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Biomedical subjects

T Ichinohe

Publications and source records attributed to T Ichinohe.

At least 37 records · Page 2Linked to original sources

[T cell non-depleted bone marrow transplantation for primary refractory erythroleukemia using a partially HLA-mismatched related donor].

We performed an HLA-mismatched T cell non-depleted bone marrow transplant on a 53-year-old man with acute erythroleukemia that was highly resistant to conventional remission-induction chemotherapy. After conditioning that included total body irradiation, the patient received a two-HLA-antigen-mismatched bone marrow graft harvested from his sister using tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. He successfully established rapid engraftment accompanied by steroid-responsive GVHD localized to the skin. Although bone marrow samples on day 31 and day 66 disclosed a complete remission with full donor chimerism, the patient relapsed and died of pulmonary infection on day 154. There is evidence that tacrolimus is effective in alleviating GVHD. Selected patients who have partially mismatched related donors with less HLA disparity may benefit from tacrolimus-based T cell non-depleted bone marrow transplants because of the more potent graft-versus-leukemia effect that can be expected compared to transplants using T cell depleted inoculum.

Bone Marrow Transplantation↗

Mucosal blood flow during various intravenous and inhalational anesthetics in the rabbit.

OBJECTIVE: The goal of this study was to compare the effects of nitrous oxide (N2O), isoflurane (ISO), fentanyl (FENT), and propofol (PROP) on the tongue mucosal blood flow (TMBF) in rabbits. STUDY DESIGN: TMBF was measured with a laser Doppler flow meter before and after the administration of 50% N2O (n = 7), 1.0 and 1.5 minimum alveolar concentration ISO (n = 6), 10, 20, and 40 micrograms/kg FENT (n = 8) or 100, 200 and 400 micrograms/kg/min PROP (n = 7). Hemodynamic variables including heart rate, systolic blood pressure (SBP), mean arterial pressure (MAP) and aortic blood flow (AoF) were continuously monitored. Total peripheral resistance (TPR) was calculated as MAP divided by AoF. RESULTS: An increase in TMBF along with reductions in SBP, MAP and TPR were observed in ISO group. In FENT group, TMBF was decreased, whereas other hemodynamic variables showed no change. TMBF in groups N2O and PROP did not change. CONCLUSION: These results indicate that TMBF depends on the anesthetic used.

Anesthetics, Inhalation↗

Inhibition of physiologic stress responses by regional nerve block during orthognathic surgery under hypotensive anesthesia.

OBJECTIVE: The purpose of this study was to investigate the inhibitory effects of nerve block on stress responses during orthognathic surgery involving general anesthesia with induced hypotension. STUDY DESIGN: Fourteen patients (ASA-1) undergoing Le Fort 1 osteotomy and sagittal splitting mandibular osteotomy were divided into 2 groups: a block group (with maxillary and mandibular nerve blocks; n = 7) and a non-block group (without nerve blocks; n = 7). Anesthesia was maintained with N2O-O2 and isoflurane (block group, 0.8%; non-block group, 1.2%). Adenosine triphosphate was administered for induced hypotension. Observed variables included hemodynamic parameters and fluctuations and adenosine triphosphate dose. Plasma norepinephrine concentrations and blood gases were observed in the block group. RESULTS: More stable hemodynamics, with a lower adenosine triphosphate dose as well as negligible changes in norepinephrine concentrations and blood gases, were obtained in the block group. CONCLUSIONS: The stress responses were inhibited by nerve blocks combined with low-concentration inhalation anesthesia during adenosine triphosphate-induced hypotension. The adenosine triphosphate requirement was reduced under stable hemodynamics achieved with nerve blocks.

Adenosine Triphosphate↗

Pain following intravenous administration of sedative agents: a comparison of propofol with three benzodiazepines.

The purpose of the present study is to compare the injection pain of propofol with that of benzodiazepines when used for intravenous sedation. In addition, we evaluated the efficacy of coadministering a small dose of 1% lidocaine (20 mg) to reduce the pain accompanying propofol injection. Intravenous propofol, diazepam, midazolam, or flunitrazepam were administered on separate occasions to volunteers and outpatients. The degree of injection pain was evaluated by the Visual Analog Scale (VAS) ruler. The efficacy of premixed lidocaine with propofol was also compared among the patients. The venous pain of propofol was significantly more intense than that of the three other drugs (P < 0.05). The injection pain of diazepam was more intense than that of midazolam (P < 0.05). Many patients reported no pain when propofol was coadministered with lidocaine. The addition of a small dose (20 mg) of lidocaine reduced the VAS pain score to comparable levels observed for benzodiazepines. Because injection pain might affect the patients' comfort during sedation, the addition of lidocaine to the propofol injection is deemed useful for intravenous sedation.

Adult↗

Cerebral cortex regional blood flow and tissue oxygen tension during the trigeminal depressor response in rabbits.

The trigeminal depressor response (TDR) is characterized with profound hypotension caused by sympathetic outflow decreases. The purpose of this study was: (1) to compare the hemodynamic changes during acute hypotension induced by the TDR with those induced by electrical stimulation of the vagal nerve (VS) as models of sympathetic inhibition and vagal activation and (2) to investigate the effects of nitrous oxide (N2O), a well-known sympathomimetic, on the hemodynamic changes during the TDR. Male Japan White rabbits were anesthetized with halothane in oxygen and mechanically ventilated. The electrode pair for the TDR was inserted into the submucosal tissue of the animal's tongue. The pair for the VS was applied to the isolated left vagal trunk. Both the TDR and the VS produced similar decreases in mean arterial pressure (MAP) and cerebral cortex regional blood flow (rCBF), although the decreases in heart rate (HR) and aortic blood flow were greater during the VS. Cerebral cortex tissue oxygen tension in both groups decreased slightly. 50% N2O, producing MAP elevation and HR decrease, ameliorated the hemodynamic changes including rCBF reduction during the TDR. A sudden diminution of sympathetic tone following noxious stimulation of the orofacial area, as in the case of the TDR, may be a possible trigger mechanism for vasodepressor reactions in dental patients. The sympathomimetic and possible antinociceptive effects of N2O may explain, at least in part, the preventive effects on vasodepressor reactions during dental procedures.

Animals↗

Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI.

Activation of circulating platelets by subendothelial collagen is an essential event in vascular hemostasis. In human platelets, two membrane glycoprotein (GP) abnormalities, integrin alpha2 beta1 deficiency and GPVI deficiency, have been reported to result in severe hyporesponsiveness to fibrillar collagen. Although it has been well established that integrin alpha2 beta1, also known as the GPIa-IIa complex, functions as a primary platelet adhesion receptor for collagen, the mechanism by which GPVI contributes to collagen-platelet interaction has been ill defined to date. However, our recent observation that GPVI cross-linking couples to cyclic AMP-insensitive activation of c-Src and Syk tyrosine kinases suggested a potential role for GPVI in regulating protein-tyrosine phosphorylation by collagen (Ichinohe, T., Takayama, H., Ezumi, Y., Yanagi, S., Yamamura, H., and Okuma, M. (1995) J. Biol. Chem. 270, 28029-28036). To further investigate this hypothesis, here we examined the collagen-induced protein-tyrosine phosphorylation in GPVI-deficient platelets expressing normal amounts of alpha2 beta1. In response to collagen, these platelets exhibited alpha2 beta1-dependent c-Src activation accompanied by tyrosine phosphorylation of several substrates including cortactin. In contrast, severe defects were observed in collagen-stimulated Syk activation and tyrosine phosphorylation of phospholipase C-gamma2, Vav, and focal adhesion kinase, implicating a specific requirement of GPVI for recruiting these molecules to signaling cascades evoked by collagen-platelet interaction.

Adult↗

Epinephrine at doses used in dentistry deteriorates platelet retention rate.

Epinephrine promotes platelet aggregation through alpha 2 receptor-mediated mechanisms. In this study, the change in the platelet retention rate (PRR) was investigated before and after submucosal epinephrine injection with or without lidocaine in oral surgical patients during isoflurane-nitrous oxide anesthesia. Thirty-nine consenting patients participated in this study. Subjects were allocated in one of five groups depending on the solution injected, the diclofenac supplement, and the patients' age. PRR was measured immediately before and 5 min after epinephrine injection using a modified form of Saltzman's method. Injection of epinephrine with lidocaine deteriorated PRR, although epinephrine without lidocaine produced no PRR change. Epinephrine at doses used in routine dental practices may activate the platelet aggregating function. Dentists should keep in mind that epinephrine elicits both hemodynamic and platelet-activating effects. The latter may be of clinical importance in some situations.

Adult↗

Effects of block analgesia on attenuating intraoperative stress responses during oral surgery.

Surgical intervention affects cardiorespiratory function and deteriorates the homeostatic mechanisms. The aim of this study was to evaluate the effect of block analgesia, which may minimize the intraoperative stress responses during oral surgery. In addition, we evaluated whether block analgesia could lessen the anesthetic requirements. Twenty-eight operative patients were randomly allocated to one of four groups: group 1, 1.3MAC without block analgesia; group 2, 1.6MAC without block analgesia; group 3, 1.0MAC with block analgesia; and group 4, 1.3MAC with block analgesia. Systolic blood pressure (SBP), heart rate (HR), and plasma norepinephrine levels (NE) were measured and compared. Results showed that the increases in SBP, HR, and NE in groups 1 and 2 were greater than those in groups 3 and 4. SBP elevation in group 1 was the greatest among all groups. These results suggest that block analgesia appears to be effective for preventing hyperreactivity of the sympathetic nervous and endocrine systems. In conclusion, general anesthesia combined with block analgesia assures safer anesthesia for patients with cardiovascular diseases or elderly patients who require cardiovascular stability during surgery.

Adult↗

Is measurement of end-tidal CO2 through a nasal cannula reliable?

When using a nasal cannula to sample gases expired by a patient, air from the room may dilute the sample. For this reason, the accuracy of the partial pressure of end-tidal carbon dioxide (ETCO2) measurements is questionable. We experimentally examined the reliability of ETCO2 measurements through a nasal cannula and found that they depended on both biological factors (tidal volume and respiratory rates) and mechanical factors (the diameter and the length of the cannula and the diameter of the prongs). These results suggest that the correct use of an appropriate sampling cannula will provide reliable ETCO2 measurements without clinical problems.

Capnography↗

Cyclic AMP-insensitive activation of c-Src and Syk protein-tyrosine kinases through platelet membrane glycoprotein VI.

Platelet glycoprotein (GP) VI is a so-far uncharacterized 62-kDa membrane protein, whose deficiency results in selective impairment in collagen-induced platelet aggregation. Our group previously reported a human polyclonal antibody (anti-p62 IgG) that induces activation of normal, but not of GPVI-deficient, platelets in an Fc-independent manner. The F(ab')2 fragments of this antibody (F(ab')2-anti-p62) stimulated tyrosine phosphorylation of numerous proteins, which was not prevented even in the presence of cAMP-increasing agents such as prostacyclin. Pretreatment of platelets with the protein-tyrosine kinase (PTK) inhibitor tyrphostin A47 completely abolished F(ab')2-anti-p62-induced platelet aggregation in parallel with dose-dependent inhibition of protein-tyrosine phosphorylation, indicating an essential requirement of PTK activity for generating GPVI-mediated signaling. We found that two cytosolic PTKs, c-Src and Syk, became rapidly activated in response to F(ab')2-anti-p62 in a way insensitive to elevation of cAMP. In contrast, in the presence of prostacyclin, F(ab')2-anti-p62 did not stimulate tyrosine phosphorylation of the focal adhesion kinase. cAMP-insensitive activation of c-Src and Syk was also observed in collagen but not thrombin-stimulated platelets. Moreover, either F(ab')2-anti-p62 or collagen stimulated cAMP-insensitive tyrosine phosphorylation of phospholipase C-gamma 2. These results indicate that the receptor-mediated activation of several PTKs in platelets is regulated through a cAMP-sensitive or -insensitive mechanism depending on the nature of each stimulus, and also suggest that GPVI engagement is coupled to cAMP-insensitive activation of c-Src and Syk accompanied by tyrosine phosphorylation of numerous substrates including phospholipase C-gamma 2 in a manner similar to collagen stimulation.

Adult↗

Functional significance of platelet membrane glycoprotein p62 (GP VI), a putative collagen receptor.

We previously suggested that platelet 62 kDa protein (p62, GP VI) is a putative collagen receptor by the studies on platelets and antiplatelet antibody in a patient (YA) with idiopathic thrombocytopenic purpura (ITP) who showed defective collagen-induced platelet function. Herein, we confirm that p62/p57 (reduced/unreduced conditions) is a specific membrane protein recognized by YA antibody using an improved immunoprecipitation technique. To further study the functional role of this protein, a crude p57 fraction ('p57') was obtained from human platelets by serial chromatography including DEAE-Sepharose CL-6B and WGA-agarose followed by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). This 'p57' diminished the platelet-aggregating activity of collagen and of YA immunoglobulin G (IgG). N-terminal amino acid sequence analysis of 'p57' showed that it contained intercellular adhesion molecule 2 (ICAM-2). Immunoprecipitation experiments using platelet lysates and anti-ICAM-2 monoclonal antibody demonstrated that ICAM-2 molecules had a molecular weight similar to p62 on SDS-PAGE. However, ICAM-2 was also expressed on YA's p62-deficient platelets both on immunoprecipitation and flow cytometric analysis. Thus, ICAM-2 seems to be different from p62.

Amino Acid Sequence↗

Involvement of GPIIb-IIIa on human platelets in phosphotyrosine-specific dephosphorylation.

Washed platelets from either normal donors or patients with thrombasthenia lacking in integrin GPIIb-IIIa were stimulated by thrombin or STA2 with stirring and their kinetics of protein-tyrosine phosphorylation were compared. The early increase in protein-tyrosine phosphorylation on 115 and 75 kDa protein bands was observed within 10 s after stimulation in both normal and thrombasthenic platelets. While both 115 and 75 kDa tyrosine-phosphorylated protein bands were quickly dephosphorylated in normal platelets, thrombin-induced 115 kDa or STA2-induced 115 and 75 kDa protein bands were not dephosphorylated in thrombasthenic platelets. The delay of phosphotyrosine-specific dephosphorylation on those protein bands was observed when thrombin- or STA2-induced aggregation of normal platelets was inhibited by RGDS, an inhibitor of fibrinogen binding to GPIIb-IIIa. These data indicate that fibrinogen binding to GPIIb-IIIa is involved in the regulation of phosphotyrosine-specific dephosphorylation on certain protein bands.

Amino Acid Sequence↗

[Two cases of hypothyroidism with echocardiographic features similar to cardiomyopathy: one simulates hypertrophic and the other dilated cardiomyopathy].

Two cases of hypothyroidism with echocardiographic features similar to cardiomyopathy were presented. In case 1 (a 68 year-old woman), moderate pericardial effusion and myocardial hypertrophy were observed on admission. In case 2 (a 69 year-old woman), dilation of the left ventricle, hypokinesis of the interventricular septum and the left ventricular free wall, and reduced left ventricular systolic function were observed on admission. These echocardiographic findings were similar to hypertrophic or dilated cardiomyopathy. In the two cases, after recovery to euthyroid state, these echocardiographic abnormalities returned to normal. We concluded that hypothyroidism led to a reversible hypertrophic or dilated cardiomyopathy, and that echocardiographic study was useful for diagnosis and for following up cardiac manifestations of hypothyroidism.

Aged↗

[The effect of acebutolol and metoprolol on noninvasive ambulatory blood pressure monitoring system in essential hypertension].

We compared the antihypertensive effects of acebutolol and metoprolol during 2-4 weeks of treatment in patients with mild to moderate essential hypertension. Acebutolol (n = 12) significantly decreased conventionally measured blood pressure from 173/100 mmHg to 148/86 mmHg (p less than 0.005), and metoprolol (n = 11) decreased it from 164/106 mmHg to 138/87 mmHg (p less than 0.01). Based on data derived from automated 24-hour ambulatory blood pressure monitoring, both drugs significantly decreased the blood pressure in the early morning (5:00-10:00). Moreover, in the metoprolol group, there were significant falls in day-time blood pressure (7:30-19:30) and night-time blood pressure (23:00-7:00). In contrast, acebutolol showed significant antihypertensive effect on day-time blood pressure, but not effect on night-time blood pressure. The study confirmed the efficacy and character of metoprolol and acebutolol. We must choose an effective beta-blocker when using an automated 24-hour ambulatory blood pressure monitoring system to get adequate blood pressure reduction for the whole 24 hours.

Acebutolol↗

[Recurrent hyperkalemia in the course of rheumatoid arthritis--a case report].

A 69-year-old woman with advanced rheumatoid arthritis (RA) suffered two episodes of hyperkalemic hyperchloremic metabolic acidosis (HCMA). Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were markedly suppressed in the first episode occurring in paralell with the administration of metoprolol during piroxicam and lobenzarit (CCA) therapy. Rechallenge with diclofenac sodium and CCA lead to the second hyperkalemia, but no significant suppression of the renin-aldosterone axis was seen at that time. This suggests that the different mechanisms contribute to the development of these episodes, including the tubulo-interstitial injury which is not uncommon in RA. The combined use of nonsteroidal anti-inflammatory drugs (NSAIDs) and beta-adrenergic blockers may increase the risk of life-threatening hyperkalemia through their suppressive effect on the renin-aldosterone system, whereas the concomitant administration of CCA with NSAIDs through the impairment in the renal tubular function. These drugs should be most carefully given to patients with a latent defect in renal potassium excretion.

Adrenergic beta-Antagonists↗

Usefulness of the pulse oximeter as a respiratory monitor during intravenous sedation.

During intravenous sedation, the pulse oximeter was applied as a respiratory monitor to 17 patients (Physical status classification of the American Society of Anesthesiologists, Class I-II) who were to have oral surgical operations, and the changes in arterial saturation of oxygen (SaO2) was observed consecutively. SaO2 dropped after administration of sedative agents in each case; there was some individual variation. Respiratory depression during sedation was evaluated from arterial blood gas analysis. The reduction in SaO2 caused by surgical manipulations was also noted. Furthermore, arterial partial pressures of oxygen (PaO2) and saturation calculated from PaO2 (SAT) measured from blood gas analysis were compared with SaO2 measured by the pulse oximeter. Both PaO2 and SAT correlated well with SaO2. The differences between SAT and SaO2 exceeded the range of error (+/- 2%) in many cases after the administration of sedative agents. These results suggest that the pulse oximeter is useful as a respiratory monitor during oral surgery. However, the pulse oximeter gives incorrect SaO2 readings in the presence of abnormal hemoglobin due to medication with nitrites or smoking habit.

Anesthesia, Dental↗