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Biomedical subjects

K Kawa

Publications and source records attributed to K Kawa.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Chronic active EB virus infection and granular lymphocytes proliferative disorders in Japan].

To clarify the characteristics of chronic active EB virus infection (CAEBV) in Japan, and to investigate the relation between granular lymphocytes proliferative disorder (GLPD) and EB virus, we conducted a survey through a questionnaire conducted throughout Japan. Among 17 registered patients with CAEBV, 9 developed various types of lymphoproliferative disorders (LPDs), and 6 patients died of LPD. Among 72 cases of GLPD, 43 were CD3-positive and 27 were CD3-negative. EB viral DNA was detected in the peripheral mononuclear cells in 6 of 7 CD3-negative and 1 of 4 CD3-positive cases. These data suggest that EB virus-associated LPDs frequently derive from patients with CAEBV. However, some GLPD patients without CAEBV, especially for CD3-negative GLPD, are associated with EB virus infection. Therefore detection of EB viral DNA is very important to understand the pathogenesis of GLPD.

Adolescent↗
PubMed1996

[LGL lymphoma].

We reported in this article two patients with large granular lymphocytic lymphoma (abbreviated as LGL lymphoma). One was the patient with LGL leukemia/lymphoma (patient 1) and other was the patient with NK-LGL lymphoma (patient 2). Because the gene of TCR delta was rearranged in the patient 1, the clonality of the LGL leukemia/lymphoma was confirmed. However, it is not determined yet whether the lineage of tumor cells is T cells or NK cells. The cytochemical features of the lymphoma cells of the patient 2 were studied. It was found that NK cell-derived lymphoma cells of the patient were positively stained with these two monoclonal antibodies that are reactive with T cell; one is anti-CD45RO (UCHL-1) and other is anti-CD3. Judging from the result, malignant NK-LGL cells in some patients are cytoplasmic CD3+ and UCHl-1+. It is emphasized that May-Grünwald-Giemsa stain of biopsied specimen of the lymphoma is required for making the diagnosis of LGL lymphoma.

Adult↗
PubMed1996

[The clinical significance of minimal residual disease of acute leukemia with t(4;11) (q21;q23)].

Hybrid fusion genes are specific tumor markers of several leukemic subtypes. The use of reverse transcription-polymerase chain reaction (RT-PCR) to amplify chimeric cDNAs allows sensitive detection of the leukemia clone. The clinical relevance of minimal residual disease (MRD) remains controversial. In this report, an infantile acute lymphoblastic leukemia with t(4;11) (q21; q23) was analyzed after each treatment for the presence of MRD by RT-PCR amplification of the MLL/LTG4 fusion gene which became available recently. The patient soon achieved a hematological CR, after induction therapy, and underwent autologous BMT following consolidation chemotherapy for 9 months. However, he relapsed three months after the BMT. MRD was always detectable during his clinical course. These findings suggest that the detection of MRD of the MLL/LTG4 fusion transcript is a useful tool for monitoring MRD and selecting treatment.

Child, Preschool↗
PubMed1995

Immunohistochemical detection of early myocardial infarction. An evaluation of antibodies against the terminal complement complex (C5b-9).

Antibodies (abs) against the terminal complement complex (C5b-9) were used on routinely processed post mortem myocardial tissue in parallel with conventional staining methods. Both monoclonal and polyclonal abs were tested using the avidin biotin peroxidase complex (ABC), alkaline phosphatase anti-alkaline phosphatase (APAAP) methods and an ab-bridge with alkaline phosphatase. Enhancement of the diaminobenzene (DAB) end product with cobalt-nickel (ABC method) was also done. The polyclonal ab gave the most satisfactory results and the alkaline phosphate conjugated ab-bridge had a slight advantage over the ABC method. Cobalt-nickel enhancement of DAB improved the visualization, but with higher background staining. APAAP was the least satisfactory method. Comparing the immunohistochemical method with the conventional staining methods, the former showed positive reaction in 97% of areas of coagulation necrosis and in 65% of contraction band necrosis. On the other hand coagulation necrosis was seen in 44% and contraction band necrosis in 68% of C5b-9 positive areas indicating that C5b-9 abs react with ischemically damaged myocytes before visible alterations are seen in hematoxilin-eosin staining. Moreover, using C5b-9 abs, it seems possible to exclude agonal/artefactual contraction bands which show a negative reaction. Immunohistochemical detection of C5b-9, using an adequate technique could increase the possibility to demonstrate early ischemic myocardial damage.

Adolescent↗
PubMed1994

Distribution and functional properties of 5-HT3 receptors in the rat hippocampal dentate gyrus: a patch-clamp study.

1. In dentate gyrus of rat hippocampal slices two distinct types of neurons, principal excitatory neurons (granule cells) and local inhibitory neurons (basket cells), could be identified under Nomarski microscopy; I investigated the actions of serotonin using the whole-cell patch-clamp technique. The identification of the neurons was later confirmed by intracellular staining with Lucifer yellow. 2. In both basket cells and granule cells, whole-cell current recordings revealed spontaneous synaptic currents ranging from < 10 pA to > 200 pA in symmetrical Cl- conditions at a holding potential of -63 mV. These currents were blocked by 10 microM bicuculline, indicating that they resulted from the spontaneous activation of GABAergic inputs (which had been morphologically described in both types of neurons). 3. By focal application of serotonin (2-50 microM) to basket cells under current clamp I evoked a train of action potentials superimposed on a baseline membrane depolarization. Under voltage-clamp conditions serotonin evoked an inward current at a holding potential of -63 mV (currents were detectable in approximately 90% of basket cells studied). The inward current was accompanied by a multitude of small inward currents of short duration (< 100 ms) that were found to be due to the stimulation by serotonin of nearby GABAergic presynaptic neurons innervating the recorded neuron. 4. In granule cells (total of 11 cells) serotonin did not produce any responses under conditions similar to those used for basket cells. The occurrence of bicuculline-sensitive spontaneous synaptic current events seemed to increase during the application of serotonin; this phenomenon reflected the excitatory action of serotonin exclusively on GABAergic interneurons. 5. The serotonin-induced inward currents in basket cells were mediated by the 5-HT3 receptor subtype because 1) they were blocked by either metoclopramide (10 microM) or [3-alpha-tropanyl]-1H-indolecarboxylic acid ester (2 nM), the latter being a specific blocker for the 5-HT3 receptor subtype, and 2) almost similar currents were induced by the application of the selective 5-HT3 receptor agonist 2-methyl 5-HT (2-50 microM) or 1-(m-chlorophenyl)-biguanide (0.1-10 microM). 6. Current-voltage (I-V) relations of serotonin-induced currents in basket cells showed that the reversal potential was close to 0 mV in external standard saline and depended on the concentrations of monovalent cations. I-V relations of serotonin-induced currents revealed inward rectification at the membrane potential range of +30 to -60 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Existence of rolipram-sensitive phosphodiesterase in rat megakaryocyte.

1. The effect of rolipram (ME3176) on ADP- and IP3-induced repetitive IK(Ca) in rat megakaryocyte was investigated by use of the nystatin perforated patch and conventional whole-cell patch-clamp techniques. 2. The ADP-induced IK(Ca) was depressed by treatment with rolipram in a concentration-dependent manner. The inhibition by rolipram disappeared after treatment with a cyclic nucleotide-dependent protein kinase inhibitor, H-8. The inhibition of IK(Ca) was also observed in the presence of cyclic AMP accumulating agents such as forskolin and isobutylmethylxanthine (IBMX). 3. Rolipram enhanced the inhibitory action of forskolin, suggesting that rolipram facilitates the accumulation of cyclic AMP by blocking its breakdown. Similar results was obtained with adenosine, an endogenous adenylate cyclase activator. 4. Intracellular application of inositol trisphosphate (IP3) induced repetitive IK(Ca) in megakaryocytes. The induced IK(Ca) was also inhibited by rolipram and by other cyclic AMP accumulating agents. 5. It was concluded that megakaryocytes possess rolipram-sensitive phosphodiesterase (PDE), which was not detected in platelets, but plays a distinct modulatory role in megakaryocytes for generating ADP-induced IK(Ca).

1-Methyl-3-isobutylxanthine↗
PubMed1993

Aggressive granular lymphocyte leukemia of natural killer cell type in an elderly patient.

A 75-year-old man was admitted to our hospital because of intermittent fever. His peripheral blood picture showed granular lymphocyte (GL) proliferation. The GLs were immunologically and functionally phenotyped as natural killer cells. Chromosomal analysis of peripheral lymphocytes with interleukin-2 stimulation revealed an inversion of chromosome 9 with an unusual breakpoint, showing abnormal monoclonal proliferation of the GLs. Progressive increase of GL count and hepatosplenomegaly necessitated the start of combined chemotherapy. His condition was complicated by icterus and renal failure, and he died finally of respiratory failure. Autopsy revealed disseminated intravascular coagulation and infiltration of GLs in the bone marrow, spleen, and liver.

Aged↗
PubMed1992

[Chronic fatigue syndrome in school children].

Chronic fatigue syndrome (CFS) is characterized by persistent or relapsing debilitating fatigue for at least 6 months without any apparent medical diagnosis that would explain the clinical presentation. Although, most of the reported patients are over age 30, CFS also affects school children. To better understand CFS, the network of the central nervous-endocrine-immune systems should be considered, and one must be careful to distinct CFS from school absenteeism and other psychosomatic disorders often seen among them.

Adolescent↗
PubMed1992

[Phenotypic and genotypic analysis of acute leukemia--current status of lineage specific classification].

More detailed identification and understanding of the heterogeneity of leukemias using a broad panel of markers seems to be essential for the successful design of more sophisticated and effective treatments. Based on the FAB system, immunological phenotypes using a panel of monoclonal antibodies, and rearrangements of immunoglobulin and T-cell receptor genes, acute leukemia can be divided into six subtypes such as B-lineage, T-lineage, AML, NK-lineage, AUL and mixed lineage leukemia. The definition of B-lineage and T-lineage cells, a new classification for mixed lineage leukemia, incidence of dual rearrangements and their clinical significance are discussed.

Acute Disease↗
PubMed1991

Effects of biological response modifiers on childhood ALL being in remission after chemotherapy.

Of 125 children with acute lymphoblastic leukemia (ALL), who had been in continuous remission for three years on chemotherapy, 108 patients received biological response modifiers (BRM) such as Bestatin, N-CWS, OK-432 and/or PSK in order to prevent relapse after treatment suspension. From 20 patients who were treated with PSK, 6 relapsed within 13 months. This relapse rate was quite similar to the rate observed with those children who were off therapy (4 relapses in 17 patients within 13 months). In contrast to these 37 patients, only 3 out of 31 patients who received Bestatin (p less than 0.05) and 8 out of 57 patients who received N-CWS or OK-432 relapsed. Based on these findings, BRMs used in the present study seems to be effective to prevent relapse of leukemia among childhood ALL who have electively stopped chemotherapy.

Antibiotics, Antineoplastic↗
PubMed1991

HTLV-I associated myelopathy (HAM) after blood transfusion in a patient with CD2+ hairy cell leukemia.

Hairy cell leukemia complicating hemolytic anemia developed in a 46-year-old woman. Morphologically and cytochemically typical hairy cells were found to express both CD20 and CD2 antigens. Expression of surface IgG of kappa-chain type and the rearrangement of Ig but not T-cell receptor beta genes confirmed a B-cell origin of the leukemia. Blood transfusion was followed by disappearance of the hemolysis and a marked improvement of the leukemia. However, the patient developed progressive spastic spinal paraplegia about seven months after transfusion and was diagnosed as having HTLV-I associated myelopathy (HAM) by the demonstration of HTLV-I antibodies in serum and cerebrospinal fluid. HTLV-I infection via the transfusion may have been involved in the hematologic improvement seen in this patient. Autopsy showed demyelination, vacuolar degeneration, gliosis, and perivascular cuffing in the white matter of spinal cord without evidence of leukemic infiltration.

Anemia, Hemolytic↗
PubMed1990

Treatment of pediatric malignant tumors with VP-16. West Japan Pediatric Oncology Group.

The West Japan Pediatric Oncology Group studied the treatment of pediatric malignant tumors with VP-16 from December 1984 to March 1988. Study subjects were divided into two groups. One group received only VP-16, while the other received VP-16 combined with other anti-tumor agents. VP-16 evaluation was possible in a total of 116 cases. The efficacy rate was calculated by considering both complete and partial remission as effective. The efficacy rate for VP-16 alone was 87.5% for primary cases of ANLL and 100% for primary cases of histiocytosis. The efficacy rates for combination therapy were as follows: 92.6% for primary cases of ANLL, 66.7% for primary cases of histiocytosis, 45.5% for relapsed cases of ANLL and 66.7% for relapsed cases of ALL. Bone marrow suppression was seen in the form of leukopenia and thrombocytopenia for 2 to 3 weeks after VP-16 administration. Alopecia, mucositis and gastrointestinal symptoms were also observed, but they presented no significant problem. From our results, we believe that chemotherapy including VP-16 is effective for remission induction therapy in primary cases of ANLL and for salvage therapy in relapsed leukemia. Additionally, VP-16 is considered to be effective for the treatment of histiocytosis.

Adolescent↗
PubMed1990

Voltage-gated calcium and potassium currents in megakaryocytes dissociated from guinea-pig bone marrow.

1. The electrophysiological properties of the cell membrane of guinea-pig megakaryocytes were studied using the whole-cell patch-clamp technique. The megakaryocytes (diameter, 17-42 microns) were dissociated mechanically from the bone marrow of adult guinea-pigs. 2. In a proportion of cells, spike-like action potentials were generated in response to depolarization when the cells were immersed in standard saline containing 10 mM-Ca2+. Under voltage clamping, a transient inward current followed by a slowly Ca2+. Under voltage clamping, a transient inward current followed by a slowly developing outward current was produced when the membrane potential was made more positive than -55 mV. 3. The inward currents were identified as Ca2(+)-carried current, since the amplitude depended distinctly on external Ca2+ concentration and since replacement of external Ca2+ with Mn2+ reversibly diminished the current. The Ca2+ channels involved are most probably of the transient type (T-type). 4. The reversal potential of the outward current changed from -87 to -46 and -7 mV when the external K+ concentration was raised from 5 to 25 and 125 mM. 5. The outward current was insensitive to chelation of internal Ca2+ but was blocked by external application of quinine, 4-aminopyridine and tetraethylammonium, and was thus very probably a membrane potential-dependent K+ current. The dependence of the current activation and inactivation on the membrane potential was consistent with that of a delayed K+ rectifier. 6. The amplitudes of the Ca2+ currents and K+ currents showed considerable intercell variation. However, the density of the Ca2+ current showed a tendency to increase with megakaryocyte size, presumably accompanying maturation. The roles of these currents in cellular function remain to be elucidated.

4-Aminopyridine↗
PubMed1990

Guinea-pig megakaryocytes can respond to external ADP by activating Ca2(+)-dependent potassium conductance.

1. The responses of megakaryocytes to adenosine diphosphate (ADP) were studied using whole-cell patch electrodes and a Ca2(+)-sensitive fluorescent dye, Fura-2. Megakaryocytes (diameter, 17-42 microns) were mechanically dissociated from the bone marrow of adult guinea-pigs and ADP (1-10 microM) was pressure-applied to megakaryocytes under recording. 2. In megakaryocytes immersed in standard saline, ADP evoked an obvious outward current at a membrane potential of -63 mV. The current was identified as a K(+)-carried current, since the reversal potential depended distinctly on the external K+ concentration, but it showed no changes after removal of external Na+. The amplitude of evoked K+ currents showed considerable intercell variation, which is presumably due to differences of current density in the membrane. 3. During application of ADP, the evoked K+ current was not sustained but slowly decayed to become negligible within 10-20 s, suggesting the appearance of desensitization. The response of the megakaryocyte to ADP recovered slowly and returned to an original level after 4-5 min of continuous washing. 4. When the intracellular free Ca2+ concentration ([Ca2+]i) was measured using the Ca2(+)-sensitive fluorescent dye, Fura-2, application of 10 microM-ADP induced an increase of [Ca2+]i by about 5-fold, which was followed by a gradual decay to the original level within 30-50 s. Roles of internal Ca2+ for activating the K+ current were confirmed by observing (1) enhancement of evoked currents by the use of internal saline containing no Ca2+ chelators and (2) generation of prolonged K+ current by application of a Ca2+ ionophore, A23187, to the megakaryocyte. 5. In a fraction of the megakaryocytes, spontaneous hyperpolarization of the resting membrane potential was observed. The hyperpolarization seemed to result from the activation of K+ channels in the membrane, which was caused by spontaneous release of Ca2+ from the internal storage site. 6. It was concluded that megakaryocytes of the guinea-pig can respond to external ADP by increasing [Ca2+]i and consequently by activating Ca2(+)-dependent K+ channels in the membrane.

Action Potentials↗
PubMed1990

[Clinical study of imipenem/cilastatin sodium in children with severe infections].

Clinical studies of imipenem/cilastatin sodium (IPM/CS) were conducted in 40 pediatric patients. 29 out of the 40 patients were treated for infections and 11 for prophylaxis. The following results were obtained. 1. The response rate in 29 patients with infections was 79.3%. Among the 29 patients, 16 patients who presented with malignant diseases showed the response rate of 68.8%. The response rate was lower in patients with severe infections than in those with mild or moderate infections, and a lower response rate was associated with severe neutropenia. However, there were no differences in the response rates between patients who had previously been treated and those who had been untreated with other antibiotics. The response rate in 6 patients from whom causative organisms were isolated was 83.3% and that in the remaining 23 patients was 78.3%. 2. The response rate in 11 patients to whom IPM/CS was administered prophylactically was 63.6%. 3. As for side effects, a rash was observed in 1 patient and hematuria in another, and the abnormal laboratory test results observed were elevations of GOT and GPT in 1 patient. However, they were not clinically significant. From the above results, it appears that IPM/CS may be used as a drug of the first choice for the treatment of patients with severe infections in which the causative organisms are unknown, and for the prophylaxis of infection in patients with neutropenia.

Bacterial Infections↗
PubMed1989

Electrophysiological properties of three types of granulocytes in circulating blood of the newt.

1. The electrophysiological properties of three subtypes of granulocytes obtained from the circulating blood of the newt, Triturus pyrrhogaster, were studied using the whole-cell variation of the patch-electrode voltage-clamp technique. 2. Neutrophils were identified by their multilobulated nucleus in the cytoplasm. Basophils and eosinophils, having characteristic granular structures in their cells, could definitely be distinguished from other leucocytes. The reliability of cellular identification using phase-contrast microscopy was confirmed by fixing and staining the granulocytes with Wright's solution. 3. In neutrophils under current-clamp conditions, a hyperpolarization-induced conductance increase was observed. With depolarization, however, no changes in regenerative potential were detected. When voltage clamped in standard saline (containing 96 mM-NaCl), hyperpolarizing voltage pulses to a potential more negative than -90 mV evoked slowly decaying inward currents. 4. The hyperpolarization-evoked membrane currents in neutrophils were identified as anomalous rectifying K+ currents, since (1) externally applied Cs+ (0.1 or 1 mM) or Ba2+ (1 mM) produced suppressive effects on the currents, (2) replacement of external Na+ with choline ions eliminated the decay of macroscopically observed currents, and (3) both the amplitude and kinetic properties of the currents were strongly dependent on membrane potential as well as on external K+ concentration; the activation of the conductance depended on the electrochemical force for K+ rather than on membrane potential alone. The magnitude of steady-state conductance was roughly proportional to the square root of the external K+ concentration. 5. In basophils and eosinophils, no major time- or voltage-dependent increase in conductance was detected at voltages between +20 and -130 mV. However, under current-clamp conditions, spontaneous fluctuation of zero-current potentials was clearly apparent, presumably due to the activities of some ion channels generating a small amount of current flux through the membranes of these cells. 6. It was concluded that the three subtypes of granulocytes in the newt differ considerably not only in appearance and structure but also in the electrical properties of their membranes. The anomalous rectifying K+ channels in neutrophils may serve to determine the resting potential of the cell at K+ equilibrium potential. The closure of the channels at depolarization might facilitate the maintenance of depolarization triggered by stimuli accompanying current influx.

Action Potentials↗