PubMed HealthSearch

Biomedical subjects

J M Zhao

Publications and source records attributed to J M Zhao.

At least 19 recordsLinked to original sources

Cluster headache: oxygen saturation and end-tidal CO2 during and without attack.

Twenty-eight cluster headache patients were examined either in remission (n = 10), in the interparoxysmal period ("cluster phase") (n = 12), or during spontaneously occurring (n = 7), or nitroglycerin provoked (n = 7) attacks. Fourteen healthy controls participated in the study. Oxygen saturation (SaO2), end-tidal CO2 (PCO2), and respiratory rate (R.R.) were recorded for the controls and the patients during the different phases of cluster headache. Both PCO2 and SaO2 tended to be lower during the interparoxysmal period of the cluster phase when compared to the control group or to the remission. During both nitroglycerin-provoked and spontaneous attacks, PCO2 and SaO2 tended to respectively decrease and increase, both when compared with the "cluster phase" and with the period immediately prior to attack ("pre-attack"). Hence the "pre-attack" state may, on an average, be characterized by a slight hypoxia and a slight hyperventilation. Marked, clinically observable hyperventilation was present only in the occasional cluster headache patient. There was no SaO2 decrease from the "cluster phase" (interparoxysmal period) to the period immediately preceding the attack ("pre-attack"), and SaO2 "dips" preceding an attack were only observed in one cluster headache patient. As demonstrated previously by our group, a considerable lowering of SaO2 (i.e. partly to less than or equal to 83%) does only exceptionally lead to attack (Zhao et al, 1990). This observation combined with the evidence presented herein may seem to indicate that the slight pre-attack oxygen desaturation probably is too small to be a symptom-producing factor in cluster headache--be it in the spontaneously occurring or in the induced attack.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The effect of hyperventilation in cluster headache patients.

The effect of voluntary hyperventilation was assessed in 22 cluster headache patients (8 in a cluster period and 14 in a remission) and 19 healthy individuals. Using an ear oximeter and a capnograph with a nasal probe, the oxygen saturation (SaO2) and the end-tidal CO2 were monitored continuously. During the hyperventilation per se, cluster headache patients and controls showed absolute values of end-tidal CO2 and of SaO2 of the same order of magnitude. In the posthyperventilation phase, however, the average of the lowest SaO2 levels was lower in controls than in cluster headache patients. In the posthyperventilation phase, headache patients outside the cluster period showed a trend more similar to that of the controls with respect to SaO2 than did those inside the cluster period. The observed discrepancy might, if reproducible, be a consequence of an altered chemoreceptor sensitivity in cluster headache patients during the bout.

Adult

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, etc. (SUNCT): III. Another Norwegian case.

"SUNCT" is a recently reported head pain syndrome characterized by shortlasting, unilateral neuralgiform paroxysms with conjunctival injection and tearing, and to a lesser extent nasal secretion, and (subclinical) sweating. Another case--that of a 56 year old male--is reported herein. The attacks lasted 1/2-1 min. and occurred only infrequently, i.e. once or twice in 1-4 weeks, except for a week recently when there were up to 20 or more typical attacks per day, with the usual ipsilateral, autonomic accompaniments. Due to the benign nature and low frequency of attacks, the diagnosis would have been most difficult to establish prior to the occurrence of this shortlasting period with more marked symptoms. A variety of precipitation mechanisms were present, partly concerning the V 2-3 areas, partly concerning the neck. Precipitation mechanisms in "SUNCT" to some extent seem to differ from those in trigeminal neuralgia. It is remarkable that all four hitherto reported cases are males.

Conjunctiva

[Dynamic changes of Ito cells in experimental cirrhosis of rat].

That Ito cells in rat liver express desmin was confirmed by immunohistochemical technique. Anyhow, changes of desmin-positive cells, lysozyme-positive cells and fibronectin were further studied in experimental cirrhosis of rat. It was found that desmin-positive cells, with the transitional features between Ito cells and myofibroblasts or fibroblasts under electron microscope, increased in number and expression of desmin in the necrotic areas as well as in the cellular fibrous septa, but decreased in number in the fibrous septa except those areas close to the edges of the septa. These results suggested that Ito cells, myofibroblasts and fibroblasts may belong to the same cellular system and play an important role in the pathogenesis of cirrhosis. Meanwhile, it was also noted that changes of both fibronectin and lysozyme-positive cells were correlated with those of desmin-positive cells. These provide evidence in vivo that fibronectin and Kupffer cells may exert certain effects on the migration and proliferation of Ito cells in cases of liver cirrhosis.

Animals

The effect of high pH upon diphtheria toxin conformation and model membrane association: role of partial unfolding.

Penetration of membranes by diphtheria toxin in vivo is at least partially triggered by a low pH-induced conformational change occurring within the lumen of an acidic organelle. In order to gain insight into the nature of this change the behavior of the toxin at high pH was characterized and compared to that previously determined at low pH. We find that near pH 10.5 a major conformational change occurs. This change is accompanied by a marked decrease in fluorescence intensity, a red shift in fluorescence emission maximum, and increased susceptibility of protein fluorescence to acrylamide quenching. Differential scanning calorimetry shows that the high pH conformational change involves a cooperative endothermic unfolding transition. These changes at high pH are very similar to those induced by low pH, supporting the conclusion that the changes at low pH also involve a denaturation-like process. In addition, at high pH the toxin gains the ability to bind to model membranes, again similar to its behavior at low pH. On the basis of these studies we conclude that exposure of hydrophobic sequences due to partial unfolding is one dominating component in inducing hydrophobic behavior at both high and low pH, but that at low pH Asp/Glu protonation also contributes to hydrophobicity.

Calorimetry, Differential Scanning

A cDNA encoding 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Solanum tuberosum L.

A cDNA encoding potato (Solanum tuberosum L.) 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, the first enzyme of the shikimate pathway, was cloned into phage lambda gt11. The clone represents the first cDNA for this enzyme from any eukaryotic source. The nucleotide sequence of the cDNA was determined, and its identity was confirmed through partial amino acid sequence analysis of the encoded enzyme. The cDNA contains a 1527-base pair open reading frame that encodes a polypeptide with a calculated molecular weight of 56,153. The amino terminus of the deduced polypeptide resembles a chloroplast transit sequence. Amino acid sequence identities between the mature potato enzyme and the homologous isoenzymes from Escherichia coli are only about 22%. The potato cDNA hybridized to various plant mRNAs that are all about 2 kilobases in size.

3-Deoxy-7-Phosphoheptulonate Synthase

Cluster headache: the effect of low oxygen saturation.

The present study concerns the possible relationship between hypoxia and the generation of cluster headache attacks. Fifteen controls and 25 cluster headache patients were studied. The patients were allocated into two groups according to cluster headache stage, i.e. cluster or remission period. During the tests, all the subjects were asked to inhale 12% oxygen (88% N2) for 30 min, and the decreasing oxygen saturation (SaO2%) was monitored. Patients in the remission period showed nearly the same decrement of SaO2% as controls. At the end of the test, patients in the bout showed significantly less reduction of SaO2% than the controls. In 5 patients, the test was carried out both in and outside the cluster periods. The tendency to less decrement in oxygen saturation in the cluster phase was as marked with this comparison, but the difference between the groups was not significant, probably partly due to the low number of tests carried out. Only one patient got a typical attack. It seems that hypoxia of this magnitude per se is not the cause of attacks. The different pattern with respect to SaO2% following 12% O2 inhalation in cluster headache may be due to an abnormality in central regulation and/or chemoreceptor sensitivity.

Adult

Cluster headache: pupillometric patterns as a function of the degree of anisocoria.

Fifty-three patients with cluster headache, mean age 42.6 years, were examined by means of pupillometry. Pharmacological stimulation was carried out by the instillation of eye drops; the sympathomimetic agents hydroxyamphetamine (a norepinephrine releaser) and phenylephrine (an agent acting directly on the postsynaptic receptors) were applied. Pupillary dilatation was measured at set time intervals, comparing the responses of the symptomatic and non-symptomatic sides. The material was divided into groups according to the degree of basal anisocoria. The subgroup with the most pronounced basal miosis of the symptomatic side demonstrated a uniform pattern of deficient symptomatic side dilatation after OH-amphetamine and supersensitivity to phenylephrine. The other groups demonstrated the same general pattern, but to a far lesser degree. In cluster headache, the extent of nonresponsiveness to OH-amphetamine and of phenylephrine supersensitivity on the symptomatic side thus, at least partly, seems to be a function of the degree of anisocoria. The response pattern in cluster headache seems to differ from that of 3rd neuron Horner's syndrome with an anisocoria of the same extent.

Adult

Shortlasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating, and rhinorrhea.

Three grown-up males with a long-lasting history of rather uniform, unilateral headache in the ocular-periocular area, in cluster fashion, are examined. Pain paroxysms of short duration (15-60 sec) appear up to 5-30 times per h. The headache is unilateral without side shift. Conjunctival injection appears at the very beginning of the attack and is partly massive, lasting the entire duration of the attack, and fading away at the end of it. Tearing (massive), forehead sweating (subclinical) and rhinorrhea, all on the symptomatic side, accompany the attack. In the youngest patient, the headache became chronic after clustering for six months initially, and after approximately 3 1/2 years it became bilateral. However, even in this patient, a clear unilateral pain preponderance prevails, and the autonomic disturbances are all on the original pain side. Attacks can partly be precipitated by chewing, eating (e.g. citrus fruits), moving the head, etc. The headache is completely refractory to drug therapy, including indomethacin.

Aged

Conformation and model membrane interactions of diphtheria toxin fragment A.

Low pH is believed to play a critical role in the penetration of membranes by diphtheria toxin in vivo. In this report, the pH dependence of the conformation of fragment A of diphtheria toxin has been studied using fluorescence techniques. As pH is decreased, fragment A in solution undergoes a reversible conformational change beginning below pH 5. The conformational change occurs rapidly upon exposure to low pH. It involves both an increase in the exposure of tryptophanyl residues to solution and a switch from a hydrophilic state to a hydrophobic state as judged by fragment A binding to micelles of a mild detergent (Brij 96). At low pH fragment A also rapidly and tightly binds to and penetrates model membranes. Binding is reversed when pH is neutralized. The transition pH, the apparent midpoint of the change between the hydrophilic state and the membrane-penetrating hydrophobic state, occurs at about pH 3.5 in the presence of Brij 96 micelles, pH 4 in the presence of small unilamellar vesicles (SUV) composed of zwitterionic phosphatidylcholine, and pH 5 in the presence of SUV composed of 25 mol % anionic phosphatidylglycerol and 75% phosphatidylcholine. The effects of high temperature provide an important clue as to the nature of the changes at low pH. At neutral pH and high temperature, i.e. in the thermally denatured state, a conformational change similar to that observed at low pH occurs, although fragment A does not become hydrophobic. In addition, the effects of low pH and high temperature on the stability of the native state are cumulative. This indicates that the changes in fragment A both at high temperature and at low pH involve denaturation, although there appears to be only partial unfolding under these conditions. Based on the results of this study, the role of fragment A in diphtheria toxin membrane penetration and translocation is evaluated.

Chromatography, High Pressure Liquid

Localization of the active site of diphtheria toxin.

Information about the location of the active site of diphtheria toxin was derived from proteolysis studies and an analysis of its sequence. It was found that a specific trypsin cleavage within whole diphtheria toxin occurs at Lys-39. Therefore, Lys-39 appears to be a surface residue. Furthermore, protection from proteolysis could be obtained upon binding of either the substrate beta-nicotinamide adenine dinucleotide (oxidized form) (NAD+) or a competing ligand, adenylyl(3'-5')uridine 3'-phosphate (ApUp). The protection by ApUp, which binds to the toxin very tightly, required only stoichiometric levels. The most likely explanation of these results is that both NAD+ binding and ApUp binding block trypsin either through a steric mechanism or through a local conformational change, suggesting Lys-39 may be near the active site. Further evidence supporting this conclusion comes from comparison of the previously determined sequences of diphtheria toxin and of Pseudomonas exotoxin A, a protein that catalyzes an identical reaction. We find a significant degree of homology between the N-terminal halves of the catalytic domains of these two proteins, which apparently represents active-site residues, and that Lys-39 is in the center of the homologous sequence. Furthermore, the location of the amino acid that is the homologue of Lys-39 within the crystal structure of Pseudomonas exotoxin A is also in agreement with a location in or near the active site. Other unusual features in the sequences of diphtheria toxin and Pseudomonas exotoxin A are also described, and on the basis of the experiments presented, a possible function for ApUp is considered.

ADP Ribose Transferases

"Mild" cluster headache(?).

Three cases of what could be considered "mild" cluster headache have been described. All three patients were generally able to carry out their work during attacks; all three were men and had unilateral headache with the predominant pain in the ocular region. Relatively few symptoms and signs indicated autonomic system involvement, but at least tearing was invariably present on the symptomatic side. The bouts were generally short-lasting in two of the patients (and partly in the third one), fitting the pattern of "mini-bouts". Thus, in one of the cases four of the five major criteria (male sex, excruciating severity, cluster phenomenon, autonomic involvement, and unilaterality) were present. In the two other patients the full-blown cluster phenomenon was lacking. Such cases may represent the left-side slope of a "Gaussian severity distribution scale" with regard to cluster headache.

Adult

Cluster headache: on the significance of so-called minibouts.

Cluster headache periods (bouts) have, at the lower end of the scale, been supposed to last for periods as short as 1-2 weeks. Patients who usually have bouts of ordinary duration occasionally have brief attacks in the remission phase ("abortive attacks"). The group described here had a temporal pattern, clearly at variance with both these patterns: The six patients had mostly or entirely bouts of less than 1 week's duration. We have termed such short-lasting bouts minibouts, on the supposition that such cases belong within the cluster headache cycle. All the patients were men and had a history of unilateral headache without side shift, and usually the solitary attacks had some autonomic accompaniments, although of a moderate degree. In four cases only mild attacks occurred, whereas in two cases the attacks were rather severe and not consistent with full working ability. The group as such may not be homogeneous. The nosologic status of patients with bouts lasting only 1-2 days is somewhat uncertain. As long as the substrate of cluster headache is not outlined, the lower end of duration of minibouts cannot be accurately identified. The fact that three patients recently have experienced bouts of ordinary length strengthens the view that such cases really belong to the cluster headache cycle.

Adult

Similarity of the conformation of diphtheria toxin at high temperature to that in the membrane-penetrating low-pH state.

At high temperature, nicked free monomers of diphtheria toxin undergo a transition to a thermally denatured state, with a midpoint of 45-50 degrees C. In this report, the high-temperature (60 degrees C) conformation has been compared to the native (neutral pH) and low-pH (pH less than 5) conformations. The low-pH and high-temperature conformations are similar although not identical. As in the conformation at low pH, and unlike the toxin in its native conformation, the protein in its conformation at high temperature is hydrophobic, has low fluorescence intensity, and has increased exposure of tryptophan to aqueous solution. As at low pH, at high temperature the circular dichroism spectrum shows at most only partial unfolding of secondary structure. In contrast, the conformation of the toxin in guanidinium chloride is much closer to a random coil. The effects of high temperature and low pH interact in the sense that sensitivity of the native conformation to one is increased by the other. That is, the transition temperature between native and thermally denatured states is decreased as pH is decreased, and the transition pH between neutral-pH and low-pH states is increased as temperature is increased. This implies that there is some region on the protein where high temperature and low pH can disrupt conformation in a similar manner. Taken together, these results indicate that the low-pH and high-temperature conformations can both be defined as partially denatured states, even though unfolding may not be extensive at low pH. Similar behavior may occur in other proteins that undergo functionally important conformational disruption at low pH.

Chemical Phenomena