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Biomedical subjects

Y Kosaka

Publications and source records attributed to Y Kosaka.

At least 37 records · Page 2Linked to original sources

Expression of the HB9 homeobox gene concomitant with proliferation accompanying epidermal stratification during development of chick embryonic tarsometatarsal skin.

A homeobox gene, HB9, has been isolated from the tarsometatarsal skin of 13-day-old chick embryos using a degenerate RT-PCR-based screening method. In situ hybridization analysis revealed that, during development of chick embryonic skin, the HB9 gene was expressed in epidermal basal cells of the placodes, but not in those of interplacodes, and in the dermal cells under the placodes at 9 days before addition of an intermediate layer by proliferation of the basal cells in the placodes. With the onset of epidermal stratification, the direction of the basal cell mitosis changed, with the axis becoming vertical to the epidermal surface. Placodes and interplacodes form outer and inner scales, respectively, after they have elongated distally (Tanaka S, Kato Y (1983b) J Exp Zool 225: 271-283). During scale ridge elongation at 12-15 days, HB9 was strongly expressed in the epidermis of the outer scale face, where the cell proliferation is more active than in the epidermis of the inner scale face; hence, stratification of the outer scale face is more prominent than that of the inner scale face. After 16 days, when mitotic activity in the epidermal basal cells decreases and the thickness of the epidermis is maintained at a constant level, the HB9 expression decreases with the onset of epidermal keratinization. These results suggest that HB9 may be involved in the proliferation of the epidermal basal cells that accompanies epidermal stratification.

Animals↗

Spinal coadministration of ketamine reduces the development of tolerance to visceral as well as somatic antinociception during spinal morphine infusion.

UNLABELLED: This study was designed to investigate the effects of ketamine, an N-methyl-D-aspartate receptor antagonist, on the development of tolerance to morphine and morphine antinociception during intrathecal infusion. Two intrathecal catheters were implanted in the subarachnoid space in male rats under pentobarbital anesthesia. One catheter was used for the intrathecal infusion with the following solutions: morphine 1 microg x kg(-1) x hr(-1)(M1) and 5 microg x kg(-1) x hr(-1) (M5);ketamine 250 microg x kg(-1) x hr(-1) (K250); morphine plus ketamine, 1 microg x kg(-1) x hr(-1) plus 250 microg x kg(-1) x hr(-1) (M1 + K250) and 5 microg x kg(-1) x hr(-1) + 250 microg x kg(-1) x hr(-1) (M5 + K250); or saline. The other catheter was used for morphine challenge tests. The responses to noxious somatic and visceral stimuli were measured by tail flick (TF) and colorectal distension (CD) tests, respectively. Measurements were performed once a day for 7 days. Challenge tests with intrathecal morphine were performed to assess the magnitude of tolerance on Day 5 and Day 7. The antinociceptive effect was evaluated by using the percent of maximal possible effect (%MPE). Morphine infusion produced significant increases in %MPEs in TF and CD tests, while the saline and K250 infusions did not show any changes. The M1 + K250 infusion significantly increased the %MPEs in TF and CD tests, although the M1 and K250 infusions alone showed no changes. M5 + K250 enhanced the increases of %MPEs in TF and CD tests compared with the M5 infusion alone. In the challenge tests, the M1 + K250 infusion showed no significant decrease in %MPEs and TF and CD tests. The M5 + K250 infusion significantly inhibited those decreases in %MPEs, although the M5 infusion showed significant decreases in TF and CD tests. We concluded that ketamine attenuated the development of morphine tolerance to antinociceptive effects and increased the somatic and visceral antinociception of morphine. IMPLICATIONS: Intrathecally coinfused ketamine attenuated morphine tolerance to somatic and visceral antinociception and increased morphine antinociception at the spinal level. These results suggest that a combination of morphine with ketamine may have an advantage in long-term use of opioids for controlling visceral as well as somatic pain.

Analgesics, Opioid↗

Estimation of stem cell fractions in peripheral blood stem cell harvest by using an SE-9000 hematology analyzer.

We inquired whether stem cell fractions in peripheral blood stem cell harvest could be precisely detected by using a hematopoietic progenitor cell (HPC) counting system applied to an automated hematology analyzer, SE-9000. Although there was an apparent increase in the HPCs 20 h after storage in nondiluted conditions, samples diluted with RPMI-1640 containing 1.0 mg/ml EDTA-2K showed a relatively stable number of HPCs. There was a significant relationship between HPCs and CD34 cells (n = 75, r = 0.769). This method may represent the least expensive and most time-effective way for stem cell estimation in harvest products.

Anticoagulants↗

[An anesthetic experience of a patient with subacute myelo-optico-neuropathy for bilateral mastectomy].

A 79-year-old woman with subacute myelo-optico-neuropathy (SMON) underwent a bilateral mastectomy for breast cancer. She has been suffering from SMON for 32 years. Her preoperative neurological examination revealed cryesthesia and dyskinesia in the lower extremity, and numbness in the crues. Physical examination revealed respiratory dysfunction. A combination of general anesthesia and epidural block was employed to minimize the dose of anesthetics which may affect the neuronal symptoms. Intraoperative course was uneventful and continuous epidural block was effective for postoperative pain control. There was no neurological deterioration postoperatively.

Aged↗

Development of the insulin-like growth factor-I assay system.

A high speed full automatic ELISA system for measurement of insulin-like growth factor-I (IGF-I) was established by using magnetic particle-linked monoclonal antibody and enzyme-labeled monoclonal antibody. A standard curve was obtained, and the effect of dilution on the assay system was investigated. An IGF-I spike recovery test of human serum samples and a study of the correlation with a radioimmunoassay system were performed, and good results were obtained from all studies. The assay range was 0.5-50 ng/ml, and the time required for the full automatic measurement was 15 minutes. This assay system will play a central role in the clinical approach to IGF-I.

Antibodies, Monoclonal↗

Effective control of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis with immunochemotherapy. Histiocyte Society.

The familial form of hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder. Although the prognosis for Epstein-Barr virus-associated HLH (EBV-HLH) remains uncertain, numerous reports indicate that it can also be fatal in a substantial proportion of cases. We therefore assessed the potential of immunochemotherapy with a core combination of steroids and etoposide to control EBV-HLH in 17 infants and children who met stringent diagnostic criteria for this reactive disorder of the mononuclear phagocyte system. Treatment of life-threatening emergencies was left to the discretion of participating investigators and typically included either intravenous Ig or cyclosporin A (CSA). Five patients (29%) entered complete remission during the induction phase (1 to 2 months), whereas 10 others (57%) required additional treatment to achieve this status. In 2 cases, immunochemotherapy was ineffective, prompting allogeneic bone marrow transplantation. Severe but reversible myelosuppression was a common finding; adverse late sequelae were limited to epileptic activity in one child and chronic EBV infection in 2 others. Fourteen of the 17 patients treated with immunochemotherapy have maintained their complete responses for 4+ to 39+ months (median, 15+ months), suggesting a low probability of disease recurrence. These results provide a new perspective on EBV-HLH, showing effective control (and perhaps cure) of the majority of EBV-HLH cases without bone marrow transplantation, using steroids and etoposide, with or without immunomodulatory agents.

Child↗

Activation and regulation of the IkappaB kinase in human B cells by CD40 signaling.

This study demonstrates that the engagement of CD40 results in the activation of the recently described IkappaB kinase (IKK) in a human B cell line. The kinase appears to reside within the cell in a cytosolic signalsome complex consisting of IKK, IkappaB, and an MKP-1-like molecule. While the binding of CD154 to CD40 induces the assembly of a CD40-TRAF receptor complex, IKK is not recruited to this complex. Nonetheless, a functional link between TRAF2 and IKK activity in B cells is demonstrated by the fact that overexpression of TRAF2 constitutively induces IKK activity, NF-kappaB luciferase and Fas expression. Synergy in the activation of IKK and NF-kappaB-dependent gene expression was observed by the simultaneous engagement of the B cell receptor and CD40, establishing an early means for cross-talk between these two B cell activation pathways. This study discusses the sequential biochemical events that transpire upon CD40 engagement by its ligand in human B cells.

Animals↗

Effects of nitroglycerin on fractal features of short-term heart rate and blood pressure variability.

PURPOSE: We investigated the effect of nitroglycerin(NTG) on fractal features of short-term heart rate variability (HRV) and blood pressure variability (BPV) using coarse-graining spectral analysis (CGSA). METHOD: Nine healthy young volunteers participated in this study. Five-minute recordings of electrocardiogram and blood pressure estimated by photoplethysmograph were made during stepwise NTG infusions of 0.2, 0.4, 0.8, and 1.6 microg.kg(-1).min(-1) under rate-controlled breathing at 0.25 Hz. CGSA broke down the total power of the time series into harmonic (low- and high-frequency) and nonharmonic (beta of 1/f(beta) and %fractal) components. RESULTS: A statistically significant difference from the control period was observed during the maximum dose of NTG infusion, with decrease in mean blood pressure, shortening of mean R-R interval, and increase in plasma norepinephrine and epinephrine. The beta in HRV increased significantly (0.89 +/- 0.06 vs. 1.27 +/- 0.13, P < 0.05). However, %fractal was not affected (47.9 +/- 6.7 vs. 50.1 +/- 4.0). Indicators of parasympathetic and sympathetic nervous system activity showed reduced and increased values, respectively. No change in BPV was observed for any measurement. CONCLUSION: The data suggest that NTG significantly affected fractal features, as well as harmonic components, of short-term HRV. NTG had no effect on BPV, suggesting a different mechanism for genesis of 1/f(beta) fluctuation in BPV and HRV.

Journal Article↗

Allogeneic hematopoietic stem cell transplantation for patients with hemophagocytic syndrome (HPS) in Japan.

Seventeen cases (age at onset, 1 month to 18 years; M/F, 9/8) of hemophagocytic syndrome which received allogeneic hematopoietic stem cell transplantation (SCT) in Japan during the period 1988-1998 are reported. The patients consisted of six familial inheritance-proven erythrophagocytic lymphohistiocytosis (FEL), five familial inheritance-unknown and infective agents-unknown HLH (of which two were highly likely to have been FEL with characteristic CNS signs), and six aggressive Epstein-Barr virus (EBV)-related HLH (of which two were natural killer cell-type large granular leukemia/lymphoma-associated hemophagocytic syndrome, EBV-NK-LGLL-HPS). All cases were treated intensively with immuno-chemotherapy, or with chemotherapy before SCT. As sources of SCT, 12 cases received bone marrow cells (sibling six, father one, URD five), two cord blood, two purified CD34-positive cells, and one PBSC. SCTs were successful in all 17 cases, apart from one receiving CD34-positive SCT. Following SCT, four patients relapsed and five died with a median follow-up of 23 months. Among the relapsed cases, the two EBV-NK-LGLL-HPS previously published as successfully transplanted were included. Among the fatal cases, three patients died from relapsed active disease and the remaining two from fatal post-SCT EBV-positive T cell lymphoma and extensive chronic GVHD, respectively. As of the end of September 1998, 10 patients are alive without disease for 3.5 months to 147 months, while two post-SCT patients are still having therapy for residual/recurrent disease. The Kaplan-Meier analysis showed a 2-year event-free survival after SCT as 54.0+/-13.0%.

Adolescent↗

A case of hemophagocytic lymphohistiocytosis with prolonged remission after syngeneic bone marrow transplantation.

We report a 7-year-old girl with hemophagocytic lymphohistiocytosis who received a syngeneic bone marrow transplant from her twin sister. She presented with high fever and cough. Laboratory findings revealed pancytopenia, elevation of liver enzymes, and hyperferritinemia. Bone marrow examination revealed histiocytic hemophagocytes and lymphoblastoid cells. Southern blot analysis of the bone marrow cells revealed a monoclonal proliferation of EBV-infected lymphocytes. Although she underwent combined chemotherapy according to the HLH-94 protocol, she developed severe pancytopenia. Following myeloablative conditioning with busulfan (16 mg/kg), cyclophosphamide (120 mg/kg), and etoposide (1.5 g/m2), she was transplanted with 6.6 x 10(8)/kg mononuclear cells from the twin sister. She remains in complete remission 23 months after transplantation.

Bone Marrow Cells↗

The non-NMDA glutamate receptor antagonist CNQX augments lidocaine antinociception through a spinal action in rats.

UNLABELLED: Non-NMDA glutamate receptor antagonists produce antinociceptive effects, but the antinociceptive interaction between non-NMDA glutamate receptor antagonists and local anesthetics has not been demonstrated. We designed this study to evaluate the antinociceptive effects of a non-NMDA glutamate receptor antagonist and its interaction with lidocaine in rats. Intrathecal catheters were implanted at the L4-5 level in rats. The tail flick (TF) and colorectal distension (CD) tests were used to assess somatic and visceral antinociceptive effects, respectively. The TF latency and CD threshold were measured before and for 180 min after the intrathecal administration of lidocaine (20-100 micrograms), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (0.4-4.0 micrograms), a combination of CNQX (0.2-0.6 microgram) and lidocaine (10-30 micrograms), or isotonic sodium chloride solution. The TF latency and CD threshold were converted to the percent maximal possible effect (%MPE). To determine synergistic interaction, isobolographic analysis was used. Lidocaine or CNQX increased %MPEs in both the TF and CD tests. The coadministration of CNQX 0.4 microgram and lidocaine 20 micrograms, which had no effect by alone, significantly increased %MPEs in the TF and CD tests for 30 min and 10 min, respectively. Isobolographic analysis revealed the synergistic antinociception of CNQX and lidocaine in the TF test. Motor impairment was not observed after that combination. We conclude that CNQX and lidocaine produce synergistic analgesia on somatic and visceral pain at the spinal level. IMPLICATIONS: We investigated the antinociceptive effects of 6-cyano-7-nitroquinoxaline-2,3-dione and its interaction with lidocaine at the spinal level in rats. Intrathecal 6-cyano-7-nitroquinoxaline-2,3-dione produced both somatic and visceral antinociception, and its coadministration with lidocaine showed synergistic antinociceptive effects.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

The interaction of antinociceptive effects of morphine and GABA receptor agonists within the rat spinal cord.

UNLABELLED: Previous reports indicate that there may be an interaction between gamma-aminobutyric acid receptors and opioid receptors systems within the spinal cord, the antinociceptive effects of which have not been elucidated. We examined the effects of intrathecally coadministered morphine and muscimol or baclofen on somatic and visceral antinociception in rats. The tail flick (TF) test and colorectal distension (CD) test were used to assess somatic and visceral antinociceptive effects, respectively. Motor function was also assessed. The measurements were performed for 180 min after the intrathecal administration of morphine (0.1-10 micrograms), muscimol (0.2-10 micrograms), baclofen (0.03-1 microgram), combination of morphine and muscimol or baclofen, or saline. Morphine, muscimol, or baclofen increased both TF latency and CD threshold in a dose-dependent fashion. Although morphine 0.1 microgram, muscimol 0.2 microgram, or baclofen 0.03 microgram alone did not significantly increase TF latency and CD threshold, the combination of morphine 0.1 microgram and muscimol 0.2 microgram or baclofen 0.03 microgram significantly increased both TF latency and CD threshold. The coadministration of muscimol or baclofen increased the antinociceptive effects of morphine in intensity and duration. None of the rats showed motor dysfunction after the coadministration of morphine and muscimol 0.2 microgram, although muscimol produced motor paralysis of the lower limbs in a dose-dependent fashion. Those results suggest a clinical relevance of the coadministration of mu-opioids and GABA receptor agonists for pain control. IMPLICATIONS: We examined the antinociceptive interaction between morphine and muscimol or baclofen at the spinal level in rats. Intrathecal muscimol or baclofen potentiated both somatic and visceral antinociceptive effects of morphine.

Analgesics, Opioid↗

[Antinociceptive effects of intrathecally administered GABA agonists at the spinal cord level].

The present study was designed to investigate antinociceptive effect of GABA agonists regarding visceral as well as somatic noxious stimuli. Following the approval by the institutional animal care committee, an intrathecal catheter was implanted in the subarachnoid space at the L 4/5 level in male Sprague-Dawley rats. The tail flick (TF) test and the colorectal distension test (CD) were used to measure responses to somatic and visceral stimuli, respectively. Threshold in TF test and CD test were measured at 5, 10, 15, 20, 30, 60, 90, 120 and 180 min after the intrathecal injection of 0.1, 1, 5, 20 micrograms of muscimol, 0.01, 0.1, 0.3, 1 microgram of baclofen or normal saline. Percent of maximum possible effect (%MPE) and %area under the curve (%AUC) were calculated by transforming response threshold in TF and CD tests. Repeated measure ANOVA followed by Fisher's PLSD test were used for statistical analysis. Muscimol 0.1 microgram increased mean %MPE in TF test at 10 min to 15% but not in CD test. Muscimol 1, 5 and 20 micrograms significantly increased %MPE at 5 min in TF and CD tests. Muscimol 20 micrograms produced 100%MPE for 180 min after drug injection. Baclofen 0.1, 0.3 and 1 microgram significantly increased %MPE at 5 min in TF and CD test. Antinociceptive effect in TF test seems to be greater than that in CD test. Muscimol caused motor disturbance but baclofen did not. It is concluded that intrathecally administered muscimol and baclofen produced somatic and visceral antinociception in a dose dependent fashion.

Analgesics↗

[Safety of continuous epidural anesthesia during heart surgery--change of coagulation-fibrinolysis under heparinization].

To confirm the safety of continuous epidural anesthesia during extracorporeal circulation under heparinization, we investigated epidural hematoma formation following the cardiopulmonary bypass in both humans and dogs. In fifteen dogs, divided into three groups, heparin was administered at the dose of 300, 600, or 900 U.kg-1, respectively. In fourteen patients, a dose of 300 U.kg-1 haparin was administered for cardiopulmonary bypass. Although blood coagulation-fibrinolysis dropped into abnormal ranges following heparinization, no epidural hematoma was observed in dog and no patient revealed spinal complication associated with epidural hematoma. These data indicate that continuous epidural anesthesia would be a safe tool for intraoperative anesthesia even during extracorporeal circulation under heparinization.

Adolescent↗

[Postoperative epidural analgesia after upper abdominal surgery: the effects of low concentrations of bupivacaine combined with a low dose of opioid].

The efficacy and safety of postoperative analgesia with continuous epidural infusion of either morphine or fentanyl in combination with a low dose of bupivacaine were evaluated in 205 patients after upper abdominal surgery. Each patient was given bupivacaine alone (0.125% or 0.25%) or one of six combinations; 0.25%, 0.125%, or 0.0625% bupivacaine with morphine (M: 10 micrograms.ml-1) or fentanyl (F: 1 microgram.ml-1). After injection of 6 ml of each solution at the end of surgery, continuous epidural infusion was started at a rate of 4.2 ml.hr-1 for 48 hr. The degree of pain relief was assessed by the necessity of supplementary analgesics, the visual analogue pain scale and the Prince Henry pain scale. The most effective analgesic situation was obtained with the 0.25% M and the 0.25% F groups. The 0.125% M and 0.125% F groups showed adequate analgesia for elderly patients with few side effects. Regarding the plasma catecholamines measured 24 hr after the surgery, there was no significant change in fentanyl groups as well as in the group given 0.125% bupivacaine alone. Although the incidence of hypotension and pruritus was slightly higher in morphine groups, no patient developed respiratory depression. It is suggested, therefore, that a small dose of opioid should be added when continuous epidural infusion is required.

Abdomen↗

[A case of pulmonary edema following upper airway obstruction after general anesthesia].

A 30-year-old man underwent tonsillectomy and laryngomicrosurgery under nitrous oxide oxygen-isoflurane anesthesia. Preoperative physical examinations and interview revealed no cardiopulmonary abnormalities. Two minutes after extubation, he showed dyspnea with marked inspiratory efforts and cyanosis due to laryngeal spasm. The SpO2 decreased from 100% to 80%. He was reintubated after administration of suxamethonium 100 mg and ventilated with 100% oxygen. At that time pink frothy sputum came out from his airway. He was diagnosed as pulmonary edema from analysis of arterial blood gases and chest X-ray. He received mechanical ventilation with positive end-expiratory pressure in the ICU. Twenty hours later the pulmonary edema was improved and he was extubated uneventfully. He was discharged from the hospital on the 8th post-operative day. We reported a case of pulmonary edema after laryngeal spasm. It was suggested that a patient after acute upper airway obstruction should be carefully treated considering secondary pulmonary edema.

Adult↗

[Hereditary hemoglobin H disease in Japanese siblings diagnosed by human parvovirus B19 infection].

Hereditary hemoglobin H (HbH) disease was diagnosed in 2 Japanese sisters who presented with aplastic crisis following acute human parvovirus B19 (HPV B19) infection. The proband, an 8-year-old girl, developed persistent fever and pallor, and samples of her peripheral blood showed hypochromic microcytic anemia. Other laboratory data were consistent with hemolytic anemia. Fever and signs of hypochromic microcytic anemia also developed in her sister 9 days later. Cation exchange HPLC analysis of their hemoglobin revealed abnormal hemoglobin migrating faster than HbF, a finding consistent with HbH. Although they presented neither arthralgia nor skin rash, we concluded that their aplastic crisis was induced by HPV B19, because HPV B19 DNA was detected in samples of their peripheral blood by PCR analysis, and HPV B19 IgM and IgG antibody titers were elevated. A genetic analysis of the alpha-globin gene in both sisters and their parents disclosed that the father was heterozygous for alpha-Thal-2, the mother, heterozygous for alpha-Thal-1, and the proband and her sister, double heterozygous for alpha-Thal-1 and alpha-Thal-2. alpha-Thal-2 is a 3.7 kb-deletion allele.

Child↗

[Infantile T cell acute lymphoblastic leukemia complicated by thrombotic microangiopathy and human herpes virus 6 infection after allogeneic peripheral blood stem cell transplantation using CD34-positive cells].

We report on a 19-month-old boy with refractory T-cell acute lymphoblastic leukemia who underwent allogeneic peripheral blood stem cell transplantation using positively selected CD34 cells from his HLA two-loci mismatched mother. The conditioning regimen consisted of busulfan (140 mg/m2/d for 2 days), total body irradiation (12 Gy) and melphalan (210 mg/m2). The patient received cyclosporin A for graft-versus-host disease (GVHD) prophylaxis. The CD34-positive cells were separated using an immunomagnetic cell-separation system (Isolex 50). The number of infused CD34-positive cells was 4.4 x 10(6)/kg. Successful engraftment was confirmed on day 14 by fluorescent in situ hybridization of X chromosomes. The patient experienced severe diarrhea due to thrombotic microangiopathy (TMA) following acute GVHD, and died on day 71 of human herpes virus type 6 pneumonitis. Stem cell transplantation using CD34 positively selected cells from HLA-mismatched related donors may be a useful treatment with low incidence of severe GVHD, but many problems remain to be overcome, including severe viral infections and TMA.

Antigens, CD34↗