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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 523 records · Page 29Linked to original sources
PubMed1988

A thermodynamic analysis of monovalent cation permeation through a K(+)-selective ion channel.

Ionic selectivity characteristics of the K+ channel from the sarcoplasmic reticulum were studied as a function of temperature in order to decompose the profile of Gibbs free energy along the conduction pore into its enthalpic and entropic components. For Li+, Na+, K+, and Rb+, the enthalpy of binding to the channel is close to zero. Activation enthalpies for transferring ions from bulk aqueous solution to the channel's selectivity region are 20-25 kJ/mol for Na+, K+, and Rb+ and substantially higher for Li+ and Cs+. Transfer of Li+ and Na+ to the selectivity region involved large favorable entropies. The results argue that the group IA cations shed about half their waters of hydration in permeating the selectivity region of this channel.

Animals↗
PubMed1988

Charybdotoxin block of single Ca2+-activated K+ channels. Effects of channel gating, voltage, and ionic strength.

Charybdotoxin (CTX), a small, basic protein from scorpion venom, strongly inhibits the conduction of K ions through high-conductance, Ca2+-activated K+ channels. The interaction of CTX with Ca2+-activated K+ channels from rat skeletal muscle plasma membranes was studied by inserting single channels into uncharged planar phospholipid bilayers. CTX blocks K+ conduction by binding to the external side of the channel, with an apparent dissociation constant of approximately 10 nM at physiological ionic strength. The dwell-time distributions of both blocked and unblocked states are single-exponential. The toxin association rate varies linearly with the CTX concentration, and the dissociation rate is independent of it. CTX is competent to block both open and closed channels; the association rate is sevenfold faster for the open channel, while the dissociation rate is the same for both channel conformations. Membrane depolarization enhances the CTX dissociation rate e-fold/28 mV; if the channel's open probability is maintained constant as voltage varies, then the toxin association rate is voltage independent. Increasing the external solution ionic strength from 20 to 300 mM (with K+, Na+, or arginine+) reduces the association rate by two orders of magnitude, with little effect on the dissociation rate. We conclude that CTX binding to the Ca2+-activated K+ channel is a bimolecular process, and that the CTX interaction senses both voltage and the channel's conformational state. We further propose that a region of fixed negative charge exists near the channel's CTX-binding site.

Animals↗
PubMed1988

Mechanism of charybdotoxin block of the high-conductance, Ca2+-activated K+ channel.

The mechanism of charybdotoxin (CTX) block of single Ca2+-activated K+ channels from rat muscle was studied in planar lipid bilayers. CTX blocks the channel from the external solution, and K+ in the internal solution specifically relieves toxin block. The effect of K+ is due solely to an enhancement of the CTX dissociation rate. As internal K+ is raised, the CTX dissociation rate increases in a rectangular hyperbolic fashion from a minimum value at low K+ of 0.01 s-1 to a maximum value of approximately 0.2 s-1. As the membrane is depolarized, internal K+ more effectively accelerates CTX dissociation. As the membrane is hyperpolarized, the toxin dissociation rate approaches 0.01 s-1, regardless of the K+ concentration. When internal K+ is replaced by Na+, CTX dissociation is no longer voltage dependent. The permeant ion Rb also accelerates toxin dissociation from the internal solution, while the impermeant ions Li, Na, Cs, and arginine do not. These results argue that K ions can enter the CTX-blocked channel from the internal solution to reach a site located nearly all the way through the conduction pathway; when K+ occupies this site, CTX is destabilized on its blocking site by approximately 1.8 kcal/mol. The most natural way to accommodate these conclusions is to assume that CTX physically plugs the channel's externally facing mouth.

Animals↗
PubMed1988

Potassium blocks barium permeation through a calcium-activated potassium channel.

Single high-conductance Ca2+-activated K+ channels from rat skeletal muscle were inserted into planar lipid bilayers, and discrete blocking by the Ba2+ ion was studied. Specifically, the ability of external K+ to reduce the Ba2+ dissociation rate was investigated. In the presence of 150 mM internal K+, 1-5 microM internal Ba2+, and 150 mM external Na+, Ba2+ dissociation is rapid (5 s-1) in external solutions that are kept rigorously K+ free. The addition of external K+ in the low millimolar range reduces the Ba2+ off-rate 20-fold. Other permeant ions, such as Tl+, Rb+, and NH4+ show a similar effect. The half-inhibition constants rise in the order: Tl+ (0.08 mM) less than Rb+ (0.1 mM) less than K+ (0.3 mM) less than Cs+ (0.5 mM) less than NH4+ (3 mM). When external Na+ is replaced by 150 mM N-methyl glucamine, the Ba2+ off-rate is even higher, 20 s-1. External K+ and other permeant ions reduce this rate by approximately 100-fold in the micromolar range of concentrations. Na+ also reduces the Ba2+ off-rate, but at much higher concentrations. The half-inhibition concentrations rise in the order: Rb+ (4 microM) less than K+ (19 microM) much less than Na+ (27 mM) less than Li+ (greater than 50 mM). The results require that the conduction pore of this channel contains at least three sites that may all be occupied simultaneously by conducting ions.

Animals↗
PubMed1988

Discrete Ba2+ block as a probe of ion occupancy and pore structure in the high-conductance Ca2+ -activated K+ channel.

In this study, high-conductance Ca2+-activated K+ channels from rat skeletal muscle were incorporated into planar phospholipid bilayers, and discrete blockade of single channels by Ba2+ was studied. With 150 mM K+ held constant in the internal solution, increasing external K+ over the range 100-1,000 mM raises the rate of Ba2+ dissociation. This "enhancement effect," which operates at K+ concentrations 3-4 orders of magnitude higher than those required for the "lockin" effect described previously, depends on applied voltage, saturates with K+ concentration, and is not observed with Na+. The voltage dependence of the Ba2+ off-rate varies with external K+ in a way suggesting that K+, entering the channel from the external side, forces Ba2+ dissociation to the internal solution. With K+ held fixed in the external solution, the Ba2+ off-rate decreases as internal K+ is raised over the range 0-50 mM. This "lock-in" effect is similar to that seen on the external side (Neyton and Miller, 1988), except that the internal lock-in site is of lower affinity and shows only a fivefold preference for K+ over Na+. All the results taken together argue strongly that this channel's conduction pathway contains four sites of very high affinity for K+, all of which may be simultaneously occupied under normal conducting conditions. According to this view, the mutual destabilization resulting from this high ionic occupancy leads to the unusually high conductance of this K+-specific channel.

Animals↗
PubMed1988

Orthotopic liver transplantation for primary sclerosing cholangitis.

The incidence or diagnostic rate of sclerosing cholangitis is increasing. Because of the lack of effective medical or surgical therapy for patients with end-stage liver disease and sclerosing cholangitis, results with orthotopic liver transplantation were examined. The results of 55 consecutive liver replacements for this disease were reviewed. The 1- and 2-year actuarial survival rates are 71% and 57%, respectively. Orthotopic liver transplantation for end-stage liver disease from sclerosing cholangitis has emerged as the most effective therapy.

Adenoma, Bile Duct↗
PubMed1988

Erratic gastric emptying of levodopa may cause "random" fluctuations of parkinsonian mobility.

The pathogenesis of "random" fluctuations in parkinsonian mobility, which are not clearly related to the dosing schedule of levodopa, has not been determined. We rated parkinsonian mobility and assayed plasma dopa in one patient with clinically random fluctuations during two modes of administration of levodopa/carbidopa: (1) standard oral route and (2) direct duodenal delivery via nasoduodenal tube. During oral therapy, mobility varied unpredictably in relation to levodopa dosing, suggesting a clinically random pattern. During duodenal delivery, however, a predictable and dramatic pattern of recurrent end-of-dose deterioration was observed; each intraduodenal levodopa dose resulted in 60 to 90 minutes of benefit. Plasma dopa levels correlated closely with mobility ratings for both modes of administration. Our findings indicate that erratic gastric emptying of levodopa is responsible for apparently "random" oscillations in mobility in at least one patient with Parkinson's disease and probably in others.

Absorption↗
PubMed1988

Myosin and Ca2+-sensitive streaming in the alga Chara: detection of two polypeptides reacting with a monoclonal anti-myosin and their localization in the streaming endoplasm.

A monoclonal antibody to the heavy chain of myosin from mouse 3T3 cells was used to detect and localize related proteins in the green alga Chara. Proteins of 200,000 and 110,000 Mr reacted on immunoblots of proteins precipitated rapidly with trichloroacetic acid to minimize proteolysis. Immunofluorescence of whole cells localized these proteins to organelles of the streaming endoplasm, to a system of endoplasmic strands and to the subcortical actin bundles. Except that fewer endoplasmic strands and organelles were found and the strands were tangled, the localization pattern was similar in cells rapidly perfused to remove the bulk of the streaming endoplasm. Actin was confined almost entirely to the system of subcortical actin bundles in both whole and perfused cells. Myosin that was associated with the tangled endoplasmic strands but not that associated with the organelles or actin bundles was removed by concentrations of Ca2+ inhibiting ATP-dependent streaming in perfused cells. ATP extracted both organelles and endoplasmic strands but left a continuous pattern of myosin immunostaining along the actin bundles. The findings are discussed in relation to the possible existence of two forms of myosin and of separate mechanisms moving the bulk endoplasm and individual organelles.

Actins↗
PubMed1988

Orthotopic liver transplantation for massive hepatic lymphangiomatosis.

Lymphangiomatosis is a rare malformation of the lymphatic system that causes severe symptoms secondary to progressive growth into or close to vital structures. A case report of liver failure related to this space-occupying intrahepatic mechanism is taken as a starting point for a discussion of the problems of liver transplantation related to large hepatomegalies.

Adult↗
PubMed1988

Early gastric cancer in clinical practice.

A description of four patients with early gastric cancer diagnosed by endoscopy is reported. All patients presented with type III (excavated or ulcerative) early gastric cancer. Early gastric cancer appeared to be slow growing in three patients, and was difficult to diagnose in two cases, especially when associated with large gastric ulcers. Endoscopic biopsy of nonhealing or recurrent gastric ulcers and endoscopic follow-up to complete ulcer healing are recommended.

Adult↗
PubMed1987

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) accelerates the accumulation of lipofuscin in mouse adrenal gland.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes degeneration of nigrostriatal dopaminergic neurons. Recently, we reported that it also destroys dopaminergic neurons in retina and it induces the accumulation of lipofuscin. We now present morphologic and biochemical evidence that MPTP causes the accumulation of lipofuscin in the adrenal cortex. We speculate, that generation of free radicals during the transformation of MPTP to metabolites might be responsible for lipofuscin formation. MPTP-induced accumulation of lipofuscin may be a useful model for studying the biochemistry of the aging process.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Patient response to sigmoidoscopy. A randomized, controlled trial of rigid and flexible sigmoidoscopy.

Sigmoidoscopy could aid in the control of large bowel cancer by early detection of the 55% of colorectal cancers that develop in the rectosigmoid and by the identification and eradication of significant rectosigmoid adenomas. Rigid sigmoidoscopy has had poor patient acceptance and therefore has not been successful. The present study is a prospective randomized trial to evaluate patient response to flexible as compared with rigid sigmoidoscopy. Patients reported significantly less discomfort (10.1% versus 29.7%), anxiety (9.8% versus 27.6%) and embarrassment (5.2% versus 12.8%) during flexible as compared with rigid sigmoidoscopy. Flexible sigmoidoscopy appears to have better patient acceptance than rigid sigmoidoscopy (P less than 0.01). This could enhance its value as a cancer-control instrument. This article addresses the feasibility of sigmoidoscopy. Its validity also needs to be addressed within the framework of a long-term trial, evaluating mortality for rectosigmoid cancer.

Clinical Trials as Topic↗
PubMed1987

Live measles vaccine: a 21 year follow up.

21 years after receiving Schwartz strain live measles vaccine 4500 trial participants showed a continuing high level of protection compared with those who were unvaccinated. Over the last seven years of the follow up no cases of measles were reported in vaccinated participants who had had close contact with the disease. Immunity induced by the vaccine seems to survive the challenge of close contact with measles in young children, even after 21 years.

Antibodies, Viral↗
PubMed1987

Characterization of cDNA clones for human myeloperoxidase: predicted amino acid sequence and evidence for multiple mRNA species.

Myeloperoxidase is a component of the microbicidal network of polymorphonuclear leukocytes. The enzyme is a tetramer consisting of two heavy and two light subunits. A large proportion of humans demonstrate genetic deficiencies in the production of myeloperoxidase. As a first step in analyzing these deficiencies in more detail, we have isolated cDNA clones for myeloperoxidase from an expression library of the HL-60 human promyelocytic leukemia cell line. Two overlapping plasmids (pMP02 and pMP062) were identified as myeloperoxidase cDNA clones based on the detection with myeloperoxidase antiserum of 70 kDa protein expressed in pMP02-containing bacteria and a 75 kDa polypeptide produced by hybridization selection and translation using pMP062 and HL-60 RNA. Formal identification of the clones was made by matching the predicted amino acid sequences with the amino terminal sequences of the heavy and light subunits. Both subunits are encoded by one mRNA in the following order: pre-pro-sequences--light subunit--heavy subunit. The molecular weight of the predicted primary translation product is 83.7 kDa. Northern blots reveal two size classes of hybridizing RNAs (approximately 3.0-3.3 and 3.5-4.0 kilobases) whose expression is restricted to cells of the granulocytic lineage and parallels the changes in enzymatic activity observed during differentiation.

Amino Acid Sequence↗
PubMed1987

Stapes vibration produced by the output transducer of an implantable hearing aid. Experimental study.

The function of the output transducer of an implantable hearing aid was assessed by applying it to the stapes head in seven fresh human cadaver temporal bones while observing vibration of the stapes under a microscope with the use of a stroboscope and a video measuring system. The transducer was a 5 X 1.2 X 0.6-mm piezoelectric ceramic bimorph with attached metal holder. Transmission changed with the amount of force holding the transducer tip on the head of the stapes. An optimal connection between the vibrator and stapes produced better transmission than a tight or loose connection. Gluing the connection with cyanoacrylate cement decreased transmission in the optimal connection, produced no change in the tight connection, and improved transmission in the loose connection. Comparison of stapes displacement produced by the vibrator at 1 kHz with that produced by normal middle-ear sound transmission revealed that the vibrator-induced stapes displacement for a 1 V peak-to-peak input was equivalent to that produced by a sound stimulus of 90-dB sound pressure level at the tympanic membrane.

Ear Ossicles↗
PubMed1987

CAPD fluid: a common cause of photon deficient lesions on 99mTc-D.T.P.A. scans in renal transplant patients.

Single or multiple transient photon deficient areas on 99mTc-DTPA scintigrams were found in 40% of a series of 34 patients who had undergone renal transplantion directly from CAPD maintenance. Ultrasound showed only loculated intraperitoneal CAPD fluid adjacent to the transplant with no evidence of local complications. We conclude that such collections are a common cause of photon deficient areas on 99mTc-DTPA transplantscintigrams and in the absence of ultrasound, these appearances should be interpreted with caution.

Humans↗