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Biomedical subjects

Akira Kitamura

Publications and source records attributed to Akira Kitamura.

15 recordsLinked to original sources
PubMed2006

Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state.

Polyglutamine (polyQ)-expansion proteins cause neurodegenerative disorders including Huntington's disease, Kennedy's disease and various ataxias. The cytotoxicity of these proteins is associated with the formation of aggregates or other conformationally toxic species. Here, we show that the cytosolic chaperonin CCT (also known as TRiC) can alter the course of aggregation and cytotoxicity of huntingtin (Htt)-polyQ proteins in mammalian cells. Disruption of the CCT complex by RNAi-mediated knockdown enhanced Htt-polyQ aggregate formation and cellular toxicity. Analysis of the aggregation states of the Htt-polyQ proteins by fluorescence correlation spectroscopy revealed that CCT depletion results in the appearance of soluble Htt-polyQ aggregates. Similarly, overexpression of all eight subunits of CCT suppressed Htt aggregation and neuronal cell death. These results indicate that CCT has an essential role in protecting against the cytotoxicity of polyQ proteins by affecting the course of aggregation.

Animals↗
PubMed2006

Type I collagen in Hsp47-null cells is aggregated in endoplasmic reticulum and deficient in N-propeptide processing and fibrillogenesis.

Heat-shock protein of 47 kDa (Hsp47) is a molecular chaperone that recognizes collagen triple helices in the endoplasmic reticulum (ER). Hsp47-knockout mouse embryos are deficient in the maturation of collagen types I and IV, and collagen triple helices formed in the absence of Hsp47 show increased susceptibility to protease digestion. We show here that the fibrils of type I collagen produced by Hsp47-/- cells are abnormally thin and frequently branched. Type I collagen was highly accumulated in the ER of Hsp47-/- cells, and its secretion rate was much slower than that of Hsp47+/+ cells, leading to accumulation of the insoluble aggregate of type I collagen within the cells. Transient expression of Hsp47 in the Hsp47-/- cells restored normal extracellular fibril formation and intracellular localization of type I collagen. Intriguingly, type I collagen with unprocessed N-terminal propeptide (N-propeptide) was secreted from Hsp47-/- cells and accumulated in the extracellular matrix. These results indicate that Hsp47 is required for correct folding and prevention of aggregation of type I collagen in the ER and that this function is indispensable for efficient secretion, processing, and fibril formation of collagen.

Animals↗
PubMed2006

Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction.

OBJECTIVE: To examine the association between decreased release of proinflammatory cytokines in response to urinary trypsin inhibitor pretreatment and decreased myocardial and lung injury after cardiopulmonary bypass. DESIGN: A prospective, randomized, double-blind study. SETTING: University hospital. SUBJECTS: Thirty patients on cardiopulmonary bypass undergoing coronary artery bypass grafting. INTERVENTIONS: Patients received 5000 units/kg intravenous urinary trypsin inhibitor (n = 15) or 0.9% saline (control, n = 15) immediately before aortic cannulation for cardiopulmonary bypass. MEASUREMENT AND MAIN RESULTS: Neutrophil elastase, tumor necrosis factor-alpha, interleukin-6, and interleukin-8 were measured after intubation (T1), immediately before aortic cannulation (T2), after separation from cardiopulmonary bypass (T3), at the end of surgery (T4), and on postoperative days 1 (T5), 3 (T6), and 5 (T7). Simultaneous hematocrit values were obtained at all sample times. Isoenzyme of creatine kinase with muscle and brain subunits, troponin-T, and myosin light chain I were also measured. Various hemodynamic and pulmonary data were obtained perioperatively. Levels of neutrophil elastase and cytokines were corrected for hemodilution. Interleukin-6 and interleukin-8 levels were lower at T3 and T4 in the urinary trypsin inhibitor group than in the control group. Stroke volume index was significantly decreased in the control group at T3, and statistical difference was found between groups at T3 (p < .01). Respiratory index and intrapulmonary shunt were significantly higher in the control group than in the urinary trypsin inhibitor group at T3. Changes in respiratory index and intrapulmonary shunt correlated with interleukin-8 levels at T3 (r = .52, p < 00001; r = .37, p < 0001, respectively) and T4 (r = .44, p < .001; r = .24, p < .05, respectively). Neutrophil elastase levels and cardiac marker responses to coronary artery bypass grafting surgery were similar in both groups. CONCLUSIONS: Prepump administration of urinary trypsin inhibitor attenuates the elevation of interleukin-6 and interleukin-8 release immediately after cardiopulmonary bypass.

Analysis of Variance↗
PubMed2006

An epidural initial dose is unnecessary in combined spinal epidural anesthesia for Caesarean section.

Combined spinal epidural anesthesia is widely used for Caesarean section. Bolus administration of an epidural initial dose introduces the risk of drug flux from the epidural space to the subarachnoid space, and the volume effect of the initial dose may cause epidural top-up and extension of subarachnoid blockade. These problems may be avoided if the initial dose is not administered. This study investigated whether epidural continuous infusion without an initial dose (continuous group) can decrease postoperative pain as well as an epidural continuous infusion with an initial dose (initial dose group). Sixty-one patients undergoing elective Caesarean section were randomly assigned to the initial dose group or the continuous group. Twenty patients undergoing emergency Caesarean section with spinal anesthesia (spinal group) were also investigated to confirm that epidural block is effective for postoperative pain. Data in this study were obtained retrospectively from each patient's records. Between the initial dose group and the continuous group, there was no significant difference in the number of times flurbiprofen or pentazocine were used for postoperative pain relief. However, the number of times that pentazocine was used was significantly higher in the spinal group than in other groups. This finding suggests that an epidural initial dose is unnecessary for postoperative pain relief in combined spinal epidural anesthesia for Caesarean section.

Amides↗
PubMed2005

Halothane modulates NMDA and non-NMDA excitatory synaptic transmission in rat cortical neurons.

PURPOSE: Although general anesthetics may decrease neuronal excitation, their detailed effects on spontaneous excitatory postsynaptic currents (EPSCs) remain controversial. We investigated and compared the effects of halothane on N-methyl-D-asparate (NMDA) and non-NMDA receptor-mediated postsynaptic currents. METHODS: Spontaneous synaptic currents were recorded by the patch clamp technique in cultured rat cortical neurons. They were isolated by specific pharmacological blocking agents and their electrophysiologic properties were examined. RESULTS: The frequency of NMDA EPSCs was preferentially decreased as compared with that of non-NMDA EPSCs at halothane 1.2 mM. The total net charge of EPSCs mediated by NMDA and non-NMDA receptors was depressed to 56% +/- 6% (mean +/- SD) and 71% +/- 7% of control by halothane 0.6 mM, and to 11% +/- 9% and 59% +/- 11% of control by halothane 1.2 mM, respectively. CONCLUSION: These results show that halothane causes decrease of excitatory synaptic activity, with NMDA EPSCs being more sensitive than non-NMDA EPSCs.

Algorithms↗
PubMed2005

Drill device for sinus lift.

A crestal approach for implant placement in deficient alveolar ridges is presented. The set of drills allows the surgeon to lift the membrane at the floor of the maxillary sinus with a bone disc, without the risk of tearing it. The plastic and cutting drills, respectively, are set in just below the floor of the maxillary sinus. The lifting drill is then slowly inserted from the socket, until a desirable length. Implants were hydroxyapatite coated and had a 3.75-mm diameter. This invention suggests that this is a reliable and predictable technique for the prosthetic rehabilitation of the maxillary posterior regions in the presence of anatomic restrictions for implanting.

Dental Implantation, Endosseous↗
PubMed2005

Effect of bicarbonated Ringer's solution on the acid-base balance in patients undergoing abdominal aortic aneurysm repair.

AIM: The present study was designed to assess whether prophylactic use of bicarbonated Ringer's solution ameliorates metabolic acidosis in patients undergoing aortic surgery. METHODS: Twenty patients undergoing elective infrarenal aortic aneurysm repair were randomly assigned to receive either bicarbonated Ringer's solution or acetated Ringer's solution. The pH, PaCO(2), and base excess (BE) were measured before surgical incision (T0), 5 min before reperfusion (T1), 5 min after reperfusion (T2), and 30 min after reperfusion (T3). Data were compared between the two groups. RESULTS: Both pH and BE initially showed a slight decrease in both groups during clamping. After unclamping of the aorta, an additional decrease in pH was observed in both groups (T0 to T2, and T3). There were no significant differences in pH between the groups throughout the study period. CONCLUSIONS: Aortic cross-clamping leads to the development of metabolic acidosis, with a decrease in pH and BE. The effect of administration of bicarbonated infusion fluid during elective abdominal aortic surgery had not significant compared with that of acetated Ringer's solution with respect to acid-base homeostasis.

Acid-Base Equilibrium↗
PubMed2005

Clinical features of hematological disorders caused by copper deficiency during long-term enteral nutrition.

OBJECTIVE: Copper deficiency has been reported to cause hematological disorders. However, its clinical and hematological characteristics are not fully understood. Therefore, we investigated bedridden patients suffering from copper deficiency and tried to clarify the clinical features of hematological disorders caused by this condition. PATIENTS AND METHODS: Five patients with typical copper deficiency who had been dependent upon enteral nutrition for a long period of time due to various diseases were investigated. We measured hematological parameters and observed the response to copper supplementation therapy and the recovery process of hematological disorders. RESULTS: Their mean age was 82.6+/-10.4 years and the mean duration of enteral nutrition was 16.4+/-5.2 months. Their serum copper concentration was extremely decreased (range, 3 to 8 microg/dl). All five patients had anemia and neutropenia. On the other hand, platelet count remained within the normal range. After copper supplementation therapy, hemoglobin concentration increased from 6.8+/-0.7 g/dl to 9.9+/-0.7 g/dl within a few months (p<0.01). Neutrophil count also increased from 750+/-370/microl to 3,690+/-1,210/microl in a few weeks (p<0.01). Mean corpuscular volume (MCV) decreased from 94.3+/-7.3 fl to 86.0+/-4.8 fl (p<0.05). Elevated serum ferritin and erythropoietin (EPO) levels were normalized after the improvement of anemia. CONCLUSION: Bicytopenia (anemia and neutropenia) with normal platelet count is a feature of hematological disorders caused by copper deficiency. MCV tends to indicate macrocytic anemia. Serum ferritin and EPO levels are elevated. These hematological abnormalities are improved within a few months after copper supplementation therapy.

Aged↗
PubMed2004

Addition of epinephrine to intrathecal tetracaine augments depression of the bispectral index during intraoperative propofol sedation.

PURPOSE: Epinephrine added to local anesthetic agents for spinal anesthesia is frequently used to prolong the duration of anesthesia. Epinephrine stimulates the alpha-adrenoceptor, and it is known that the alpha2-adrenoceptor agonists have a central inhibitory effect. We investigated the effect of intrathecal epinephrine during propofol sedation with spinal anesthesia, using a bispectral index (BIS) monitor. METHODS: Twenty adult patients, scheduled for spinal anesthesia, were allocated to the control group ( n = 10) or epinephrine group ( n = 10). Patients in the control group received 14 mg of tetracaine, whereas the epinephrine group received 14 mg of tetracaine and 0.2 mg of epinephrine. Immediately after the pinprick test, propofol was administered at 0.5 mg x kg(-1) by infusion for the initial dose, then continuously at 2 mg x kg(-1) x h(-1) in both groups. BIS scores were recorded before subarachnoid block, and then every 5 min for 90 min after subarachnoid block. RESULTS: There were significant differences in the BIS score between the two groups at 45-55 min and at 60-70 min after subarachnoid block. CONCLUSION: Intrathecal epinephrine augments the sedative effect of propofol during spinal anesthesia.

Adult↗
PubMed2004

Systemic ATP infusion improves spontaneous pain and tactile allodynia, but not tactile hypesthesia, in patients with postherpetic neuralgia.

PURPOSE: Activation of purinoceptors may improve neuropathic pain. Accordingly, the effects of systemic ATP infusion were assessed in patients with postherpetic neuralgia (PHN). METHODS: Eight patients with PHN lasting over 3 months were enrolled. Initially, patients received the vehicle (20% dextrose) or ATP (at a dose of 1 mg x kg(-1) in 20% dextrose) infused intravenously for 60 min on two separate occasions in a single-blinded manner. The levels of spontaneous continuous pain, paroxysmal pain, and tactile allodynia were assessed by a visual analogue scale (VAS), and tactile hypesthesia was assessed by Semmes-Weinstein monofilament before and after infusion. Subsequently, the eight patients received an ATP infusion (1 mg.kg(-1) in 20% dextrose) once a week for 5-12 weeks in an open-label manner, and changes in the above parameters were assessed. RESULTS: In the initial study, VAS for spontaneous continuous pain and tactile allodynia decreased significantly with ATP infusion but not with placebo infusion. After repeated ATP infusions for 5-12 weeks, the median VAS for spontaneous continuous pain, paroxysmal pain, and tactile allodynia decreased significantly from 32.1 to 13.0, from 46.9 to 17.5, and from 49.5 to 15.6 respectively. However tactile hypesthesia did not improve significantly. CONCLUSION: This study demonstrated that repetitive intravenous ATP infusion could improve spontaneous continuous pain and paroxysmal pain, as well as improving tactile allodynia, but did not influence tactile hypesthesia.

Adenosine Triphosphate↗
PubMed2004

Halothane and propofol modulation of gamma-aminobutyric acidA receptor single-channel currents.

Halothane and propofol enhance the activity of the gamma-aminobutyric acid (GABA) system, which is one of the most important systems in the mechanism of anesthesia. To determine whether halothane and propofol enhance GABAergic responses by the same mechanism, we performed single-channel patch-clamp experiments with rat cortical neurons in primary culture. Each of the open-time and closed-time distributions of GABA(A) receptor single channels was expressed by a sum of fast and slow time constants. Neither halothane nor propofol changed the single-channel conductance. Halothane increased the probability of the channel being open via a prolongation of the slow phase of open time, whereas propofol increased the channel open probability via a shortening of the slow phase of closed time. Thus, although both halothane and propofol augmented the channel open probability, thereby causing an increase in charge transfer during inhibitory transmitter action, they acted by different mechanisms.

Algorithms↗
PubMed2003

Bleomycin-mediated electrochemotherapy in mouse NR-S1 carcinoma.

PURPOSE: To determine whether or not low-voltage electrochemotherapy has cell killing effects. MATERIALS: Dorsally transplanted NR-S1 carcinomas in mice were stimulated with electric pulses (40 V/cm) after bleomycin (1 microg/g) had been injected around them. The tumors were fixed with a forceps electrode and electroporation was carried out three times a day for 4 days per week for 2 weeks. RESULTS: After 8 weeks of experimentation, the tumor had disappeared in four of the ten mice. The cell killing effects were mainly apoptosis and necrosis. CONCLUSION: Electroporation should be clinically introduced into the cosmetic and functional treatment of the head and neck region. Further investigation is also necessary to determine suitable carcinostatic agents and clarify the electric pulse conditions.

Animals↗
PubMed2003

Effects of halothane and propofol on excitatory and inhibitory synaptic transmission in rat cortical neurons.

General anesthetics are thought to act on both excitatory and inhibitory neuronal pathways at both post- and presynaptic sites. However, the literature in these regards is somewhat controversial. The aim of the present study was to reassess the relative importance of the various anesthetic actions using a common preparation. Rat cortical neurons in primary culture were used to record spontaneous miniature postsynaptic currents by the whole-cell patch-clamp technique. Halothane at clinically relevant concentrations prolonged the decay phase of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in the presence of tetrodotoxin and at higher concentrations decreased the frequency of mIPSCs. The mIPSC amplitudes underwent little change. Spontaneous action potential-dependent IPSCs recorded in the absence of tetrodotoxin were similarly affected by halothane. Halothane also decreased the frequency of spontaneous miniature non-N-methyl-D-aspartate (NMDA) excitatory postsynaptic currents (mEPSCs) as well as spontaneous action potential-dependent NMDA EPSCs and non-NMDA EPSCs without affecting their decay phase. The halothane effect on mIPSC and mEPSC frequency was dependent on the external calcium concentration. In contrast to halothane, the only effect of propofol was the prolongation of the decay phase of mIPSCs and IPSCs. The prolongation of mIPSCs and IPSCs by halothane and propofol coupled with the ineffectiveness on mEPSCs and EPSCs suggests a selective postsynaptic modulation of GABA(A) receptors. The additional calcium-dependent inhibition of mIPSC and mEPSC frequency by halothane (but not propofol) suggests a more general mechanism by this anesthetic on presynaptic transmitter release.

Anesthetics, Inhalation↗