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Biomedical subjects

M Rendell

Publications and source records attributed to M Rendell.

53 records · Page 3Linked to original sources
PubMed1981

General quantitative treatment for the binding of divalent antibodies to antigens immobilized on a solid phase.

A general expression for the binding isotherm of divalent antibodies to antigens bound to solid lattices with excluded volume effects is derived by using a statistical mechanical approach. The method is based on matrix generation of the partition function for the system, from which the degree of saturation of the antigen lattice may be computed directly. The saturation function has a simple form that under appropriate conditions reduces to forms derived previously for simpler cases (such as monovalent binding with and without excluded volume effects). Solution by numerical techniques of a simple secular equation for each concentration of antibody allows computation of the saturation function. Thus, the binding expression derived is easily fit to any set of binding data obtained and results in the determination of such parameters as intrinsic affinity constants, length of excluded space (and hence molecular size), and number of sites. It predicts that under conditions wherein divalent binding is favored over univalent binding, biphasic adsorption isotherms will be obtained.

Journal Article↗
PubMed1981

Endogenous insulin secretion measured by C-peptide in maturity-onset diabetes controllable by diet alone.

Endogenous insulin secretion was quantified in patients with maturity-onset diabetes (MOD) whose diabetes was controllable solely by caloric regulation as primary therapy. Insulin was used adjunctively only and persistent attempts were made to withdraw it as weight loss occurred in response to diet. Insulin secretory capacity was measured by C-peptide response during a standard 100-g oral glucose tolerance test in 24 patients who achieved normalization of plasma glucose level as a result of dietary therapy alone. Summed C-peptide levels for the diet-controlled diabetic patients was 7.8 +/- 0.7 pmol/mL as compared with 6.1 +/- 0.45 pmol/mL for a group of ten normal-weight, nondiabetic volunteers.

Adult↗
PubMed1979

A case of maturity-onset diabetes mellitus resistant to insulin but responsive to tolbutamide.

A nonobese patient with maturity-onset diabetes mellitus was hospitalized for treatment of an ulcer on his right foot. During this episode, his diabetic control worsened, and he proved unresponsive to exogenous insulin. Unresponsiveness to insulin persisted after healing of the ulcer. Tolbutamide therapy was then begun and produced a marked reduction in blood sugar levels. Withdrawal of the drug was accompanied by a progressive rise in blood sugar level. Intravenous infusion of regular pork insulin at rates of 45 U/h and single-component pork insulin at rates of 120 U/h had minimal effect on the blood sugar level. High levels of antibody to beef insulin were measured, with lower levels of pork insulin antibodies. C-peptide values were in a normal range before tolbutamide treatment and increased after use of the drug.

Administration, Oral↗
PubMed1978

Fatal compulsive water drinking.

In two cases of psychogenic polydipsia, water intoxication developed and contributed to the patient's death. The treatment of the patient with psychogenic polydipsia has been based on the presumed reversibility of the condition. Treatment of such patients must be reconsidered in light of these deaths.

Adult↗
PubMed1975

The hepatic adenylate cyclase system. I. Evidence for transition states and structural requirements for guanine nucloetide activiation.

Previous studies have shown that guanine nucleotides, acting at a site termed nucleotide regulatory site, are required for activation of hepatic adenylate cyclase and that glucagon facilitates this process. This study shows that only guanine nucleotides containing triphosphate groups at the 5' position of ribose (or 3'-deoxyribose) are capable of activating the enzyme. The terminal phosphate is not utilized in the activation process since 5'-guanylylimidodiphosphate (Gpp(NH)p and 5'-guanylyl methylenediphosphonate, analogues of GTP that are not utilized in transferase or hydrolase reactions, stimulate enzyme activity. The nucleotides bind in their free form at the regulatory site; chelation by magnesium ion shifts the apparent concentration dependence for activation by Gpp(nh)p. GDP inhibits competitively Gpp(NH)p-stimulated activity and inhibits basal activity and activities stimulated by glucagon. Activation of the enzyme by Gpp(NH)p is a slow process; the length of the lag time increases as an inverse function of nucleotide concentration and is as long as 4 min before onset of increased enzyme activity. Following pretreatment with Gpp(NH)p and extensive washing of hepatic membranes, the enzyme displays immediate increases in activity with rates that are a function of the nucleotide concentration during pretreatment; the rates remain constant for at least 6 min despite the absence of Gpp(NH)p in the medium. Studies with labeled Gpp(NH)p show that the intact nucleotide remains firmly bound to the membranes after extensive washing, suggesting that the persistence of adenylate cyclase activity may be related to slow dissociation of the nucleotide from the regulatory site. Addition of 1 nM glucagon, a submaximal concentration, does not abolish the lag phase of Gpp(NH)p activation even at saturating concentration of the nucleotide (1 muM or higher). The maximal steady state rate is achieved under these conditions. Addition of 2 muM glucagon, a saturating hormone concentration, does not alter the steady state rate but abolishes the lag phase of Gpp(NH)p activation. The transient kinetics of Gpp(NH)p activation and the effects of glucagon thereon are discussed in terms of a three state model in which the guanine nucleotide induces the formation of an intermediate transition state that displays no increase in enzyme activity over the basal state and which slowly isomerizes to a high activity state of the adenylate cyclase system; glucagon acts by accelerating the rate of isomerization.

Adenylyl Cyclases↗
PubMed1975

The hepatic adenylate cyclase system. III. A mathematical model for the steady state kinetics of catalysis and nucleotide regulation.

This paper presents a steady state kinetic model for hepatic adenylate cyclase. The activity of the enzyme has been assayed in the presence of a range of concentrations of magnesium, adenylylimidodiphosphate (App(NH)p), 5'-guanylylimidodiphosphate (Gpp(NH)p), and in the presence and absence of saturating concentrations of glucagon. The data were tested against proposed models using an iterative least squares curve fitting program (SAAM25) and confidence estimates for the model parameters were obtained. Hepatic adenylate cyclase is viewed as an enzyme having three characteristic states of catalytic function (E, E', E''). Each state has its own intrinsic activity in carrying out the catalysis of MgApp(NH)p-3 minus to form cyclic adenosine 3':5'-monophosphate. It is shown, in agreement with a proposal by de Haën, that unchelated substrate can inhibit adenylate cyclase activity. It is further concluded that this inhibition is principally due to App(NH)pH-3 minus. The three catalytic states differ markedly in their susceptibility to inhibition as well as in their Vmax, but the Km for MgApp(NH)p-2 minus is essentially the same for all states. The state transitions induced by Gpp(NH)p and by hormone are considered. Gpp(NH)p binding to state E causes transformation to state E'. State E' undergoes spontaneous transformation to state E''. Glucagon augments the transition from E' to E''. We conclude that the activating species of Gpp(NH)p is an unchelated form, most probably Gpp(NH)p-4 minus. Our results indicate that state E' is significantly more susceptible to inhibition by App(NH)pH-3 minus than the other two states. Certain phenomena occurring in fat cell adenylate cyclase are discussed in light of our findings in hepatic adenylate cyclase.

Adenine Nucleotides↗
PubMed1975

The hepatic adenylate cyclase system. II. Substrate binding and utilization and the effects of magnesium ion and pH.

The kinetic characteristics of substrate utilization by hepatic adenylate cyclase were investigated under a variety of incubation conditions, including veriations in pH, [substrate], [Mg2+], and in the absence or presence of glucagon. Activities were compared with ATP and 5'-adenylylimidodiphosphate (App(NH)p) as substrates. The Km for both substrates was about 50 muM; Vmax given with App(NH)p was about 40% lower than obtained with ATP as substrate. In the presence of a saturating concentration of substrate (1 mM), basal activity was increased 4-fold by increasing [Mg2+] from 5 to 50 mM. The stimulatory effect of Mg2+ was not due to an allosteric action since basal activity was only marginally enhanced (40%) when the substrate concentration was reduced to 10 muM. As suggested by deHaen ((1974 J. Biol. Chem. 249, 2756), it is likely that Mg2+ increases enzyme activity by decreasing the concentration of an inhibitory, unchelated form of substrate that competes with the productive magnesium-substrate complex at the active site. Activity-pH profiles differed with ATP and App(NH)p as substrates; a shift in pH optimum was observed which correlated with the different pKa of the terminal phosphate groups of ATP and App(nh)p, and which reflect the concentration of protonated substrate (ATPH-3 minus) present in the incubation medium. Accordingly, protonated substrate is the predominant inhibitory species of unchelated substrate and probably has a considerably higher affinity for the active site than does the magnesium-substrate complex. Glucagon-stimulated activity was less susceptible to inhibition by protonated substrate than is the basal state as evidenced by lower stimulatory effect when the [Mg2+] was increased from 5 to 20 mM. However, increasing the [Mg2+] from 20 to 50 mM resulted in marked inhibition of glucagon-stimulated activity, particularly in the presence of 10 muM substrate. Conversely, at a fixed [Mg2+], concentrations of substrate at least 20-fold higher than the Km were required to achieve maximal hormone-stimulated activity. These findings suggest that the unchelated, fully ionized form of substrate serves as an activating ligand, as has been observed with guanine nucleotides at considerably lower concentrations. Thus, Mg2+ affects adenylate cyclase activity by forming the productive substrate complex and by titrating the inhibitory protonated and activating free forms of substrate. As a result of these effects of unchelated substrate, it proved difficult to evaluate the kinetic parameters involved in substrate binding and utilization and the effects of hormone thereon when substrate was added as the only source of activating ligand. However, linear Michaelis kinetic data were obtained by adding the activating ligand 5'-guanylylimidodiphosphate with glucagon and by making appropriate adjustments of pH and [Mg2+]. Vmax was increased 4-fold without changes in Km by the actions of 5'-guanylylimidodiphosphate and glucagon.

Adenine Nucleotides↗
PubMedDate not supplied

The expanding clinical use of C-peptide radioimmunoassay.

C-peptide levels are in many ways a better measure of endogenous insulin secretion than peripheral insulin levels. C-peptide may be measured in either blood or urine. Perhaps the major advantage of measuring C-peptide levels is the ability to readily distinguish endogenous insulin levels in the presence of exogenous administration of insulin. Early C-peptide immunoassays were troubled by lack of sensitivity. This problem has now been overcome, and it is possible to measure C-peptide values down to extremely low levels. The clinical indications for C-peptide measurement include diagnosis of insulinoma and differentiation from factitious hypoglycemia, follow-up of pancreatectomy and evaluation of viability of islet cell transplants. Recently these indications have been dramatically expanded to permit evaluation of insulin dependence in maturity onset diabetes mellitus.

Antibodies↗
PubMedDate not supplied

Current perception threshold screening for carpal tunnel syndrome.

Screening for the onset of carpal tunnel syndrome (CTS), which is associated with excess ergonomic stresses of the wrist and hand, is a major concern in occupational medicine. CTS questionnaires, physical examinations, and quantitative sensory function determination through neuroselective current perception threshold (CPT) measurements were obtained from the median digital nerves of 16 assembly line workers who were symptomatic with hand pain. Median nerve evaluations by CPT detected sensory abnormalities in 75% of the workers, and abnormalities in 50% of the workers were detected by clinical evaluations (p less than .05, df = 22). CPT abnormalities were characterized as "hypoesthetic" in 25% and hyperesthesic in 42% of the workers. The noninvasive, nonaversive CPT technique provided sensitive and easily obtained quantitative measures. Regular use of this procedure in the occupational setting may assist in preventing the development of advanced CTS for it provides early detection of median nerve abnormalities.

Carpal Tunnel Syndrome↗
PubMedDate not supplied

Exacerbation of diabetes mellitus by antibodies to exogenous insulin.

Three nonobese maturity-onset diabetic patients has worsening hyperglycemia and ketonuria unresponsive to marked increases in dose of beef/pork insulin. In each case, significant cross-reactivity with human insulin of anti-insulin antibodies generated by exogenous insulin therapy was demonstrated by competition experiments using solid phase radioimmunoassay. Normal or near normal levels of endogenous insulin secretion as determined by C-peptide radioimmunoassay were measured in the three cases. The sequence of events that we postulate to explain the initial presentation with severe hyperglycemia in each case begins with a slight deficiency in endogenous insulin reserve. Mild hyperglycemia then led to treatment with beef/pork insulin. The beef component elicited an antibody response that not only bound exogenous insulin, reducing its effectiveness, but also inactivated each patient's endogenous human insulin, provoking an exacerbation of underlying mild diabetes.

Adult↗
PubMedDate not supplied

Fingerstick glycosylated hemoglobin, plasma protein, and albumin.

We have developed techniques that permit the affinity-chromatographic determination of glycosylated hemoglobin, plasma protein, and albumin on fingerstick samples of whole blood. The fingerstick glycohemoglobin technique takes advantage of the high sensitivity of measurement of hemoglobin by absorbance at 414 nm. The glycosylated plasma protein is assayed by a highly sensitive method based on binding of Coomassie blue. An enzyme-linked immunosorbent assay is used to measure albumin in the bound and nonbound fractions of an aminophenylboronic acid chromatographic separation. The fingerstick method for assay of glycosylated plasma albumin gives results that are approximately 40% higher than comparable values obtained on the same patient with a 1-ml plasma sample determined with the bromcresol green technique. There is good correlation of fingerstick glycoalbumins with fingerstick glycohemoglobins and glycosylated plasma protein values. These procedures should be useful for children and for large-scale ambulatory screening for diabetes mellitus.

Blood Chemical Analysis↗
PubMedDate not supplied

Recovery from decompensated non-insulin-dependent diabetes mellitus: studies of C-peptide secretion.

Eleven non-insulin-dependent diabetic patients presented with decompensated hyperglycemia. Nine had pronounced ketonuria, five with acidosis. In seven cases, precipitating factors were identified. In the other four cases, including three cases of diabetic ketoacidosis, no identifiable triggering events were present. In each case, recovery from the initially decompensated diabetic state occurred. Eventually, all patients were managed by diet alone. Seven patients demonstrated nondiabetic glucose tolerance tests (GTT). Several patients underwent stressful situations after "recovery" without recurrence of hyperglycemia. Glucose-stimulated C-peptide levels were determined postrecovery. C-peptide secretion was in the normal range and, in fact, was identical, in relation to glucose levels, to that in a group of nondiabetic volunteers. In 6 of the 11 cases, C-peptide secretion was measured at the time of initial presentation. These levels were markedly lower than comparable values during the GTT postrecovery. Non-insulin-dependent diabetes, even when presenting in a decompensated state, is subject to a considerable degree of reversibility and even recovery to a nondiabetic state in some cases. Recovery is associated with a return to normal C-peptide secretion.

Adult↗
PubMedDate not supplied

The dawn phenomenon, an early morning glucose rise: implications for diabetic intraday blood glucose variation.

Eleven insulin-dependent (type I) diabetic subjects were studied during a 24-h period to assess intraday blood glucose (BG) variation and related free insulin (FI) levels. Ten patients exhibited the dawn phenomenon, a rise in early morning fasting blood glucose (123 +/- 81.1 m/dl; mean +/- SD). This increase was positively and significantly correlated with the morning postprandial BG peak (r = 0.723; P = 0.012). FI/BG ratios were highest during the night (0.717 and 0.666 at 2200 and 0400 h, respectively) and lowest during the early morning (0.294 at 0800 h) (P less than 0.01). Three of the four observed hypoglycemic episodes occurred during the period when free insulin levels were high relative to BG. We conclude that the dawn phenomenon contributed directly and significantly to the BG maximum and indirectly, in some cases, to nocturnal hypoglycemia. It thus played an important role in the intraday blood glucose variation of such patients.

Adolescent↗