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B C Wang

Publications and source records attributed to B C Wang.

At least 127 records · Page 7Linked to original sources
PubMed1985

Novel arrangement of immunoglobulin variable domains: X-ray crystallographic analysis of the lambda-chain dimer Bence-Jones protein Loc.

We have characterized and crystallized a human lambda I light-chain dimer, Bence-Jones protein Loc, which has variable (V) region antigenic determinants characteristic for the lambda I subgroup and constant (C) region determinants of the C lambda I gene Mcg. The crystal structure was determined to 3-A resolution; the R factor is 0.27. The angle formed by the twofold axes of the V and C domains, the "elbow bend", is 97 degrees, the smallest found so far for an antibody fragment. The antigen-binding site formed by the two V domains of the Loc light chain differs significantly from those of other immunoglobulin molecules (light-chain dimers and Fab fragments) for which X-ray crystallographic data are available. Whereas, in other antibody fragments, the V domains are related by a local twofold axis, a local twofold screw axis with a translational component of 3.5 A relates the V domains in protein Loc. In contrast to the classic antigen binding "pocket" formed by V domain interactions in the previously characterized antibody structures, the V region associations in protein Loc result in a central protrusion in the binding site, with grooves on two sides of the protrusion. The structure of protein Loc indicates that immunoglobulins are physically capable of forming a more diverse spectrum of antigen-binding sites than has been heretofore apparent. Moreover, the unusual protruding nature of the binding site may be analogous to structures required for some anti-idiotypic antibodies. Further, the complementarity-determining residues form parts of two independent grooves.(ABSTRACT TRUNCATED AT 250 WORDS)

Bence Jones Protein↗
PubMed1985

Crystal structure of Azotobacter cytochrome c5 at 2.5 A resolution.

The crystal structure of cytochrome c5 from Azotobacter vinelandii has been solved and refined to an R value of 0.29 at 2.5 A resolution. The structure of the oxidized protein was solved using a monoclinic crystal form. The structure was solved by multiple isomorphous replacements, re-fit to a solvent-leveled multiple isomorphous replacement map, and refined by restrained least squares. The structure reveals monomers associated about the crystallographic 2-fold axis by hydrophobic contacts at the "exposed heme edge". The overall conformation for the monomer is similar to that of Pseudomonas aeruginosa cytochrome c551. However, relative to a common heme conformation, c5 and c551 differ by an average of 6.8 A over 82 alpha-carbon positions and the propionates of c5 are much more exposed to solvent. The shortest heme--heme contact at the "dimer" interface is 6.3 A (Fe to Fe 16.4 A). Alignment of c5 and c551 shows that the two cytochromes, in spite of sequence differences, have remarkably similar charge distributions. A disulfide stacks on a tyrosine between the N- and C-terminal helices.

Amino Acid Sequence↗
PubMed1985

Crystallographic structure of the octameric histone core of the nucleosome at a resolution of 3.3 A.

The structure of the (H2A-H2B-H3-H4)2 histone octamer has been determined by means of x-ray crystallographic techniques at a resolution of 3.3 angstroms. The octamer is a prolate ellipsoid 110 angstroms long and 65 to 70 angstroms in diameter, and its general shape is that of a rugby ball. The size and shape are radically different from those determined in earlier studies. The most striking feature of the histone octamer is its tripartite organization, that is, a central (H3-H4)2 tetramer flanked by two H2A-H2B dimers. The DNA helix, placed around the octamer in a path suggested by the features on the surface of the protein, appears like a spring holding the H2A-H2B dimers at either end of the (H3-H4)2 tetramer.

Animals↗
PubMed1985

Molecular structure of troponin C from chicken skeletal muscle at 3-angstrom resolution.

The x-ray structure of chicken skeletal muscle troponin C (TnC), the Ca2+-binding subunit of the troponin complex, shows that the protein is about 70 angstroms long with an unusual dumbbell shape. The carboxyl and amino domains are separated by a single long alpha helix of about nine turns. Only the two high-affinity Ca2+-Mg2+ sites of the COOH-domain are occupied by metal ions resulting in conformational differences between the COOH- and NH2-domains. These differences are probably important in the triggering of muscle contraction by TnC. Also the structure of TnC is relevant in understanding the function of other calcium-regulated proteins, in particular that of calmodulin because of its strong similarity in amino acid sequence.

Animals↗
PubMed1985

Plasma vasopressin, renin activity, and aldosterone responses to maximal exercise in active college females.

The effect of maximal treadmill exercise on plasma concentrations of vasopressin (AVP); renin activity (PRA); and aldosterone (ALDO) was studied in nine female college basketball players before and after a 5-month basketball season. Pre-season plasma AVP increased (p less than 0.05) from a pre-exercise concentration of 3.8 +/- 0.5 to 15.8 +/- 4.8 pg X ml-1 following exercise. Post-season, the pre-exercise plasma AVP level averaged 1.5 +/- 0.5 pg X ml-1 and increased to 16.7 +/- 5.9 pg X ml-1 after the exercise test. PRA increased (p less than 0.05) from a pre-exercise value of 1.6 +/- 0.6 to 6.8 +/- 1.7 ngAI X ml-1 X hr-1 5 min after the end of exercise during the pre-season test. In the post-season, the pre-exercise PRA was comparable (2.4 +/- 0.6 ngAI X ml- X hr-1), as was the elevation found after maximal exercise (8.3 +/- 1.9 ngAI X ml- X hr-1). Pre-season plasma ALDO increased (p less than 0.05) from 102.9 +/- 30.8 pg X ml-1 in the pre-exercise period to 453.8 +/- 54.8 pg X ml-1 after the exercise test. In the post-season the values were 108.9 +/- 19.4 and 365.9 +/- 64.4 pg X ml-1, respectively. Thus, maximal exercise in females produced significant increases in plasma AVP, renin activity, and ALDO that are comparable to those reported previously for male subjects. Moreover, this response is remarkably reproducible as demonstrated by the results of the two tests performed 5 months apart.

Adult↗
PubMed1985

Aortic baroreceptor discharge during nonhypotensive hemorrhage in anesthetized dogs.

We tested the hypothesis that arterial baroreceptor discharge remains constant during nonhypotensive hemorrhage. Aortic baroreceptor activity was recorded from anesthetized dogs during slow, continuous hemorrhage until 24 ml blood/kg body wt had been removed. The relationship between simultaneously recorded hemodynamic variables and single-unit aortic baroreceptor activity was evaluated by a unique computer program that sampled all variables 500 times/s and analyzed data from each consecutive cardiac cycle throughout the entire experiment. In three hemorrhages performed on three dogs, aortic blood pressure did not decrease during the experiment (nonhypotensive hemorrhage), but aortic nerve activity decreased progressively when data from individual cardiac cycles having identical mean aortic pressures were compared. Reduced baroreceptor activity correlated closely with progressive reductions in pulse pressure. In other hemorrhages, mean aortic pressure decreased by a variable amount; decreases in recorded single-unit baroreceptor activity occurred during each of these hemorrhages also. In summary, hemorrhage consistently caused decreases in the activity of aortic baroreceptors regardless of whether mean aortic pressure decreased or remained constant during hemorrhage. We conclude that experimental techniques employing nonhypotensive hemorrhage do not provide an effective method for selectively studying reflexes from cardiopulmonary receptors in the absence of changes in arterial baroreceptor input.

Action Potentials↗
PubMed1985

Factors influencing the secretion of vasopressin into cerebrospinal fluid.

Vasopressin (VP) has been found in the cerebrospinal fluid (CSF) of several species of animals. Although it is known that hemorrhage, hypertonicity of body fluid, hypoxia, and hypercapnia all increase VP in plasma, little is known regarding the stimuli that cause the secretion of VP into the CSF. We therefore performed several studies to examine whether stimuli capable of increasing plasma levels of VP can also increase VP in the CSF of anesthetized dogs. We found that hemorrhage, intracerebroventricular infusion of hypertonic artificial CSF, hypoxia, and hypercapnia all produced increases in the concentration of VP in plasma and in CSF, but the time courses and the magnitude of the increases in the two compartments were different. In addition, an i.v. infusion of hypertonic saline or of hydrochloric acid produced an increase in plasma VP without significantly changing CSF VP. Thus, although the secretion of VP into plasma and CSF may be influenced by the same stimuli, changes in one compartment do not necessarily correlate with changes in the other. Taken together, our results are consistent with the hypothesis that the plasma and CSF VP may derive from different sources.

Acidosis↗
PubMed1984

Vasopressin in plasma and cerebrospinal fluid of dogs during hypoxia or acidosis.

Hypoxia and hypercapnia have been shown to cause an increase in the concentration of vasopressin in plasma, but their effects on vasopressin in cerebrospinal fluid (CSF) are not known. In addition, the effect of metabolic acidosis on plasma and CSF vasopressin has not been reported. In this study, plasma and CSF vasopressin levels were measured in anesthetized dogs subjected to either hypoxia, hypercapnia, or metabolic acidosis. Rate and depth of respiration were closely regulated with the aid of muscle paralysis and mechanical ventilation. Vasopressin increased markedly in both plasma and CSF during severe hypoxia (10% O2) and during hypercapnia (10% CO2) but did not change during either mild (15% O2) or moderate (12.5% O2) hypoxia. Although mild hypoxia by itself did not affect either plasma or CSF vasopressin, it did potentiate the increase in plasma and CSF vasopressin that was induced by severe hypercapnia, thus suggesting that hypoxia and hypercapnia may exert synergistic effects on vasopressin secretion. Metabolic acidosis produced by slow intravenous infusion of 1 N hydrochloric acid decreased arterial pH to values comparable to those induced by hypercapnia and increased vasopressin in plasma; CSF vasopressin was unchanged. These results are consistent with the concept that the source of vasopressin secreted into plasma may be different from that secreted into CSF.

Acidosis↗
PubMed1984

Cardiac receptor influences on the plasma osmolality-plasma vasopressin relationship.

Changes in blood volume are capable of altering the relationship between plasma osmolality (Posmol) and plasma arginine vasopressin (PAVP), presumably via a reflex elicited from cardiovascular receptors, but the precise location of the receptors involved in this response has not been established. Because cardiac receptors are capable of influencing AVP secretion, their specific effect was examined by producing volume changes in cardiac-denervated (CD) dogs and comparing the Posmol-PAVP relationship in these dogs with data from comparable experiments on sham-operated control dogs (cardiac-sham, CS). Posmol was increased by water deprivation for 96 h (volume depletion) and also by administration of hypertonic saline for 2 h (volume expansion). The slope of the regression line describing the Posmol-PAVP relationship in CS control dogs was steeper (P less than 0.01) during volume depletion (0.390) than it was during volume expansion (0.228), thus suggesting that volume depletion had enhanced and volume expansion had inhibited the secretion of AVP. In contrast, the slope of the regression line delineating the Posmol-PAVP relationship in CD dogs was essentially the same during volume depletion (0.288) as it was during volume expansion (0.291). It would seem that most, if not all, of the volume influences on the Posmol-PAVP relationship are mediated via reflex effects elicited by cardiac receptors.

Animals↗
PubMed1984

Cardiovascular and renin responses to vanadate in the conscious dog: attenuation after calcium channel blockade.

The effects of vanadate on cardiovascular function and on the secretion of renin and vasopressin were investigated by infusing sodium orthovanadate (0.32 mu mole/kg X min) intravenously into five conscious dogs. Vanadate caused significant increases in mean arterial pressure, total peripheral resistance, pulmonary arterial pressure, and cardiac output. These data illustrate that the hemodynamic effects of vanadate in the conscious dog are similar to those of the anesthetized dog but that minor differences do exist. Vanadate significantly suppressed plasma renin activity, but plasma vasopressin was unchanged. The effects of vanadate also were investigated in the same dogs on another day after administration of the calcium channel blocker, verapamil (0.3 mg/kg bolus + 0.01 mg/kg X min). After calcium channel blockade, the increases in arterial pressure and pulmonary arterial pressure induced by vanadate were attenuated, and cardiac output did not increase. Calcium channel blockade also prevented the vanadate-induced decrease in plasma renin activity. These data suggest that the cardiovascular and humoral alterations produced by vanadate in the conscious dog are at least partially mediated by changes in intracellular calcium.

Animals↗
PubMed1984

Comparative effects of cardiac receptors and sinoaortic baroreceptors on elevations of plasma vasopressin and renin activity elicited by haemorrhage.

Increases in plasma vasopressin and renin activity that occur in response to haemorrhage have been attributed in part to reflex effects from cardiac receptors and sinoaortic baroreceptors, but the relative importance of these different receptors in causing humoral changes during haemorrhage in conscious dogs has not been reported. We investigated this question by hemorrhaging 6 sham-operated (SO), 6 cardiac-denervated (CD), 4 sinoaortic-denervated (SAD), and 4 combined sinoaortic and cardiac-denervated (SACD), conscious dogs. Blood was removed at a rate of 0.9 ml/kg X min. Plasma vasopressin and renin samples were taken during a control period and after 10, 20, and 30 ml/kg of blood had been removed. Results (mean +/- SE) are shown in the tables below. (table; see text) These experiments illustrate that: resting plasma levels of vasopressin and renin in conscious dogs are unaffected by the denervation procedures used in these experiments, the increase in plasma vasopressin that occurs during haemorrhage is mediated largely via cardiac receptors, with a considerably smaller contribution from the sinoaortic baroreceptors, during moderately severe haemorrhage (30 ml/kg) vasopressin secretion can be increased by a mechanism independent of sinoaortic and cardiac reflexes, the increase in plasma renin activity that occurs during haemorrhage is not dependent upon either cardiac or sinoaortic reflexes.

Animals↗
PubMed1984

Chronic neurological deficits and Nesacaine-CE--an effect of the anesthetic, 2-chloroprocaine, or the antioxidant, sodium bisulfite?

Chronic neurological deficits have been described in patients after presumed accidental subarachnoid injection of 2-chloroprocaine-CE (Nesacaine-CE; N-CE) intended for epidural block. This study investigated the possible role of pure 2-chloroprocaine (2-CP) and sodium bisulfite, two components of Nesacaine-CE, in causing these complications when injected separately into the lumbar subarachnoid space of neurologically intact awake rabbits. Repeated 2-4-mg spinal anesthetic doses of pure 2-CP in lactated Ringer's solution did not produce chronic hindlimb paralysis even though accumulated doses reached 50 mg. However, 1.2-2.4 mg of sodium bisulfite, the antioxidant in N-CE added to prolong shelf-life, resulted in irreversible hindlimb paralysis in 12 out of 14 animals. This amount of bisulfite is contained in 12-24 mg of 2% N-CE. The demonstration that persistent paralysis resulted from low dosages of sodium bisulfite contained in commercially available 2-CP requires reevaluation of the suitability of this antioxidant for products prepared for intrathecal use.

Anesthetics, Local↗
PubMed1983

Structure of a novel Bence-Jones protein (Rhe) fragment at 1.6 A resolution.

The crystal structure of Rhe, a lambda-type Bence-Jones protein fragment, has been solved and refined to a resolution of 1.6 A. A model fragment consisting of the complete variable domain and the first three residues of the constant domain yields a crystallographic residual RF value of 0.149. The protein exists as a dimer both in solution and in the crystals. Although the "immunoglobulin fold" is generally preserved in the structure, there are significant differences in both the monomer conformation and in the mode of association of monomers into dimers, when compared to other known Bence-Jones proteins or Fab fragments. The variations in conformation within monomers are particularly significant as they involve non-hypervariable residues, which previously were believed to be part of a "structurally invariant" framework common to all immunoglobulin variable domains. The novel mode of dimerization is equally important, as it can result in combining site shapes and sizes unobtainable with the conventional mode of dimerization. A comparison of the structure with other variable domain dimers reveals further that the variations within monomers and between domains in the dimer are coupled. Some possible functional implications revealed by this coupling are greater variability, induced fitting of the combining site to better accommodate antigenic determinants, and a mechanism for relaying binding information from one end of the variable domain dimer to the other. In addition to providing the most accurate atomic parameters for an immunoglobulin domain yet obtained, the high resolution and extensive refinement resulted in identification of several tightly bound water molecules in key structural positions. These water molecules may be regarded as integral components of the protein. Other water molecules appear to be required to stabilize the novel conformation.

Amino Acid Sequence↗
PubMed1983

Vasopressin and renin responses to hemorrhage in conscious, cardiac-denervated dogs.

We measured plasma arginine vasopressin (AVP) and plasma renin activity (PRA) during continuous hemorrhage in cardiac-denervated and sham-operated conscious dogs. Hemorrhage produced comparable decreases in aortic pressure, cardiac output, stroke volume, pulmonary arterial pressure, and left and right atrial pressures in each group of dogs. After 10 ml blood/kg body wt had been removed, AVP was increased in sham-operated dogs (P less than 0.05) but not in cardiac-denervated dogs. After 20 and 30 ml blood/kg body wt had been removed, AVP was increased in all dogs, but the response was markedly attenuated in cardiac-denervated dogs. Hemorrhage at 10 and 20 ml/kg caused comparable increases in PRA in each group of dogs. However, at 30 ml/kg hemorrhage the increase in PRA was significantly higher in cardiac-denervated dogs than in sham-operated dogs. Our results suggest that cardiac receptors play a dominant role in mediating the release of AVP during hemorrhage in conscious dogs. In contrast, we found no evidence for a dominant role of cardiac receptors in mediating renin secretion during hemorrhage.

Animals↗
PubMed1983

Intracerebroventricular captopril does not inhibit osmotically stimulated vasopressin release.

Experiments were carried out to determine the effect of intracerebroventricular (icv) administration of the angiotensin-converting enzyme inhibitor, captopril, on osmotically stimulated vasopressin secretion. During icv infusion of captopril (3.1 micrograms/kg . min), dogs were infused intravenously (iv) with either 2.5 or 0.15 M NaCl. Control groups received an osmotically equivalent mannitol solution icv with the 2.5 or 0.15 M NaCl iv infusion. As a result of the iv hypertonic saline infusion, plasma vasopressin concentrations increased progressively and in concert with the plasma osmolality; this response was not altered by icv captopril. Plasma vasopressin levels were unchanged during iv isotonic saline infusion, and, again, icv captopril was without effect. At the completion of the icv infusions, injection of angiotensin I icv (310 ng/kg) produced a markedly greater increase in plasma vasopressin levels in animals which had received mannitol icv, compared to those which had received captopril icv. On the basis of these findings, a role for an intrinsic brain renin-angiotensin system, if such a system exists, in the osmotic control of vasopressin secretion is seriously questioned, but not ruled out.

Animals↗
PubMed1983

Effects of changes in steady state plasma vasopressin levels on renal and urinary vasopressin clearances in the dog.

A study was made of the effects of changes in the plasma vasopressin concentration on the extraction ratio and the renal organ and urinary clearances of vasopressin. Plasma vasopressin levels were increased in a stepwise fashion in anesthetized dogs by the iv infusion of vasopressin at rates of 100, 400, and 800 microU/min . kg. A steady state was achieved by infusing vasopressin for 60 min at each dose. Before the infusion of vasopressin, the extraction ratio and the renal and urinary clearances of vasopressin (one kidney) were 0.30 +/- 0.04, 1.8 +/- 0.2, and 1.4 +/- 0.1 ml/min . kg, respectively. The urinary clearance of vasopressin did not differ significantly from the inulin clearance (1.5 +/- 0.1 ml/min . kg). The infusion of vasopressin, which increased the plasma vasopressin concentration from an initial value of 4.3 +/- 1.3 to 54.6 +/- 2.4 microU/ml at the highest rate of infusion, was without effect on the vasopressin extraction ratio and the renal and urinary clearances of vasopressin. The MCR of vasopressin was estimated to be approximately 16 ml/min . kg. The renal clearance of vasopressin, calculated for both kidneys in all periods of all experiments, accounted for approximately 27% of the total clearance of vasopressin from the plasma. Thus, over a broad range of plasma vasopressin concentrations, a constant fraction of the vasopressin delivered to the kidney was removed from the blood perfusing the kidney, and the mechanisms for the renal extraction of vasopressin were not saturated.

Animals↗