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Biomedical subjects

A Mokashi

Publications and source records attributed to A Mokashi.

At least 19 recordsLinked to original sources
PubMed2004

Patient communication during cataract surgery.

PURPOSE: Most cataract surgery is now performed under local anaesthesia on a day-case basis. As patients are fully conscious during the procedure, it is important that they remain still. There are a variety of reasons why patients may need to move, and it is important that the surgeon is made aware that this may happen. Some centres offer a nurse's hand as a means of perioperative patient communication. We sought to study the safety and efficacy of using an electronic patient-controlled alert device. METHOD: We compared hand-holding with the use of a patient alert device, and with both communication methods at the same time, on 150 subjects undergoing cataract surgery under local anaesthesia. Assessment of pre- and postoperative state anxiety was undertaken and patients' satisfaction with the communication strategies was assessed. RESULTS: There was a significant difference between pre- and postoperative state anxiety for each group (P<0.001) but no significant differences in pre-, peri-, or postoperative state anxiety between groups. There were no significant differences in confidence, pain, understanding, satisfaction, memory, and reassurance between the three groups. A total of 46% of all patients reported experiencing one or more of the potential problems enquired about, during the operation. Significant correlations were also identified between some of the psychological variables investigated. CONCLUSIONS: An electronic patient alert device is as effective a means of perioperative patient communication as holding a nurse's hand, during cataract surgery under local anaesthesia. It is safe, reassuring and it allows patients to communicate directly with the surgeon.

Aged↗
PubMed2003

ATP causes glomus cell [Ca2+]c increase without corresponding increases in CSN activity.

The hypothesis that an increase in intracellular calcium [Ca(2+)](c) in carotid body (CB) glomus cells will cause enhanced afferent carotid sinus nerve (CSN) activities was tested in the rat CB in-vitro with the use of extracellular ATP. ATP caused a dose dependent [Ca(2+)](c) increase in identified glomus cells. A major part of total [Ca(2+)](c) increase (2/3) was due to the [Ca(2+)] influx. The rest of [Ca(2+)](c) increase (1/3) was due to the release of [Ca(2+)] from the endoplasmic reticulum (ER) [Ca(2+)] stores, and it was inhibited by the pretreatment of cells with cyclopiazonic acid (CPA), an intracellular Ca(2+)-ATPase blocker. Suramin, a purinergic P(2) receptor membrane blocker, blocked [Ca(2+)] influx due to ATP in the presence of extracellular [Ca(2+)]. Perfusion with 5 and 10 microM ATP stimulated CSN activities in both normoxia (Nx) and hypoxia (Hx). Above that level, 100 microM ATP induced slight initial stimulation in CSN activities which were subsided subsequently in Nx and partly diminished in Hx, while 500 microM ATP completely inhibited CSN activities in Nx and Hx after a slight initial stimulation. Electrophysiological measurements of the glomus cell membrane potential in the presence of ATP (100 microM) during Nx indicated cellular enhanced outward K(+) current and hyperpolarization, suggesting potential mechanism for the inhibition of CSN activities. Thus, ATP dependent linear increases in [Ca(2+)](c) did not give rise to a corresponding increase in CSN activities, contravening the normally expected increase in CSN activities following [Ca(2+)](c) rise.

Adenosine Triphosphate↗
PubMed2003

Sustained hypoxia promotes hyperactive response of carotid body in the cat.

Carotid body chemosensory activities were measured before and after 0.2, 5,6 and 7 h of sustained isocapnic (PaCO(2) approximately equal to 30 Torr) hypoxia (PaO(2) approximately equal to 43 Torr) in the cats (n=7). The activity increased from 5.4 impsec(-1) at 0.2 h to about 13 impsec(-1) at 7 h. This increase in chemosensory activities were due to both an augmented sensitivity and to a long-term facilitation and not due to arterial [H(+)] changes.

Animals↗
PubMed2003

Atrial natriuretic peptide stimulates cat carotid body chemoreceptors in vivo.

It is known that atrial natriuretic peptide (ANP) is released from cardiac myocyte and other stores during hypoxia and is involved in pulmonary-cardiovascular reflexes and in natriuresis and diuresis. Since the carotid body initiates hypoxic chemoreflexes, we hypothesized that ANP could potentiate the hypoxic stimulation of the carotid body chemoreceptor in vivo. We studied the effect of close intra-arterial injection of ANP on carotid chemoreceptor activity in anesthetized male cats which were paralyzed and artificially ventilated. Graded doses of ANP (0-10 nmoles) were administered by intra-arterial injections and they produced an excitatory response. Single dose of ANP (6.5 nmoles) at four steady-state levels of arterial PO(2), at constant PCO(2), produced increases of chemoreceptor activity. This increase of chemoreceptor activity with ANP in the presence of CO(2)-HCO(3)(-) in vitro could make a difference from those without CO(2)-HCO(3)(-) in vivo.

Adaptation, Physiological↗
PubMed2001

Ryanodine receptor-mediated [Ca(2+)](i) release in glomus cells is independent of natural stimuli and does not participate in the chemosensory responses of the rat carotid body.

The hypothesis that intracellular calcium ([Ca(2+)](i)) release in glomus cells via ryanodine receptor (RyR) activation by caffeine may be independent of natural stimuli and chemosensory discharge was tested in the rat carotid body (CB). CB type I cells were isolated, plated and preloaded with calcium-sensitive fluorescent probe, Indo-1AM. With the increase of caffeine dose (0-50 mM) cytosolic calcium ([Ca(2+)](c)) increased from 85+/-15 nM to 1933+/-190 nM (n=6) at normoxia (PO(2)=125-130 Torr, PCO(2)=25-30 Torr, pH 7.30-7.35). Hypoxia (PO(2)=10-15 Torr) increased and hypocapnia (PCO(2)=7-9 Torr) decreased the cytoplasmic calcium [Ca(2+)](c) levels, independent of caffeine. Caffeine-related [Ca(2+)](c) increase was the same in the presence and the absence of extracellular calcium ([Ca(2+)](o)), indicating the source of Ca(2+) ions is the cellular store. Permeabilization of the cell membrane with saponin (25 microg/ml) retained the caffeine response. Additional treatment of the cells with 50 microM ryanodine (an inhibitor of the caffeine-activated RyR site) abolished caffeine-stimulated response. In vitro CB chemosensory (carotid sinus nerve, CSN) responses to hypoxia (PO(2)=35-40 Torr) were not altered by caffeine. These results suggest that [Ca(2+)](i) stores in CB cells, mobilized by RyR activation, do not participate in the CSN responses to natural stimuli.

Action Potentials↗
PubMed2001

The basic helix-loop-helix domain of the aryl hydrocarbon receptor nuclear transporter (ARNT) can oligomerize and bind E-box DNA specifically.

The aryl hydrocarbon receptor nuclear transporter (ARNT) is a basic helix-loop-helix (bHLH) protein that contains a Per-Arnt-Sim (PAS) domain. ARNT heterodimerizes in vivo with other bHLH PAS proteins to regulate a number of cellular activities, but a physiological role for ARNT homodimers has not yet been established. Moreover, no rigorous studies have been done to characterize the biochemical properties of the bHLH domain of ARNT that would address this issue. To begin this characterization, we chemically synthesized a 56-residue peptide encompassing the bHLH domain of ARNT (residues 90-145). In the absence of DNA, the ARNT-bHLH peptide can form homodimers in lower ionic strength, as evidenced by dynamic light scattering analysis, and can bind E-box DNA (CACGTG) with high specificity and affinity, as determined by fluorescence anisotropy. Dimers and tetramers of ARNT-bHLH are observed bound to DNA in equilibrium sedimentation and dynamic light scattering experiments. The homodimeric peptide also undergoes a coil-to-helix transition upon E-box DNA binding. Peptide oligomerization and DNA affinity are strongly influenced by ionic strength. These biochemical and biophysical studies on the ARNT-bHLH reveal its inherent ability to form homodimers at concentrations supporting a physiological function and underscore the significant biochemical differences among the bHLH superfamily.

Amino Acid Sequence↗
PubMed2001

Barium-stimulated chemosensory activity may not reflect inhibition of background voltage-insensitive K+ channels in the rat carotid body.

To test the hypothesis that the voltage-insensitive background leak K+ channel is responsible for the oxygen-sensitive properties of glomus cells in the rat carotid body (CB) we used Ba2+, a non-specific inhibitor of K+ currents. In vitro changes in cytosolic calcium ([Ca2+]c) and chemosensory discharge were studied to measure the effect of Ba2+. In normal Tyrode buffer, Ba2+ (3 and 5 mM) significantly increased carotid sinus nerve (CSN) discharge over baseline firing rates under normoxia (PO2 approximately 120 Torr) from approximately 150 to approximately 600 imp/0.5 s. However, addition of 200 microM Cd2+ which completely blocked increase in CSN activity stimulated by hypoxia (PO2 approximately 30 Torr), hypercapnia (PCO2 approximately 60 Torr, PO2 approximately 120 Torr) and high CO (PCO approximately 550 Torr, PO2 approximately 120 Torr) did not significantly inhibit Ba2+-stimulated CSN discharge. The response to hypoxia is abolished with Ca2+-free tyrode buffer containing 10 mM EGTA. Yet, in the same buffer, Ba2+ increased CSN discharge from approximately 2 to approximately 180 imp/0.5 s. With 200 microM Cd2+ and 10 mM EGTA, Ba2+ still increased CSN discharge from approximately 2 to approximately 150 imp/0.5 s. Oligomycin (2 microg) abolished the hypoxic response. However, in the presence of oligomycin CSN response to Ba2+ was significant. Since Ba2+ increased neural discharge under conditions where hypoxia stimulated CSN discharge is completely abolished, we suggest that the effect of Ba2+ on CSN discharge may not have anything to do with the oxygen sensing mechanism in the CB.

Animals↗
PubMed2001

Reduced glutathione, dithiothreitol and cytochrome P-450 inhibitors do not influence hypoxic chemosensory responses in the rat carotid body.

Glomus cells and carotid sinus afferents are anatomically connected, and the chemical events in the glomus cells are expected to be conveyed reflexly as afferent signals. Accordingly, K(+) channel inhibition of the glomus cell membrane is expected to be followed by excitation of the afferents. In order to test the redox inhibition of K(+) channels of glomus cells by reduced glutathione (GSH), dithiothreitol (DTT) and by cytochrome P-450 inhibitors (clotrimazole and miconazole), we measured the carotid sinus nerve (CSN) discharge using an in vitro perfused adult rat carotid body (CB) in the presence and absence of these chemicals which are expected to excite the afferents. Our findings were that these agents did not stimulate the CSN activities during normoxia and kept the hypoxic responses intact. These results led us to conclude that the redox modulation of glomus cells was not conveyed to the afferents, and this functional disconnection did not support the redox hypothesis of O(2) chemoreception in the whole carotid body.

Animals↗
PubMed2001

Selective intracellular retention of extracellular matrix proteins and chaperones associated with pseudoachondroplasia.

Mutations in the cartilage oligomeric matrix protein (COMP) gene result in pseudoachondroplasia (PSACH), which is a chondrodysplasia characterized by early-onset osteoarthritis and short stature. COMP is a secreted pentameric glycoprotein that belongs to the thrombospondin family of proteins. We have identified a novel missense mutation which substitutes a glycine for an aspartic acid residue in the thrombospondin (TSP) type 3 calcium-binding domain of COMP in a patient diagnosed with PSACH. Immunohistochemistry and immunoelectron microscopy both show abnormal retention of COMP within characteristically enlarged rER inclusions of PSACH chondrocytes, as well as retention of fibromodulin, decorin and types IX, XI and XII collagen. Aggrecan and types II and VI collagen were not retained intracellularly within the same cells. In addition to selective extracellular matrix components, the chaperones HSP47, protein disulfide isomerase (PDI) and calnexin were localized at elevated levels within the rER vesicles of PSACH chondrocytes, suggesting that they may play a role in the cellular retention of mutant COMP molecules. Whether the aberrant rER inclusions in PSACH chondrocytes are a direct consequence of chaperone-mediated retention of mutant COMP or are otherwise due to selective intracellular protein interactions, which may in turn lead to aggregation within the rER, is unclear. However, our data demonstrate that retention of mutant COMP molecules results in the selective retention of ECM molecules and molecular chaperones, indicating the existence of distinct secretory pathways or ER-sorting mechanisms for matrix molecules, a process mediated by their association with various molecular chaperones.

Aggrecans↗
PubMed2000

Mice lacking in gp91 phox subunit of NAD(P)H oxidase showed glomus cell [Ca(2+)](i) and respiratory responses to hypoxia.

The hypothesis that NAD(P)H oxidase may serve as an oxygen sensor was tested using the mice deficient (knock-out) in gp91phox subunit of NAD(P)H oxidase enzyme complex and compared with wild-type (C57BL/6J) strain measuring the ventilatory and glomus cell intracellular calcium ([Ca(2+)](i)) responses of carotid body to hypoxia. The hypoxic ventilatory responses as well as the [Ca(2+)](i) were preserved in the NAD(P)H oxidase knock-out mice. NAD(P)H oxidase, though a major source of oxygen radical production, is not the oxygen sensor in mice carotid body.

Animals↗
PubMed2000

A cartilage oligomeric matrix protein mutation associated with pseudoachondroplasia changes the structural and functional properties of the type 3 domain.

Cartilage oligomeric matrix protein (COMP) is a member of the thrombospondin family of extracellular matrix glycoproteins. All members of the family contain a highly conserved region of thrombospondin type 3 sequence repeats that bind calcium. A mutation in COMP previously identified in a patient with pseudoachondroplasia resulted in abnormal sequestration of COMP in distinctive rER vesicles. The mutation, Asp-446 --> Asn, is located in the type 3 repeats of the molecule. This region was expressed in a mammalian culture with and without the mutation to study the structural or functional properties associated with the mutation. The biophysical parameters of the mutant peptide were compared with those of the wild type and revealed the following difference: secondary structural analysis by circular dichroism showed more alpha-helix content in the wild-type peptides. The calcium binding properties of the two peptides were significantly different; there were 17 calcium ions bound/wild-type COMP3 peptide compared with 8/mutant peptide. In addition, wild-type COMP3 had a higher affinity for calcium and bound calcium more cooperatively. Calcium bound by the wild-type peptide was reflected in a structural change as indicted by velocity sedimentation. Thus, the effect of the COMP mutation appears to profoundly alter the calcium binding properties and may account for the difference observed in the structure of the type 3 domain. Furthermore, the highly cooperative binding of calcium to COMP3 suggests that these type 3 sequence repeats form a single protein domain, the thrombospondin type 3 domain.

Achondroplasia↗
PubMed2000

The metabolic hypothesis revisited.

High levels of CO are used to mimic the stimulatory response of the CSN initiated by hypoxia. Using light of different wavelengths we show that the stimulatory effects of high CO can be pinpointed to the cytochrome c oxidase in the mitochondrial respiratory chain. This supports the metabolic theory of oxygen sensing in the mitochondria.

Animals↗
PubMed2000

Effects of 2,4-dinitrophenol (DNP) on the relationship between the chemosensory activities of the rat carotid body and the intracellular calcium of glomus cells.

To test the hypothesis that the uncoupler 2,4-dinitrophenol (DNP) increases [Ca2+]i equally well, independent of pHi, we studied the effects of 250 microM DNP on [Ca2+]i and carotid sinus nerve (CSN) activity of rat carotid body (CB). CSN activity was measured in CB perfused and superfused with hypocapnic (pHo 7.80) and normocapnic (pHo 7.42) Tyrode solutions. [Ca2+]i of glomus (type I cells) was assessed by superfusion techniques under identical conditions as for CSN recording experiments. The results indicate that 250 microM DNP increased [Ca2+]i of type I cells as well as CSN activity at both pHos, although alkalosis diminished these responses. Given that pHi will change with pHo, DNP did not make any additional pHi change, although [Ca2+]i changed. We conclude that DNP effects were due to [Ca2+]i change alone, and the relationship between [Ca2+]i and CSN activity are internally consistent.

2,4-Dinitrophenol↗