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Biomedical subjects

F V Flynn

Publications and source records attributed to F V Flynn.

15 recordsLinked to original sources
PubMed1992

Urinary excretion of beta 2-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in "non-tubular" renal disease.

AIM: To determine whether urinary beta 2-glycoprotein-1 assays can provide improved discrimination between chronic renal diseases which are primarily of tubular or glomerular origin. METHODS: Urinary beta 2-glycoprotein-1, retinol-binding protein, alpha 1-microglobulin, beta 2-microglobulin, N-acetyl-beta-D-glucosa-minidase and albumin were measured in 51 patients with primary glomerular disease, 23 with obstructive nephropathy, and 15 with polycystic kidney disease, and expressed per mmol of creatinine. Plasma beta 2-glycoprotein-1 was assayed in 52 patients and plasma creatinine in all 89. The findings were compared between the diagnostic groups and with previously published data relating to primary tubular disorders. RESULTS: All 31 patients with plasma creatinine greater than 200 mumol/l excreted increased amounts of beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin, and 29 had increased N-acetyl-beta-D-glucosaminidase; the quantities were generally similar to those found in comparable patients with primary tubular pathology. Among 58 with plasma creatinine concentrations under 200 mumol/l, increases in beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin excretion were less common and much smaller, especially in those with obstructive nephropathy and polycystic disease. The ratios of the excretion of albumin to the other proteins provided the clearest discrimination between the patients with glomerular or tubular malfunction, but an area of overlap was present which embraced those with obstructive nephropathy and polycystic disease. CONCLUSIONS: Increased excretion of beta 2-glycoprotein-1 due to a raised plasma concentration or diminution of tubular reabsorption, or both, is common in all the forms of renal disease investigated, and both plasma creatinine and urinary albumin must be taken into account when interpreting results. Ratios of urinary albumin: beta 2-glycoprotein-1 greater than 1000 are highly suggestive of primary glomerular disease and those less than 40 of primary tubular disease. Used in this way, beta 2-glycoprotein-1 assays provide superior discrimination between glomerular and tubular malfunction when compared with retinol binding protein but the best discrimination is provided by albumin: alpha 1-microglobulin ratios.

Acetylglucosaminidase↗
PubMed1991

Absence of increased urinary excretion of adenosine-deaminase-binding protein by patients with chronic renal tubular malfunction.

The urinary excretion of adenosine-deaminase-binding protein, a constituent of the brush border of proximal renal tubule cells, has been investigated in 39 patients with disorders associated with malfunction of the renal tubules, and its excretion has been compared with that of two low molecular mass plasma proteins and an enzyme derived from renal tubular cells. None of the 36 patients with disorders associated with chronic renal tubular malfunction were found to be excreting significantly increased quantities of adenosine-deaminase-binding protein but 30 had increased excretion of retinol-binding protein, alpha 1-microglobulin, or N-acetyl-beta-D-glucosaminidase. Measurement of urinary adenosine-deaminase-binding protein may be useful in the assessment of acute renal tubular injuries but it is not of value in the detection of chronic renal tubular disorders.

Acetylglucosaminidase↗
PubMed1991

Beta 2-glycoprotein-1 (apolipoprotein H) excretion in chronic renal tubular disorders: comparison with other protein markers of tubular malfunction.

Urinary beta 2-glycoprotein-1 was measured in 60 patients with conditions recognised as causing renal tubular impairment and compared with established markers of early tubular malfunction. Increased beta 2-glycoprotein-1 excretion was found in 49 (82%) of the subjects; raised excretion of alpha 1-microglobulin, retinol-binding protein, and beta 2-microglobulin was found in 46 (77%), 45 (75%), and 31 (52%), respectively, and increased urinary N-acetyl-beta-D-glucosaminidase activity in 32 of 54 of the subjects (59%). The increase was particularly pronounced in those with proximal tubule malfunction, although considerable variation occurred. beta 2-glycoprotein-1 was shown to be stable in urine over the physiological pH range, and it is concluded that its measurement provides a means of detecting chronic malfunction of the renal tubules that is marginally more sensitive than assays of alpha 1-microglobulin or retinol-binding protein, and more reliable than assays of beta 2-microglobulin or N-acetyl-beta-D-glucosaminidase.

Acetylglucosaminidase↗
PubMed1991

A sandwich enzyme-linked immunosorbent assay for beta 2-glycoprotein I.

A solid-phase sandwich enzyme-linked immunosorbent assay for determining beta 2-glycoprotein I in urine has been developed. It has a working concentration range of 5-40 micrograms/L and a detection limit of approximately 1.4 micrograms/L. The within-plate coefficient of variation (CV) falls between 1.4% and 2.1%, and the between-batch CV ranges from 5.2 to 6.0%. Recovery of beta 2-glycoprotein I added to urine varies between 96 and 110%. The assay can also be used for determining beta 2-glycoprotein I in serum.

Adult↗
PubMed1991

Excretion of beta 2-glycoprotein I (apolipoprotein H) in renal tubular disease.

beta 2-Glycoprotein I (beta 2GI) was identified as a major urinary protein excreted by patients with several renal tubular diseases, including adult Fanconi syndrome, nephrocalcinosis associated with autoimmune diseases, Lowe's syndrome, and Dent's disease (a familial renal tubular disease). Sixteen patients excreted between 2 and 40 mg of beta 2GI per millimole of creatinine. In contrast, 18 healthy controls had undetectable amounts of beta 2GI in urine. Isoelectric focusing followed by immunoblotting demonstrated multiple forms of beta 2GI with pls between 6.4 and 8.2. These pls are higher than for several other "tubular proteins"; beta 2GI may therefore be less retarded than more-anionic proteins by the glomerular charge-barrier. This could explain why large quantities of beta 2GI are excreted despite its relatively high molecular mass (50 kDa). Excretion of beta 2GI was easily demonstrated by routine electrophoresis of urine proteins. beta 2GI migrates in the beta-gamma region and may be confused with Bence Jones protein. beta 2GI is stable for at least two years in urine frozen at -25 degrees C.

Adolescent↗
PubMed1990

Assessment of renal function: selected developments.

Tests commonly used to assess the glomerular filtration rate (GFR) and to detect renal tubular damage are critically reviewed. Creatinine clearance which is frequently used for assessment of the GFR is prone to several errors. The plasma creatinine can be used to provide a rough guide but for reliable measurement of the GFR, 51Cr-EDTA clearance is recommended. Measurements of the urinary excretion of low molecular weight proteins, enzymes and kidney tissue proteins have been used to detect tubular damage. Of the low molecular weight proteins excreted, beta-2-microglobulin is unstable and measurement of retinol-binding protein or alpha-1-microglobulin is recommended for the detection of chronic renal tubular malfunction. Of the many enzymes that have been studied, urinary N-acetyl-beta-D-glucosaminidase or alanine aminopeptidase are recommended as being the most useful for the early detection of acute renal tubular damage. Among renal tissue proteins that have been measured in urine adenosine-deaminase-binding protein, a tubular brush border antigen appears to have considerable potential for providing early warning of renal allograft rejection.

Glomerular Filtration Rate↗
PubMed1989

Renal impairment in myeloma: negative association with isoelectric point of excreted Bence-Jones protein.

The isoelectric point (pI) of the major form of Bence-Jones protein excreted by 62 patients with myeloma and six with macroglobulinaemia was measured by combining isoelectric focusing with immunoblotting techniques. The distribution of the pI values for both kappa and lambda type proteins was bimodal, most falling in the ranges 5.0-6.0 and 7.0-7.5. Plasma creatinine and creatinine clearance and the urine excretion of alpha-1-microglobulin and beta-2-microglobulin were measured in 24 of the patients. These patients, who were free of additional factors known to have an association with the development of renal impairment, were followed up for a mean period of 16 months (range three to 28 months). It was found that renal impairment was not related to the pI of the Bence-Jones protein excreted.

Alpha-Globulins↗
PubMed1987

Immunoglobulin light-chain immunoblots of urine proteins from patients with tubular and Bence-Jones proteinuria.

Immunoglobulin excretion by patients with monoclonal gammopathies and tubular proteinuria has been analysed by agarose gel isoelectricfocussing of untreated urine and immunoblotting. About three-quarters of the Bence-Jones proteins detected occurred as multiple bands on isoelectricfocussing; in about half of these cases the multiple forms were due to polymerisation or fragmentation of the light chains. In specimens with tubular proteinuria, a characteristic light chain pattern of three broad bands covering the pI ranges 7.1-7.3, 7.8-8.0 and 8.3-8.5 was found. This pattern also occurred in 53% of specimens with Bence-Jones proteinuria and was identical to that found in concentrated normal urine. Intact monoclonal immunoglobulin usually appeared as three or more evenly spaced bands of similar intensity whereas polyclonal intact immunoglobulins produced diffuse staining from pI 5.0-8.5. A scheme for the qualitative analysis of urinary immunoglobulin excretion using this technique has been developed.

Adult↗
PubMed1978

The effect of age, sex and other factors on blood chemistry in health.

Quantitative data is presented concerning the influence that age, sex, the menopause, oral contraception, blood group and time of blood collection have on 19 commonly-determined blood chemistry values. The data were derived from 1000 healthy blood donors in whom blood sampling conditions were standardised to conform with those applying to hospital out-patients. Statistical techniques were used to allow for the effects of analytical variation and to enable the effects of the various factors and their interactions to be expressed in a practically useful manner. Age and sex effects are shown to be the rule and to interact in many instances. Creatinine, urea, glucose, cholesterol, potassium and globulin show a tendency to increase in concentration with age, while total protein, albumin, calcium, inorganic phosphate and iron levels tend to fall progressively. Evidence is given to suggest that many of the changes occurring in women at about 50 years should be attributed to hormonal changes. In all instances when the menopause has a significant influence there is a rise in the concentration of the constituent concerned. It is proposed that other laboratories should assemble age and sex stratified reference ranges from (a) figures given for the mean values for defined age and sex groups, adjusted if necessary to allow for different analytical bias, (b) figures given for nonsystematic biological variation, and (c) their own measurements of analytical precision. Details of the necessary procedure are given, allowance being made for logarithmic transformation of the results where necessary.

Adolescent↗
PubMed1977

Balkan (endemic) nephropathy and a toxin-producing strain of Penicillium verrucosum var cyclopium: An experimental model in rats.

Cultures of an isolate of Penicillium verrucosum var. cyclopium, obtained from stored maize in an area of Balkan (endemic) nephropathy--Vratza, Bulgaria--has consistently induced renal tubular lesions when force-fed to rats for 20 days. The lesions, confined to the lower reaches of the proximal convoluted tublues (pars recta and junctional zone), closely resemble the tubular changes in patients with Balkan nephropathy. Preliminary evidence suggests that this nephrotoxin-producing strain of P. verrucosum var. cyclopium may be implicated in the aetiology of Balkan nephropathy.

Animals↗
PubMed1976

Biological and analytical variation of commonly determined blood constituents in healthy blood donors.

The relative contributions of analytical error and non-systematic biological variation to the reference range for 19 commonly-determined blood chemistry values have been estimated during the course of studying 1000 healthy blood donors. Estimates of non-systematic biological variations are arrived at by determining the variation found in donors matched for factors known to affect blood chemistry such as age and sex, and deducting the within-batch analytical error which applied. Comparison of the within-batch and between-batch analytical precision with the biological variation showed that the percentage increases in the normal range attributable to between-batch analytical error varies between 1 and 29%. This contribution is particularly large in the case of the electrolytes and amounts to no less than 29% in the case of calcium. Apart from well-known relationships a remarkable lack of correlation between the concentration of the different constituents in health is demonstrated.

Adolescent↗