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Biomedical subjects

J W Hicks

Publications and source records attributed to J W Hicks.

At least 55 records · Page 3Linked to original sources
PubMed1995

Ventilation and pulmonary gas exchange during exercise in the savannah monitor lizard (Varanus exanthematicus).

During exercise, pulmonary gas exchange in reptiles was predicted to differ from that in mammals because of their less complex lung structure, which might reduce ventilation-perfusion heterogeneity (V/QL) at the expense of pulmonary diffusion limitation. To investigate this, the multiple inert gas elimination technique was used in six Varanus exanthematicus at rest and during maximal exercise. Trace amounts of six inert gases were infused into the external jugular vein and blood samples were collected from the pulmonary artery and the left atrium. Mixed expired gas samples and ventilatory and metabolic data were acquired. Indices of V/QL heterogeneity, calculated using a 50-compartment model, were low at rest (log standard deviation of perfusion distribution, logSDQ = 0.39) and increased significantly with exercise (logSDQ = 0.78). Oxygen diffusion limitation was apparent during exercise and was comparable to reported mammalian values. A molecular-mass-dependent limitation, suggesting limited intrapulmonary gas mixing, was evident only at rest. An increase in left atrial PO2 from 82mmHg at rest to 96 mmHg during exercise was associated with a corresponding decrease in PCO2. These data indicate adequacy of pulmonary ventilation and gas exchange for metabolic demands in exercising varanid lizards and suggest that less complex lung structures are not necessarily linked to increased pulmonary diffusion limitation.

Animals↗
PubMed1994

Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor.

Secretory mucins consist of a protein backbone that is catenated by disulfide bonds, heavily O-glycosylated, and packaged into storage granules prior to release from cells. In this paper, we identify and sequence cDNAs that encode the amino terminus of the MUC2 protein, a major form of mucin found in human intestines and airways. The protein sequence was found to contain a repetitive element of approximately 350 amino acids with considerable sequence similarity to the D domains of prepro-von Willebrand factor. A total of four of these D domains were found to be present in the MUC2 protein, three in the amino-terminal region, and one in the carboxyl-terminal region. Prepro-von Willebrand factor contains four D domains itself, and the overall positioning of the D domains in the two proteins is similar. Prepro-von Willebrand factor contains a 741 residue pro-protein that has been implicated in both the disulfide-linked oligomerization of von Willebrand factor and its packaging into secretory vacuoles. A similar region is present in the MUC2 amino terminus sequence, suggesting that the mechanisms involved in the polymerization and packaging of MUC2 may parallel those already described for von Willebrand factor.

Amino Acid Sequence↗
PubMed1994

Regulation of central vascular blood flow in the turtle.

The purpose of this study was to determine the effects of vagal nerve stimulation on the pulmonary and systemic circulations in the turtle Pseudemys scripta. The heart rate (HR), systemic vascular resistance (Rsys), pulmonary vascular resistance (Rpul), total pulmonary blood flow (Qpul), and total systemic blood flow (Qsys) were measured during electrical stimulation of the vagal efferent and the vagal afferent nerves. Vagal efferent nerve stimulation resulted in a bradycardia, increased Rsys and Rpul, and a 60% reduction in the Qpul and Qsys. These cardiovascular changes were eliminated after an intravenous injection of atropine. In contrast, vagal afferent nerve stimulation resulted in a tachycardia, a twofold increase in Rsys, a reduction in Rpul, and an 85% increase in Qpul. These changes were eliminated after pretreating the animals with bretylium tosylate (10 mg/kg). An intravenous infusion of epinephrine (0.1 micrograms/kg) produced cardiovascular changes similar to vagal afferent stimulation. The cardiovascular changes resulting from afferent and efferent nerve stimulation were similar to the cardiovascular adjustments often associated with intermittent lung ventilation in reptiles. The results of our study suggest that such cardiovascular changes are under cholinergic and adrenergic control.

Afferent Pathways↗
PubMed1994

Pitfalls in the assessment of vascular resistance.

Vascular resistance (R) to flow is calculated as the ratio of perfusion pressure between two points (P1-P2) to flow rate (Q). In high-pressure circuits (e.g., systemic), it is justifiable to use arterial pressure (P1) to represent perfusion pressure. It is not permissible to calculate resistance without measuring Q unless a comparison is being made in the resistance of different segments of a vascular bed; Q being constant, R: (P1-P2). In a low-pressure circuit (lower vertebrates, pulmonary) it is imperative to measure P2 to quantify the perfusion pressure. In closed circuits with a vertical orientation the effect of gravity on both the arterial and the venous pressures must be considered. In such circuits the perfusion pressure is due to viscous resistance only, excluding the gravitational pressure between the two points.

Animals↗
PubMed1993

Human gastric mucin. Identification of a unique species by expression cloning.

Gastric mucin is a large glycoprotein which is thought to play a major role in the protection of the gastrointestinal tract from acid, proteases, pathogenic microorganisms, and mechanical trauma. In this paper we describe the isolation by expression cloning and characterization of cDNAs which code for human gastric mucin. The cDNA sequence is characterized by a tandem repeat region whose individual repeat unit is 507 base pairs (169 amino acids) long. The translated sequence is rich in threonine, serine, and proline (31, 18, and 15%, respectively) and contains a relatively large amount of histidine (7.1%) and alanine (5.6%). RNA blot analysis shows a polydisperse pattern which is characteristic of mucins. Expression of this gene is highest in the stomach and gall bladder, with weaker expression in the terminal ileum and right colon. This expression pattern is different from other human mucins and indicates that this gene codes for a unique mucin. Fluorescence in situ hybridization techniques have localized this gene to chromosome 11p15.4-11p15.5. This is the third mucin to be localized to the 11p15 region and suggests a clustering of secretory mucin genes. We propose that this gene for human gastric mucin be called MUC6.

Amino Acid Sequence↗
PubMed1992

The human MUC2 intestinal mucin has cysteine-rich subdomains located both upstream and downstream of its central repetitive region.

The human MUC2 mucin is a large secretory glycoconjugate that coats the epithelia of the intestines, airways, and other mucus membrane-containing organs. Previous work has shown that this mucin contains an extended tandem repeat-containing domain rich in Thr and Pro. In the present work we describe two additional regions of this mucin located both upstream and downstream of the tandem repeat array. The carboxyl-terminal domain contains 984 residues and can be divided into mucin-like (139 residues) and cysteine-rich (845 residues) subdomains. This latter subdomain exhibits varying degrees of sequence similarity to a wide range of mucins and mucin-like proteins including those isolated from rats, pigs, cows, and frogs. We also report here the sequence of 1270 residues lying immediately upstream of the tandem repeats. This region contains a repetitive, mucin-like subdomain and a second cysteine-rich stretch of more than 700 residues. Both cysteine-rich subdomains of this mucin have sequence similarity with von Willebrand factor, a serum protein that exists as a disulfide-linked polymer. This suggests that these cysteine-rich subdomains are important in the catenation of mucin monomers into oligomers, the structures that confer viscoelasticity upon mucus.

Amino Acid Sequence↗
PubMed1992

Hemodynamics of vascular 'waterfall': is the analogy justified?

The concept of 'vascular waterfall' has been used for collapsible vessels in different hemodynamic states which have little similarity to each other from a dynamic standpoint. Examples include (a) flow through large systemic veins entering the thorax, (b) flow through microvessels, such as pulmonary, cardiac, hepatic, cerebral, and (c) flow through the jugular vein of the giraffe. The dynamics of freely falling liquids (waterfall) as compared with flow through collapsible blood vessels (in vivo and in vitro) and in collapsible tubes are dissimilar in too many respects to justify analogy. The flow through collapsible tubes and blood vessels can be explained satisfactorily on the basis of elementary principles of fluid mechanics (Bernoulli-Poiseuille). Hence, the term waterfall as a metaphor is misleading and unjustified. We suggest that the use of the term be discontinued for describing vascular dynamics.

Animals↗
PubMed1992

Gravity and the circulation: "open" vs. "closed" systems.

The elementary principles of liquid dynamics are described by the equations of Bernoulli and Poiseuille. Bernoulli's equation deals with nonviscous liquids under steady streamline flow. Pressures in such flows are related to gravity and/or acceleration. Changes in elevation affect the gravitational potential energy of the liquid and the velocity of flow determines the kinetic energy. The sum of these three factors represented in the Bernoulli equation remains constant, but the variables are interconvertible. In contrast, the Poiseuille equation describes the pressures related to viscous resistance only, and the energy of flow is dissipated as heat. A combination of the two equations describes the flow in tubes more realistically than either equation alone. In "open" systems gravity hinders uphill flow and causes downhill flow, in which the liquid acts as a falling body. In contrast, in "closed" systems, like the circulation, gravity does not hinder uphill flow nor does it cause downhill flow, because gravity acts equally on the ascending and descending limbs of the circuit. Furthermore, in closed systems, the liquid cannot "fall" by gravity from higher levels of gravitational potential to lower levels of potential. Flow, up or down, must be induced by some source of energy against the resistance of the circuit. In the case of the circulation, the pumping action of the heart supplies the needed energy gradients. Flow in collapsible tubes, like veins, obeys the same basic laws of liquid dynamics except that transmural pressures near zero or below zero reduce markedly the cross-sectional area of the tube, which increases the viscous resistance to flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1992

Mechanism of intracardiac shunting in the turtle Pseudemys scripta.

Two principal hypotheses account for right-left (R-L) intracardiac shunting in reptiles. The "pressure shunting" hypothesis proposes no functional separation between the ventricular cava during systole. The "washout shunting" hypothesis suggests that during systole, the cavum pulmonale (CP) is functionally separate from the rest of the ventricle. The purpose of this study was to test these hypotheses during control, after acetylcholine (ACh) administration, after epinephrine (Epi) administration, and during apnea. Anesthetized (pentobarbital) turtles (Pseudemys scripta) were mechanically ventilated and three nonocclusive catheters were implanted into the right atrium (RAt), left atrium (LAt), and CP. In addition, three blood gas catheters connected to a mass spectrometer were implanted into the RAt, LAt, and right or left aortic arch for measurement of PO2. A tracer gas, He dissolved in saline, was sequentially injected into the three cardiac chambers and was detected by the mass spectrometer. The presence of R-L shunting was assessed with the blood PO2 and PHe measurements. ACh produced R-L shunting in all animals. No R-L shunting occurred after Epi administration and 20 min of apnea. In all animals after ACh administration, He was detected in an aorta after He infusion in the RAt and LAt, but never after infusion of He into the CP. These results from this preparation are inconsistent with the pressure hypothesis and support the washout hypothesis of intracardiac shunting.

Acetylcholine↗
PubMed1992

Purification and biological activity of alligator bradykinin.

Incubation of plasma form the alligator (Alligator mississipiensis) with glass beads in the presence of a kininase inhibitor resulted in the activation of the kallikrein-kinin system and generation of bradykinin-like immunoreactivity. The kinin peptides were purified to homogeneity and were shown to comprise [Thr6]-bradykinin and des-Arg9[Thr6]bradykinin in the molar ratio of approximately 10:1. Bolus injections of synthetic [Thr6]bradykinin into the jugular vein of the anesthetized alligator resulted in a dose-dependent decrease in mean arterial blood pressure. The minimum dose of kinin producing a significant fall in pressure was 0.07 micrograms/kg body wt and the maximum response (25 +/- 6% fall; mean +/- SD, n = 8) was produced by a dose of 0.56 micrograms/kg body wt. The dose producing a half-maximum response was 0.19 +/- 0.08 micrograms/kg. The data indicate that alligator plasma contains all the components of the kallikrein-kinin system found in mammals and suggest that the system may be of physiological importance in the regulation of cardiovascular function in these reptiles.

Alligators and Crocodiles↗
PubMed1991

Molecular cloning of rat intestinal mucin. Lack of conservation between mammalian species.

We have prepared antisera to deglycosylated rat intestinal mucin and used it to obtain immunoreactive clones from a rat jejunum cDNA library. Four of these clones were sequenced, and all were found to be partial cDNAs that contained 18-base pair tandem repeats characteristic of a mucin. These cDNAs encoded a repetitive peptide with a consensus sequence of TTTPDV. Thus, they bear little resemblance to either of the two human intestinal mucin cDNAs isolated previously (Gum, J. R., Byrd, J. C., Hicks, J. W., Toribara, N. W., Lamport, D. T. A., and Kim, Y. S. (1989) J. Biol. Chem. 264, 6480-6487 and Gum, J. R., Hicks, J. W., Swallow, D. M., Lagace, R. E., Byrd, J. C., Lamport, D. T. A., Siddiki, B., and Kim, Y. S. (1990) Biochem. Biophys. Res. Commun. 171, 407-415). One of these rat mucin clones, designated RMUC 176, was chosen for further analysis. This clone recognized a band of approximately 9 kilobases when used to probe RNA blots. A strong hybridization band was present using rat small intestine and colon RNA but was not detectable when RNA isolated from heart, liver, or kidney was tested. The RMUC 176 clone and the two previously isolated human intestinal mucin cDNA clones were used to probe blots prepared from BamHI-digested DNA of various species. Here, the human probes detected fragments present only in human and chimpanzee DNA, whereas the RMUC 176 clone recognized fragments only in rat and mouse DNA. Thus, the repetitive portions of intestinal mucin genes are apparently not well conserved between phylogenetically distant species.

Amino Acid Sequence↗
PubMed1991

MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism.

MUC-2, the first described intestinal mucin gene, has become important as a prototype for secreted mucins in several organ systems. However, little is known about its protein backbone structure and hence its role in diseases such as colon cancer, ulcerative colitis, and cystic fibrosis, which are known to have mucin abnormalities. Studies in this manuscript show that MUC-2 contains two distinct regions with a high degree of internal homology, but the two regions bear no significant homology to each other. Region 1 consists mostly of 48-bp repeats which are interrupted in places by 21-24-bp segments. Several of these interrupting sequences show similarity to each other, creating larger composite repeat units. Region 1 has no length polymorphisms. Region 2 is composed of 69-bp tandem repeats arranged in an uninterrupted array of up to 115 individual units. Southern analysis of genomic DNA samples using TaqI and HinfI reveals both length and sequence polymorphisms which occur within region 2. The sequence polymorphisms have different ethnic distributions, while the length polymorphisms are due to variable numbers of tandem repeats.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of cDNAs derived from a novel human intestinal mucin gene.

A human small intestinal lambda gt11 cDNA library was screened with antibodies to deglycosylated small intestinal mucin. Four partial cDNA clones were isolated that define a novel human mucin gene. These include two partial cDNA clones, SIB 124 and SIB 139, that contain 51 nucleotide tandem repeats which encode a seventeen amino acid repetitive peptide with a consensus sequence of HSTPSFTSSITTTETTS. SIB 139 hybridized to messages produced by small intestine, colon, colonic tumors and also by high mucin variant LS174T colon cancer cells. The gene from which cDNAs SIB 124 and SIB 139 are derived (proposed name MUC 3) maps to chromosome 7, distinct from other known human mucin genes.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of complementary DNAs encoding alkaline phosphatase in human colon cancer cells.

We have isolated a set of complementary DNA (cDNA) clones that together encode the alkaline phosphatase of human colon cancer LS174T cells. These clones include two cDNAs isolated from a conventionally prepared oligodeoxythymidylate-primed lambda ZAP cDNA library and three cDNA clones prepared by using the polymerase chain reaction. The deduced amino acid sequence of the alkaline phosphatase primary transcript contains 532 amino acids. This enzyme is similar to, but not identical with, placental alkaline phosphatase (PLAP); it exhibits 12-19 amino acid substitutions when compared to the various alleles of PLAP. Also, it is similar to PLAP in that it is apparently attached to the cell membrane by a phosphatidylinositol-containing anchor as judged by the ability of phosphatidylinositol-specific phospholipase C to release it from membranes. It is different from PLAP however, in terms of its signal sequence which only contains 19 amino acids as compared to 22 for PLAP. Moreover, the 3'-untranslated region of the LS174T cell alkaline phosphatase message diverges considerably from the PLAP message. The LS174T cell alkaline phosphatase cDNAs are actually much more similar to the "germ cell" alkaline phosphatase gene than they are to PLAP. Only 7 amino acid substitutions exist between the LS174T cell enzyme and the alkaline phosphatase encoded by the germ cell alkaline phosphatase genomic DNA clone isolated by Millan and Manes (Proc. Natl. Acad. Sci. USA, 85: 3024-3028, 1988). Furthermore, the 3'-untranslated region of the LS174T cell alkaline phosphatase message is very similar to the sequence immediately downstream of the coding region of the germ cell alkaline phosphatase genomic DNA clone. Thus, these results indicate that this colon cancer cell alkaline phosphatase is likely to represent an allelic variant encoded at the germ cell alkaline phosphatase locus.

Alkaline Phosphatase↗
PubMed1990

Isolation and biological activity of a novel kinin ([Thr6] bradykinin) from the turtle, Pseudemys scripta.

Incubation of plasma from the red-eared turtle with glass beads in the presence of the kininase inhibitor 1,10-phenanthroline resulted in activation of the kallikrein-kinin system and generation of bradykinin-like immunoreactivity. The immunoreactive material comprised a single molecular form that was purified to homogeneity by reverse phase HPLC. The primary structure of the peptide was determined by automated Edman degradation and fast atom bombardment mass spectrometry. The amino acid sequence of the turtle kinin Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg contains the substitution Thr for Ser at position 6 compared with mammalian bradykinin. [Thr6] bradykinin was synthesized using solid phase methodology, and bolus injections of the peptide into the left atrium of the anaesthetized turtle produced rapid vasodilation. A dose-dependent increase in blood flow in the left aortic arch was accompanied by a decrease in peripheral vascular resistance, so that systemic blood pressure did not change. The data suggest that the kallikrein-kinin system may play an important physiological role in the regulation of cardiovascular function in reptiles.

Amino Acid Sequence↗
PubMed1989

Evidence that neuromedin U may regulate gut motility in reptiles but not in mammals.

Neuromedin U-8 induced a monophasic and concentration-dependent contraction of intact small intestine from the turtle, Pseudemys scripta, whereas the peptide had no effect upon the motility of rat and guinea pig gut. The maximum response produced by neuromedin U-8 was 56% of that produced by acetylcholine and 62% of that produced by potassium chloride. The potency and maximum response to neuromedin U-8 were unaffected by tetrodotoxin and atropine. The data suggest that neuromedin U may play a role in regulation of gut motility in lower vertebrates but not in mammals.

Acetylcholine↗
PubMed1989

Molecular cloning of human intestinal mucin cDNAs. Sequence analysis and evidence for genetic polymorphism.

A human small intestine lambda gt11 cDNA library was screened using antisera prepared against the deglycosylated protein backbone of human colon cancer xenograft mucin. Three cDNAs were isolated from this screening, designated SMUC 40-42. These cDNAs were all found to contain tandem repeats of 69 nucleotides which encoded a threonine- and proline-rich protein consensus sequence of PTTTPITTTTTVTPTPTPTGTQT. RNA blots probed with one of these cDNAs, SMUC 41, exhibited large, polydisperse hybridization bands at approximately 7,600 bases. Band intensities were strongest when human small intestine, colon, and colon cancer poly(A)+ RNA was used. In vitro translation of poly(A)+ RNA from human small intestine, colon, and colon cancer cells produced a 162,000-dalton peptide that was immunoprecipitated with antibodies to deglycosylated mucin. SMUC 41 was also used to probe DNA blots, which indicated the presence of restriction fragment length polymorphisms in the intestinal mucin gene. These findings may be important in assessing the abnormal mucins found associated with several human diseases.

Amino Acid Sequence↗