'Slings' enable neutrophil rolling at high shear.

Most leukocytes can roll along the walls of venules at low shear stress (1 dyn cm−2), but neutrophils have the ability to roll at tenfold higher shear stress in microvessels in vivo. The mechanisms involved in this shear-resistant rolling are known to involve cell flattening and pulling of long membrane tethers at the rear. Here we show that these long tethers do not retract as postulated, but instead persist and appear as 'slings' at the front of rolling cells. We demonstrate slings in a model of acute inflammation in vivo and on P-selectin in vitro, where P-selectin-glycoprotein-ligand-1 (PSGL-1) is found in discrete sticky patches whereas LFA-1 is expressed over the entire length on slings. As neutrophils roll forward, slings wrap around the rolling cells and undergo a step-wise peeling from the P-selectin substrate enabled by the failure of PSGL-1 patches under hydrodynamic forces. The 'step-wise peeling of slings' is distinct from the 'pulling of tethers' reported previously. Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation.

Anti-Oxidant and Fucoxanthin Contents of Brown Alga Ishimozuku (Sphaerotrichia divaricata) from the West Coast of Aomori, Japan.

Fucoxanthin is a specific carotenoid in brown seaweeds with remarkable biological properties. Ishimozuku (Sphaerotrichia divaricata), an edible brown alga from northern Japan, has morphology that is almost identical to that of Okinawa-mozuku (Cladosiphon okamuranus) harvested off Okinawa, Japan. However, because of Ishimozuku's lower availability compared to Okinawa-mozuku, the contents of its nutrient compounds remain unclear. The present study analyzed fucoxanthin and anti-oxidant compound contents of Ishimozuku harvested off the northern coast of Japan from 2014 to 2016. First, 80% ethanol extract solutions were prepared from Ishimozuku harvested from several west coast areas of Aomori, Japan. Then, polyphenol content was analyzed using the Folin⁻Ciocalteu method. Then anti-oxidative effects were analyzed by their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and hydrogen peroxide scavenging activity. Furthermore, fucoxanthin contents were measured using high performance liquid chromatography (HPLC) analysis. Fucoxanthin contents of Ishimozuku were 105.6⁻1148.5 µg/g dry weight. Total polyphenol contents of Ishimozuku were of 0.296⁻0.958 mg/g dry weight: higher than Okinawa-mozuku (0.082 ± 0.011 mg/g dry weight). The anti-oxidation effects of Ishimozuku accompanied the polyphenol content. These results suggest that Ishimozuku contains various anti-oxidant components and has high potential to provide the promotion of human health.

Enhanced podocyte vesicle transport in the nephrotic rat.

Albumin endocytosis is enhanced in the podocytes of minimal change nephrotic syndrome. We investigated that the endocytic vesicle transport in the podocyte using three-dimensional observation in a rat model of puromycin aminonucleoside (PAN)-induced nephrotic syndrome. At day 7, Evans Blue-labeled albumin was intravenously injected in PAN rats, and one kidney was fixed for a morphological analysis; the other was used for the isolation of glomeruli through sieving and protein analyses. Evans Blue-labeled albumin was found to accumulate in an increased number of vesicles in the podocytes of PAN rat. Continuous sections and its three-dimensional observation demonstrated that vesicles may be transported from the cytoplasm to the apical membrane of the podocytes. The increased protein bands in the gel electrophoresis of the sieved glomeruli of nephrotic rats were analyzed by mass spectrometry in comparison to the control rats. The major proteins increased in the nephrotic rats were cytoplasmic dynein 1 heavy chain, myosin IX, and myosin VIIb. In conclusion, the podocyte endocytic vesicles carrying albumin increased with glomerular cytoplasmic dynein and myosin in minimal change nephrotic rats.

Calcium-induced calcium release from the sarcoplasmic reticulum can be evaluated with a half-logistic function model in aequorin-injected cardiac muscles.

PURPOSE: Release of calcium (Ca(2+)) from the sarcoplasmic reticulum (SR) induced by Ca(2+) influx through voltage-dependent sarcolemmal L-type Ca(2+) channels (CICR) in cardiac muscle cells has been implicated as a potential target contributing to anesthetic-induced myocardial depression. In an earlier study, we found that (1) a half-logistic (h-L) function, which represents a half-curve of a sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phases of the isometric myocardial tension and isovolumic left ventricular (LV) pressure waveforms better than a mono-exponential (m-E) function and (2) the h-L time constants are useful as inotropic indices. We report here our investigation of the potential application of an h-L function to the analysis of the first half of the ascending phase of the Ca(2+) transient curve (faCaT) that precedes and initiates myocardial contraction and the increase in LV pressure. METHODS: Ca(2+) transients (CaT) were measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into seven isolated rabbit right ventricular and 15 isolated mouse LV papillary muscles. The faCaT data from the beginning of twitch stimulation to the maximum of the first-order time derivative of Ca(2+) concentration (dCa/dt(max)) was curve-fitted by the least-squares method using h-L and m-E function equations. RESULTS: The mean correlation coefficient (r) values of the h-L and m-E curve-fits for the faCaTs were 0.9740 and 0.9654 (P < 0.05) in the rabbit and 0.9895 and 0.9812 (P < 0.0001) in the mouse. CONCLUSION: The h-L curves tracked the amplitudes and time courses of the faCaTs in cardiac muscles more accurately than m-E functions. Based on this result, we suggest that the h-L time constant may be a more reliable index than the m-E time constant for evaluating the rate of CICR from the SR in myocardial Ca(2+) handling. The h-L approach may provide a more useful model for the study of CICR during the contraction process induced by anesthetic agents.

[Effect sites of anesthetics in the central nervous system network--looking into the mechanisms for natural sleep and anesthesia].

We showed the effect sites of anesthetics in the central nervous system (CNS) network. The thalamus is a key factor for loss of consciousness during natural sleep and anesthesia. Although the linkages among neurons within the CNS network in natural sleep are complicated, but sophisticated, the sleep mechanism has been gradually unraveled. Anesthesia disrupts the link-ages between cortical and thalamic neurons and among the cortical neurons, and thus it loses the integration of information derived from the arousal and sleep nuclei. It has been considered that anesthesia does not share the common pathway as natural sleep at the level of unconsciousness, because anesthetics have multiple effect sites within CNS network and may induce disintegration among neurons. Recent literatures have shown that the effects of anesthetics are specific rather than global in the brain. It is interesting to note that thalamic injection of anti-potassium channel materials restored consciousness during inhalation anesthesia, and that the sedative components of certain intravenous anesthesia may share the same pathway as natural sleep. To explore the sensitivity and susceptibility loci for anesthetics in the thalamocortical neurons as well as arousal and sleep nuclei within CNS network may be an important task for future study.

Microinjection of propofol into the perifornical area induces sedation with decreasing cortical acetylcholine release in rats.

BACKGROUND: Among many neurotransmitter systems in the central nervous system, the cholinergic system has been shown to contribute to propofol's sedative/anesthetic effects, because it has been shown that cholinesterase inhibitor reverses the level of propofol-induced unconsciousness in humans. It has been reported that intraperitoneal injection of propofol induced sedative/anesthetic actions and decreased the release of acetylcholine (Ach) from the rat cortex. However, the sites of action of propofol in the cholinergic pathway and its related pathways remain unresolved. We studied whether microinjection of propofol into the nuclei in the cholinergic pathway and its related pathways may induce sedation and decrease Ach from the cortex. METHODS: Thirty-seven male Wistar rats weighing 270 to 320 g were used. Almost 5 days before the experiments, 23 rats anesthetized with pentobarbital (50 mg/kg) were outfitted with an electroencephalogram (EEG) socket, a microdialysis cannula in the cortex, and an intraperitoneal tube or a microinjection tube into the basal forebrain (BF), the perifornical area (Pef), or the striatum. The Ach effluxes in the somatosensory cortex were detected using in vivo intracerebral microdialysis in freely moving rats. Once basal levels of Ach were stabilized, samples were collected every 20 minutes and measured by high-performance liquid chromatography. In the intraperitoneal group, propofol was cumulatively administered (10, 30, and 100 mg/kg) into the peritoneal cavity. In the microinjection groups, propofol (40 ng in 0.2 microL) was administered into the BF, the Pef, or the striatum (control), and the cortical changes in Ach efflux and EEG were observed for 2 hours. In another 14 rats, the sedative/anesthetic score was obtained after intraperitoneal, Pef, or striatal injection of propofol. The placement of the tip of the microdialysis probe and the microinjection tube was confirmed by histological examination. RESULTS: Intraperitoneal injection of propofol dose-dependently decreased the Ach efflux and induced light sedative to moderate anesthetic states. Loss of righting reflex was observed with significant increases in the relative alpha-power band at 100 mg/kg propofol. Microinjection of propofol into the BF significantly decreased the cortical Ach efflux to -40.2% + or - 19.9% at 40 to 60 minutes. However, there was no difference in the total Ach efflux for 2 hours between BF and control groups. In contrast, microinjection of propofol into the Pef immediately decreased the Ach efflux at 0 to 20 min and maximally to -59.3 + or - 20.4 at 100 to 120 minutes. The total Ach efflux in the Pef microinjection group was significantly less than that in the control group. The same dose of propofol injected into the Pef induced light to deep sedation. There was no significant change in the relative EEG power band between BF or Pef and control groups. CONCLUSION: The nuclei in the Pef are, at least in part, responsible for the sedative action of propofol in rats.

Differential responses of porcine anterior spinal and middle cerebral arteries to carbon dioxide and pH.

OBJECTIVE: Dysfunction of the anterior spinal arteries (ASAs) may induce paresis or paraplegia after thoracoabdominal aortic aneurysm or spine surgery. However, there have been no reports of the effects of CO2 and pH on ASAs. Information on these effects on ASAs might contribute to the perioperative management or critical care of spinal cord function. Thus, we investigated the effects of CO2 and pH on the vasomotor tone of ASAs and the third branch of the middle cerebral artery (bMCA). DESIGN: Prospective study of the effects of CO2 and pH on vasomotor response of porcine ASA and bMCA in vitro. SETTING: University laboratories. SUBJECTS: Porcine heads and spinal cords obtained from a slaughterhouse. INTERVENTION: ASAs and bMCAs were isolated, and changes in the intraluminal region of these pressurized arteries ( approximately 80 mm Hg) were observed for 30 minutes after perfusion with a solution saturated with various concentrations of CO2 and pH. MEASUREMENTS AND MAIN RESULTS: Respiratory acidosis (pH/Pco2 approximately 7.10-7.15/ approximately 60-80 mm Hg) constricted the ASAs, followed by a partial but gradual decrease in tone, whereas the bMCAs were exclusively dilated. The respiratory alkalosis (pH/Pco2 approximately 7.60/ approximately 20 mm Hg) did not influence ASA tone. Vasoconstriction of the ASAs induced by respiratory acidosis was abolished by removal of the endothelium, but not by N-nitro-L-arginine (1 microM). Respiratory acidosis dilated the ASAs in all preparations treated with ONO-3708 (1 microM), a specific thromboxane A2 receptor antagonist, and OKY-046 (1 microM), a specific thromboxane synthase inhibitor. Metabolic acidosis (pH/Pco2 approximately 7.10/ approximately 40 mm Hg) caused dilation of both bMCAs and ASAs, which was abolished by glibenclamide (1 microM). CONCLUSIONS: CO2-induced endothelium-dependent constriction in porcine ASAs through releasing thromboxane A2-like substance(s). Thus, hypercarbia might not be favorable for the perioperative or critical care management of spinal cord function during thoracoabdominal aortic aneurysm and spine surgery.

A new approach for observing cerebral cisterns and ventricles via a percutaneous lumbosacral route by using fine, flexible fiberscopes.

OBJECT: To establish a new method for the diagnosis of central nervous system diseases, the authors visualized the cerebral cisterns and ventricles via a percutaneous lumbosacral route by using newly developed fine, flexible fiberscopes. METHODS: Fine, flexible fiberscopes, 0.9 and 1.4 mm in diameter, were introduced up to the cerebral cisterns and ventricles through a percutaneous lumbosacral route in awake patients with chronic headache and/or neck pain or those undergoing spinal surgery and in whom MR imaging did not disclose any particular abnormalities in the brain. A lumbosacral subarachnoid puncture was made with a modified method of a continuous epidural block. RESULTS: In 25 of 31 patients tested, the cerebellomedullary and/or pontine/interpeduncular cisterns were easily and safely reached, and the brainstem structures were visualized. Advancement of the fiberscope beyond the spinal level was abandoned in 6 patients with adhesive spinal arachnoiditis, because the fiberscopes encountered resistance seemingly caused by arachnoid adhesions. Further advancement of the fiberscopes up to the fourth and third ventricles was successfully achieved in 2 patients. A number of arachnoid filaments were found in the cerebellomedullary cistern in 4 patients: 2 with chronic spinal arachnoiditis, 1 with a spinal arachnoid cyst, and 1 with posttraumatic pain syndrome. None of the patients reported pain or any major complication except a postspinal headache and light fever, which were encountered in 4 and 1 patient, respectively. CONCLUSIONS: The approach to the supraspinal structures via the lumbosacral route by using a fine, flexible fiberscope may provide a new, minimally invasive, and safe way to observe the cerebral cisterns and/or brainstem regions.

Characterization and expression profiles of small heat shock proteins in the marine red alga Pyropia yezoensis.

Small heat shock proteins (sHSPs) are found in all three domains of life (Bacteria, Archaea, and Eukarya) and play a critical role in protecting organisms from a range of environmental stresses. However, little is known about their physiological functions in red algae. Therefore, we characterized the sHSPs (PysHSPs) in the red macroalga Pyropia yezoensis, which inhabits the upper intertidal zone where it experiences fluctuating stressful environmental conditions on a daily and seasonal basis, and examined their expression profiles at different developmental stages and under varying environmental conditions. We identified five PysHSPs (PysHSP18.8, 19.1, 19.2, 19.5, and 25.8). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed that expression of the genes PysHSP18.8, PysHSP19.5, and PysHSP25.8 was repressed at all the developmental stages under normal conditions, whereas PysHSP19.1 and PysHSP19.2 were overexpressed in mature gametophytes and sporophytes. Exposure of the gametophytes to high temperature, oxidative stress, or copper significantly increased the mRNA transcript levels of all the five genes, while exogenous application of the ethylene precursor 1-aminocylopropane-1-carboxylic acid (ACC) significantly increased the expression levels of PysHSP19.2, PysHSP19.5, and PysHSP25.8. These findings will help to further our understanding of the role of PysHSP genes and provide clues about how Pyropia species can adapt to the stressful conditions encountered in the upper intertidal zone during their life cycle.

Structural features and gene-expression profiles of actin homologs in Porphyra yezoensis (Rhodophyta).

The marine red alga Porphyra yezoensis contains an actin gene family consisting of at least four isoforms (PyACT1, 2, 3 and 4). The amino acid identity between isoforms exceeds 83%, and each contains a putative nuclear export signal (NES). We scanned the sequences for amino acids in regions homologous to the intermonomeric interface of actin filaments. Few residues expected to engage in cross-linking were conserved between the four isoforms. The results of the sequence analyses suggest that PyACT2 probably functions in the nucleus as a monomer (G-actin) or in other unconventional forms. In addition, the distribution and position of the introns were different from those in florideophycean actin genes. The expression level of PyACT3 in matured gametophytes was significantly higher than in those in a vegetative state, although the mRNA was detected at similar levels in both apical and basal parts of thalli. The expression levels of PyACT2 and 4, on the other hand, did not change significantly between the matured and vegetative gametophytes. The PyACT3 may serve as a molecular marker for monitoring thallus maturation in this species.

[Preface and comments : multi-functions of orexin in physiological and pathological conditions--state of the art].

Recent advances in searching endogenous peptide ligands for multiple orphan receptors led to the identification of the new peptides, orexin-A and -B in the hypothalamus. Their function was initially considered to be associated with food consumption. However, these peptides have revealed their multiple functions in physiological and pathological conditions, such as sleep-wake control, the hypothalamic-pituitary-adrenal axis, pain modulation and so on. In the present reviews, I focused on the role of orexin on the norepinephrine and acetylcholine arousal system during anesthesia, the autonomic/endocrine regulation and pain pathways. These state-of-the-art reviews might contribute to the discoveries of the new functions of orexins in the anesthetic fields.

[Role of orexin in the cholinergic ascending arousal system--orexin-induced arousal from anesthesia].

The cholinergic ascending arousal pathway is one of the most powerful cortical activation systems. The origins of this system is from the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDT), which relay their signals to the posterior hypothalamus, the basal forebrain and then the cerebral cortex. The cholinergic activation by selective agonists or cholinesterase inhibitors has been shown to produce cortical activation and induce awareness from anesthesia. Orexin neurons are localized in the lateral to posterior hypothalamus. In this review, we presented the antagonistic action of orexin-A to isoflurane anesthesia in terms of the cortical release of acetylcholine and EEG arousal. Microinjection of orexin-A into the basal forebrain induced the increases in acetylcholine release and EEG arousal through orexin-1 receptors. Furthermore, electrical stimulation of the PPTg induced the increases in acetylcholine release and EEG arousal under isoflurane anesthesia, and SB334867, an orexin-1 receptor antagonist, attenuated these arousal responses. These findings suggest that the orexinergic system may contribute to the arousal from anesthesia through the cholinergic ascending arousal pathway.

Neuropeptide glutamic acid-isoleucine (NEI)-induced paradoxical sleep in rats.

Neuropeptideglutamic acid-isoleucine (NEI) as well as melanin concentrating hormone (MCH) is cleaved from the 165 amino acid protein, prepro-melanin concentrating hormone (prepro-MCH). Among many physiological roles of MCH, we demonstrated that intracerebroventricular (icv) injection of MCH induced increases in REM sleep episodes as well as in non REM sleep episodes. However, there are no studies on the effect of NEI on the sleep-wake cycle. As for the sites of action of MCH for induction of REM sleep, the ventrolateral periaqueductal gray (vlPAG) has been reported to be one of its site of action. Although MCH neurons contain NEI, GABA, MCH, and other neuropeptides, we do not know which transmitter(s) might induce REM sleep by acting on the vlPAG. Thus, we first examined the effect of icv injection of NEI on the sleep-wake cycle, and investigated how microinjection of either NEI, MCH, or GABA into the vlPAG affected REM sleep in rats. Icv injection of NEI (0.61µg/5µl: n=7) significantly increased the time spent in REM episodes compared to control (saline: 5µl; n=6). Microinjection of either NEI (61ng/0.2µl: n=7), MCH (100ng/0.2µl: n=6) or GABA (250mM/0.2µl: n=7) into the vlPAG significantly increased the time spent in REM episodes and the AUC. Precise hourly analysis of REM sleep also revealed that after those microinjections, NEI and MCH increased REM episodes at the latter phase, compared to GABA which increased REM episodes at the earlier phase. This result suggests that NEI and MCH may induce sustained REM sleep, while GABA may initiate REM sleep. In conclusion, our findings demonstrate that NEI, a cleaved peptide from the same precursor, prepro-MCH, as MCH, induce REM sleep at least in part through acting on the vlPAG.

[Progress in perioperative neuromonitoring: preface and comments].

The aims of the neuromonitoring during perioperative period are 1) to detect the brain, spinal cord and peripheral nerve ischemia immediately and hence prevention from neuronal injury, 2) to measure the depth of anesthesia, especially sedative effect of anesthetics and 3) to evaluate brain death. For the detection of brain and spinal cord ischemia during operation, we have to bear in mind 1) whether we truly monitor the possible ischemic risk sites in the brain and spinal cord; 2) whether we know the false-negative and false-positive ratio of the neuromonitoring with account being taken of the effect of anesthetics, the patient's own pathologies, the body temperature etc. If we detect the abnormal change through neuromonitoring, we should immediately warn the surgeon to improve his subsequent procedures and confirm his decision to prevent neuronal damage. To understand these reviews, we have to know the fundamental basic knowledge such as International 10-20 System on EEG monitoring, the expression of negative wave and positive wave in evoked potential, the meaning of near-field potential and far-field potential, temporal dispersion and so on. In this issue, the recent progress in neuromonitoring is described by the specialists in each fields. I hope the anesthesiologists understand the significance of neuromonitoring and apply these techniques for the patient undergoing the neurological operation during perioperative periods.

[Somatosensory evoked potential].

Somatosensory evoked potential (SEP) has been widely used for monitoring the abnormal nerve conduction in various diseases. In non-anesthetized patients, Abeta fibers are electrically stimulated during SEP measurements. In anesthesiological field, it is used as a short latency somatosensory potential (SSEP), because its latency and amplitude are relatively constant. To detect the conduction abnormality from the upper extremities to the brain, median nerve stimulation is used. For the detection of spinal cord abnormality during operation, posterior tibial nerve stimulation is often used. It is important to know the origin of the wave appearing in SSEP to find the lesion in the nervous system. SSEP has been used in scoliosis surgery, carotid endarterectomy, thoracoabodominal aortic surgery and cervical operations to detect brain and spinal ischemia. In an intensive care unit, it is used for the diagnosis of brain death or ischemia and other neuronal diseases such as Guillain-Barre syndrome and polyneuritis etc. In pain clinic, laser evoked potential (LEP) has been recently introduced for the analysis of the mechanisms of nerve and spinal cord diseases. Using the LEP, pain mechanism would be clarified. During SSEP measurements, it is necessary for the anesthesiologists, intensivists and pain clinicians to understand the effect of anesthetic drugs and hypothermia on SSEP.

[The management of the difficult pediatric airway].

BACKGROUND: We are faced sometimes with the difficult pediatric airway due to congenital abnormalities. However, there has been no systematic examination for the management of the difficult pediatric airway. METHODS: We retrospectively examined the incidence of difficult airway in 13,557 pediatric patients who had undergone general anesthesia with tracheal intubation. The difficulties of the intubation were classified into grade 1 to 4; grade 1: intubated one time, grade 2: two times, grade 3: three times or more, grade 4: changed to another way. We defined grade 3 and 4 as "difficult airway". RESULTS: Twenty-five patients (0.17%) are "difficult airway" among 13,557 patients in which 21 patients (0.15%) are classified as grade 3, and 4 patients (0.02%) are grade 4. The difficulties were significantly different among the syndromes (P< 0.001). The rate of the incidence in the difficulty is high in Treacher Collins syndrome, arthrogryposis multiprex congenita and first and second brachial arch syndrome, but few is in Pierre-Robin syndrome, Crouzon syndrome and Apert syndrome which are known to accompany difficult airway. CONCLUSIONS: We demonstrated that the incidence of difficult airway is different among the syndromes.

[Comparison of semitransparent colored labels with opaque colored labels for prevention of adverse drug administration].

BACKGROUND: We made a semitransparent color label to supplement a demerit of an opaque color label for prevention of adverse drug administration, and evaluated whether a semitransparent color label is superior to an opaque color label. METHODS: We prepared a total of 16 syringes (8 colors; two syriges of each color) in the opaque (NC) group and in the semitransparent (CL) group. Each ten subjects were asked to pick up the same drug label alternately in each group, and we measured the time and the number of syringes until the examinee can pick up the five correct syringes. We also examined the adhesiveness of the label to the syringe for six hours in each group. RESULTS: The time and syringe number until the examinee could pick up five correct syringes were 24.6+/-4.6 seconds and 16.2+/-2.7 in NC group (P= 0.0004) and 10.9+/-3.7 seconds and 6.5+/-1.7 in CL group, respectively (n-10, each, P <0.0001). In CL group the label adhered to the syringes tightly for six hours, whereas all the labels in NC group were detached (P<0.0001). CONCLUSIONS: The semitransparent color label is superior to the opaque color label in discrimination and adhesion.

Unique roles of G protein-coupled histamine H2 and gastrin receptors in growth and differentiation of gastric mucosa.

Disruption of histamine H2 receptor and gastrin receptor had different effects growth of gastric mucosa: hypertrophy and atrophy, respectively. To clarify the roles of gastrin and histamine H2 receptors in gastric mucosa, mice deficient in both (double-null mice) were generated and analyzed. Double-null mice exhibited atrophy of gastric mucosae, marked hypergastrinemia and higher gastric pH than gastrin receptor-null mice, which were unresponsive even to carbachol. Comparison of gastric mucosae from 10-week-old wild-type, histamine H2 receptor-null, gastrin receptor-null and double-null mice revealed unique roles of these receptors in gastric mucosal homeostasis. While small parietal cells and increases in the number and mucin contents of mucous neck cells were secondary to impaired acid production, the histamine H2 receptor was responsible for chief cell maturation in terms of pepsinogen expression and type III mucin. In double-null and gastrin receptor-null mice, despite gastric mucosal atrophy, surface mucous cells were significantly increased, in contrast to gastrin-null mice. Thus, it is conceivable that gastrin-gene product(s) other than gastrin-17, in the stimulated state, may exert proliferative actions on surface mucous cells independently of the histamine H2 receptor. These findings provide evidence that different G-protein coupled-receptors affect differentiation into different cell lineages derived from common stem cells in gastric mucosa.

Isoflurane ameliorates the posthypoxic deoxygenation of the rat brain--the role of cell adhesion molecules of polymorphonuclear leukocytes.

One of the serious problems that occurs after cardiopulmonary resuscitation is brain posthypoxic/ischemic deoxygenation. However, there has been no report concerning the effect of isoflurane (ISO) on the brain oxygenation during hypoxia-reoxygenation in relation to cell adhesion molecules (CD11b) in polymorphonuclear leukocyte. Rats were anesthetized with a low concentration of ISO (0.5 MAC: low ISO) or high concentration of ISO (1.5 MAC: high ISO) and brain oxygenation was detected by near infrared spectroscopy during 10-min hypoxia (5% O(2)) and a subsequent 120-min reoxygenation period. Hypoxia induced a decrease in oxyhemoglobin (HbO(2)) and an increase in deoxyhemoglobin (Hb). Reoxygenation induced a significant decrease in total hemoglobin (tHb) and HbO(2) with low ISO, but not with high ISO. The changes in Hb were minimal during reoxygenation in both groups. CD11b increased during reoxygenation with low ISO anesthetization, but not with high ISO. A significant negative correlation was observed between CD11b and two of the measured oxyparameters, HbO(2) and tHb, during reoxygenation at low ISO, but not at high ISO. These findings suggest that brain deoxygenation during hypoxia-reoxygenation is partly related to the expression of CD11b. We conclude that ISO modifies the brain circulation at least in part through attenuating the expression of CD11b during hypoxia-reoxygenation.

Sarcolemmal fragility secondary to the degradation of dystrophin in dilated cardiomyopathy, as estimated by electron microscopy.

A common gene deletion or mutation of delta-sarcoglycan (delta-SG) in dystrophin-related proteins (DRPs) is identified in both TO-2 strain hamsters and human families with dilated cardiomyopathy. We have succeeded in the long-lasting in vivo supplementation of a normal delta-SG gene by recombinant adeno-associated virus vector, restoration of the morphological and functional degeneration, and improvement in the prognosis of the TO-2 hamster. To evaluate the integrity of the sarcolemma (SL) and the subsequent change of organelles in cardiomyocytes of the TO-2 strain hamster, we examined electron microscopy (EM) images focusing on the sarcolemmal stability at the end stage of heart failure. Two types of sarcolemmal degradation were detected: the widened and locally thickened SL, and blurred and discontinuous SL. Bizarrely formed mitochondria of varying sizes were also observed. Immuno-EM revealed clear expression of dystrophin in the SL and intense expression at the costamere as well as at the T-tubules in the control F1B strain hearts, but a patchy deposition of dystrophin was observed along the SL without the transgene of delta-SG. In contrast to the previous reports that dystrophin's integrity was intact, the present results suggest that the gene deletion of delta-SG and the loss of delta-SG protein in the SL cardioselectively cause the morphological and functional deterioration of dystrophin and the resultant instability of the SL. The sarcolemmal fragility may be similar to Duchenne-type progressive muscular dystrophy in skeletal muscle. In addition to the mechanical role, another aspect of DRPs for the intracellular signal transmission is also discussed.