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Biomedical subjects

K Iwatsuki

Publications and source records attributed to K Iwatsuki.

At least 145 records · Page 8Linked to original sources
PubMed1990

Effects of N-(2-hydroxyethyl)nicotinamide nitrate (nicorandil; SG-75) and its derivatives on pancreatic exocrine secretion in the dog.

Nicorandil, a compound containing a nitrate moiety, can act as a K+ channel opener. Previously we reported stimulatory effects of an intraarterial injection of nicorandil on pancreatic exocrine secretion in the isolated, blood-perfused pancreas under a constant perfusion pressure. To clarify this mechanism in relation to the chemical structure we studied the effects of nicorandil and its derivatives [nitrate containing structure, N-(3-hydroxy-propyl)nicotinamide nitrate (SG-89); nitrate lacking structure, N-(2-acetoxyethyl)nicotinamide (SG-209)], in addition to nitroglycerin (TNG) and pinacidil (a potent K+ channel opener) under a constant perfusion flow rate to the pancreas. Nicorandil, SG-89, and TNG elicited a dose-dependent increase in pancreatic fluid secretion, showing increases in bicarbonate and amylase concentrations. In contrast, SG-209 and pinacidil did not stimulate pancreatic secretion. Furthermore, stimulatory action of nicorandil was not inhibited by treatment with an intraarterial infusion of tetraethylammonium (TEA). These results suggest that nicorandil has direct secretory properties on pancreatic exocrine glands and its nitrate moiety has an important role in the stimulation of pancreatic exocrine secretion, but increasing flow rate and K+ channel opening action do not participate in the secretion.

Amylases↗
PubMed1990

Production of antikeratin autoantibodies by hybrid spleen cells of naive mice.

The mechanism of the occurrence of natural antikeratin antibodies in human sera was studied using hybrid spleen cells obtained from experimentally naive or from immunized mice. Antikeratin antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 5.9-9.5% of the culture supernatants of fused spleen cells taken from naive mice. When mice were immunized with keratins, the number of supernatants containing antikeratin antibodies was increased to eight out of 51 (15.7%). When immunized with non-keratin materials such as activated human T cells, adult T-cell leukaemia cell lysates, and human T-cell lymphotropic virus type-I (HTLV-I), 16.7-20.8% of the supernatants were found to contain antikeratin antibodies by ELISA. The antikeratin antibodies in the supernatants showed cytoplasmic staining of keratinocytes in human as well as mouse skin by indirect immunofluorescence. The antibodies reacted with extracted human epidermal keratins by dot-blot and Western blot analysis. Most antikeratin antibodies in the supernatants did not show cross-reactivity with exogenous antigens used for immunization and vimentin-type intermediate-sized filaments. These findings demonstrate that B cells producing antikeratin antibodies are common in naive mice, and produce various types of antikeratin antibodies following specific activation with epidermal keratins and non-specific immunological stimuli.

Animals↗
PubMed1990

Exchange of dominant lymphoid cell clones in a patient with adult T-cell leukemia/lymphoma.

We performed a genotypic study on lymphoid cells from a patient with adult T-cell leukemia (ATL). Clonal proliferation of human lymphotropic virus type-1(HTLV-1)-infected helper T-cells was detected in the primary skin tumors, while no clonality of the virus-infected lymphocytes was observed in the peripheral blood. Following intensive chemotherapy, however, we detected the presence of two genotypically different HTLV-1-infected lymphocyte clones in different samples taken from the peripheral blood. These data demonstrated the exchange of the dominant neoplastic clone in the clinical course of ATL, suggesting the possibility that a certain clone among many repertoires of HTLV-1-infected T-cells has a capability of leukemogenesis, instead of the primary tumour cells.

Biopsy↗
PubMed1990

Gabexate and camostat, synthetic proteinase inhibitors, as direct inducing factors of water and bicarbonate secretion in the isolated and blood-perfused dog pancreas.

The effects of proteinase inhibitors on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas as compared with those of secretin. Each drug tested was administered i.a. Graded doses of gabexate (1-10 mg) elicited dose-dependent biphasic responses for the secretory rates, bicarbonate concentrations and outputs of pancreatic juice, with maximum effects at approximately 5 mg, but had little effect on the protein concentrations. Camostat, at a high dose of 10 mg, caused significant increases in the secretory rate, bicarbonate concentration and output of pancreatic juice over their basal levels, but had little influence on the protein concentration. Secretin (0.03-0.3 U) usually produced similar to gabexate-induced results (1-5 mg). Both bicarbonate and protein concentrations of the juice obtained with gabexate or camostat were almost the same as those obtained with secretin at a similar secretory rate of pancreatic juice, suggesting the secretory action of gabexate or camostat might be similar to that of secretin. In addition, gabexate (3 mg) and camostat (10 mg) elicited more than the respective additive secretory responses in the presence of i.a. infusion of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (12 micrograms/min) as well as secretin (0.1 U). These results indicate that gabexate and camostat induce water and bicarbonate secretion by acting directly on ductular cells of the dog pancreas, which might be mediated at least partially through cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed1989

The ratio of extracellular Ca2+ to K+ ions affects the photoresponses in Stentor coeruleus.

1. Stentor coeruleus exhibits negative phototaxis (due to phototactic orientation response) and step-up photophobic response (avoiding reaction) to visible light. 2. The effect of Ja-value ([K+]/[Ca2+]1/2) and calcium ion concentration of the surrounding medium on the photoresponses in Stentor were studied. 3. The both types of photoresponses in Stentor are greatly affected by the Ja-value. A higher Ja-value medium suppressed the step-up photophobic response of Stentor, whereas the organism showed a higher degree of phototactic orientation response in higher Ja-value solutions. 4. The effect of the Ja-value on the step-up photophobic response was opposite to that on the phototactic orientation response. 5. With increasing calcium concentration but at a constant Ja-value, the number of Stentor showing the step-up photophobic response increased, whereas the phototactic orientation response of Stentor was suppressed at higher Ca2+ concentrations. 6. The effect of the calcium concentration on the photophobic response was also opposite to that on the phototactic orientation response, as in the case of Ja-value effect.

Animals↗
PubMed1989

In vivo binding site of pemphigus vulgaris antibodies and their fate during acantholysis.

Ultrastructural localization of pemphigus vulgaris antigen-antibody complexes and their fate during acantholysis were studied in epidermal sheets obtained from the area surrounding the bullae and in acantholytic cells in blister fluid. The distribution of pemphigus vulgaris antibodies already bound to the keratinocytes in early acantholytic lesions was detected with ferritin-conjugated goat antihuman IgG. Ferritin particles were observed on the surface of keratinocytes with particular affinity for desmosomal structures. The acantholytic cells in the blister fluid bound only a small number of ferritin particles on their surface. During incubation at 37 degrees C, pemphigus vulgaris antigen-antibody complexes on the surface of separated desmosomes were internalized and recognized in cytoplasmic vesicles. Endocytosis of separated desmosomes also was observed in vivo when freshly obtained epidermal sheets were immediately processed for routine electron microscopic study. These findings suggest that pemphigus vulgaris antibodies are densely located on desmosomes and that the antigen-antibody complexes, together with other serum proteins on the keratinocyte surface, are internalized by a process of endocytosis.

Acantholysis↗
PubMed1989

Clear cell hidradenoma with whorl formation of squamoid cells: immunohistochemical and electron microscopic studies.

Many groups of squamoid cells arranged in whorls were found in a case of clear cell hidradenoma. These cells showed positive staining for carcinoembryonic antigen, but S-100 protein was not detected. Electron microscopic examination showed considerable amounts of tonofilaments, but neither keratohyalin granules nor multivesicular dense bodies were present in these cells. These features suggest that the constituting cells of whorls differentiated toward the eccrine ductal cells, in particular the intraepidermal ductal cells.

Adenoma, Sweat Gland↗
PubMed1989

Allopurinol stimulates pancreatic exocrine secretion in the dog.

The effects of allopurinol on the secretion of pancreatic juice were investigated both in live animals and in preparations of isolated, blood-perfused dog pancreas and were compared with those of secretin. An i.v. administration of allopurinol (3-10 mg/kg) caused a dose-dependent increase in the pancreatic secretion. The secretory responses to 3 and 10 mg/kg of allopurinol were approximately equal to those to 0.03 and 0.1 U/kg of secretin, respectively. An intra-arterial (i.a.) infusion of allopurinol (0.5-1.2 mg/min) also elicited dose-dependent increases in flow rates, bicarbonate concentrations, and outputs of pancreatic exocrine secretion, but protein concentrations were little affected by allopurinol. Similar results were obtained in the juice induced by an i.a. infusion of secretin (0.012-0.05 U/min). Both bicarbonate and protein concentrations in the juice obtained with allopurinol were almost the same as those obtained with secretin at a similar flow rate of pancreatic secretion. The secretory activities at 0.5, 1.0, and 1.2 mg/min of i.a. allopurinol infusion corresponded roughly to those at 0.012, 0.025, and 0.05 U/min of i.a. secretin infusion, respectively. Therefore, the secretory action of allopurinol was similar to that of secretin. The allopurinol-induced secretion was not modified by pretreatment with atropine sulfate, cimetidine, or sulpiride hydrochloride. These results suggest that allopurinol stimulates pancreatic secretion by acting directly on ductular cells of the dog pancreas.

Allopurinol↗
PubMed1989

Subtypes of muscarinic receptors in pancreatic exocrine secretion in anesthetized dog.

Characterization of muscarinic receptor subtypes on the dog pancreas in situ was examined by using specific muscarinic receptor antagonists to study pancreatic exocrine secretion. Bethanechol caused an increase in pancreatic exocrine secretion, with a high concentration of protein and little effect on bicarbonate concentration. Thus bethanechol may mainly affect the muscarinic receptors of the acinar cells. Bethanechol-stimulated secretion was inhibited by pirenzepine (a specific M1 muscarinic antagonist), 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP, a specific M3 muscarinic antagonist), and atropine (a mixed muscarinic receptor antagonist). However, [11-[[2-(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11- dihydro-6H-pyrido[2,3-b][1,4]benzo-diazepine-6-one (AF-DX 116, a specific cardioselective M2 antagonist) did not have any effects on bethanechol-stimulated secretion. Increased protein secretion in pancreatic juice stimulated by bethanechol was significantly inhibited by 4-DAMP and atropine and was suppressed by pirenzepine, but was not modified by AF-DX 116. Bicarbonate concentration was not modified by these antagonists. 4-DAMP, atropine, and pirenzepine caused a progressive parallel rightward shift in the dose-response curve of pancreatic secretion for bethanechol. Schild analysis of the data indicated a pA2 value of 8.7 for 4-DAMP, 7.9 for atropine, and 6.2 for pirenzepine, respectively. Thus 4-DAMP has 7.5 times and 440 times greater potency than atropine and pirenzepine to inhibit bethanechol-stimulated secretion. The slope of the Schild regression line was not different from 1. These results suggest that inhibitions of bethanechol-stimulated pancreatic secretion are competitive for 4-DAMP, atropine, and pirenzepine and that bethanechol-stimulated pancreatic secretion is mediated by M3 muscarinic receptors in dogs.

Animals↗
PubMed1989

Involvement of endogenous prostaglandins in pancreatic endocrine and exocrine secretion in dog pancreas.

The involvement of endogenous prostaglandins (PGs) in pancreatic endocrine and exocrine secretion was investigated, using the isolated and perfused dog pancreas. Spontaneous production of both PGE2 and 6-keto-PGF1 alpha was recorded in venous effluent. Prostaglandin production increased following stimulation with both 10 x 10(-11) and 20 x 10(-11) mol of CCK-8, but was not affected by a 5 x 10(-11) mol infusion. Insulin, glucagon, and amylase release was stimulated by 10 x 10(-11) mol of CCK-8. Indomethacin pretreatment with 10 mg/kg totally abolished endogenous PG production, but failed to suppress an insulin and glucagon response. On the other hand, an amylase response was accelerated by indomethacin pretreatment. Although low dose CCK-8 failed to stimulate endogenous prostaglandin production, a brisk exocrine secretion was not suppressed by indomethacin pretreatment. From the above results, we conclude that endogenous PGs do not appear to play an important role in pancreatic endocrine and exocrine secretion, but might have a cytoprotective effect on the pancreatic acinar cells damaged by CCK-8.

Amylases↗
PubMed1989

Adult T-cell leukemia/lymphoma and cutaneous T-cell lymphoma. Are they related?

Comparative studies were performed on clinical and laboratory features of four patients with different types of T-cell lymphoma of the skin; adult T-cell leukemia/lymphoma (ATLL), Sézary syndrome, mycosis fungoides, and Ki-1-positive lymphoma. All neoplastic cells studied showed a helper-inducer T-cell phenotype. A Ki-1-positive lymphoma is distinct from other types of cutaneous lymphomas because of unique morphologic and phenotypic features. Clonal proliferation of lymphocytes infected by human T-cell lymphotrophic virus (HTLV)-1 distinguishes ATLL from other T-cell lymphomas of the skin, especially in the endemic area of ATLL. From the pathogenic point of view, ATLL should not be included in a group with mycosis fungoides and Sézary syndrome.

Aged↗
PubMed1989

Inhibitory effect of ouabain and acetazolamide on secretin-stimulated pancreatic exocrine secretion in anaesthetized dog.

1. The effects of ouabain and acetazolamide on the secretion of pancreatic juice stimulated by secretin in anaesthetized dogs were investigated. 2. Intra-arterial injection of ouabain (1-10 micrograms) and acetazolamide (1-10 mg) caused dose-dependent decreases in the volume of pancreatic juice. When both drugs were added together, the inhibitory effects were significantly higher than for each drug alone. 3. The bicarbonate concentration in the pancreatic juice was decreased and the chloride concentration was increased by ouabain and acetazolamide, but sodium and protein concentrations were not modified. 4. The results suggest that the Na+,K+-ATPase and carbonic anhydrase activities play important roles in water and electrolyte secretion, and that ouabain and acetazolamide inhibit secretin-stimulated pancreatic secretion by acting on different systems in the exocrine cells in dogs.

Acetazolamide↗
PubMed1989

Effects of DN-9693, a synthesized phosphodiesterase inhibitor, on pancreatic exocrine secretion in dogs.

The effects of DN-9693, a synthesized phosphodiesterase inhibitor, on the secretion of pancreatic juice were investigated in preparations of the isolated and blood-perfused dog pancreas. DN-9693 injected intraarterially caused a dose-dependent increase in the secretion of pancreatic juice and decrease in the perfusion pressure. The threshold doses to increase the pancreatic secretion and to decrease the perfusion pressure were about 100 micrograms and 1 microgram, to decrease the perfusion pressure were about 100 micrograms and 1 micrograms, respectively. Thus, the secretory response was less effective than the vascular response. The secretory activity of DN-9693 (0.3 mg) was approximately equal to that of 0.03 mg of 3-isobutyl-1-methylxanthine, 0.5 mg of papaverine, 5 mg of theophylline, 0.08 0.5 mg of papaverine, 5 mg of theophylline, 0.08 units of secretin and 0.2 units of cholecystokinin. The concentration of bicarbonate in the pancreatic juice induced by DN-9693 was increased, but protein concentration was not. DN-9693-induced pancreatic secretion was not modified by pretreatments with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin-induced pancreatic secretion was significantly potentiated by infusion of DN-9693 (10 micrograms/min), but cholecystokinin-induced one was not. From these results, it is concluded that DN-9693 may produce an increase in pancreatic secretion by acting directly on the pancreatic exocrine gland of the dog, which might be mediated through an increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Do D-1 dopamine receptors mediate dopamine-induced pancreatic exocrine secretion in anesthetized dogs?

Characterization of dopamine (DA) receptor subtypes was examined on the canine exocrine pancreas using selective DA receptor agonists and antagonists in the isolated and blood-perfused pancreas of anesthetized dogs. Each drug was injected i.a. in a single bolus fashion. Graded doses of DA (0.01-3 mumol) produced dose-dependent increases in the secretory rate of pancreatic juice, with a maximum effect at approximately 1 mumol. SCH23390 (3-30 nmol), a selective D-1 DA receptor antagonist, caused a progressive parallel shift to the right in the dose-response curve for DA-induced pancreatic secretion without changes in the maximal response. High doses of RS-sulpiride (0.3-3 mumol) or haloperidol (1-3 mumol), a mixed D-1/D-2 DA receptor antagonist, also caused a rightward shift in the DA dose-response curve. However, domperidone (3 mumol), a selective D-2 DA receptor antagonist, did not antagonize the DA-induced pancreatic exocrine secretion. A modified Schild analysis of the data indicates that SCH23390 is approximately 2 and 3 orders of magnitude more potent than RS-sulpiride and haloperidol, respectively. In addition, the stimulatory effects of DA (0.01-3 mumol), SKF38393 (0.1-10 mumol, a selective D-1 DA receptor agonist) and LY171555 (1-10 mumol, a selective D-2 DA receptor agonist) on pancreatic secretion were demonstrated. The rank order of agonist potency was DA greater than SKF38393 greater than LY171555. The secretory response to LY171555 was inhibited completely by pretreatment with SCH23390 (30 nmol).(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1989

[Production of monoclonal antibodies to human T-cell lymphotropic virus type 1 (HTLV-1) and studies of their specificity].

Mouse monoclonal antibodies to HTLV-1 core proteins, p19 and p24, were obtained by hybridoma technique. The specificity was studied by indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA), dot blot, and Western blot studies. Polyclonal antibodies reactive with HTLV-1 viral proteins were raised by rabbits and guinea pigs. A sandwich ELISA and a dot blot method using these antibodies detected the soluble viral antigens in the ATL cell lysate and ATL culture media. No reaction was observed when IL-2-activated human T-cell lysate and the culture media were used as controls. These data showed that our sandwich ELISA and dot blot systems are available for quantitative analysis of the soluble HTLV-1 viral antigens and contribute to understanding the ability of viral replication by ATL cells.

Animals↗
PubMed1988

Ki-1+ cutaneous lymphoma. Gene rearrangement analysis of tumor cells in tissue and short-term culture of a patient.

Cutaneous malignant lymphomas developed in an 80-year-old man without any evidence of leukemic disseminations of lymphoma cells. Immunohistologic staining showed the expression of Leu-3a, Leu-4, Ki-1, Tac, and HLA-DR antigens on tumor cells in tissue and large lymphoid cells in long-term, interleukin 2-containing culture of tumor explants. DNA samples extracted from the skin tumors and cultured lymphoid cells showed a clonal rearrangement of T-cell receptor (TCR) gene C beta 1 with the molecular size of 9 kilobases. These findings suggested the T-cell origin of Ki-1+ cutaneous lymphoma cells and the occurrence of a clonal proliferation of tumor cells in culture.

Aged↗
PubMed1988

Mechanism of pancreatic hypersecretion in dogs with obstructive jaundice.

Pancreatic exocrine function in experimental obstructive jaundice was examined using dogs. Outputs of pancreatic juice, bicarbonate and amylase were greater in dogs with obstructive jaundice than in control dogs. To further examine the hypersecretory mechanism in obstructive jaundice, we examined pancreatic exocrine secretion stimulated by secretin and pancreozymin in both the isolated perfused pancreas and pancreatic dispersed cell culture. The perfused pancreas stimulated with secretin and pancreozymin in dogs with obstructive jaundice showed higher secretion of volume, bicarbonate and amylase than in control dogs. Dispersed pancreatic cells of jaundiced dogs stimulated by secretin and pancreozymin released more bicarbonate and amylase into the media than dispersed cells of control dogs. These data suggest pancreatic hypersecretion in obstructive jaundice is not due to excessive serum levels of secretin and pancreozymin or impaired metabolism of these hormones.

Amylases↗