Biomedical subjects

C Holcomb

Publications and source records attributed to C Holcomb.

13 recordsLinked to original sources

PubMed2006

Multitude of core-localized shear Alfvén waves in a high-temperature fusion plasma.

Evidence is presented for a multitude of discrete frequency Alfvén waves in the core of magnetically confined high-temperature fusion plasmas. Multiple diagnostic instruments confirm wave excitation over a wide spatial range from the device size at the longest wavelengths down to the thermal ion Larmor radius. At the shortest scales, the poloidal wavelengths are comparable to the scale length of electrostatic drift wave turbulence. Theoretical analysis confirms a dominant interaction of the modes with particles in the thermal ion distribution traveling well below the Alfvén velocity.

Journal Article↗

PubMed2002

Suppression of MHD fluctuations leading to improved confinement in a gun-driven spheromak.

Magnetic fluctuations have been reduced to approximately 1% during discharges on the Sustained Spheromak Physics Experiment by shaping the spatial distribution of the bias magnetic flux in the device. In the resulting quiescent regime, the safety factor profile is nearly flat in the plasma and the dominant ideal and resistive MHD modes are greatly reduced. During this period, the temperature profile is peaked at the magnetic axis and maps onto magnetic flux contours. Energy confinement time is improved over previous reports in a driven spheromak.

Journal Article↗

PubMed1993

Expression and localization of two low molecular weight GTP-binding proteins, Rab8 and Rab10, by epitope tag.

Small GTP-binding proteins of the YPT/SEC4/Rab family have been shown to play an essential role in intracellular membrane trafficking. In mammals, Rab8 and Rab10 are the two small GTP-binding proteins identified so far that are closest to SEC4, an essential gene product involved in post-Golgi constitutive secretion in the yeast Saccharomyces cerevisiae. To study the localization of Rab proteins, we have expressed the cDNAs with an influenza virus hemagglutinin (HA) epitope tag at the N terminus. The feasibility of this method was tested by using yeast SEC4. HA-tagged SEC4 functionally complemented a temperature-sensitive sec4 mutant similarly to wild-type SEC4, indicating that the modified protein retained functional integrity. Monoclonal antibody 12CA5, raised against the HA tag, was used to determine the expression and localization of HA-tagged proteins after transfection. In stably transfected CHO and Swiss 3T3 cells, HA-tagged Rab8 was localized to the cell periphery, with the highest concentration in the ruffling areas. In contrast, epitope-tagged Rab10 expressed in CHO and BHK cells was concentrated on membranes in the perinuclear region. By light microscopy, the staining partially overlapped with that of a Golgi marker, beta-COP. Thus, despite the high degree homology of Rab8 and Rab10 (66% identity), the two proteins are localized to distinct cellular compartments. This approach should provide a general tool for the analyses of other members of the YPT/SEC4/rab gene family.

Animals↗

PubMed1993

A randomized study of cefepime versus the combination of gentamicin and mezlocillin as an adjunct to surgical treatment in patients with acute cholecystitis.

In patients with acute cholecystitis, antibiotics are used as an adjunct to cholecystectomy to reduce the incidence of postoperative septic complications thought to be related to bactibilia. Combinations of penicillins, or cephalosporins or aminoglycosides, or both, are often used. Cefepime is a fourth-generation cephalosporin with excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas species. It has a prolonged serum half-life, allowing twice-daily dosing, and is not nephrotoxic. This study was undertaken to determine whether or not cefepime was as effective as the combination of gentamicin and mezlocillin in patients with acute cholecystitis. One hundred and forty-nine patients were randomized, two to one, to receive cefepime or gentamicin and mezlocillin. Cefepime was given intravenously at 2 grams every 12 hours; gentamicin, 1.0 to 1.5 milligrams per kilograms every eight hours, and mezlocillin, 3 to 4 grams every four to six hours. All patients underwent cholecystectomy. Bile cultures were obtained, and concentrations of cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a subset of patients. There were 56 evaluable cefepime-treated and 34 evaluable gentamicin and mezlocillin-treated patients. Bactibilia was present in 17 of 56 cefepime-treated patients (30.4 percent) and ten of 34 gentamicin and mezlocillin-treated patients (29.4 percent). Enterococci were recovered in six cefepime-treated patients. Clinical and bacteriologic responses were similar for the cefepime-treated and gentamicin and mezlocillin-treated groups, with one failure in each group, a wound infection in a patient receiving cefepime and a subhepatic abscess in a patients receiving gentamicin and mezlocillin. Other measures of outcome, such as the number of days of fever, days nothing by mouth, days of hospitalization and days of antibiotic therapy were similar in both groups. Cefepime, with every 12 hour dosing, achieved extremely high concentrations in all tissues assayed at the time of the operation, a mean of eight hours after administration. Adverse clinical events were similar in both treatment groups. Cefepime is as effective as gentamicin and mezlocillin in preventing septic complications after cholecystectomy for acute cholecystitis. Cefepime requires fewer doses, does not require drug monitoring, is not associated with nephrotoxicity and may therefore prove to be a cost-effective alternative to combination therapy that uses an aminoglycoside.

Acute Disease↗

PubMed1991

Mammalian Sec23p homologue is restricted to the endoplasmic reticulum transitional cytoplasm.

The yeast Sec23 protein is required in vivo and in vitro for transport of proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. Ultrastructural localization of the Sec23p mammalian homologue (detected by antibody cross-reaction) in exocrine and endocrine pancreatic cells shows a specific distribution to the cytoplasmic zone between the transitional ER cisternae and Golgi apparatus where it appears associated with the tubular protuberances of the transitional ER cisternae, as well as with a population of vesicles, and surrounding cytoplasm. When ER-Golgi transport is interrupted with an energy poison, protuberances and transfer vesicles markedly decrease but Sec23p immunoreactive sites remain in the transitional cytoplasm not apparently tethered by membrane attachment. This unanticipated degree of organization suggests that cytosolic proteins, such as Sec23p, may be retained in specialized areas of the cytoplasm. A structure within the transitional zone may organize the flux of transport vesicles and Sec proteins so as to ensure efficient protein traffic in this limb of the secretory pathway.

Animals↗

PubMed1991

Immunolocalization of Kex2 protease identifies a putative late Golgi compartment in the yeast Saccharomyces cerevisiae.

The Kex2 protein of the yeast Saccharomyces cerevisiae is a membrane-bound, Ca2(+)-dependent serine protease that cleaves the precursors of the mating pheromone alpha-factor and the M1 killer toxin at pairs of basic residues during their transport through the secretory pathway. To begin to characterize the intracellular locus of Kex2-dependent proteolytic processing, we have examined the subcellular distribution of Kex2 protein in yeast by indirect immunofluorescence. Kex2 protein is located at multiple, discrete sites within wild-type yeast cells (average, 3.0 +/- 1.7/mother cell). Qualitatively similar fluorescence patterns are observed at elevated levels of expression, but no signal is found in cells lacking the KEX2 gene. Structures containing Kex2 protein are not concentrated at a perinuclear location, but are distributed throughout the cytoplasm at all phases of the cell cycle. Kex2-containing structures appear in the bud at an early, premitotic stage. Analysis of conditional secretory (sec) mutants demonstrates that Kex2 protein ordinarily progresses from the ER to the Golgi but is not incorporated into secretory vesicles, consistent with the proposed localization of Kex2 protein to the yeast Golgi complex.

Cell Cycle↗

PubMed1987

Effects of prenatal testosterone propionate treatment on saccharin preference of adult rats exposed to ethanol in utero.

Prenatal exposure to alcohol feminizes saccharin consumption patterns in adult male rats. To study the involvement of testosterone in this effect, testosterone propionate (TP) was administered to pregnant dams in an attempt to reverse that feminized saccharin consumption pattern in the male offspring. Female offspring were also studied to determine the effect of TP on saccharin preference in normal males and females. During the last week of gestation, dams were administered a liquid diet containing 35% ethanol derived calories, an isocaloric liquid diet containing no ethanol, or Purina Lab Chow. Half of the dams in each group received twice daily injections of TP, the other half were injected with the oil vehicle. Saccharin consumption of adult fetal alcohol exposed (FAE) males from dams administered oil or TP was significantly greater than controls, indicating that the feminized pattern of saccharin consumption of FAE males cannot be overcome with TP administration during the prenatal period. In controls, prenatal TP exposure alone was found to increase adult saccharin consumption in both sexes. Prenatal administration of TP was also found to markedly depress body weight of offspring of dams receiving the liquid diets compared to offspring from dams receiving the same diets plus oil injections. Body weights of offspring from TP or oil injected dams receiving the chow fed diets during pregnancy did not differ.

Animals↗

PubMed1985

Electroencephalographic study of nighttime panic attacks.

A woman whose condition was diagnosed as agoraphobia with panic attacks participated in an all-night polysomnographic study. During the night she experienced a panic attack that was phenomenologically similar to her daytime attacks. The attack occurred suddenly, arising from stage 3-4 (delta) sleep. There was no disruption of sleep architecture immediately before awakening. The occurrence of this panic attack during sleep is discussed in the context of other nighttime sleep disorders.

Adult↗

PubMed1984

Studies of the relationship between the catalytic activity and binding of non-substrate ligands by the glutathione S-transferases.

The dimeric enzyme glutathione S-transferase B is composed of two dissimilar subunits, referred to as Ya and Yc. Transferase B (YaYc) and two other transferases that are homodimers of the individual Ya and Yc subunits were purified from rat liver. Inhibition of these three enzymes by Indocyanine Green, biliverdin and several bile acids was investigated at different values of pH (range 6.0-8.0). Indocyanine Green, biliverdin and chenodeoxycholate were found to be effective inhibitors of transferases YaYc and YcYc at low (pH 6.0) but not high (pH 8.0) values of pH. Between these extremes of pH intermediate degrees of inhibition were observed. Cholate and taurochenodeoxycholate, however, were ineffective inhibitors of transferase YcYc at all values of pH. The observed differences in bile acids appeared to be due, in part, to differences in their state of ionization. In contrast with the above results, transferase YaYa was inhibited by at least 80% by the non-substrate ligands at all values of pH. These effects of pH on the three transferases could not be accounted for by pH-induced changes in the enzyme's affinity for the inhibitor. Thus those glutathione S-transferases that contain the Yc subunit are able to act simultaneously as both enzymes and binding proteins. In addition to enzyme structure, the state of ionization of the non-substrate ligands may also influence whether the transferases can perform both functions simultaneously.

Bile Acids and Salts↗

PubMed1979

Midazolam compared with thiopentone as a hypnotic component in balanced anaesthesia: a randomized, double-blind study.

Midazolam is a short-acting water soluble benzodiazepine derivative. It is a hypnotic used for intravenous anaesthesia induction. The present investigation was designed in a prospective double-blind fashion to compare midazolam with thiopentone as hypnotic components in balanced anaesthesia. The study included 50 healthy patients undergoing relatively short surgical procedures. The results revealed that thiopentone is faster in onset than midazolam for induction of anaesthesia, with less variation of dose response. However, maintenance of anaesthesia was superior with midazolam, requiring fewer supplemental anaesthetic drugs, having better patient acceptance and providing more amnesia. Postoperative complications were very low with both techniques. Midazolam was surprisingly similar to thiopentone in most parameters including emergence time from anaesthesia. Midazolam is a new drug with potential both for induction of anaesthesia and maintenance of balanced anaesthesia.

Adult↗

PubMed1979

The Swan-Ganz catheter and management of patients undergoing pelvic exenteration.

A Swan-Ganz catheter has been used in 10 consecutive patients undergoing pelvic exenteration and has made the intraoperative and postoperative management of these patients a much easier task. Use of this catheter eliminates the guesswork involved in managing fluid and volume status by providing an accurate assessment of left ventricular end diastolic pressure. The complication rate is reported as 5% and consists mostly of ruptured balloons, infection, coiling of the catheter, and cardiac irritability. There have been no complications in the 10 patients in whom we have used the catheter. We believe that the use of the Swan-Ganz catheter in these difficult-to-manage patients is justified because of its low complication rate, easy use, and the accurate valuable information obtained.

Cardiac Catheterization↗

PubMed1978

Comparison of two benzodiazepines for anaesthesia induction: midazolam and diazepam.

Ro 21-3981 is a newly synthesized water soluble benzodiazepine derivative. Its pharmacological properties are similar to diazepam. This investigation was designed to establish the effective induction dosage of Ro 21-3981 and to compare it with diazepam for induction of anaesthesia. The ED50 for Ro 21-3981 induction is 0.15 mg/kg and ED 100 is 0.2 mg/kg. Ro 21-3981 is one and one-half times as potent as diazepam (0.3 mg/kg) and more rapid in action. There is significantly less pain on injection with Ro 21-3981 as compared to diazepam. Cardiovascular stability and apnoea were observed with both drugs. Ro 21-3981 is a promising anaesthetic induction drug that merits further human study.

Anesthetics↗

PubMed1976

The significance of diffusion hypoxemia.

The phenomenon of "diffusion hypoxemia" seems to be a well-defined entity. To determine the degree of deoxygenation of the arterial blood due to diffusion hypoxemia, experiments were performed in monkeys which were anesthetized with ketamine, intubated, and allowed to breathe spontaneously. Blood PaO2 values were continuously monitored with the aid of an intra-arterially placed IBC PO2 electrode capable of instantly recording changes in oxygen tension. After stabilization of the blood PaO2 values with the animal breathing different mixtures of oxygen and nitrous oxide, the inspired mixture was abruptly changed to normal air. The blood PaO2 values did not show any significant fall in PaO2 with any mixture containing more than 21% oxygen. It is suggested that diffusion hypoxemia of any degree can be seen only if a patient is breathing a gas mixture containing no more than 21% oxygen.

Anesthesia, Endotracheal↗