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Biomedical subjects

N Kawai

Publications and source records attributed to N Kawai.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Clinical effects of combination therapy with cefozopran and amikacin for infections in patients with hematological disorders].

Cefozopran (CZOP) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases. A total of 103 subjects were evaluated, and the all over efficacy rate was 69.9%. Acute leukemia was found in the largest number of patient, 57, followed by 29 cases of malignant lymphoma and 7 cases of myelodysplastic syndrome. By type of infection, patients having unknown origin were the largest in number, being 66, and the efficacy rate was 71.2%. The efficacy rates for sepsis, pneumonia and upper respiratory infection were 42.9% (7 cases), 71.4% (14 cases) and 90% (10 cases) respectively. The efficacy rates by neutrophil counts before administration of CZOP and AMK and at 1 week after administration were both 53.3% in the group of less than 100/microliter, both 60% in the group of less than 500/microliter. The efficacy rate by neutrophil counts at 1 week after administration was 58.6% in the group of less than 100/microliter. The efficacy rate was 75.4% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 61.9% in the group of non-concomitant usage group. The efficacy rates by serum albumin levels before administration of CZOP and AMK and at 1 week after administration were both 92.9% in the group of over than 4 g/dl, both 50% in the group of less than 3 g/dl. Concomitant treatment with CZOP and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases.

Adult↗
PubMed2001

Novel wasp toxin discriminates between neuronal and cardiac sodium channels.

Pompilidotoxins (PMTXs), derived from the venom of solitary wasp has been known to facilitate synaptic transmission in the lobster neuromuscular junction, and a recent further study from rat trigeminal neurons revealed that the toxin slows Na+ channel inactivation without modifying activation process. Here we report that beta-PMTX modifies rat brain type II Na+ channel alpha-subunit (rBII) expressed in human embryonic kidney cells but fails to act on the rat heart alpha-subunit (rH1) at similar concentrations. We constructed a series of chimeric mutants of rBII and rH1 Na+ channels and compared modification of the steady-state Na+ currents by beta-PMTX. We found that a difference in a single amino acid between Glu-1616 in rBII and Gln-1615 in rH1 at the extracellular loop of D4S3-S4 is crucial for the action of beta-PMTX. PMTXs, which are small peptides with 13 amino acids, would be a potential tool for exploring a new functional moiety of Na+ channels.

Cells, Cultured↗
PubMed2001

Aortic valve replacement combined with endoventricular circulatory patch plasty (Dor operation) in a patient with aortic valve stenosis and severe ischemic cardiomyopathy.

A 58-year-old woman with ischemic cardiomyopathy and aortic valve stenosis, underwent aortic valve replacement and simultaneous endoventricular circulatory patch plasty (Dor operation). She underwent coronary artery bypass grafting for severe triple vessel disease 10 years ago. Recently she started to show severe congestive heart failure. Aortic valve stenosis with pressure gradient of 85-mmHg was also found. Coronary bypasses were all patent, but the left ventricle (LV) was severely dilated (LVDd/Ds=71/61 mm) and the ischemic cardiomyopathy was considered as the cause. She successfully underwent aortic valve replacement and endoventricular circulatory patch plasty. The initial postoperative course was complicated with intractable ventricular arrhythmia, but subsequent course was smooth and the patient was discharged with improved symptoms (NYHA Class II). Postoperative catheterization showed decreased left ventricular volume and improved contractility. This case implies the role of LV remodeling procedure in the ischemic cardiomyopathy combined with aortic valve lesion

Aortic Valve Stenosis↗
PubMed2001

[Chemotherapy for gliomas based on the expression levels of drug resistant genes].

Drug resistance, which often occurs during chemotherapy, is still a great obstacle to the success of human malignancy treatment. Among many possible mechanisms of drug resistance (biological, biochemical, kinetic or pharmacological), both typical and atypical multidrug-resistance (MDR) have been extensively studied. We picked up MDR-1, MXR, MRP1, MRP2, TopoII alpha, MGMT, and GST-pi as drug-resistant gene, based on experimental data and previous reports. Expression of these genes were measured in 14 malignant glioma specimens by reverse transcription polymerase chain reaction assay. We chose anticancer drugs for each patient, based on results of drug resistant gene expression to acquire good response to drugs. Though our follow-up periods are not long enough to analyze the results of our chemotherapy, 78% (7/9) of our glioma patients who were treated with our chemotherapy are free from tumor progression. The assays, which measure the expression of drug resistant genes, are necessary to allow rapid detection of the drug-sensitivity to chemotherapy in malignant glioma patients.

Adult↗
PubMed2001

[CD7(+) acute myeloid leukemia (M0) associated with a mediastinal bulky mass lesion].

A 41-year-old man visited his doctor in May 2000 because of a sore throat and high fever. His symptoms did not improve, despite administration of antibiotics and nonsteroidal anti-inflammatory drugs. Since a chest X-ray examination revealed an anterior mediastinal bulky tumor, he was referred and admitted to our hospital on June 21, 2000. The peripheral white blood cell count was 44,540/microliter with 74% myeloblasts. Bone marrow aspiration revealed a hypercellular marrow with 82% myeloblasts, which were negative for peroxidase and alpha-naphthyl butylate esterase staining. Blast cells were positive for CD7, CD13, CD33, CD34, and HLA-DR, and negative for CD56. A needle biopsy specimen of the mediastinal tumor consisted of myeloblasts. We diagnosed the patient as having CD7 (+) acute myeloid leukemia (AML) (M0) with a bulky mediastinal mass based on the surface marker analysis, although the clinical features resembled myeloid/NK precursor acute leukemia. The patient achieved a complete remission after two courses of induction therapy. We are planning an allogeneic stem cell transplantation during his first remission because of the high risk of relapse.

Adult↗
PubMed2001

[Percutaneous hot ethanol injection therapy (PHEIT) for hepatocellular carcinoma].

Percutaneous ethanol injection therapy (PEIT) is widely performed as a local treatment for hepatocellular carcinoma (HCC). However, PEIT must be repeated because only a limited amount of ethanol can be injected in a single treatment. In addition, PEIT is only indicated for up to 3 tumors of 30 mm or less in diameter. We therefore invented a percutaneous hot ethanol injection therapy (PHEIT) to enhance the antitumor effect of PEIT. For this, we developed a liquid-heating and injection device to heat the liquid to the intended temperature and inject it from the tip of the needle safely and accurately using a puncture technique under ultrasonographic guidance. An experiment on normal rat livers demonstrated that injected ethanol at temperatures over 60 degrees C enhances the necrotizing effect on tissue. The technique was clinically applied to patients with HCC using ethanol heated to 60 degrees C or 70 degrees C. The total volume of the ethanol injection was smaller in PHEIT than in PEIT, and the frequency of injection was lower in PHEIT than in PEIT, while the necrotic area obtained by a single treatment was larger with PHEIT than with PEIT. PHEIT is a potential radical treatment for patients with multiple hepatoma with 4 more lesions or those with large hepatomas exceeding 30 mm in diameter that do not respond to PEIT.

Aged↗
PubMed2001

[Phase I study with irinotecan hydrochloride (CPT-11) for advanced neuroblastoma].

A Phase I trial of irinotecan hydrochloride (CPT-11) was performed to determine the maximum tolerated dose (MTD), the dose-limiting toxicities, and the incidence and severity of other toxicities in children with advanced neuroblastoma. Three children received 11 courses of CPT-11 administered as a 90-min i.v. infusion, daily for 3 days every 21 days. Doses ranged from 100 mg/m2 to 220 mg/m2. Two peaks in the total number of instances of diarrhea was observed, 25 stools at 3 days and 32 stools at 10 days. Myelosuppression was well controlled and of brief duration. One child achieved a clinical complete response (CR) and 2 had a partial response (PR). The MTD of CPT-11 administration was 180 mg/m2 for 3 days. These results indicate the usefulness of CPT-11 for the treatment of advanced neuroblastoma. Further investigation is necessary to establish its role in combination chemotherapeutic regimens.

Adrenal Gland Neoplasms↗
PubMed2000

Observation of X-ray lines from a gamma-ray burst (GRB991216): evidence of moving ejecta from the progenitor.

We report on the discovery of two emission features observed in the x-ray spectrum of the afterglow of the gamma-ray burst (GRB) of 16 December 1999 by the Chandra X-ray Observatory. These features are identified with the Ly(alpha) line and the narrow recombination continuum by hydrogenic ions of iron at a redshift z = 1.00 +/- 0.02, providing an unambiguous measurement of the distance of a GRB. Line width and intensity imply that the progenitor of the GRB was a massive star system that ejected, before the GRB event, a quantity of iron approximately 0.01 of the mass of the sun at a velocity approximately 0.1 of the speed of light, probably by a supernova explosion.

Journal Article↗
PubMed2000

Molecular determinants of binding of a wasp toxin (PMTXs) and its analogs in the Na+ channels proteins.

The structural specificity of alpha-PMTX, a novel peptide toxin derived from wasp venom has been studied on the neuromuscular synapse in the walking leg of the lobster. alpha-PMTX is known to induce repetitive action potentials in the presynaptic axon due to sodium channel inactivation. We synthesized 29 analogs of alpha-PMTX by substituting one or two amino acids and compared threshold concentrations of these mutant toxins for inducing repetitive action potentials. In 13 amino acid residues of alpha-PMTX, Arg-1, Lys-3 and Lys-12 regulate the toxic activity because substitution of these basic amino acid residues with other amino acid residues greatly changed the potency. Determining the structure-activity relationships of PMTXs will help clarifying the molecular mechanism of sodium channel inactivation.

Amino Acid Substitution↗
PubMed2000

Effects of hypothermia on intracranial hemodynamics and ischemic brain damage-studies in the rat acute subdural hematoma model.

Brain ischemia is the leading pathophysiological mechanism in the development of secondary brain damage after subdural hematoma (SDH). Hypothermia has been used as the effective neuroprotective treatment in clinical and laboratory studies of ischemic brain injury. In this study, we have examined the rat acute SDH model to assess the effect of hypothermia upon intracranial hemodynamics and also upon ischemic brain injury 4 hours after the induction of hematoma. Moderate hypothermia (32 degrees C) did not affect the intracranial pressure nor cerebral perfusion pressure, and it significantly reduced cortical brain edema formation underneath the hematoma (80.88 +/- 0.17%; p < 0.01) compared with the normothermic control group (81.65 +/- 0.52%). This reduction in brain edema formation was comparable to the result of MK-801 (2 mg/kg) treatment (80.95 +/- 0.35%; p < 0.01). Ischemic brain damage detected by H-E staining was also significantly reduced in the hypothermia and MK-801 treated groups (59.1 +/- 12.3 mm3 and 66.4 +/- 13.8 mm3; p < 0.01 and p < 0.05) compared with the normothermic control group (86.6 +/- 20.7 mm3). In conclusion, the present study demonstrates that hypothermia is a potent neuroprotective method and an inhibition of the glutamate excitotoxic process may contribute the protective mechanisms of hypothermia in this rat acute SDH model.

Animals↗
PubMed2000

Protective effect of mild hypothermia on symptomatic vasospasm: a preliminary report.

Mild hypothermia (32-34 degrees C of brain temperature) was used for brain protection in patients with progressive ischemic neurological deficits associated with severe cerebral vasospasm and who did not respond to medical treatment or intravascular angioplasty. Results showed that 2 of 3 patients in Hunt & Kosnik grade I to III and 2 patients who underwent delayed operation on day 5 and 9 each and had ischemic neurological deficits made good recovery with this treatment. Favourable outcome was obtained in 4 of 9 patients in grade IV and V. Mild hypothermia is thought to provide brain protection in critical ischemia due to severe cerebral vasospasm and can lengthen therapeutic time to employ angioplasty and intraarterial Papaverin infusion.

Brain Ischemia↗
PubMed2000

Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado).

A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile-Asn-Leu-Leu-Lys-Ile-Ala-Lys-Gly-Ile-Ile-Lys-Ser-Leu-NH(2), was similar to that of mastoparan, a mast cell degranulating peptide from a hornet venom; tetradecapeptide with C-terminus amidated and rich in hydrophobic and basic amino acids. In fact, EMP-AF exhibited similar activity to mastoparan in stimulating degranulation from rat peritoneal mast cells and RBL-2H3 cells. It also showed significant hemolytic activity in human erythrocytes. Therefore, this is the first example that a mast cell degranulating peptide is found in the solitary wasp venom. Besides the degranulation and hemolytic activity, EMP-AF also affects on neuromuscular transmission in the lobster walking leg preparation. Three analogs EMP-AF-1 approximately 3 were snythesized and biologically tested together with EMP-AF, resulting in the importance of the C-terminal amide structure for biological activities.

Amino Acid Sequence↗
PubMed2000

Facilitation of neurotransmitter release at the spiny lobster neuromuscular junction.

Stimulation-induced facilitation of transmitter release was examined at spiny lobster (Palinurus japonicus) neuromuscular junctions by measuring excitatory junctional potentials (EJPs). We found three components of facilitation with the decay time constants about 16, 200 and 1000 ms, respectively. The decay time constants of the nerve terminal free Ca(2+) concentration after stimulation agreed well with the two slower time constants of facilitation. The relationship among the three components of facilitation and a yet slower component, S, was investigated on the basis of several models. The models that have a multiplicative relationship between any two components of facilitation, and the additive model between all components could not account for the results of experiments. Only the 'unified power model', which assumes that facilitation and S are described by the 3-4th power of the sum of underlying components, could account for both the growth process of EJPs during stimulation and the effects of Ca(2+)-chelators. Loading Ca(2+)-chelators, BAPTA and EGTA, into the presynaptic terminals resulted in reduction, but not elimination, of any component of the facilitation. These results suggest that in the spiny lobster neuromuscular junction, the 'unified power model' can describe the relationship between three components of facilitation and S, and that residual free Ca(2+) enhances all three components of facilitation, although it may not be essential for them.

Animals↗