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Biomedical subjects

T Kadoya

Publications and source records attributed to T Kadoya.

At least 55 records · Page 3Linked to original sources

[Anesthetic management of a patient with Bartter's syndrome].

A 48-year-old woman with Bartter's syndrome underwent right mastectomy under general anesthesia. Her operative course was uneventful. She was preoperatively complicated with severe hypokalemia but had no signs and symptoms of hypokalemia. In anesthetic care of patients with Bartter's syndrome, even when they have no symptoms of hypokalemia, the meticulous intravenous administration of potassium chloride is required in order to maintain the preoperative level of the serum potassium during anesthesia. In addition, attention should be paid to factors causing an additional reduction in the serum potassium concentration, such as alkalosis, elevated beta 2-adrenergic activity, increased availability of insulin and hypothermia.

Anesthesia, General↗

[Light-guided tracheal intubation using a Trachlight: causes of difficulty and skill acquisition].

We studied the reasons why tracheal intubation using a lighted stylet (Trachlight) was sometimes difficult for unexperienced intubators. We also examined light-guided intubation skill acquisition in inexperienced anesthesiologists. Two anesthesiologists, with no prior experience in using a Trachlight, performed orotracheal intubation using a Trachlight in 60 anesthetized patients (30 patients each). During intubation, an assistant observed the advancement of the tracheal tube using a fiberscope passed nasally and recorded the reason for difficulty in intubation. The time to successful intubation was also measured. Data were divided into epochs of 10 cases, and the intubation time and the incidence of difficult cases were compared between the groups. Tracheal intubation was successful using the Trachlight in 59 of 60 patients. The incidence of difficult cases, defined as cases requiring two or more attempts, was 31.7%. Fiberscopy showed that when the tube tip was located in the vallecula or in the esophagus, it was sometimes difficult to determine the position of the tube tip by transillumination of the soft tissues of the neck, and this results in the need for multiple attempts. Both the intubation time and the incidence of difficult cases decreased significantly between the first and last epoch. The present study confirms that light-guided intubation is sometimes difficult when the tube tip is advanced to the vallecula or to the esophagus. An acceptable level of skill in light-guided intubation is achieved within 30 uses.

Adult↗

Early Breast Cancer Following Treatment of Myelodysplastic Syndrome: Report of a Case.

A 45-year-old woman was admitted to our hospital complaining of a mass in herleft breast. She had previously been diagnosed with myelodysplastic syndrome(MDS), a type of refractory anemia, based on bone marrow findings and chromosome analysis. She received a preoperative transfusion of fresh packed platelets and a recombinant human granulocyte colony-stimulating factor(rhG-CSF)injection. Left partial mastectomy and axillary lymph nodes dissection were performed to treat early breast cancer. Postoperatively, prophylactic radiotherapy of the residual breast and administration of medroxyprogesterone acetate(MPA)were performed because the tumor tissue was positive for progesterone receptors. She has remained clinically stable, with no evidence of recurrence, for more than three years to date. We report a rare case of breast cancer with MDS, treated with breast-conserving therapy. The strategy of pre- or postoperative platelet transfusion, rhG-CSFinjections, and hormonal therapy (MPA) appears to be suitable treatment for progesterone receptor(PgR)-positive breast cancer patients with MDS.

Journal Article↗

IL-1 beta enhances neurite regeneration from transected-nerve terminals of adult rat DRG.

We clarified the roles of IL-1 beta in peripheral neural regeneration after axotomy in a three-dimensional collagen gel culture system ranging from a single neurone to a dorsal root ganglion (DRG) explant with its associated nerve bundles. Application of 30 U/ml IL-1 beta to the culture systems clearly enhanced neural regeneration. This regeneration was evident in transected nerve terminals of DRG explants with or without associated nerve bundles, but not in dissociated single neurones. Neural survival was not affected by IL-1 beta in any of these culture systems. These results suggest that IL-1 beta stimulates surrounding non-neuronal cells to secrete neurotrophic factors, thus enhancing neurite regeneration from transected nerve terminals in cultured adult DRG explants.

Animals↗

Thrombin cleaves recombinant human thrombopoietin: one of the proteolytic events that generates truncated forms of thrombopoietin.

A heterogeneity in the molecular weight (Mr) of thrombopoietin (TPO) has been reported. We found several thrombin cleavage sites in human, rat, murine, and canine TPOs, and also found that human TPO undergoes selective proteolysis by thrombin. Recombinant human TPO (rhTPO) was incubated with human platelets in the presence of calcium ions to allow the generation of thrombin, and was cleaved into low Mr peptide fragments. The cleavage was completely inhibited by hirudin, indicating that the proteolysis was mediated by thrombin. In a platelet-free system, analyses of thrombin cleavage by immunoblotting using anti-human TPO peptide antibodies revealed that the four major thrombin-cleaved peptide fragments were selectively generated depending on the digestion time. The amino acid sequences of the thrombin-polypeptides were further analyzed, and two major thrombin cleavage sites were determined. One of them was at AR191-T192 in the C-terminal domain of TPO, and thrombin cleaved first at this site. The other site at GR117-T118 in the N-terminal domain was subsequently cleaved by prolonged thrombin digestion. As a result, the biological activity of TPO was modulated. The generation of truncated forms of TPO by thrombin may be a notable event in view of the platelet-related metabolism of TPO.

Amino Acid Sequence↗

Action of thrombopoietin at the megakaryocyte progenitor level is critical for the subsequent proplatelet production.

Formation of proplatelets from megakaryocytes is believed to be the first step of platelet production in vitro. In this study, we evaluated the effects of recombinant human thrombopoietin (hTPO) on the development of proplatelets from a GpIIb/IIIa+ population of rat bone marrow cells highly enriched for late megakaryocyte progenitors (GpIIb/IIIa+ CFU-MK) that we recently found to be a primary target population of TPO. Quantitative measurement of hTPO-induced proplatelet formation was performed in liquid cultures. Proplatelet formation from megakaryocytes derived from GpIIb/IIIa+ CFU-MK in the presence of hTPO began on day 4 of culture and peaked the following day. On day 5 of culture, lower concentrations of hTPO expanded the number of megakaryocytes, increased the number of proplatelets and the percentage of proplatelet-developing megakaryocytes. Increasing hTPO concentrations resulted in a modest decrease in proplatelet development. We next used hTPO to derive immature or mature megakaryocytes from GpIIb/IIIa+ CFU-MK. These populations of cultured megakaryocytes spontaneously formed proplatelets when recultured in the absence of exogenous hTPO. The addition of hTPO at higher concentrations modestly augmented proplatelet production from immature megakaryocytes derived from 2-day liquid cultures. However, either murine interleukin-6 (IL-6) or human IL-11, but not rat IL-3, was more potent than hTPO in augmenting proplatelet formation from immature megakaryocytes. Each of these four cytokines had an inhibitory effect on proplatelet formation from more differentiated megakaryocytes derived from 3-day liquid cultures. These results indicate that TPO enhances proplatelet production primarily by stimulating CFU-MK to increase the number of proplatelet-forming megakaryocytes and that its action is clearly different from those of other cytokines that also stimulate megakaryocytopoiesis.

Animals↗

A highly enhanced thrombopoietic activity by monomethoxy polyethylene glycol-modified recombinant human interleukin-6.

Interleukin-6 (IL-6) is a novel cytokine with activities that can affect hematopoietic cells including those of the megakaryocytic lineage. We have examined the effects of monomethoxy polyethylene glycol-modified recombinant human interleukin-6 (Peg-IL-6) on thrombopoiesis in vivo. To compare the thrombopoietic activity between Peg-IL-6 and unmodified IL-6, each was administered subcutaneously to mice every 24 hours at various doses. A dose-response experiment showed that Peg-IL-6 and IL-6 increased platelet counts in a dose-dependent fashion at a plateau stimulation level of 0.5 micrograms/day and 10 micrograms/day, respectively. This dose of Peg-IL-6 and IL-6 induced the elevated platelet counts by approximately 140% to 160% and 50% to 60%, respectively. Peg-IL-6 treatment (0.5 micrograms/day) for x-ray (6.0 Gy) irradiated mice induced an increase in the rate of platelet recovery, and a higher dosage (5 micrograms/day) completely blocked the induction of thrombocytopenia in this model. In contrast, IL-6 (10 micrograms/day) could not protect the animals from platelet nadir but reduced the period of thrombocytopenia after x-ray irradiation. Furthermore, when administered to 5-fluorouracil-treated mice, 5 micrograms/day of Peg-IL-6 diminished the platelet nadir and increased platelet counts on individual days during the recovery phase. The potent thrombopoietic activity of Peg-IL-6 were due to prolongation of circulating IL-6 levels that were reverted from Peg-IL-6 in vivo. These findings indicate that reduction of total body clearance of IL-6 induces potent thrombopoiesis and that Peg-IL-6 may be a useful thrombopoietic agent.

Animals↗

[Anesthetic management of a patient with pheochromocytoma using autotransfusion].

Autotransfusion was employed for a 51 year-old male patient with intravesical pheochromocytoma and paroxysmal hypertension in an attempt to avoid side-effects of conventional blood transfusion and to minimize the change in intravascular volume after removal of the tumor. Blood was withdrawn twice (980g in all) before surgery. Anesthesia was maintained with N2O-O2-sevoflurane and epidural anesthesia. Sodium nitroprusside was administered when necessary to control blood pressure. Hypotension associated with removal of the tumor could be successfully prevented by autotransfusion. This case demonstrates usefulness of autotransfusion to control hypotension following removal of pheochromocytoma.

Adrenal Gland Neoplasms↗

In vivo effects of interleukin-6 on thrombopoiesis in healthy and irradiated primates.

We have studied the in vivo effects of recombinant human interleukin-6 (rhIL-6) on hematopoiesis in eight healthy and nine irradiated cynomolgus monkeys. Of the healthy animals, three received rhIL-6 alone (10 micrograms/kg/d, subcutaneously [SC]), one received rhIL-6 in combination with rhIL-3 (10 micrograms/kg/d, SC), one received rhIL-6 in combination with recombinant cynomolgus granulocyte-macrophage colony-stimulating factor (rcGM-CSF; 10 micrograms/kg/d, SC), two received rhIL-6 in combination with recombinant human granulocyte-CSF (rhG-CSF; 10 micrograms/kg/d, SC), and one received rhIL-6 in combination with recombinant human leukemia inhibitory factor (rhLIF; 10 micrograms/kg/d, SC). All animals were treated for at least 2 weeks with rhIL-6 or the above mentioned combinations. rhIL-6 alone significantly increased the peripheral blood platelet counts (2- to 3.5-fold). The platelets reached a plateau between days 10 and 15 of treatment. No synergistic effects on platelet numbers were observed when rhIL-6 was combined with rhIL-3, rcGM-CSF, rhG-CSF, or rhLIF. In addition to rhIL-6, only rhLIF increased the platelet numbers when administered alone. To test whether rhIL-6 might also protect the animal from thrombocytopenia or shorten the time of thrombocytopenia after irradiation, we treated nine animals with total body irradiation (3.8 Gy). Six of the animals were additional treated with rhIL-6 (4 with 10 micrograms/kg/d; and 2 with 100 micrograms/kg/d) from day -1 or +1 to day 28 post irradiation. In these animals, rhIL-6 at the same dose effective in healthy animals (10 micrograms/kg/d) was not capable of protecting the animals from platelet nadir. However, when pegylated rhIL-6 was used at a dosage of 100 micrograms/kg/d post irradiation, the mean of the nadirs was 71,000/microL as compared with 39,000/microL in control animals and the time of thrombocytopenia was shorter (3 v 5 days). In all animals (healthy and irradiated), rhIL-6 did not increase the number of bone marrow megakaryocytes but induced a right shift of DNA ploidy in megakaryocytes. These data suggest that IL-6 acts as "thrombopoietin"-like activity, but not as "megakaryocyte-CSF"-like activity.

Animals↗

The substitution of cysteine 17 of recombinant human G-CSF with alanine greatly enhanced its stability.

Human recombinant granulocyte-colony stimulating factor (rhG-CSF) has one free cysteine at position 17 and has two disulfide bridges (Cys36-Cys42 and Cys64-Cys74). The Cys17 of rhG-CSF was substituted with Gly, Ala, Ser, Ile, Tyr, Arg, and Pro, or deleted using site-directed mutagenesis in order to improve its thermostability. With the exception of Pro17-rhG-CSF, all mutant proteins retained biological activity which promotes the growth of mouse bone marrow cells in vitro. Among these mutant proteins, Ala17-rhG-CSF had more than 5 times higher stability than rhG-CSF. But Ser17-rhG-CSF had almost same stability as rhG-CSF and other mutant proteins had only lower stability.

Alanine↗

The changes of gasoline compounds in blood in a case of gasoline intoxication.

A 44 year-old man, found in his gasoline vapor filled car, died of multiple organ failure on d 9. Blood samples from d 2-7 were analyzed by gas chromatography/mass spectrometry. The estimated half-lives of gasoline, toluene, ethylbenzene, m,p-xylene, and o-xylene were 16.9, 21.4, 27.5, 32.8, and 25.8 h respectively. The estimated initial gasoline concentration in blood was 247 micrograms/ml.

Acidosis↗

[Clinical study on hypotensive anesthesia with nitroglycerin].

Deliberate hypotension was induced by using nitroglycerin (NG) during anesthesia in 13 patients with intracranial aneurysm, who underwent clipping surgery. The following results were obtained: Changes in blood pressure were rapid and smooth, before, during and after administration of NG. No patients showed resistance to the drug in this study. Heart rate increased significantly during induced hypotension while a significant reduction was observed in the rate-pressure product (RPP), which correlates with the myocardial oxygen demand. No significant changes were found in pH, PaO2, PaCO2 and base excess (B. E.) while the respiratory index (PaO2/FIO2) as an indicator of pulmonary oxygenation appeared to be significantly reduced.

Adult↗

Large scale preparation and crystallization of neuron-specific enolase.

A simple method has been developed for the large scale purification of neuron-specific enolase [EC 4.2.1.11]. The method consists of ammonium sulfate fractionation of brain extract, and two subsequent column chromatography steps on DEAE Sephadex A-50. The chromatography was performed on a short (25 cm height) and thick (8.5 cm inside diameter) column unit that was specially devised for the large scale preparation. The purified enolase was crystallized in 0.05 M imidazole-HCl buffer containing 1.6 M ammonium sulfate (pH 6.39), with a yield of 0.9 g/kg of bovine brain tissue.

Amino Acids↗