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Biomedical subjects

K Kawa

Publications and source records attributed to K Kawa.

At least 91 records · Page 5Linked to original sources
PubMed1989

[Aggressive natural killer cell leukemia/lymphoma--possible existence of a new clinical entity originating from the third lineage of lymphoid cells].

The morphologic, immunologic, genotypic, and functional properties of peripheral blood and bone marrow cells or cultured cells from two patients with a clinically aggressive non T, non B natural killer cell lymphoma/leukemia (ANKL/L) were described. The leukemic cells possessed medium to large granules in the cytoplasm, antigens against CD 38, CD 2, OKIal, and NKH-1 (N 901) monoclonal antibodies on their cell-surface, and also showed a high natural killer (NK) activity. In addition, these ANKL/L belonged to neither T-nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta and T gamma receptor, and immunoglobulin. After we compared and investigated them with 9 cases of ANKL/L reported in other institutions, concerning immunophenotype, genotype and function, we reached the conclusion that the existence of ANKL/L originating from the third lineage in lymphoid cells is an obvious fact, suggesting this new clinical entity. It is important that all patients who have this type of a clinical disorder be diagnosed that there is no effective form of therapy at present.

Adult↗
PubMed1989

[Hairy cell leukemia of European-American type with dual T and B-cell phenotype].

A 46-year-old woman was admitted because of palpitation and conjunctival jaundice. Physical examination revealed hepatosplenomegaly and purpura without lymphadenopathy. Blood count showed 4.7 g/dl hemoglobin with increased reticulocytosis. The platelet count was 1.5 X 10(4)/microliters and the leukocyte count was 6,000/microliters with 17% abnormal mononuclear cells (hairy cells). Hairy cells had nuclei of frequently folded shape and abundant cytoplasma with irregular edges on blood films. The hair-like cytoplasmic projections of the cells were clearly seen under the phase-contrast microscopy. Hairy cells were strongly positive for tartrate resistant acid phosphatase. Bone marrow aspiration was unsuccessful. The biopsy specimens showed small patchy and scattering infiltrations by hairy cells. Surface marker studies of hairy cells revealed that they were strongly positive for SmIg (IgG kappa). They also reacted with alpha B 1, alpha Tac, alpha Leu-M 5 monoclonal antibodies and a rabbit anti-hairy cell serum (alpha HC-M). 53% of hairy cells were shown to react with alpha B 1 and alpha OKT 11 simultaneously by double labelling. The southern blot analysis of peripheral blood mononuclear cells showed IgH chain genes rearrangement and germ line patterns of T-cell receptor genes. Hemolysis was promptly disappeared after blood transfusion. Moreover, the red blood cells, platelets and leukocytes have spontaneously returned to normal levels with disappearance of circulating hairy cells and palpable spleen one year after admission.

B-Lymphocytes↗
PubMed1988

Voltage-gated sodium and potassium currents and their variation in calcitonin-secreting cells of the chick.

1. The electrical properties of dissociated ultimobranchial cells from chick embryos (18-20 days after fertilization) were studied using whole-cell patch electrodes. Antibodies for immunohistological identification of calcitonin-secreting cells in the preparation were obtained by immunizing rabbits with a conjugated analogue of eel calcitonin. 2. In a proportion of cells, spike-like action potentials were generated in response to depolarization when cells were immersed in standard saline containing 140 mM-Na+ but no Ca2+. When the membrane potential was shifted from a holding potential (-83 - -103 mV) to a test depolarization (-50 mV or more positive) under voltage-clamp conditions, a transient inward current was produced which was followed by a slowly developing outward current. 3. The inward current was identified as a Na+-carried current, since (1) the kinetics of the current seemed fast and the amplitude consistently depended on the holding potential, (2) replacement of external Na+ with choline ions reversibly abolished the current, and (3) external application of tetrodotoxin (1 microM) abolished the current completely. The cells in which inward currents were detected showed intense to intermediate degrees of staining with anti-calcitonin antibodies. 4. In some other cells, no regenerative potentials were evoked even with intense depolarization, but a delayed decrease in membrane depolarization during the current pulse was observed. Voltage-clamp experiments in these cells revealed the existence of slowly developing outward currents, and the cells showed an intermediate degree of antibody staining. 5. The outward currents in both types of cells were selectively diminished in the presence of K+ channel blockers such as tetraethylammonium (1-10 mM) or 4-aminopyridine (1 mM). When the pipette contained 120 mM-CsCl, none of the dissociated cells exhibited any appreciable outward currents. Thus, the outward currents were most likely to be membrane potential-dependent K+ currents. The potential dependency of activation and inactivation of the currents were consistent with those of delayed K+ rectifier. 6. In the remaining cells, only passive responses of membrane potentials were observed with current injection. No discernible voltage-dependent inward or outward currents were detected under voltage-clamp conditions. Although these cells had a similar appearance to the two types of cells previously mentioned under phase-contrast microscopy, none of them showed significant antibody staining. These cells were presumed to represent non-secretory or supporting cells within the gland.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Transient outward currents and changes of their gating properties after cell activation in thrombocytes of the newt.

1. The electrical properties of the cell membrane of thrombocytes in the newt, Triturus pyrrhogaster, were studied using the whole-cell variation of the patch-electrode voltage-clamp technique. 2. In medium containing Ca2+ (1.8 mM), activated thrombocytes became round and then spread on the glass. Activation of thrombocytes was inhibited by the removal of external Ca2+ and addition of 1 w/v% albumin to the external media. 3. For thrombocytes kept in the resting state, depolarizations more positive than -30 mV evoked transient outward currents which decayed completely during the duration of the depolarization (150 ms). The half-decay time of the currents became smaller as the depolarizing pulse strengthened, reaching about 20 ms at +30 mV (20 degrees C). 4. The outward currents are identified as K+ currents, since (1) their reversal potential depended on extracellular K+ concentration and (2) the outward currents were suppressed either by external application of 4-aminopyridine (1 mM) or by internal application of Cs+ (120 mM). The monovalent cation selectivities of the K+ channels were evaluated from the reversal potential as Tl (1.68) greater than K(1.0) greater than Rb (0.89) greater than NH4 (0.13) greater than Na(less than 0.03). 5. When the thrombocytes had been activated, depolarization again evoked K+ currents. The currents, however, showed negligible or small decay during the duration of the depolarization (150 ms). The rate of recovery from preceding depolarization was also reduced to about one-sixth. 6. The sensitivity to 4-aminopyridine and the selectivity of the K+ channels were not changed by cell activation. 7. We conclude that during activation of thrombocytes the inactivation of the K+ channels is almost eliminated. Removal of inactivation of the K+ channels was also induced in resting thrombocytes by intracellular application of 4-bromoacetamide (50 microM).

4-Aminopyridine↗
PubMed1987

Existence of calcium channels and intercellular couplings in the testosterone-secreting cells of the mouse.

1. The electrophysiological properties of testosterone-secreting cells (i.e. Leydig cells) in the mouse were studied using patch electrodes. The cells appeared solitarily or in clusters after mechanical dissociation from testes. They were confirmed to be Leydig cells on the basis of 3 beta-hydroxysteroid dehydrogenase staining. 2. Under current-clamp conditions in the whole-cell configuration, Leydig cells immersed in standard saline were able to generate action potential-like responses. The active responses occurred after cessation of membrane hyperpolarization or when cells were held in a hyperpolarized condition and stimulated with depolarizing current pulses. 3. In Leydig cells under voltage clamp, depolarizations more positive than -50 mV evoked transient inward currents which decayed completely during the duration of depolarization (130 ms). No obvious outward currents were evoked by pulses less positive than 30 mV. 4. The inward currents were identified as Ca2+ current, since replacement of external Ca2+ with Mn2+ reversibly diminished the current whereas Ba2+ or Sr2+ substituted for Ca2+. 5. With voltage pulses more positive than 40 mV, outward currents were evoked. The currents were dependent on K+ concentration and were blocked by quinine or tetraethylammonium. The amplitudes of outward currents were increased with raised internal Ca2+ concentration. 6. Single-channel recordings of the outward currents revealed that the unitary conductance was 130 pS when internal K+ was 131-143 mM and external K+ was 5 mM. The open probability of the channel showed marked dependence on the membrane potential and the internal Ca2+ concentration. Thus, the current was identified as being Ca2+- and membrane potential-dependent K+ current. 7. Leydig cells within a cluster possessed distinct intercellular couplings. The mean coupling ratio obtained by applying two patch electrodes to a pair of cells was 0.84. Transfer of injected dye (Lucifer Yellow) to adjacent cells was also confirmed. 8. It was concluded that Leydig cells have at least two kinds of voltage-dependent channels in the membrane. The Ca2+ channel may be activated by physiological changes in membrane potential, leading to an influx of Ca2+. The Ca2+-dependent K+ channel hardly seems to be activated unless the internal Ca2+ concentration increases remarkably. It is presumed that intercellular coupling may play a role in synchronizing or intensifying the endocrine activities of Leydig cells located within a cluster.

Action Potentials↗
PubMed1984

On the two subdivisions and intrinsic synaptic connexions in the submandibular ganglion of the rat.

Parasympathetic neurones in the submandibular ganglion of the rat innervate the submandibular and sublingual salivary glands. Neurones which innervate the submandibular gland (s.m. neurones) are usually located along the salivary ducts which drain both glands. Neurones which innervate the sublingual gland (s.l. neurones) are located in the thin sheet of tissue which lies between the salivary ducts and the lingual nerve. The existence and characteristics of intrinsic synaptic connexions were studied electrophysiologically in these two divisions of the submandibular ganglion. Three days or more after denervating the ganglion two types of excitatory intrinsic synaptic potentials--chemical and electrical--were recorded in ganglion cells. Chemical synaptic responses were reversibly blocked by nicotinic antagonists such as hexamethonium (10 microM) and D-tubocurarine (100 microM). Intrinsic chemical synapses were common among s.m. neurones (present in 72% of neurones) but only 12% of s.l. neurones were coupled with chemical synapses. Electrical coupling was found among 31% of s.m. neurones but was not observed between s.l. neurones. Electrotonic coupling in s.m. neurones in denervated and intact ganglia was directly demonstrated by impaling adjacent neurones with separate micro-electrodes. The average coupling ratio for current pulses injected into one cell and recorded in the adjacent cell was 0.06. During the first 30 days after birth, the number of synaptic inputs from preganglionic (chorda tympani) axons was markedly reduced in both s.m. and s.l. neurones, whereas the incidence of electrical synaptic connexions remained unchanged. The effect of long-term denervation (up to 4 months) on intrinsic synapses was examined. The membrane properties of the parasympathetic neurones and the intrinsic synaptic connexions were maintained without marked changes. It is concluded that the submandibular ganglion in the rat consists of two distinct populations of parasympathetic neurones. The two classes of neurones differ in (1) their location within the ganglion, (2) their target organs and (3) the incidence of intrinsic synapses. Possible mechanisms for the development, maintenance and function of these intrinsic synapses are discussed.

Action Potentials↗
PubMed1984

Calcium and potassium currents in spermatogenic cells dissociated from rat seminiferous tubules.

The electrophysiological properties of the cell membrane of rat spermatogenic cells were studied using the whole-cell variation of the patch-electrode voltage-clamp technique. In late primary spermatocytes and early spermatids isolated from adult testis, a transient inward current followed by a slowly developing outward current was produced when the membrane potential was made more positive than -60 mV. Early spermatogenic cells which consist of spermatogonia and early spermatocytes were isolated either from new-born rats (12-14 days old) of from adult cryptorchid rats 15-21 days after the operation. In early spermatogenic cells, some showed a slowly developing outward current with negligible initial inward current, while others showed a recognizable inward current followed by the slowly developing outward current. The inward currents are identified as Ca2+-carried current, since replacement of external Ca2+ with Mn2+ reversibly diminished the current whereas Ba2+ or Sr2+ substituted for Ca2+. The reversal potential of the outward current changed from -65 to -12 mV when [K+]o was raised from 5 to 100 mM. The outward current was independent of [Ca2+]o and was blocked by tetraethylammonium chloride. Thus the current was identified as membrane-potential-dependent K+ current. During spermatogenesis from spermatogonia to early spermatids, the density of Ca2+ current increased while the K+ current density decreased significantly.

Animals↗
PubMed1982

Altered developmental changes of neuromuscular junction in hypo- and hyperthyroid rats.

1. Effects of thyroid hormone on the development of neuromuscular junctions (n.m.j.s.) were investigated electrophysiologically in the diaphragms (sternal region) of normal, hypo- and hyperthyroid rats from the age of birth (day 0) to day 35.2. Hypothyroidism in new-born rats was induced either by daily administration of propylthiouracil to mothers or by subcutaneous injection of 150 muCi (131)I on day 1. Hyperthyroidism was induced by daily injection of thyroxine.3. In normal rats up to day 10, muscle fibres were innervated polyneuronally. By day 20, multiple innervation was eliminated and muscle fibres received only a single input. In hypothyroid rats elimination of polyneuronal innervation was retarded by 5-8 days, while in hyperthyroid rats the elimination was accelerated by 2-3 days.4. The frequency of miniature end-plate potentials (m.e.p.p.s) in normal rats increased from one per 40 sec on days 0-5 to 1/sec on days 25-35. The m.e.p.p. frequency in hypothyroid rats was 25-65% of that in normal rats of the same age. In hyperthyroid rats the m.e.p.p. frequency was normal up to day 18 but subnormal afterwards. The duration of m.e.p.p. measured on day 22-23 was slower in hypothyroid rats and faster in hyperthyroid rats, relative to m.e.p.ps in normal rats.5. The sensitivity to acetylcholine (ACh) at extrajunctional regions in normal rats was about 100 mV/nC at birth and declined to 1 mV/nC by day 26. In hypothyroid rats, the ACh sensitivity was as high as 30 mV/nC on day 26; in hyperthyroid rats, ACh sensitivity on day 26 was undetectable.6. With pairs of nerve stimuli (applied at a 50 msec interval), the second end-plate potential was facilitated until day 10 and depressed after day 16 in normal rats. This shift from facilitation to depression during development was not altered in either hypo-or hyperthyroid rats.7. It is concluded that the lack and excess of thyroid hormone retards and facilitates the development of n.m.j.s. respectively. Possible mechanisms for this altered development are discussed.

Acetylcholine↗
PubMed1982

[Maturation therapy for advanced neuroblastoma-therapeutic effects and problems].

Seven children with advanced neuroblastoma were treated with maturation therapy. This therapy consisted of 12 hours drip infusion of papaverine (40-45 mg/kg/day) for 2 days with or without high dose cyclophosphamide (2,000-3,600 mg/m2). During maturation therapy all patients received intravenous hyperalimentation. One patient who had received papaverine alone did not respond to the therapy. Among 6 patients treated with papaverine and high dose cyclophosphamide, 3 responded to the therapy, 2 did not and one died soon after the therapy. However, similar responses were obtained in 2 of 3 responders with high dose cyclophosphamide alone. After all, papaverine infusion was evaluated to be effective only in one patient. The clinically severe complications of papaverine infusion were somnolence in all patients and extrapyramidal symptoms in 6 patients. Because of these extremely high toxicity rates with little evidence of therapeutic effect, selection for this therapy should be carefully done and the treatment plan should be reconsidered.

Adrenal Gland Neoplasms↗
PubMed1979

Zinc-dependent action potentials in giant neurons of the snail, Euhadra quaestia.

In giant neurons of subesophageal ganglion of the Japanese land snail, Euhadra quaestia Deshayes, permeation of Zn ions through Ca channels were investigated with a conventional current clamp method. All-or-none action potentials of long duration (90 to 120 sec) were evoked in 24 mM Zn containing salines. The overshoots were about +10 mV and the maximum rate of rises (MRRs) was about 2.9 V/sec. The amplitudes and the MRRs of the action potentials depended on external Zn ion concentrations. The action potentials were suppressed by specific Ca-channel inhibitors such as Co2+, La3+ and Verapamil, but they were resistant to Na-channel inhibitor, tetrodotoxin, even at 30 microM. It is concluded that these action potentials are generated by Zn ions permeating Ca channels in snail neuronal membrane. On the basis of Hagiwara and Takahashi's (S. Hagiwara & K. Takahashi, 1967, J. Gen. Physiol. 50:583) model of Ca channels, it is inferred that Zn ions are 5 to 10 times stronger in affinity to Ca channels than Ca ions, but 10 to 20 times less permeable.

Action Potentials↗
PubMed1977

Permeation of manganese, cadmium, zinc, and beryllium through calcium channels of an insect muscle membrane.

Larval muscle fibers of a beetle, Xylotrupes dichotomus, produce calcium spikes that are maintained when the fibers are bathed in saline solutions containing manganese, cadmium, zinc, or beryllium instead of calcium. This indicates that these cations permeate the calcium channels of the muscle fiber. By contrast, cobalt, nickel, and magnesium are nonpermeating and behave as competitive inhibitors of the permeation of the other divalent cations. Some of the permeating cations suppress delayed rectification.

Action Potentials↗