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Biomedical subjects

T Kanno

Publications and source records attributed to T Kanno.

At least 325 records · Page 18Linked to original sources

Enhancement of cell killing and increase in cytosolic calcium concentration by combined treatments with hyperthermia and TMB-8 in mouse mammary carcinoma FM3A cells.

Mouse mammary carcinoma FM3A cells were exposed 42 degrees C or 44 degrees C hyperthermia for 60 min in a culture medium with or without 8-(N,N-diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) at a concentration of 100 microM. Cell survival, cytosolic calcium ion concentration, [Ca2+]C, and influx of 45Ca2+ were investigated to examine the cardinal role of intracellular Ca2+ in hyperthermic cell killing. The [Ca2+]C in a single cell was measured by a digital image analyzing technique using Fura-2. TMB-8 enhanced cell killing, increase in [Ca2+]C, and influx of 45Ca2+ induced by both hyperthermic treatments. In contrast, TMB-8 abolished the increase in [Ca2+]C induced by hyperthermia at 42 degrees C and 44 degrees C in the absence of extracellular Ca2+. These results suggest that TMB-8, an agent usually called an inhibitor of intracellular calcium mobilization at 37 degrees C or lower, enhances Ca2+ entry from the extracellular space at 42 degrees C or 44 degrees C and, in turn, promotes cell killing under hyperthermic conditions.

Animals↗

H1- and H2-receptor influences of histamine and ammonia on rapidly adapting pulmonary stretch receptor activities.

Studies were designed to establish the difference of the excitatory mechanisms between histamine and ammonia on rapidly adapting pulmonary stretch receptors (RARs). We therefore examined the responses of RARs to histamine administered as an aerosol and ammonia inhaled as a vapor before and after aerosol administration of mequitazine or cimetidine in spontaneously breathing rabbits. The excitatory responses of RARs to aerosols of histamine at different concentrations were completely blocked by administration of aerosol mequitazine but potentiated by aerosol cimetidine. However, the increases of RAR activity produced by inhalation of ammonia vapor at different concentrations were not significantly affected by aerosol administration of either a H1-receptor blocker or a H2-receptor antagonist. These results suggest that the stimulation of RARs by aerosol histamine occurs as a result of the interaction between H1 (excitatory)- and H2 (inhibitory)-receptor effects, whereas these two receptor effects do not contribute to the ammonia-induced RAR stimulation.

Administration, Inhalation↗

Effects of atropine on the responses of rapidly adapting pulmonary stretch receptors and dynamic lung compliance to sodium cyanide-induced hyperpnea.

The responses of tracheal pressure (PT) and heart rate (HR) to electrical stimulation of the peripheral cut-ends of the vagus nerves (10-15 V, 10 Hz, 1 ms) to activate both myelinated and non-myelinated fibers were examined before and after administration of atropine (1 mg/kg) in artificially ventilated, bilaterally vagotomized rabbits. Vagal stimulation caused an increase in PT and a decrease in HR. The PT response to vagal stimulation was completely blocked by atropine which significantly reduced the bradycardia evoked by the stimulation. In other series of experiments, we also examined the responses of rapidly adapting pulmonary stretch receptors (RARs) and dynamic lung compliance (Cdyn) to intravenous injections of sodium cyanide (NaCN, 20 and 30 micrograms/kg) before and after administration of atropine (1 mg/kg) in spontaneously breathing rabbits with vagal efferent activities. Administration of NaCN led to an increase in RAR activity associated with a decrease in Cdyn, and these two effects became more prominent by increasing the dose of NaCN. Atropine treatment did not significantly alter the responses of RARs and Cdyn to the injections of NaCN with different doses. These results suggest that the changes of RAR activity and Cdyn produced by hyperpnea due to NaCN administration are not influenced by the vagally mediated bronchoconstriction.

Animals↗

Safety of ablation of the sigmoid and transverse sinuses: an experimental study.

If the sigmoid and transverse sinuses could be divided safely, surgeons could broaden their access during skull base surgery without retracting the brain extensively. We undertook this study in monkeys to assess the risk of sacrificing these sinuses. We learned that when bilateral transverse sinuses were occluded, the sinus pressure measured in the superior sagittal sinus increased significantly as blood was purged from sinus venules. Unilateral sacrifice of sigmoid and transverse sinuses, however, did not change proximal sinus pressure in any ipsilateral or contralateral sinus. Furthermore, no change in regional cerebral blood flow or motor evoked potentials was seen in the parietal lobe nor did auditory brainstem response change significantly with sinus ablation. We conclude that, unilaterally, sigmoid and transverse sinuses may be ablated safely because collateral circulation via the vein of Labbé, superior petrosal sinus, petrosal vein, and backflow from the transverse sinus to the contralateral sinus may be established.

Journal Article↗

Localization of Ca(2+)-calmodulin to the kinetochore of C6 glioma cells: an investigation of the anti-tumour effects of calmodulin antagonists in the treatment of brain tumours.

As part of our research on the anti-tumour effects of calmodulin antagonists, we examined the localization of Ca(2+)-calmodulin in mitotic C6 glioma cells. Monoclonal anticalmodulin antibodies which require Ca2+ for binding and CREST serum which recognizes kinetochores were used to stain ultrathin frozen sections. By indirect immunofluorescence and immunoelectron microscopy of colcemid-treated cells, Ca(2+)-calmodulin was present in the kinetochore region of the cell. By double label indirect immunofluorescence using anticalmodulin antibodies and CREST serum to stain untreated cells, calmodulin was found to colocalize with kinetochores. On the basis of these results, we hypothesize that Ca(2+)-calmodulin in the kinetochore depolymerizes the microtubules which are transported by dynein in the kinetochore during metaphase oscillating and anaphase poleward chromosomal movements. This hypothesis, which is currently under further investigation, may help explain a mechanism for the antitumour effects of calmodulin antagonists in the treatment of brain tumours.

Animals↗

Dual effects of chlorobutanol on secretory response and intracellular Ca2+ dynamics in isolated pancreatic acini of the rat.

1. The effects of chlorobutanol, a widely used drug preservative, on exocrine response and intracellular Ca2+ dynamics were examined in isolated pancreatic acini of the rat. 2. Chlorobutanol (1 mg ml-1) markedly inhibited the secretory response to cholecystokinin octapeptide (CCK-8), carbamylcholine chloride (carbachol), or sodium fluoride, a direct G-protein activator. However, chlorobutanol itself induced a maximal release of amylase when the dose was increased to 4 mg ml-1. 3. An oscillatory fluctuation of cytoplasmic Ca2+ concentration, [Ca2+]c, induced by 5 pM CCK-8 or 0.3 microM carbachol was totally abolished in the presence of 1 mg ml-1 chlorobutanol. 4. A biphasic change in [Ca2+]c induced by 100 pM CCK-8, a rapid rise followed by a gradual decay, was transformed to an oscillatory fluctuation by the preservative. 5. Chlorobutanol inhibited 13 pM [125I]-CCK-8 or 0.5 nM [3H]-methylscopolamine chloride binding to the acinar cells in a dose-dependent manner. 6. These results indicate that chlorobutanol produces discernible pharmacological effects on the secretory response in rat pancreatic acinar cells through changes in the Ca2+ dynamics. Possible sites of action could be at a binding process of secretagogues to their receptors, at an activation process of a G-protein located in the plasma membrane, or at the processes following G-protein activation. However, the possibility that the preservative may distort the Ca(2+)-transport function of the plasma membrane or the membrane of intracellular organella, especially Ca(2+)-sequestering pools, cannot be excluded.

Amylases↗

Competitive inhibition by procaine of carbachol-induced stimulus-secretion coupling in rat pancreatic acini.

1. Procaine (0.03-10 mM) inhibited carbachol (CCh)-induced amylase release from rat isolated pancreatic acini in a competitive manner. Kinetic analysis of the relation between CCh concentrations and the amount of amylase released in the presence of various procaine concentrations indicated that procaine caused competitive inhibition with the affinity constant (pA2) value of 5.00 +/- 0.08. 2. Receptor binding assay confirmed that procaine (0.01-10 mM) competitively inhibited [N-methyl-3H]-scopolamine chloride ([3H]-NMS) binding to its receptor with binding affinity (pKi) of 4.63 +/- 0.10. 3. Procaine transformed CCh-evoked [Ca2+]i dynamics: the initial rise in [Ca2+]i followed by a gradual decay during continuous stimulation with 3 microM CCh was transformed by 0.3 mM procaine to the oscillatory [Ca2+]i dynamics, which resembled the response to 0.3 microM CCh in the absence of procaine. The initial phase of [Ca2+]i oscillation corresponded to the initial phase of CCh-induced amylase release in isolated perfused acini. 4. Procaine (0.3-3 mM) did not inhibit the secretory response to cholecystokinin octapeptide (CCK-8) in isolated incubated acini. A higher concentration of procaine (10 mM) caused weak but significant inhibition of the response to only limited concentrations of CCK-8, 30 and 100 pM. Procaine lower than 10 mM was ineffective on [125I]-BH-CCK-8 binding, although procaine (10 mM) caused weak but significant inhibition of the binding.

Amylases↗

Role of 830 nm low reactive level laser on the growth of an implanted glioma in mice.

The effect of low reactive level laser therapy (LLLT:830 nm, 60 mW, continuous wave) was studied using the model of a glioma implanted in mice. Two different models were used. In the first model, therapies were applied post the first day of glioma implantation; in the second model, post the fourteenth day of glioma implantation. Using the first model, therapies were designed as follows. 1) control group (no therapy), 2) direct LLLT (15 seconds twice per day; on the skin covering the implanted glioma), 3) indirect LLLT (15 seconds twice per day; on abdominal skin area rather than the site of the implanted glioma), 4) indirect LLLT (30 seconds twice per day), 5) anti-cancer drug (ACNU) group, 6) mouse beta-interferon (Mu-beta-IFN) group, 7) direct LLLT plus Mu-beta-IFN group, 8) ACNU plus Mu-beta-IFN group, 9) indirect LLLT (15 seconds twice per day) plus ACNU plus Mu-beta-IFN group. Using the second model, therapies were designed as follows. 1) control group (no therapy), 2) indirect LLLT (15 seconds twice per day), 3) indirect LLLT (15 seconds twice per day) plus Mu-beta-IFN group, 4) Mu-beta-IFN plus ACNU group. Our results indicated that, applied on the first day after glioma implantation, both direct and indirect LLLT were effective in inhibiting the tumor growth. In addition, it appeared that the effect of LLLT might be dose-dependent. Finally, the group of direct LLLT plus Mu-beta-IFN was most effective in limiting the tumor growth and the incidence of growth as compared with the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinical assessment of serum intestine type alkaline phosphatase using Japan Society of Clinical Chemistry (JSCC) recommended method--assessment of JSCC recommended method followed by indoxylphosphate staining].

We assessed a clinical usefulness of JSCC (Japan Society of Clinical Chemistry) recommended method for the measurement of serum alkaline phosphatase. The recommended method is completely correlated both in the liver-bone and intestine isoenzymes with Kind-King method recommended by the expert panel of liver function tests in Japanese Society of Gastroenterology. On the other hand, mixed tests of liver-bone and intestine isoenzyme completely show the full recovery at any combinations of both enzymes using indoxylphosphate isoenzyme staining method. These results indicated that the quantitative analysis of blood alkaline phosphatase is possible employing the combination of JSCC recommended and indoxylphosphate staining methods. Employing these combinations, we could effectively assess the pathophysiological significance of intestine alkaline phosphatase appeared in liver cirrhosis and portal hypertension.

Alkaline Phosphatase↗

Phenotypic alteration of glioma cells during culture.

Tissue specimens and culture cells from three human gliomas (two astrocytomas and one glioblastoma) were immunohistochemically investigated, using GFAP, S-100P, vimentin, FN and TNF antibodies. Primary culture consisted of two cell types, flat cells and fibrous cells. Phenotypic alternation was observed during successive subculture. Differences between fibrous cells in astrocytoma and those in glioblastoma were remarkable, while flat cells in astrocytoma and glioblastoma examined in this study, were similar.

Adult↗

Anaplastic astrocytoma in the cerebellopontine angle.

In this paper we present a case of glioma which was located in the cerebellopontine angle. The patient, a 3-year-old male, experienced difficulty with gait for one month before admission. He was admitted to Toyota Memorial Hospital on February 2, 1991, suffering from severe headache and vomiting. Neurological examination upon admission revealed horizontal nystagmus and ataxia. MRI revealed a mass in the cerebellopontine angle. Craniotomy was performed on February 4, 1991, and a tumor was revealed in the cerebellopontine angle. The tumor was clearly demarcated and encapsulated; the cerebellum and brainstem were compressed without damage. Most of the tumor was removed. A histopathological summary of the tumor follows. The tumor appeared as exophytic lesions on the pons, extending into the cerebellopontine angle. Tumor cells contained small round nuclei and acidophilic cytoplasm. The oncocyte, which was growing endomorphically, revealed a short-cell projection, suggesting a tendency to penetrate blood vessels. Intercellular microcystic degeneration was observed clearly, with some parts of the oncocyte forming a myxoid matrix. Immunohistochemically, most of the tumor cells reacted positively to Vimentin, but negatively to S-100 protein and GFAP. Given the pathological information, the tumor was interpreted as anaplastic astrocytoma. Postoperative radiation therapy was performed, but the patient died four months later because the tumor had spread to the brainstem. In this paper we discuss the differential diagnosis of the cerebellopontine angle tumor and the appearance of anaplastic astrocytoma as exophytic lesions on the pons and the spread of the tumor into the cerebellopontine angle.

Brain Neoplasms↗

New approaches in the treatment of hypertensive intracerebral hemorrhage.

A comparison of the long-term outcome after surgical and nonsurgical treatment of hypertensive putaminal hemorrhage was performed in Japan over the last 15 years to determine the appropriate role of surgery. The overall results show a poor response to surgical treatment, but neurosurgeons also know that hematoma evacuation may bring about a dramatic result in some cases. In addition, experimental studies have shown that hematoma evacuation improves neuronal function at the penumbra. The discrepancy between the results of this study and the neurosurgeon's clinical impression is probably a reflection of the following. In the past, the decision to operate was determined mainly by the location of the hemorrhage as determined by computed tomography and/or magnetic resonance imaging. However, this method of deciding surgical indications is probably not correct. We are trying to change the method of determining the surgical indications from morphological to physiological criteria as follows: All patients are initially treated with hyperbaric oxygen, and those who show improvement of their symptoms are clearly indicated for surgery. If the somatosensory evoked potential or auditory brain stem response shows an improvement after administration of mannitol or glycerol, this is also an indication that surgery should be performed.

Animals↗

Mastoparan evokes exocytosis without Ca2+ movement in adrenal chromaffin cells.

The secretagogue action of mastoparan, a tetradecapeptide from wasp venom, was studied in adrenal chromaffin cells. Pulsatile stimulation with mastoparan evoked a sharp transient release of CA in a dose-dependent manner, as measured by real-time monitoring system. The secretagogue action of mastoparan in these cells was apparently independent of extracellular Ca2+, and may not require the intracellular mobilization of Ca2+ since BAPTA failed to block its secretagogue action. Video-imaging data also suggested that mastoparan evokes CA release without an increase in the intracellular Ca2+. In addition, visualization of exocytotic events with video-enhanced light microscopy demonstrated that CA release evoked by mastoparan at relatively low concentration was indeed mediated by exocytotic process, not by cell lysis.

Animals↗

[Evaluation of serum enzyme levels considering biological half lives of enzymes--alteration of lactate dehydrogenase isoenzyme pattern due to computer simulation].

The rapid clearance of certain releasing enzymes from blood stream may modify their usefulness as markers of disease. Serum LD isoenzyme patterns are often quite different from those in the affected tissues. Such differences result from differences in the biological half lives of the individual isoenzyme. In order to reveal such phenomena, we applied the one-compartment model to simulate the time dependent changes in the serum LD isoenzyme patterns as a most simple model. When we simulated leukemic cells as an affected origin, LD isoenzyme patterns obtained at a stage of clinical deterioration or active stage, were characterized by a high proportion of LD-2, LD-3 and LD-4, and resembled those of the original leukemic cells. In general, strong similarities in alterations of LD isoenzyme patterns were obtained between the clinical observed time course and simulated time course. These changes in LD isoenzyme patterns are practically observed in the cases of leukemia, lymphoma, and so on. If the original organs are identical, then it is change of disease stage that is responsible for modification of variable LD isoenzyme patterns. Such phenomena must therefore be noted--in doing so, we shall be able to estimate the origin of enzyme release, disease stage, and prognosis.

Computer Simulation↗