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Biomedical subjects

E H Cooper

Publications and source records attributed to E H Cooper.

At least 91 records · Page 5Linked to original sources

An evaluation of the immunochemical measurement of prostatic acid phosphatase and prostatic specific antigen in carcinoma of the prostate.

Serum prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) were evaluated with double monoclonal radioimmunoassays. In 250 patients with prostatic cancer the normal limits were as follows: PSA 0.1-2.7 ng/ml, and PAP 1.09 +/- 0.45 ng/ml (mean +/- SD). In 91 untreated patients with non-metastatic tumours, 42.8% had PSA greater than 10 ng/ml and 18.6% had PAP greater than 2 ng/ml. In 60 untreated patients with metastatic disease PSA was greater than 10 ng/ml in 91.7%; PAP was greater than 2 ng/ml in 65%. In prolonged remission PSA was generally less than 5 ng/ml and PAP less than 2 ng/ml. Longitudinal studies of 2-4 years showed the independence of these markers and a higher correlation of changes in the PSA level and clinical status than given by parallel PAP measurements. In non-metastatic disease, PSA greater than 10 ng/ml at presentation, with or without a coincidentally raised PAP, carried an increased risk of progression within 2 years.

Acid Phosphatase↗

Evaluation of a double-monoclonal radioimmunoassay for the measurement of carcinoembryonic antigen in the urine of patients with bladder cancer.

A double-monoclonal radioimmunoassay (RIA) has been used to detect urinary carcinoembryonic antigen (CEA) in 204 patients attending for diagnostic cystoscopy. Elevated levels of urinary CEA were found in 50% of patients with bladder tumours, and these levels correlated with both the grade and stage of the tumour. The sensitivity proved to be 58% and the specificity 74%, which compares with previous studies using polyclonal RIA kits. As a monitoring test, urinary CEA proves to be as useful as urine cytology. The use of a more specific assay does not increase the clinical value of the test which still lacks the sensitivity and specificity needed to allow it to be used to monitor recurrence of low grade tumours (Ta, Tis and T1).

Aged↗

Measurements of serum gamma-seminoprotein and prostate specific antigen evaluated for monitoring carcinoma of the prostate.

We have compared the concentrations in serum of gamma-seminoprotein (gamma-SM) and prostate specific antigen (PSA), two antigens of prostatic origin that are synthesized independently of prostatic acid phosphatase (PAP, EC 3.1.3.2), to assess their potential in monitoring prostatic cancer. At presentation, 27/30 (90%) patients with metastases had a PSA concentration greater than 10 ng/mL, and 29/30 (97%) a gamma-SM concentration greater than 10 ng/mL; 21/61 (34%) with disease but without metastases had an abnormal content of PSA, and 23/61 (38%) an abnormal gamma-SM. Concentrations of PSA and gamma-SM were significantly correlated (r = 0.68, p less than 0.001). In 20 patients without metastases followed longitudinally, the median concentrations of gamma-SM, PSA, and PAP in the 13 patients who developed bony metastases or showed signs of local spreading of the tumor were 58 ng/mL, 34 ng/mL, and 2.1 U/L, respectively. The corresponding median values in the seven patients who remained clinically stable were 2.5 and 3.9 ng/mL, and 2.3 U/L. We conclude that either PSA or gamma-SM can warn of disease progression when PAP activities are still within normal limits.

Acid Phosphatase↗

Alpha 1-protease inhibitor in serous effusions: differences in lectin crossed immuno-affinoelectrophoresis precipitin profiles between benign and malignant disease.

Differences in the lectin crossed immuno-affinoelectrophoresis (LCIE) precipitin profile of the antiprotease alpha 1-protease inhibitor (alpha 1-PI) have been detected between serous effusions of benign and malignant origin. Extra proteins with antigenicity towards anti-human alpha 1-PI appear in both malignant pleural effusions and malignant ascitic fluid caused by ovarian cancer that are not detected in effusions of benign origin. These compounds may be protease-antiprotease complexes caused by tumour excretion of proteases into the serous effusions.

Ascitic Fluid↗

Urinary alpha 1 microglobulin levels in surveys of Balkan endemic nephropathy.

The urinary alpha 1-microglobulin (alpha 1m) concentration was measured in 644 adults living in districts where Balkan nephropathy (BEN) is endemic. Comparison of alpha 1m with other indicators of tubular proteinuria, which is a classical sign of BEN, showed alpha 1m was a satisfactory marker. Using a cut-off of 20 mg alpha 1m/L none of 102 normal UK residents had a positive level. Whilst a raised level of alpha 1m was present in 85.7% of definitive cases of BEN and in 8.1%, 10.2% and 50% of subjects previously classified as normal, at risk and suspicious respectively according to the criteria used for epidemiological surveys of BEN.

Balkan Nephropathy↗

Low molecular weight proteinuria in insulin-dependent diabetes.

Although the protein leak of early diabetic nephropathy is said to be purely a glomerular lesion, there is still controversy as to the existence of a tubular component. We have, therefore, assessed the urine of insulin-dependent diabetics for tubular proteinuria as a feature of early diabetic nephropathy. The urine of 25 patients with increased albumin excretion rate was analyzed by sodium dodecyl polyacrylamide gel electrophoresis. One patient showed high molecular weight proteinuria, 2 showed low molecular weight proteinuria and 2 patients showed both low and high molecular weight proteinuria. The urine was also analyzed for 3 tubular proteins by single radial immunodiffusion. No patient showed elevated beta-2-microglobulin, but alpha-1-microglobulin (A1M) (corrected for creatinine excretion) was elevated in 3 out of 25 patients including 2 of the 4 patients with a low molecular weight pattern. One of the patients with raised A1M also had raised retinol-binding protein concentration. We conclude that, in early diabetic nephropathy, proteinuria can have a proximal tubular, as well as a glomerular, component.

Adult↗

An enzyme-amplified monoclonal immunoenzymometric assay for prostatic acid phosphatase.

An immunoassay for prostatic acid phosphatase is described in which a high degree of specificity for the prostatic isoenzyme, obtained by the use of monoclonal antibodies, is combined with great sensitivity, made possible by enzyme-amplified measurement of the combination of the isoenzyme with its antibody. The increase in sensitivity thus achieved is of the order of 170 times that of conventional methods of measurement. The advantages of the enzyme-amplified method have been shown to be particularly useful in detecting and monitoring small abnormalities of prostatic acid phosphatase levels in patients with prostatic cancer.

Acid Phosphatase↗

Chromatographic study of the interrelationships of immunoglobulin A and alpha 1-microglobulin in myelomatosis.

The binding of alpha 1-microglobulin (alpha 1-m) to serum immunoglobulin A (IgA) myeloma proteins have been examined by analytical and preparative Superose high-performance gel chromatography. Enzyme immunoassays showed that in the serum alpha 1-m was bound to monomeric IgA, but not to the polymeric IgA, and was also present in a free form. The IgA-alpha 1-m complexes involved covalent and non-covalent bonds. Considerable variation in the ratio of bound to unbound forms of alpha 1-m was observed that appears to be a result of variation of the IgA alpha heavy chains. Reduction of monomeric IgA produced alpha 1-m-heavy chain complexes, free alpha 1-m, light and alpha heavy chains, and traces of alpha 1-m attached to IgA that was resistant to reduction.

Alpha-Globulins↗

Fast protein liquid chromatography scale-up procedures for the preparation of low-molecular-weight proteins from urine.

A system for the rapid isolation of low molecular weight proteins from urine has been devised, and illustrated by alpha 1-microglobulin, beta 2-microglobulin, retinol binding protein, lysozyme and monoclonal light chains. Urine proteins from patients with tubular dysfunction were concentrated, either by ultrafiltration or ammonium sulphate precipitation. This was followed by gel chromatography on Sephadex G-50. The appropriate fractions were then separated by chromatography on Pharmacia monobead columns. A Mono Q strong anion exchanger was used for beta 2-microglobulin, retinol binding protein, alpha 1-microglobulin and free monoclonal light chains. Lysozyme was separated on a Mono S cation exchanger. The chromatography was first optimized on HR 5/5 columns and then scaled up to HR 16/10 columns.

Alpha-Globulins↗

Factors affecting survival in patients presenting with synchronous hepatic metastases from colorectal cancer: a clinical and computer analysis.

A review of 90 patients presenting in Leeds over the period 1976-80 with synchronous hepatic metastases from colorectal cancer has been undertaken. The median survival for the group was 10.3 months (range 1-48 months). A multivariate analysis identified factors in the history and examination of the patient, results of biochemical and haematological investigations and characteristics of both the primary and secondary tumour, which influenced survival. Recognition of these factors allowed both a clinical scoring index and computer survival model to be constructed. When applied to the group as a whole both were reasonably accurate at predicting survival (62 per cent for the survival model and 66 per cent for the scoring index). However, the computer model correctly identified 80 per cent of the 'long-term' survivors (greater than 12 months from the time of diagnosis). It is concluded that many trials of therapy for hepatic metastases from colorectal cancer have failed to consider the natural history of the disease and the identification of prognostic indices should allow for adequate stratification within the treatment arms of any future study.

Adult↗

Evaluation of an amplified enzyme-linked immunoassay of placental alkaline phosphatase in testicular cancer.

The levels of serum placental alkaline phosphatase (PLAP) have been examined in 81 male controls, 51 untreated testicular tumours (41 seminomas and ten non-seminomatous testicular tumours) and 34 patients in complete remission (11 seminoma and 23 non-seminoma). Smoking induced a significant rise of serum PLAP in the controls, with a median level of 0.055 U/1 in non-smokers compared to 0.25 U/l in smokers. The levels found in pre-treatment seminoma (median 1.7 U/1) were significantly higher than in untreated teratoma (median 0.7 U/1). Treatment produced a significant fall in seminomas in remission (median 0.07 U/1). The role of PLAP in routine monitoring of seminomas was evaluated in 17 patients studied for 1-4 yr. PLAP shows similar trends to beta HCG but is an independent variable. The main role of PLAP is to help determine that the response to treatment has been satisfactory and that there are no unexpected foci of tumour.

Adult↗

The role of serum tumour markers to aid the selection of lung cancer patients for surgery and the assessment of prognosis.

We have measured the following ten serum proteins in a sample of 290 patients presenting with possible lung cancer: carcinoembryonic antigen (CEA), alpha 1-acid glycoprotein (AGP), C-reactive protein (CRP), ferritin (FER), prealbumin (PAB), third component of complement (C3), immunoglobin E (IgE), alpha 2-pregnancy-associated glycoprotein (PAG), beta 2-microglobulin (beta 2-m) and retinol binding protein (RBP). It is found that, with the exception of PAG, C3 and IgE, there are significant differences between protein concentrations in the subsequently diagnosed cancer and non-cancer patients. However, protein concentrations in the cancer patients who were suitable for surgery do not differ significantly from the concentrations in inoperable patients. The prognostic significance of the proteins in the inoperable and operable cancer patients is also envisaged. In the operable group C3 appears to be useful, whilst AGP and RBP are prognostic indicators in the inoperable group.

Blood Proteins↗

A collaborative study of a preparation of normal human serum for use as a reference in the assay of beta 2 microglobulin.

A biological standard for beta 2 microglobulin (beta 2m) determination has been prepared from pooled human serum by sampling and freeze-drying. A preliminary study of parallelism between the dose-response curves of the preparation and pure beta 2m or biological fluids was made with four different methods of assay and gave satisfactory results. In a collaborative study in five laboratories in five countries using a common method of assay, evidence was obtained that the preparation coded 80-12-3200 was suitable to serve as a standard for the assay of beta 2 microglobulin. Criteria included the constancy of the amount of material per vial and the stability of the freeze-dried product. The technique used for beta 2m determination was a radioimmunoassay.

Drug Stability↗

The prognostic value of serum beta 2 microglobulin compared with other presentation features in myelomatosis.

The levels of serum beta 2 microglobulin, blood urea concentration, serum creatinine, haemoglobin and performance status have been measured in 476 patients in the Medical Research Council's 4th trial for myelomatosis. Levels of serum beta 2 microglobulin were also subsequently measured in 208 patients who achieved a stable "plateau" condition. Serum beta 2 microglobulin levels, uncorrected for serum creatinine, were found to be the single most powerful prognostic variable available at presentation. Multivariate analysis showed that only the addition of haemoglobin levels could improve upon this and the improvement, though statistically significant (P = 0.006), appeared to be of much less clinical value. The prognostic value of serum beta 2 microglobulin at plateau appeared to be equally large for a given difference in value, but the variability between patients was much less at that time. Serum beta 2 microglobulin would appear to be a key measurement for assessing the prognosis and response to treatment in patients with myelomatosis.

Creatinine↗

Evaluation of a radioimmunoassay for neuron specific enolase in small cell lung cancer.

A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (greater than 13 ng ml-1), in extensive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitudinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accompanied by a rising NSE in 25/29 patients, with doubling times of 7-90 days. In patients with progression with a normal NSE the recurrence was a NSCLC. Cerebral metastases occurring as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a valuable monitor for SCLC during and after chemotherapy.

Carcinoma, Small Cell↗

Urinary pseudouridine excretion in myelomatosis.

Urinary psi excretion is independent of the main indices of tumour activity in myelomatosis (serum paraprotein, serum beta 2-microglobulin, serum creatinine and urinary light chain production). The mean (+/- s.d.) psi at presentation was 40.7 +/- 22.6 nmol. mumol ucr-1, compared to 25.4 +/- 4.8 nmol. mumol ucr-1 in controls. Urinary psi levels at presentation are significantly related to prognosis, the higher the level the poorer the prognosis. However, when these levels have been stratified according to the corresponding level of serum beta 2m, the level adds little as a prognostic factor.

Adult↗

Changes in plasma fibronectin during donor apheresis and therapeutic plasma exchange.

Changes in plasma levels of the opsonic glycoprotein fibronectin were studied during machine apheresis in 32 healthy plasma donors and 18 patients undergoing a total of 86 therapeutic plasma exchanges. Donation of 500 ml of plasma at 3-monthly intervals produced a 10% immediate decrease in plasma fibronectin with no evidence of a long-term affect on levels of this protein. One plasma volume exchange with fibronectin-poor plasma protein fraction produced subnormal plasma fibronectin levels in 98% of post-exchange samples. Efficiency of exchange was significantly lower in patients with paraproteinaemia, probably reflecting increased plasma volume in such patients. Daily plasma exchange produced progressive depletion of plasma fibronectin (index of recovery 0.68) whereas levels were maintained close to the initial value with longer exchange intervals, except in the more severely ill patients. Reduction of plasma fibronectin by plasma exchange may increase susceptibility to infection and reduce the efficacy of this procedure when the object of exchange is to reverse reticuloendothelial blockade.

Adult↗

Fever and proximal tubular function in acute pyelonephritis.

The urinary excretion of alpha 1-microglobulin (alpha 1M), beta 2-microglobulin (beta 2M), retinol-binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) as markers of proximal tubular dysfunction was measured in various forms of urinary tract infections (UTI) and in fever due to non-renal infections. The urinary concentration of these proteins was significantly increased in acute pyelonephritis compared with acute cystitis and asymptomatic bacteriuria. Tubular proteinuria and enzymuria could also be demonstrated in subjects with fever of non-renal origin and corresponded to the findings of pyelonephritis. It is suggested that fever per se is the most likely cause of the tubular proteinuria seen in acute pyelonephritis. In localizing an acute UTI characterization of the urinary protein profile seems to have no advantage over a carefully measured body temperature. The urinary excretion of alpha 1M,beta 2M and RBP were highly correlated, while urinary NAG activity was less correlated to these low-molecular weight proteins. Fibrin degradation product D (FDP-D) was detected in the urines in 60% of the patients with acute pyelonephritis and in one third of those with acute cystitis. The estimation of FDP in urine therefore seems to be of little value in the level diagnosis of UTI.

Acetylglucosaminidase↗