each HPLC fraction yielded several amino acids. Glycine, leucine, serine, phosphoserine, glutamic acid, and phenylalanine were found in greatest frequency in the four CRF patients.

Amino Acids↗

Biochemical elucidation and HPLC fractionation of fluorescent peptides in patients with chronic renal failure.

We evaluated the biochemical characteristics of endogenous fluorescent substances, Ex 380 nm/Em 440 nm and Ex 400 nm/Em 460 nm, present in sera of patients with chronic renal failure (Clin. Chem. 31:1988, 1985). Sera from 23 patients with chronic renal failure (CRF) and from 10 normal subjects were filtered through ultrafiltration membranes (cutoff limit of 500 Da). Fluorescence intensity of the aforementioned substances was significantly elevated as compared to normals (p less than 0.001). Fluorescence characteristics of these substances remained unaltered after ultrafiltration and treatment with beta-glucuronidase. Extraction of these fluorescent compounds with organic solvents (dichloromethane, ethyl acetate, chloroform:methanol) could not be achieved after ultrafiltrates were subjected to 6N hydrochloric acid (HC1) hydrolysis. In addition, treatment with 6N HC1 enhanced fluorescence intensity without altering fluorescence excitation/emission maxima. Removal of fluorescence could be accomplished in toto by adsorption onto activated charcoal with subsequent recovery from charcoal by treatment with sodium hydroxide, pH 12 (Ex 380 nm: 51.1%, Ex 400 nm: 91.8%). Analysis of alkali-treated specimens by high performance liquid chromatography demonstrated that peptides associated with these fluorescent substances were denatured, although fluorescence at these previously described excitation/emission maxima persisted. Our studies indicate that the unique fluorescence observed in the sera of patients with CRF is not an intrinsic characteristic of a specific peptide or its amino acids, but rather an inherent property of fluorescent molecules which may bind to these peptides.

Chromatography, High Pressure Liquid↗

Pharmacologic role of rubidium in psychiatric research.

Rubidium appears to exert several biologic and pharmacologic effects that are similar if not identical to those of many of the classic antidepressant drugs. This mineral element, if given orally as rubidium chloride, appears to be nontoxic and therapeutically effective in several types of depressive disorders. Currently, however, it is unclear whether or not rubidium will serve as an invaluable pharmacologic agent of a direct clinical nature. Further pharmacometric studies and clinical evaluations are needed to elucidate its mechanism of action and to ascertain its future therapeutic role as an antidepressant drug in clinical psychiatry.

Antidepressive Agents↗

Evidence for the existence of 5-hydroxytryptamine receptors, which are not of the 5-HT2 type, mediating contraction of rabbit isolated basilar artery.

In the rabbit isolated basilar artery the contractile action of 5-hydroxytryptamine (5-HT) was little affected by high concentrations of ketanserin (1.0 X 10(-6) M) indicating that 5-HT-receptors other than those of the 5-HT2-type were involved. The contractile action of 5-HT was mimicked by methysergide and 5-carboxamidotryptamine (5-CT) with equipotent concentration ratios (5-HT = 1) of about 22 and 0.6 respectively. This profile is characteristic of that in the dog saphenous vein which contains a 5-HT receptor type that may be described as '5-HT1-like'.

Animals↗