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A K Cheung

Publications and source records attributed to A K Cheung.

107 records · Page 6Linked to original sources
PubMed1985

Determinants of bone gamma-carboxyglutamic acid-containing protein in plasma of healthy aging subjects.

The gamma-carboxy glutamic acid (Gla)-containing protein of mammalian bone (BGP, also called osteocalcin) is a 49 amino acid polypeptide containing two to three residues of gamma-carboxyglutamic acid. BGP is synthesized by osteoblastlike cells, and plasma BGP in laboratory animals is derived principally from recently synthesized BGP. These data, taken together with observations that plasma BGP levels are elevated in patients with disorders of high bone turnover, suggest that plasma BGP is a marker of osteoblast activity. Since low bone formation rates may play an important role in the loss of bone mass with age, we have examined the determinants of plasma BGP levels in aging subjects, using a region-specific radioimmunoassay for human BGP based on the synthetic C-terminal peptide hBGP37-49. In 147 carefully screened healthy subjects, aged 23-91, BGP did not change with age, whereas alkaline phosphatase (AP) showed a significant positive correlation (r = 0.30, P less than 0.001). Creatinine clearance (GFR) declined by 0.9 ml/min/yr and correlated with both BGP (r = -0.21, P less than 0.001) and AP (r = -0.21, P less than 0.001). However, correlation of AP with age persisted after controlling for GFR. BGP was not correlated with serum PTH, urine Ca/GFR, or urine cAMP/GFR. In 48 patients with known parenchymal renal disease studied for comparison, plasma BGP was increased at a serum creatinine of greater than or equal to 1.8 mg/dl. Our results indicate that plasma BGP, a specific marker of bone metabolism, is not predictably related to age per se. This result is in contrast to the age-related rise in total AP. Subtle changes in renal function can affect plasma BGP levels.

1-Carboxyglutamic Acid↗
PubMed1983

Inhibitors of peripheral-type benzodiazepine receptors present in human urine and plasma ultrafiltrates.

Several endogenous substances that inhibit central-type benzodiazepine (BZD) receptor binding have recently been identified. We have found that ultrafiltrates of human uremic plasma, normal plasma, and urine contain competitive inhibitors of peripheral-type benzodiazepine receptors. Using urine as source, we have partially purified a peripheral-type BZD receptor inhibitor(s) by adsorption to and selective elution from small octadecyl-silane (Sep-pak) columns and thin layer chromatography. The inhibitor has a 125-fold greater affinity for peripheral-type than central-type BZD receptors and has been purified 8000-fold from urine.

Adsorption↗
PubMed1983

Choosing a membrane.

Explore the source record for details and available documents.

Biocompatible Materials↗
PubMed1983

Urea movement across erythrocyte membrane during artificial kidney treatment.

Previous work by other investigators indicates that erythrocyte urea and creatinine in uremic whole blood leaving the hemodialyzer do not move down the concentration gradients established by loss of these solutes across the dialyzer membrane. This puzzling disequilibrium is at odds with work indicating ready movement of both solutes across the erythrocyte membrane of nonuremic erythrocytes studied in vitro. The present study shows that contact with the dialyzer does not noticeably alter the erythrocyte membrane of the uremic patient, so that urea distribution between plasma and erythrocyte water is the same as that in the blood of normal control subjects. Furthermore, urea does not show a disequilibrium in concentration across the erythrocyte membrane in response to 50% dilution with a modified Ringer's solution but rather equilibrates swiftly and completely.

Biological Transport↗
PubMed1983

Determinants of serum 1,25(OH)2D levels in renal disease.

Serum 1,25(OH)2D and factors related to its production were studied in 39 patients with various degrees of renal insufficiency. Serum 1,25(OH)2D levels correlated positively with 1/serum creatinine values (r = 0.54, P less than 0.001) and negatively with serum phosphorus (r = -0.39, P less than 0.02) and age (r = -0.33, P less than 0.05). There was no significant correlation between 1,25(OH)2D levels and serum calcium or calcitonin or PTH, although the logarithm of PTH correlated inversely with 1,25(OH)2D levels (r = -0.47, P less than 0.01). Patients who had normal or supranormal 1,25(OH)2D levels despite low GFR tended to have low serum phosphorus values. Serum levels of bone Gla protein (BGP), a biochemical marker for bone metabolism, correlated negatively with 1/serum creatinine (r = -0.39, P less than 0.02) and positively with PTH (r = 0.57, P less than 0.001) and age (r = 0.33, P less than 0.05). Prophylaxis with 1,25(OH)2D should be considered in patients with significantly decreased serum 1,25(OH)2D levels, as seem to occur when serum creatinine is greater than 4.0 mg/dl. However, despite the statistically significant correlation between serum 1,25(OH)2D and 1/serum creatinine, direct measurement should be used to ascertain the serum concentration of 1,25(OH)2D in chronic renal insufficiency.

Adult↗
PubMed1983

Anaphylatoxin formation during hemodialysis: effects of different dialyzer membranes.

Measurable complement activation resulting in the formation of both C3a and C5a anaphylatoxins was observed in 12 patients undergoing maintenance dialysis treatment with cuprophan hollow fiber dialyzers. Specific radioimmunoassay measurements demonstrated that these patients displayed significantly elevated levels of C3a antigen in the venous (outflow) line of the dialyzer after only 2 min of dialysis. During hemodialysis, venous plasma C3a levels continued to increase and became maximally elevated after 15 min. Thereafter, C3a concentrations gradually declined, suggesting that the rate of complement activation abates with continued cuprophan hemodialysis. Complement activation, as judged by venous plasma C3a levels, was also temporally correlated with hemodialysis leukopenia. The factor believed to be responsible for pulmonary vascular leukosequestration, C5a, could also be detected in venous plasma, but levels of this antigen were not strikingly elevated until the later stages of dialysis. By contrast, six patients dialyzed with polyacrylonitrile dialyzers failed to exhibit hemodialysis leukopenia and displayed only very modest increases in their plasma C3a levels during the initial phases of hemodialysis. These observations provide direct evidence that anaphylatoxin formation during hemodialysis is a transient phenomenon and indicate that the biocompatibility of dialysis membranes, as reflected by their complement activating potential, may be significantly different.

Acrylic Resins↗
PubMed1983

Anaphylatoxin formation during hemodialysis: comparison of new and re-used dialyzers.

Hemodialysis of 11 endstage renal failure patients with new cuprophan hollow fiber dialyzers produced significant leukopenia as well as increased plasma levels of both C3a and C5a antigens during the initial phases of the procedure. Formalin-fixed new dialyzers produced quantitatively similar phenomena in eight of these same patients. By contrast, hemodialysis with re-used dialyzers, that is dialyzers exposed to blood prior to formalin sterilization, produced only a 20 to 30% decline in peripheral blood leukocyte counts. Correspondingly, C3a antigen formation within re-used dialyzers was only 20% of that observed in new dialyzers. Re-used dialyzers also differed significantly from either new or formalin-fixed new dialyzers in that C3b antigen could be readily detected within them even after extensive washing. These observations suggest that C3b deposition on the cellulosic membrane surface during first use markedly diminishes the complement activating potential of cuprophan dialyzers when they are subsequently re-used.

Adult↗
PubMed1980

Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells.

A clone of human cells (Detroit 6) latently infected by adeno-associated virus (AAV) has been characterized with regard to the status of the viral DNA. In both early (9 to 10) and late (118) passages of the clone, AAV-DNA was recombined with host DNA, at least in some cases as a head-to-tail tandem repeat, via the terminal sequences of the viral genome. However, it was not possible to distinguish between integration into chromosomal DNA and very large plasmids (< 20 x 10(6) molecular weight) which contain both viral and cellular DNA sequences. Although evidence for some modifications of the viral sequence was obtained, most of the integrated sequences appeared to be intact. In some cases sequences of undetermined origin separated adjacent copies of the viral genome. Free copies of the AAV genome were detectable in late passage cells, but not in early passage cells. The orientation of nucleotide sequences present in the free AAV DNA from late passage cells was indistinguishable from that of virion DNA. With the notable exception, the organization of the integrated AAV sequences as determined by restriction enzyme digestion remained constant with continued passage. Digestion with SmaI, which cleaves within the palindromic region of the terminal repetition in AAV DNA, produced reproducibly different patterns when early and late passage DNAs were compared. Several models for rescue of free copies of the genome from the integrated DNA are possible, all of which involve the terminal repetition.

Base Sequence↗
PubMed1979

Are class I (pre-early) proteins of bacteriophage T5 sufficient to induce abortive infection of ColIb+ Escherichia coli?

When T5 bacteriophage infect a colicin Ib-containing host, a variety of membrane changes and inhibition of macromolecular synthesis occur. This work shows that all these changes also occur when a mutant of T5 that can only inject 8% of its DNA is used. This indicates that all the information necessary for the abortive infection is present on this 8% (first-step-transfer) DNA.

Colicins↗
PubMed1977

Membrane damage in abortive infections of colicin Ib-containing Escherichia coli by bacteriophage T5.

Strains of Escherichia coli K-12 containing the colicin Ib (Col Ib) factor did not produce progeny phage when infected by T5 bacteriophage. The cells were killed but did not lyse. If sodium dodecyl sulfate (SDS) was added to T5-infected E. coli (Col Ib), lysis occurred prematurely, but no phage were produced. SDS had no effect on infected cells that did not contain the Col Ib factor or on uninfected cells with or without the Col Ib factor. Cells that contained a mutant Col Ib factor that allowed phage production were not prematurely lysed after infection in the presence of SDS. When the Col Ib-containing cells were infected, protein and RNA synthesis stopped at about 10 min postinfection, and the cells released abnormal amounts of 32P-containing material, ATP, and beta-galactosidase into the medium. They also became inhibited in their ability to accumulate thiomethyl-beta-D-galactopyranoside and to utilize glycerol. Two alternative hypotheses are presented to explain these results.

Adenosine Triphosphate↗
PubMedDate not supplied

Quantification of middle molecular weight solute removal in dialysis.

The pioneering work of Gotch emphasized the critical need to be quantitative with respect to treatment prescription. Through his meticulous derivations and analyses regarding Kt/V(urea), he has provided powerful insight into the standard therapy prescriptions that we now employ clinically. However, time has seen the proliferation of treatment techniques, most of which are too "young" to have been characterized with respect to clinical outcomes. Further, the relationship between removal of urea and removal of middle molecular size solutes associated with these newer techniques deviates from that associated with conventional, clinically qualified techniques. In this article we examine the solute clearance profile of some of these new methodologies and their relationship to current criteria for treatment adequacy. Our approach is to discuss components of the overall transport process and then utilize modeling of surrogate molecules over the size range of interest whose transport characteristics are known. Alteration in the solute clearance profile of these surrogate markers in response to changes in prescription variables will thus offer insight into the spectrum of toxic middle molecules that are removed when size, space of distribution, and generation rate are known.

Humans↗
PubMedDate not supplied

Hematocrit as an indicator of blood volume and a predictor of intradialytic morbid events.

Hematocrit (H) levels can change during hemodialysis, and these changes in H are inversely related to changes in blood volume (BV). The objectives of this study were to determine whether mean arterial pressure (MAP) decreases with decreasing BV and rising H during hemodialysis, and to determine the relationship between dialysis induced intravascular volume depletion and intradialytic morbid events (IME), defined as hypotension, cramping, or lightheadedness that led to dialysis staff intervention. We monitored H continuously using a noninvasive optical technique in 93 hemodialysis sessions in 16 patients. IME occurred in 48 sessions. MAP decreased with increasing H in 10 of 16 patients (P < 0.05), but the relationship between MAP and H varied among the patients. The rate of BV change during sessions without morbidity (5.6 +/- 3.6 [SD] %/hr) was lower (P < 0.001) than that preceding IME in the other sessions (12.2 +/- 5.5 [SD] %/hr). Twelve of 16 patients who exhibited recurrent IME during this study experienced these events when H reached a patient specific threshold. It is concluded that MAP decreases with decreasing BV and increasing H in many patients on hemodialysis, and that a high rate of BV change often indicates that IME are forthcoming. It is further hypothesized that a patient specific H threshold is indicative of a critical BV level below which certain patients experience IME.

Blood Pressure↗
PubMedDate not supplied

Single compartment models for evaluating beta 2-microglobulin clearance during hemodialysis.

Methods for evaluating dialyzer clearance of beta 2-microglobulin during clinical hemodialysis have not been well established. The authors show, theoretically, that the postdialysis-to-predialysis concentration ratio, a parameter often used to estimate dialyzer clearance of beta 2-microglobulin, depends on KdT/V (the dialyzer clearance times the treatment time divided by the distribution volume for beta 2-microglobulin) and the ultrafiltration rate, assuming that a single compartment kinetic model is valid. They also show that adjustment of the postdialysis concentration of beta 2-microglobulin for changes in its volume of distribution does not entirely correct for fluid removal when the adjusted postdialysis-to-predialysis concentration ratio is significantly below one. These considerations suggest that estimates of dialyzer clearance of beta 2-microglobulin using single compartment models are more reliable than those using only the postdialysis-to-predialysis concentration ratio. To illustrate these constructs, the authors compared experimental estimates of beta 2-microglobulin clearance during clinical hemodialysis using single compartment models with those measured directly from the arteriovenous concentration difference across the dialyzer. First-use low flux and high flux-dialyzers and those reprocessed with Renalin were studied. Single compartment estimates of beta 2-microglobulin clearance for low flux dialyzers were similar to those measured directly across the dialyzer, but single compartment estimates of beta 2-microglobulin clearance for high flux dialyzers exceeded (p < 0.001) those measured directly across the dialyzer, independent of whether fluid removal during hemodialysis was assumed to be removed entirely from the extracellular compartment or proportionally from both intracellular and extracellular compartments. The authors conclude that accurate estimates of beta 2-microglobulin clearance for high flux dialyzers will require kinetic models that are more complex than those assuming a uniform distribution of beta 2-microglobulin in a single, well-mixed compartment.

Adult↗
PubMedDate not supplied

Risk factors for hypertension in chronic hemodialysis patients: baseline data from the HEMO study.

A cross-sectional analysis was performed to determine risk factors associated with hypertension in 1,238 chronic hemodialysis patients upon enrollment into the HEMO Study. The mean pre- and post-dialysis systolic blood pressure were 152.4 +/- 25.0 (mean +/- SD) and 137.8 +/- 24.6 mm Hg, respectively. The mean pre- and post-dialysis diastolic blood pressures were 82.1 +/- 14.8 and 74.7 +/- 13.8 mm Hg, respectively. Less than 30% of the study cohort had blood pressures that were normotensive by JNC VI guidelines. Risk factors associated with higher pre- and post-dialysis systolic blood pressures included the presence of diabetes mellitus, older age, increased number of prescribed antihypertensive medications, lower hematocrit, and absence of arrhythmias. Variables associated with higher pre- and post-dialysis diastolic blood pressures included younger age, increased number of prescribed anti-hypertensive medications and absence of arrhythmias. There was also a nonlinear relationship between blood pressure and prescribed total ultrafiltration volume. A total ultrafiltration volume of >2.5 kg was associated with an elevation in pre-dialysis systolic and diastolic blood pressures. A total ultrafiltration volume of < or =2.5 kg was associated with an elevation in post-dialysis systolic and diastolic blood pressures. These data on ultrafiltration volume suggest that higher pre-dialysis blood pressures may be associated with excessive interdialytic weight gains due to patient noncompliance with fluid restriction and that higher post-dialysis blood pressures may be associated with a prescribed dry weight that is higher than the patient's true dry weight. Better management of these parameters may improve the prevalence and severity of hypertension in this population.

Clinical Trials as Topic↗
PubMedDate not supplied

Increased urinary lipoperoxide levels in renal transplant patients.

Using high performance liquid chromatographic methods, both plasma and urine lipoperoxide concentrations were measured, as malondialdehyde (MDA), in 30 stable renal transplant patients receiving daily cyclosporine and/or azathioprine therapy. Their MDA concentrations were compared with previously reported reliable reference values using the same liquid chromatographic methods. Although their plasma concentrations were within the reference range, their mean urine MDA values averaged 3.7 to 5.0 times the normal reference values (p less than 0.001). The primary cause of the increased urine MDA concentrations following renal transplantation in these patients is unknown; it could be due to (a) renal lipid peroxidation directly related to the cyclosporine/azathioprine therapy, (b) drug-induced or other nephrotoxicity by an alternative mechanism with secondary lipid peroxidation, (c) increased lipid peroxidation owing to an immunologic response to the kidney graft, or (d) a combination of these possibilities.

Azathioprine↗