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C H Baker

Publications and source records attributed to C H Baker.

At least 37 records · Page 2Linked to original sources
PubMed1993

Relation of phenotype evolution of HIV-1 to envelope V2 configuration.

Biological variability of human immunodeficiency virus type-1 (HIV-1) is involved in the pathogenesis of acquired immunodeficiency syndrome (AIDS). Syncytium-inducing (SI) HIV-1 variants emerge in 50 percent of infected individuals during infection, preceding accelerated CD4+ T cell loss and rapid progression to AIDS. The V1 to V2 and V3 region of the viral envelope glycoprotein gp120 contained the major determinants of SI capacity. The configuration of a hypervariable locus in the V2 domain appeared to be predictive for non-SI to SI phenotype conversion. Early prediction of HIV-1 phenotype evolution may be useful for clinical monitoring and treatment of asymptomatic infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Arteriolar endothelium-dependent vasodilation occurs during endotoxin shock.

Endotoxin shock has been reported to alter endothelial structure as well as function of large arteries from in vitro experiments. Cremaster muscle arteriolar dilator reactivity of pentobarbital-anesthetized rats was determined by videomicroscopy at control and 30, 90, 150, and 210 min after intravenous infusion of Escherichia coli endotoxin (6 mg/kg, 1-h period). The dilator response was tested by intra-arterial injections of 90 ng acetylcholine (ACh). At control A1, A2, and A3 arterioles dilated 45, 21, and 34%, respectively. Postendotoxin arterial pressure decreased progressively, the A1 arterioles constricted (P < 0.05), A2 diameters were unchanged and A3 diameters increased. Postendotoxin ACh dilations averaged 28, 23, and 25%. A1 dilation was significantly (P < 0.05) less than at control. Methylene blue (2.5 mg ia) attenuated the ACh response at control, but after endotoxin an intense downstream vasoconstriction resulted in stasis and reduced survival time occurred. Hydroquinone (HQ) partially blocked the responses to ACh postendotoxin. HQ significantly increased the survival time postendotoxin. It is evident postendotoxin that the endothelia of arterioles are functional and able to release nitric oxide (NO) throughout the entire survival period. The microvascular release of NO and the dilation response to ACh were substantially attenuated by methylene blue and HQ. The latter may block the more lethal effects of the inducible NO synthase.

Acetylcholine↗
PubMed1993

Effect of muscle length on the in vitro comparison of femoral arteries before and after endotoxin shock.

Control and endotoxin-treated femoral arteries were compared in vitro for the effect of muscle length. Rats were anesthetized with pentobarbital, and endotoxin (6 mg/kg) was infused for 1 h. A control ring before endotoxin treatment and a ring after endotoxin treatment (blood pressure = 40 mmHg) were excised from the contralateral artery for length-tension and dose-response experiments with phenylephrine. The initial length for resting tension (Li) was shorter for endotoxic rings (1.23 +/- 0.01 vs. 1.41 +/- 0.02 mm in control), but the length of maximum active tension (Lmax) was the same. In length-tension experiments the values for active tension (6.36 +/- 0.61 vs. 4.06 +/- 0.60 x 10(3) dyn/cm), preload at Lmax (1,333 +/- 204 vs. 733 +/- 146 mg), and passive stiffness were increased after endotoxin. In dose-response experiments at the same preload, the endotoxic rings had a lower active tension (3.28 +/- 0.28 vs. 6.55 +/- 0.27 x 10(3) dyn/cm) but the same sensitivity. At Lmax, active tension (12.45 +/- 0.48 vs. 5.01 +/- 0.89 x 10(3) dyn/cm in control vessels) and sensitivity (half-maximum effective dose = 0.68 +/- 0.8 x 10(-6) vs. 1.39 +/- 0.29 x 10(-6) M in control vessels) were greater for endotoxic rings. These experiments show that phenylephrine sensitivity and active tension in the rat femoral artery are increased by endotoxin shock, and the importance of muscle length is implied.

Animals↗
PubMed1993

Differences in arterial and arteriolar endothelial structure during endotoxin shock.

Previous studies of physiological and ultrastructural assessment changes in the walls of the femoral artery and A1, A2, and A3 arterioles in the rat cremaster muscle after infusion of Escherichia coli endotoxin (ENDT) (6 mg/kg-1 hr. period) indicate there may be a difference in the alteration of the endothelial structure of arteries and arterioles. Functionally, ENDT has been shown to abolish acetylcholine (ACh)-induced relaxation in the femoral artery [Zhou, PhD dissertation, University of South Florida, Tampa, 1992]. Dilations of A1 arterioles were shown to be reduced, but dilations of A2 and A3 arterioles were not significantly changed from control [Baker and Sutton, Am J Physiol, 264:H 1118-H 1123, 1993]. In the current study, ultrastructural evaluation of femoral arterial tissue post-ENDT at the mean arterial pressure (MAP) of 100 mm Hg revealed partially destroyed endothelial cells. The MAP decreased as the animal progressed into shock. At 80 mm Hg, 60 mm Hg and 40 mm Hg, essentially all endothelial cells were destroyed, with the internal elastic lamina denuded. In contrast, endotoxin damage in the A1, A2, and A3 arterioles was minimal even at a MAP of 40 mm Hg. Endothelial cells of A1 arterioles post-ENDT had more vacuoles than at control. Therefore, arteriolar endothelium was functionally and anatomically relatively undamaged, consequent to endotoxin administration, in contrast to femoral arteries where the endothelium was destroyed in a short time.

Animals↗
PubMed1993

Antagonism of acetylcholine and adenosine rat cremaster arteriolar vasodilation by combination of NO antagonists.

It has become evident that complete elimination of the vasodilator response to agonists that require the release of nitric oxide (NO) is necessary for certain studies of the microcirculation. The A2 and A3 arterioles of the rat cremaster muscle microcirculation were studied by video-microscopy. At control, arterioles at rest or constricted by arginine vasopressin (AVP) were dilated by intra-arterially injected acetylcholine (ACh), intra-arterially injected adenosine (ADO) and topical adenosine. The NO antagonists, Nw-nitro-L-arginine methyl ester (L-NAME) and hydroquinone (HQ), which acts as an antagonist by generating free radicals, in maximal doses, individually partially blocked the vasodilator actions of intra-arterial ACh and intra-arterial ADO. Combining L-NAME and HQ eliminated the vasodilation by intra-arterial ACh and intra-arterial ADO. Sodium nitroprusside dilated the arterioles to the resting level or above at control and in the presence of the antagonists either individually or when combined. However, the NO antagonists did not block the arteriolar vasodilator responses to topical ADO. The reduction of the production of NO and enhancement of its destruction by superoxide radicals results in the total absence of the vasodilator response due to intra-arterially injected acetylcholine and adenosine. The data suggest that luminal ADO receptors cause arteriolar dilation by endothelial-dependent mechanisms and abluminal receptors cause dilation by another mechanism.

Acetylcholine↗
PubMed1992

Overexpression, purification, and characterization of yeast cyclophilins A and B.

Two isoforms of yeast cyclophilins, yCyPA and yCyPB, have been subcloned, expressed in Escherichia coli, and purified to homogeneity. The full-length (163-amino acid) yeast CyPA was easily expressed and purified; however, only a genetically truncated, 186-residue form of yCyPB lacking a putative 20-amino acid signal sequence could be purified. Each yeast cyclophilin isoform is a peptidyl-prolyl isomerase, inhibitable by the immunosuppressive drug CsA (IC50's of 40 +/- 8 nM and 101 +/- 14 nM at 18 nM concentrations of yCyPA and yCyPB, respectively). Polyclonal antibodies raised against recombinant yCyPA detected native yCyPA in yeast cell extracts by both immunoprecipitation and Western blot analysis. However, polyclonal antibodies raised against recombinant yCyPB detected no native yCyPB in yeast cell extracts by Western blot analysis; small amounts of yCyPB were found in the culture broth, suggesting secretion extracellularly of this isoform. Northern analysis indicated that both yCyPA mRNA and yCYPB mRNA (at a much lower level) were detectable in cell-free extracts. Characterization of the yeast cyclophilin proteins demonstrated that their catalytic properties and sensitivity to CsA parallel those of the human cyclophilins.

Amino Acid Isomerases↗
PubMed1992

Endotoxin alteration of muscle microvascular renin-angiotensin responses.

Endotoxin decreases arteriolar sensitivity to norepinephrine and sympathetic neural activity, but vasopressin sensitivity is increased. Vascular responses to the renin-angiotensin system may also be altered by endotoxin (ENDT). Reactivity of cremaster muscle microvessels of pentobarbital anesthetized Wistar rats was studied using videomicroscopy. Escherichia coli endotoxin (6 mg/kg) was infused i.v. over a 1 hr period. Femoral arterial pressure (Pm) and arteriolar diameter changes, to i.a. bolus injections (60 ng) of angiotensin II (AII) were obtained in Group A at control and at 30 and 90 min post-ENDT, and in Group B at control, 30 min after continuous infusion of saralasin (10 micrograms/min/kg) began, and at 30 and 90 min post-endotoxin. In Group A, the control Pm was 106 +/- 4 mm Hg, and at 30 and 90 min post-ENDT was 96 +/- 4 and 89 +/- 7 mm Hg. All increased Pm 29 +/- 4% before ENDT but the increase was significantly less (P less than .05) at 7 +/- 1% and 6 +/- 1% 30 and 90 min post-ENDT. In Group B, the control Pm was 116 +/- 6 mm Hg, 103 +/- 5 after saralasin, 85 +/- 2 after ENDT infusion, and 83 +/- 4 and 63 +/- 8 mm Hg at 30 and 90 min post-ENDT. All increased Pm 34 +/- 7% before saralasin but only 5 +/- 2% (P less than .05) during saralasin infusion. In Group A, the A1 and A2 arterioles were constricted significantly more post-endotoxin by AII than during control. A3 arterioles post-endotoxin were constricted similar to control amounts by AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence.

We report the cloning and characterization of a cDNA encoding a second human cyclosporin A-binding protein (hCyPB). Homology analyses reveal that hCyPB is a member of the cyclophilin B (CyPB) family, which includes yeast CyPB, Drosophila nina A, and rat cyclophilin-like protein. This family is distinguished from the cyclophilin A (CyPA) family by the presence of endoplasmic reticulum (ER)-directed signal sequences. hCyPB has a hydrophobic leader sequence not found in hCyPA, and its first 25 amino acids are removed upon expression in Escherichia coli. Moreover, we show that hCyPB is a peptidyl-prolyl cis-trans isomerase which can be inhibited by cyclosporin A. These observations suggest that other members of the CyPB family will have similar enzymatic properties. Sequence comparisons of the CyPB proteins show a central, 165-amino acid peptidyl-prolyl isomerase and cyclosporin A-binding domain, flanked by variable N-terminal and C-terminal domains. These two variable regions may impart compartmental specificity and regulation to this family of cyclophilin proteins containing the conserved core domain. Northern blot analyses show that hCyPB mRNA is expressed in the Jurkat T-cell line, consistent with its possible target role in cyclosporin A-mediated immunosuppression.

Amino Acid Isomerases↗
PubMed1991

2'-Deoxy-2'-methylenecytidine and 2'-deoxy-2',2'-difluorocytidine 5'-diphosphates: potent mechanism-based inhibitors of ribonucleotide reductase.

It has been found that 2'-deoxy-2'-methyleneuridine (MdUrd), 2'-deoxy-2'-methylenecytidine (MdCyd), and 2'-deoxy-2',2'-difluorocytidine (dFdCyd) 5'-diphosphates (MdUDP (1) MdCDP (2) and dFdCDP (3), respectively) function as irreversible inactivators of the Escherichia coli ribonucleoside diphosphate reductase (RDPR). 2 is a much more potent inhibitor than its uridine analogue 1. It is proposed that 2 undergoes abstraction of H3' to give an allylic radical that captures a hydrogen atom and decomposes to an active alkylating furanone species. RDPR also accepts 3 as an alternative substrate analogue and presumably executes an initial abstraction of H3' to initiate formation of a suicide species. Both 2 and 3 give inactivation results that differ from those of previously studied inhibitors. The potent anticancer activities of MdCyd and dFdCyd indicate a significant chemotherapeutic potential. The analogous RDPR of mammalian cells should be regarded as a likely target and/or activating enzyme for these novel mechanism-based inactivators.

Cytosine↗
PubMed1990

Nutrient and nonnutrient renal blood flow.

The role of prostaglandins in the distribution of total renal blood flow (TRBF) between nutrient and nonnutrient compartments was investigated in anesthetized mongrel dogs. Renal blood flow distribution was assessed by the xenon 133 freeze-dissection technique and by rubidium 86 extraction after ibuprofen treatment. Ibuprofen (13 mg/kg) significantly decreased TRBF by 16.3% +/- 1.2% (mean +/- SEM electromagnetic flow probe; p less than 0.005), but did not alter blood flows to the outer cortex (3.7 vs 4.3 ml/min per gram), the inner cortex (2.6 vs 2.7 ml/min per gram), and the other medulla (1.5 vs 1.5 ml/min per gram), which suggests a decrease in nonnutrient flow. In a separate group of animals the effect of reduced blood flow on the nutrient and nonnutrient components was determined by mechanically reducing renal arterial blood flow by 48%. Unlike the ibuprofen group, nutrient blood flows were proportionally reduced with the mechanical decrease in TRBF in the outer cortex (1.9 ml/min per gram, p less than 0.05), the inner cortex (1.4 ml/min per gram, p less than 0.05), and the outer medulla (0.8 ml/min per gram, p less than 0.01). These results indicate no shift between nutrient and nonnutrient compartments. Nutrient and nonnutrient renal blood flows of the left kidney were also determined by 86Rb extraction. After ibuprofen treatment, nonextracted 86Rb decreased to 12.1% from the control value of 15.6% (p less than 0.05). Mechanical reduction of TRBF did not significantly decrease the proportion of unextracted 86Rb (18.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Reduced microvascular adrenergic receptor activity due to opioids in endotoxin shock.

Arteriolar sensitivity to norepinephrine is decreased in endotoxin shock, and sympathetic activity appears altered. We have tested involvement of arteriolar opioid receptors in the response to endotoxin. Cremaster muscle arteriolar reactivity of anesthetized rats was studied using videomicroscopy. Escherichia coli endotoxin (6 mg/kg, i.v., LD100) was infused over a 1-hr period. Mean arterial pressure (Pm), frequency/diameter curves of A1, A2, and A3 arterioles to lumbar sympathetic nerve stimulation (1-16 Hz), and plasma velocity were obtained in group I at control, 30 min, and 90 min postendotoxin and in group II at control and during i.v. infusion of the opiate antagonist naltrexone (0.5 mg/kg/min) at 30 and 90 min postendotoxin. Frequency-diameter curves (percentage of control diameter) were significantly (P less than 0.05) shifted to the right postendotoxin in group I indicating reduced response to lumbar sympathetic stimulation or norepinephrine from the nerve terminals. In group II rats receiving naltrexone after endotoxin, the frequency-diameter curves were significantly (P less than 0.05) shifted to the left indicating enhanced vasoconstriction to lumbar sympathetic stimulation in comparison to control and to group I postendotoxin curves. Postendotoxin, Pm and plasma velocities decreased progressively in group I but were not changed from control in group II. Since opiate receptor blockade during endotoxin shock enhances adrenergic responses of arterioles, opiate receptor stimulation appears to suppress adrenergic receptors.

Animals↗
PubMed1990

Microvascular vasopressin effects during endotoxin shock in the rat.

We have demonstrated decreased microvascular sensitivity to norepinephrine during endotoxin shock possibly related to reduced sympathetic receptor activity (Baker et al.: Circ Shock 12:165-176, 1984). The response to other vascular controls such as arginine vasopressin (AVP) may also be altered. Reactivity of the left cremaster muscle microvessels of pentobarbital anesthetized Wistar rats was studied using videomicroscopy and videodensitometry. Femoral arterial pressure (Pm), dose response curves of vessel diameters to topical arginine vasopressin (10(-15) to 10(-6) M), FITC-albumin mean transit times, and plasma velocities were obtained. Escherichia coli endotoxin (6 mg/kg i.v., LD100) was infused over a 1-hr period. Parameter measurements were repeated at 30 min and 90 min post-endotoxin. Both Pm and plasma velocities progressively decreased. Arteriolar constriction and the mean transit times of FITC-labeled albumin progressively increased. The threshold dose for AVP averaged 10(-9) M at control and decreased to 10(-14) M post-endotoxin. Venular diameters were not altered by AVP. The AVP antagonist did not alter the microvascular diameter response to endotoxin but did block the responses to topical and endogenous AVP since arterial pressure and flow velocity decreased at a significantly greater rate than in rats without antagonist. Plasma AVP levels were significantly increased by endotoxin. Reduced alpha adrenergic sensitivity may unmask the responsiveness to AVP or increase the sensitivity of AVP receptors. Increased endogenous AVP may require a smaller exogenous concentration of AVP for constriction.

Animals↗
PubMed1989

Blood flow distribution with adrenergic and histaminergic antagonists.

Superficial fibular nerve stimulation (SFNS) causes increased pre- and post-capillary resistances as well as increased capillary permeability in the dog hind paw. These responses indicate possible adrenergic and histaminergic interactions. The distribution of blood flow between capillaries and arteriovenous anastomoses (AVA) may depend on the relative effects of these neural inputs. Right hind paws of anesthetized heparinized dogs were vascularly and neurally isolated and perfused with controlled pressure. Blood flow distribution was calculated from the venous recovery of 85Sr-labeled microspheres (15 microns). The mean transit times of 131I-albumin and 85Sr-labeled microspheres were calculated. The effects of adrenergic and histaminergic antagonists with and without SFNS were determined. Phentolamine blocked the entire response to SFNS. Prazosin attenuated increases in total and AVA resistance. Yohimbine prevented increased total resistance, attenuated the AVA resistance increase, and revealed a decrease in capillary circuit resistance. Pyrilamine attenuated total resistance increase while SFNS increased capillary and AVA resistances. Metiamide had no effect on blood flow distribution with SFNS. The increase in AVA resistance with SFNS apparently resulted from a combination of alpha 1 and alpha 2 receptor stimulation but not histaminergic effects.

Animals↗
PubMed1988

Adrenergic and histaminergic neural interactions in dog paws.

The mechanisms underlying the vascular responses of superficial fibular nerve stimulation (SFNS) have not been defined. Right hindpaws of anesthetized heparinized dogs were vascularly and neurally isolated, enclosed in a volume recorder, and perfused with controlled pressure. Vascular volume (VV) (131I-labeled albumin) and rate of tissue volume changes (VT) (plethysmography) were determined. SFNS increased blood flow resistance, reduced capillary filtration coefficient (CFC) and permeability-surface area product (PS) of 86Rb, increased VV, and reduced 131I-albumin recovery. VT increased at the rate of 3.35 +/- 0.45 ml/min. SFNS during terbutaline increased resistance, CFC, PS, and VV were unchanged, 131I-albumin recovery was complete, and VT increased at one-fourth the control rate. Phentolamine and yohimbine blocked all responses to SFNS. Prazosin with SFNS attenuated hemodynamic changes and VT increased to two-thirds of control, decreased VV, albumin, and Rb recovery but not PS and CFC. SFNS during pyrilamine maleate reduced VT increase to two-thirds of control rate and blocked decreases in PS and CFC. Metiamide did not change the SFNS responses, except to reduce vascular volume and VT. The combined histamine H1 and H2 blockers reduced VT increase to one-third of control and attenuated albumin loss, prevented histamine dilation, attenuated vasopressin and norepinephrine but not angiotensin constriction. SFNS stimulation increased precapillary resistance by alpha 1- and alpha 2-receptors and venous resistance by alpha 2-receptors and increased permeability by histamine release from endothelium.

Adrenergic alpha-Antagonists↗
PubMed1988

Microvascular responses of intact and adrenal medullectomized rats to hemorrhagic shock.

Evidence indicates that during the later stages of hemorrhagic shock there appears to be a loss of response to the control systems that would normally maintain an adequate peripheral resistance. Therefore, the reactivity of the cremaster muscle microcirculation of pentobarbital-anesthetized Wistar rats, intact and adrenal medullectomized, was studied using videomicroscopy. The left cremaster muscle was spread over an optical port in a bath filled with modified Krebs solution (pH 7.4, 34 degrees C). The right femoral artery was cannulated for determination of mean arterial pressure (Pm) and for hemorrhage of the rat. Following control measurements of Pm and microvessel diameters, cumulative dose-response curves of arteriolar and venular diameters to topical norepinephrine (NE) (10(-9) - 10(-4) M) were obtained. The protocols for intact and medullectomized groups were: 1) hypovolemic shock (shed blood not reinfused)--hemorrhage of 3.2 ml/100 g, compensation allowed, and NE dose-response curves repeated and obtained again during late shock as determined by Pm declining below 60 mmHg; and 2) normovolemic shock (condition after reinfusion of shed blood)--hemorrhage into a reservoir to Pm of 40 mmHg, maintenance at this level until 25% of the bled volume had been taken back (irreversible shock), and then reinfusion of the remainder of the blood. After blood reinfusion, the NE dose-response curves were repeated and obtained again during late shock, as determined by Pm below 60 mmHg. In all of the bled animals, the A1 arterioles were constricted posthemorrhage. The A2 arterioles were constricted only in the hypovolemic intact group. The A3 arterioles of all groups were not significantly changed from control. The constricted arterioles remained so. However, the other arterioles in all groups were unchanged during the several hours until death. The threshold concentration of NE for constriction of arterioles (10% or greater) was significantly increased (decreased sensitivity) during shock in all four groups. The response of the medullectomized rats to normovolemic shock was similar to that of the intact group, indicating that the circulating catecholamines were not essential. The response of medullectomized rats to hypovolemic shock was more severe and indicated the need for circulating catecholamines to compensate for the blood volume loss.

Adrenal Medulla↗
PubMed1987

Taking care of the doctors: the hospital's duty to evaluate, monitor, and discipline its medical staff.

The heart of a hospital's credentialing responsibilities lies in its duties to evaluate, to monitor, and to discipline its medical staff. Some key elements of an effective credentialing system are the skills of the medical staff coordinator, the use of physician proctors to evaluate new applicants, careful investigation of applicants for initial appointment and for reappointment, and education for department chairmen. Inevitable problems include physicians who do not work harmoniously with others and allegations of incompetence and impairment.

Clinical Competence↗
PubMed1986

Tibial nerve and deep fibular nerve effects on venous and extravascular volumes.

The innervation of the vasculature of the dog hindpaw separately controls the series and parallel coupled vessels by means of the tibial, deep fibular, and superficial fibular nerves. The latter primarily affects veins. The venous effects of the tibial and deep fibular nerves have not been adequately defined. The right hindpaw of anesthetized dogs was vascularly and neurally isolated in a volume recorder. The animals were heparinized and the preparation autoperfused (constant pressure). Total tissue volume changes were determined by the volume recorder. Total vascular volume changes were calculated from changes in paw 51Cr-red blood cell radioactivity measured by a scintillation detector. Arterial pressure and paw blood flow were monitored. The tibial and deep fibular nerves were each separately stimulated at 1, 5, and 15 Hz. Deep fibular nerve stimulations resulted in progressively significant increases in precapillary flow resistance. Vascular and tissue volumes decreased with stimulation frequency but vascular volume decreased significantly less than tissue volume change. Tibial nerve stimulation resulted in significant precapillary resistance increases. Vascular and tissue volumes decreased by similar amounts. Thus, deep fibular nerve stimulation causes passive decrease in venous volume, reduced capillary pressure, and fluid absorption. Tibial nerve stimulation causes active arterial and venous constriction maintaining capillary pressure with minimal fluid transfer.

Animals↗