Biomedical subjects

T Izawa

Publications and source records attributed to T Izawa.

At least 37 records · Page 2Linked to original sources

PubMed1999

alpha-Fetoprotein-producing adenocarcinoma of the pancreas presenting focal hepatoid differentiation.

We report a rare case of pancreatic carcinoma producing alpha-fetoprotein (AFP), showing focal hepatoid differentiation in metastatic lymph nodes. A 65-yr-old female was admitted because of abdominal pain. The serum AFP was measured at 16,170 ng/mL. Radiological examinations revealed a mass measuring 6 cm in diameter in the body and tail of the pancreas. A right supraclavicular lymphadenopathy was found and biopsied. Light microscopy showed a tumor consisting of a portion of a hepatoid area and well-differentiated adenocarcinoma, which was suggestive of a hepatoid adenocarcinoma. Immunohistochemical analysis showed that the tumor cells expressed AFP, alpha 1-antitrypsin (AT) and albumin. Although the pathological diagnosis of the primary pancreatic tumor was not obtained, this appears to be the first case of hepatoid adenocarcinoma of the pancreas.

Adenocarcinoma↗

PubMed1998

Down-regulation of RFL, the FLO/LFY homolog of rice, accompanied with panicle branch initiation.

FLORICAULA (FLO) of Antirrhinum and LEAFY (FLY) of Arabidopsis regulate the formation of floral meristems. To examine whether same mechanisms control floral development in distantly related species such as grasses, we isolated RFL, FLO-LFY homolog of rice, and examined its expression and function. Northern analysis showed that RFL is expressed predominantly in very young panicle but not in mature florets, mature leaves, or roots. In situ hybridization revealed that RFL RNA was expressed in epidermal cells in young leaves at vegetative growth stage. After the transition to reproductive stage, RFL RNA was detected in all layers of very young panicle including the apical meristem, but absent in the incipient primary branches. As development of branches proceeds, RFL RNA accumulation localized in the developing branches except for the apical meristems of the branches and secondary branch primordia. Expression pattern of RFL raised a possibility that, unlike FLO and LFY, RFL might be involved in panicle branching. Transgenic Arabidopsis plants constitutively expressing RFL from the cauliflower mosaic virus 35S promoter were produced to test whether 35S-RFL would cause similar phenotype as observed in 35S-LFY plants. In 35S-RFL plants, transformation of inflorescence meristem to floral meristem was rarely observed. Instead, development of cotyledons, rosette leaves, petals, and stamens was severely affected, demonstrating that RFL function is distinct from that of LFY. Our results suggest that mechanisms controlling floral development in rice might be diverged from that of Arabidopsis and Antirrhinum.

Amino Acid Sequence↗

PubMed1998

Multifocal serous cystadenoma of the pancreas. A case report and review of the literature.

Serous cystadenoma of the pancreas is usually unifocal; multifocal tumors are rare. We report a case of multifocal serous cystadenoma of the pancreas in a 48-yr-old female complaining of general malaise. Serum tumor markers, such as CA 19-9, DUPAN-2, and Span-1, were elevated. Abdominal ultrasound (US) and computed tomography (CT) scans revealed two distinct cystic masses in the head and body of the pancreas, respectively. The patient underwent total pancreatectomy. The resected pancreas contained two discrete cystic masses in the head and body; no solid components were observed. Microscopically, the inner surfaces of the cysts were evenly lined by a single layer of low cuboidal or significantly attenuated epithelial cells containing clear cytoplasm and abundant glycogen without other morphological alterations. The histogenesis of serous cystadenoma is not clear; multicentric tumors may be helpful in understanding histogenesis.

Abdomen↗

PubMed1998

Effect of KRN4884 on lipid metabolism in hyperlipidemic rats.

1. KRN4884 is a novel pyridinecarboxamidine type potassium channel opener. 2. To determine whether KRN4884 affects lipid metabolism, we investigated its effects on serum lipid levels by using two types of hyperlipidemic rats: genetically hyperlipidemic obese Zucker rats and diet-induced hyperlipidemic rats fed a high fat diet. KRN4884 dose dependently decreased systolic blood pressure in Zucker rats. 3. Oral administration of KRN4884 (1-10 mg/(kg day) for 14 days dose dependently reduced serum triglyceride levels in Zucker rats. The reductions in serum triglyceride were associated with reductions in triglyceride in chylomicron and very low density lipoprotein. 4. KRN4884 produced no change in serum insulin and glucose levels in Zucker rats. 5. KRN4884 exhibited a similar triglyceride lowering effect in diet-induced hyperlipidemic rats. 6. These results suggest that KRN4884 has a beneficial effect on serum triglyceride levels as well as a hypotensive effect.

Animals↗

PubMed1998

Protective effect of the K+ channel opener KRN4884 on peripheral occlusive arterial disease in rats.

1. The effect of the potassium channel opener KRN4884 on the peripheral arterial occlusion model induced by laurate was examined and compared with that of beraprost sodium and nilvadipine. 2. KRN4884 or beraprost sodium prevented macroscopic changes in the paw after the injection of laurate. In contrast, nilvadipine did not improve the lesions. 3. KRN4884 produced a dose-dependent increase in gastrocnemius blood flow in the chronic femoral artery-ligated rats. The effect of KRN4884 on the blood flow was stronger in the hypoxic muscle than in the normal muscle. 4. KRN4884 did not have a direct antiplatelet aggregation activity. 5. These findings suggest that KRN4884 is useful for the therapy of peripheral arterial occlusive disease and that the effect of KRN4884 is associated with an increase in blood flow in ischemic skeletal muscle.

Animals↗

PubMed1998

A naturally occurring functional allele of the rice waxy locus has a GT to TT mutation at the 5' splice site of the first intron.

In cultivated rice two wild-type alleles, Wxa and Wxb, predominate at the waxy locus, which encodes granule-bound starch synthase. The activity of Wxa is 10-fold higher than that of Wxb at the level of both protein and mRNA. Wxb has a +1G to T mutation at the 5' splice site of the first intron. Sequence analysis of Wxb transcripts revealed that splicing occurs at the mutant AG/UU site and at two cryptic sites: the first is A/GUU, one base upstream of the original site and the second is AG/GU found approximately 100 bases upstream of the mutant splice site. We introduced single base mutations to the 5' splice sites of both Wxa and Wxb, fused with the gus reporter gene and introduced them into rice protoplasts. Analysis of GUS activities and transcripts indicated that a G to T mutation in Wxa reduced GUS activity and the level of spliced RNA. Conversely, a T to G mutation of Wxb restored GUS activity and the level of spliced RNA to that of wild-type Wxa. These results demonstrated that the low level expression of Wxb results from a single base mutation at the 5' splice site of the first intron. It is of interest that the Wxb allele of rice carrying the G to T mutation of intron 1 has been conserved in the history of rice cultivation because there is a low amylose content of the seed caused by this mutation.

Alleles↗

PubMed1998

Solitary true cyst of the pancreas in two adults: analysis of cyst fluid and review of the literature.

Solitary true cyst of the pancreas in adults is extremely rare. We report two adult cases of solitary true cyst of the pancreas. In a 53-yr-old woman there was discovered, incidentally, a unilocular cyst of 7.0 x 6.5 cm in size in the tail of the pancreas that was noted on abdominal US and CT scan. A 16-yr-old boy presented with abdominal pain, and an abdominal US and CT scan revealed a 6.5 cm cystic mass located in the tail of the pancreas. Both patients underwent distal pancreatectomy. Histologically, the cyst was lined with flattened cuboidal and squamous epithelium without morphological alterations. Analysis of the cyst fluid revealed high CA 19-9 (>100,000 U/L) and Span-1 levels (>60,000 U/L) in both cases. Immunohistochemically, the lining epithelial cells of true cyst were positive for CA 19-9 staining. The clinicopathological features of solitary true cyst of the pancreas in adults are briefly reviewed.

Adolescent↗

PubMed1998

Effect of running training on brown adipose tissue activity in rats: a reevaluation.

The effect was investigated of running training on the thermogenic activity of brown adipose tissue (BAT) in rats. The exercised rats were trained on a rodent treadmill for 5 days per week and a total of 9 weeks. After the training, a significantly lower rate of increase in body weight was found, suggesting some training effect, whereas the training failed to induce a decrease in BAT mass. As previously reported (Yamashita, Yamamoto et al., 1993), there was also a markedly lower expression of uncoupling protein (UCP) mRNA in BAT from trained rats; nevertheless, no definite effect of the running training was noted on either UCP content or guanosine 5'-diphosphate binding in the mitochondria recovered from BAT. The results obtained suggest that running training has no overt effect on the thermogenic activity of BAT in rats.

Adipose Tissue, Brown↗

PubMed1997

Effects of KRN4884, a novel pyridinecarboxamidine type KATP channel opener, on serum triglyceride levels in rats.

1. The effects of KRN4884, a novel pyridinecarboxamidine type KATP channel opener, on serum triglyceride levels were investigated in Sprague-Dawley rats. 2. Oral administration of KRN4884 (3 mg kg-1) for 10 days caused a significant reduction in serum triglyceride levels, which was comparable to that of clofibrate (160 mg kg-1). Reduction in serum triglyceride levels by KRN4884 and clofibrate were accompanied by a reduction in triglyceride levels both in chylomicron and in very low density lipoprotein. KRN4884 treatment did not affect serum concentrations of total cholesterol and phospholipid, but did increase free fatty acid levels. Clofibrate reduced total cholesterol, phospholipid and free fatty acid levels. 3. Administration of clofibrate significantly decreased triglyceride secretion rate as measured by the Triton WR-1339 injection procedure, while KRN4884 did not. 4. Rats receiving KRN4884 exhibited an increase in lipoprotein lipase (LPL) activity both in adipose tissue and in skeletal muscle. There was an inverse correlation between serum triglyceride levels and tissue LPL activities. KRN4884 did not change hepatic triglyceride lipase (HTGL) activity. Clofibrate affected neither LPL nor HTGL activities. 5. It is concluded that administration of KRN4884 results in reduced serum triglyceride levels which may be due to the enhancement of LPL activity in peripheral tissues.

ATP-Binding Cassette Transporters↗

PubMed1997

KRN4884, a novel K channel opener: antihypertensive effects in conscious renal hypertensive dogs.

We examined the antihypertensive effects of KRN4884, 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarbocamidine+ ++, in normotensive dogs, a high-renin model acute renal hypertensive dog (RHD), and a low-renin model chronic RHD in the conscious state, compared with levcromakalim and nilvadipine. KRN4884 decreased mean blood pressure (MBP) at a dose of 0.1 mg/kg p.o. in normotensive dogs and both RHDs. The decrease in MBP was greater in both RHDs than in normotensive dogs, and there were no significant differences between the two RHDs. A transient increase in heart rate (HR) accompanied the increase in MBP in all three types of dogs. In the chronic RHD, KRN4884 at doses of 0.05, 0.1, and 0.2 mg/kg produced a dose-dependent decrease in MBP. The antihypertensive effect of KRN4884 (0.1 mg/kg) was similar to those of levcromakalim (0.05 mg/kg) and nilvadipine (1.0 mg/kg) in magnitude and more prolonged than those of the compounds. The tachycardia induced by KRN4884 was similar to that induced by levcromakalim and was stronger than that induced by nilvadipine. In the 15-day repeated oral-administration study, KRN4884 (0.1 mg/kg) induced sustained hypotensive effects and transient increases in HR and plasma renin activity. No tolerance to the antihypertensive effect of KRN4884 was observed during a 15-day repeated dosing period. After withdrawal of KRN4884, no rebound phenomena in MBP and HR were observed. Neither the maximal concentration nor area under the curve (AUC) of KRN4884 in plasma were changed at days 1, 8, and 15. These data indicate that KRN4884 produces a strong and persistent antihypertensive response in both low-renin and high-renin models of RHD in a conscious state, which suggests that KRN4884 may be useful as an antihypertensive agent.

Animals↗

PubMed1997

Effects of endurance training on superoxide dismutase activity, content and mRNA expression in rat muscle.

1. The purpose of the present study was to investigate the changes in superoxide dismutase (SOD) isoenzyme (Mn(2+)-SOD and Cu2+, Zn(2+)-SOD) activities, contents and mRNA expressions in rat skeletal muscle during endurance training and a single bout of exercise. 2. Thirty-eight male Wistar rats were divided into untrained (U) and trained (T) groups. The T group rats were treadmill-trained for 9 weeks. The activity, content and mRNA expression of Mn(2+)-SOD and Cu2+, Zn(2+)-SOD were determined in the soleus muscle of each rat. 3. Mn(2+)-SOD activity and content in the T group were significantly higher than in the U group, both at rest (22 and 21%, respectively) and after exercise (24 and 46%, respectively), while a single bout of exercise affected neither the activity nor content of Mn(2+)-SOD in either group. 4. The content of Cu2+,Zn(2+)-SOD in both groups was not different at rest and after exercise, although its activity at rest was significantly higher in the T group than in the U group (by 29%). 5. After exercise, the expression of Mn(2+)-SOD mRNA was markedly attenuated only in the U group (49%); the expression of Cu2+,Zn(2+)-SOD mRNA was not influenced by exercise. 6. Our results suggest that adequate endurance training increases both the activity and content of Mn(2+)-SOD and that untrained rats are rather susceptible to oxidative stress during physical exercise. It thus appears that Mn(2+)-SOD provides a reliable index of physical training. 7. The results obtained in the present study also suggest that muscle has the capacity of responding to training in such a manner as to reduce the potential harm arising from the accumulation of oxygen free radicals resulting from enhanced metabolic activity.

Animals↗

PubMed1997

In vitro and in vivo vasodilating effects of KRN4884, Ki1769 and Ki3005, pyridinecarboxamidine derivatives.

The vasodilating potencies and mechanism of action of a novel pyridinecarboxamidine derivative, KRN4884 [5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine ] were compared with those of Ki1769 [N-cyano-N'-(2-phenylethyl)-3-pyridinecarboxamidine] and Ki3005 [N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine] in rat isolated aortas and in anesthetized normotensive rats. In vitro. KRN4884 (10(-10)-10(-6) M). Ki1769 (10(-8)-10(-5) M) and Ki3005 (10(-10)-10(-6) M) produced concentration-dependent relaxations. KRN4884 was about 100- and 10-fold more potent than Ki1769 and Ki3005, respectively. The relaxant effects of these compounds were antagonized by glibenclamide. In vivo, KRN4884 (1-10 micrograms/kg, intravenously [i.v.]), Ki1769 (10-100 micrograms/kg, i.v.) and Ki3005 (3-30 micrograms/kg, i.v.) produced dose-dependent decreases in mean blood pressure with slight increases in heart rate. At 10 micrograms/kg, i.v., the hypotensive effect of KRN4884 was about the same as that of Ki3005 and about 5-fold more pronounced than that of Ki1769. The hypotensive action remained for a longer period after KRN4884 administration. In rats pre-treated with glibenclamide (20 mg/kg, i.v.), the hypotensive effect of KRN4884 was abolished. These results suggest that the effect of KRN4884 in vitro and in vivo is based on its K channel opening action and that the in vitro vasorelaxant effect of these compounds in aortic rings does not predict their relative hypotensive effect in vivo.

Animals↗

PubMed1997

Relationship between cold tolerance and generation of suppressor macrophages during acute cold stress.

Acute cold stress induces suppressor macrophages expressing large numbers of receptors to the crystallizable fragment (Fc) portion of immunoglobulin G (MAC-1+ FcgammaRII/IIIbright cells), resulting in the immunosuppression of splenocyte mitogenesis. The generation of MAC-1+ FcgammaRII/IIIbright cells is mediated by the action of glucocorticoids (GCs) through the GC-receptor. In the present study, the generation of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cells was closely related to the decrease of rectal temperature during 3-day exposure to 5 degrees C. We next investigated the effects of improved cold tolerance on the generation of MAC-1+ FcgammaRII/IIIbright cells during acute cold stress. Mice were adapted to cold by exposure to 5 degrees C for 3 wk (cold-acclimated mice) and then reexposed to 5 degrees C for 3 h (acute cold stress) after living at 25 degrees C for 24 h. The rectal temperature of cold-acclimated mice was not decreased by the acute cold stress. In addition, the proportion of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cell population from cold-acclimated mice was unaffected by the acute cold stress. The cold acclimation significantly attenuated the increases in serum corticosterone levels and the expression of the GC-receptor mRNA on peritoneal exudate cells in response to acute cold stress. These results suggest that the altered GC response to acute cold stress by the improvement of cold tolerance inhibits the generation of suppressor macrophages during acute cold stress.

Acclimatization↗

PubMed1997

Endurance training improves the resistance of rat diaphragm to exercise-induced oxidative stress.

The current study was designed to test the hypothesis that endurance training improves the ability of the diaphragm muscle to resist exercise-induced oxidative stress. Twenty-eight male Wistar rats were assigned to either untrained or trained groups. Trained rats were treadmill-trained for 9 wk. Each group was subdivided into acutely exercised or nonexercised groups. Diaphragm muscle from each rat was analyzed to determine the levels of certain antioxidant enzymes: Mn-superoxide dismutase (Mn-SOD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase, and catalase. In addition, interleukin-1 and myeloperoxidase levels were determined. Endurance training upregulated all of the antioxidant enzymes. Conversely, acute exercise increased glutathione peroxidase and catalase in untrained rats, while it had no overt effect on any antioxidant enzymes in trained rats. Both Mn-SOD and Cu,Zn-SOD contents and activities were increased with endurance training. However, the mRNA expressions of both forms of SOD did not show any significant change with endurance training. Acute exercise also increased the levels of interleukin-1 and myeloperoxidase in untrained rats but not in trained rats. Moreover, acute exercise significantly increased the ability of neutrophils to produce superoxide, especially in untrained rats. The results from this study demonstrate that endurance training can upregulate certain antioxidant enzyme activities in rat diaphragm muscle, indicating the potential for improvement of the resistance to intracellular reactive oxygen species. The results of this study also suggest that acute exercise may cause oxidative damage in rat diaphragm through the activation of the inflammatory pathway and that endurance training may minimize such an extracellular oxidative stress by acute exercise.

Animals↗

PubMed1997

Transposon tagging in rice.

To develop an efficient gene isolation method for rice we introduced the maize Ac/Ds system into rice. Extensive analysis of their behavior in rice for several generations indicated that Ac and Ds in the presence of Ac transposase gene actively transpose in rice. A wide spectrum of mutations affecting growth, morphogenesis, flowering time and disease resistance have been obtained in the population carrying Ac/Ds and some of them were genetically analyzed. Main efforts are currently being made to isolate genes responsible these mutations. In addition, a number of Ac/Ds were mapped on chromosomes and mapped elements will be used in the future for directed tagging of genes with known chromosomal positions.

Cloning, Molecular↗

PubMed1996

Altered intracellular Ca2+ regulation in pancreatic acinar cells from acute streptozotocin-induced diabetic rats.

We investigated intracellular Ca2+ regulation in pancreatic acinar cells from rats with diabetes induced by a single injection of streptozotocin (80 mg/kg). Experiments were performed 2 days and 7 days after the injection of streptozotocin. The density of muscarinic receptors, measured by [3H]N-methyl scopolamine binding, was unchanged in 2-day-diabetic rats, but was significantly increased in 7-day-diabetic rats. The percentage of high affinity receptors (RH) and low affinity receptors (RL) determined from the competitive curves with [3H]N-methyl scopolamine and carbachol was not change in 2-day-diabetic rats compared to controls, whereas 7-day-diabetic rats showed a decrease in %RH and an increase in %RL. The carbachol-evoked initial peak of intracellular Ca2+ concentration ([Ca2+]i) was increased in 2-day-diabetic rats and decreased in 7-day-diabetic rats, compared to controls. In the carbachol-induced sustained phase in [Ca2+]i, the response in 7-day-diabetic rats was significantly decreased; however, there was no difference between controls and 2-day-diabetic rats. Carbachol (100 microM)-induced [3H]inositol 1,3,4-trisphosphate generation was significantly lower in diabetic rats than in the controls. The addition of inositol 1,4,5-trisphosphate (1,4,5-IP3) significantly increased 45Ca2+ release from saponin-permeabilized cells in 2-day-diabetic rats, but did not do so in 7-day-diabetic rats. Ca2+ refilling into the intracellular stores, determined by second cholecystokinin-8 (10 nM) stimulation after 10 microM carbachol stimulation, was increased in 2-day-diabetic rats and decreased in 7-day-diabetic rats. These observations indicate that the alterations in intracellular Ca2+ regulation accompanied by changes in transmembrane signaling occur in the earlier stage of the diabetic state. The findings also suggest that the increase in the carbachol-evoked [Ca2+]i peak in 2-day-diabetic rats is related predominantly to the higher sensitivity of 1,4,5-IP3-sensitive Ca2+ stores and the increase in the capacity of Ca2+ refilling in these animals, whereas the reduction in the [Ca2+]i peak in 7-day-diabetic rats appears to be related to the essential decrease in receptor-mediated 1,4,5-IP3 generation and the decrease in Ca2+ refilling capacity.

Acute Disease↗

PubMed1996

Effects of the potassium channel openers KRN4884 and levcromakalim on the contraction of rat aorta induced by A23187, compared with nifedipine.

We examined the different vasodilatory effects of the K+ channel openers levcromakalim and 5-amino-N- [2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine (KRN4884), and the Ca2+ channel blocker nifedipine in the rat aorta. KRN 4884 (10(-10)-10(-5) M) and nifedipine (10(-10)-10(-5) M) produced concentration-dependent relaxation in the rat aorta precontracted by 25 mM KCl. The K+ channel blocker glibenclamide (1 microM) inhibited the relaxation induced by KRN4884 but did not influence nifedipine-induced relaxation. KRN4884 had almost no effect on contraction induced by 80 mM KCl, whereas nifedipine completely relaxed the muscle precontracted by 80 mM KCl, whereas nifedipine completely relaxed the muscle precontracted by 80 mM KCl. These results indicate that KRN4884 is a K+ channel opener. We investigated the relaxant effects of KRN4884 (10(-10)-10(-5) M), levcromakalim (10(-9)-10(-5) M) and nifedipine (10(-9)-10(-5) M) on A23187 (1 microM)-induced contraction. KRN4884 and levcromakalim had a potent relaxant effect but nifedipine only a weak effect on the smooth muscle contracted by A23187. Glibenclamide (1 microM) inhibited the relaxation induced by KRN4884 and levcromakalim, but did not influence the nifedipine-induced relaxation. KRN4884 (1 microM) produced a larger relaxation of A23187-induced contraction but had little effect on the increase in intracellular [Ca2+] induced by A23187. These results suggest that KRN4884 is a specific K+ channel opener and its vasodilating mechanisms involve not only deactivation of Ca2+ channels but also a decrease in the Ca2+ sensitivity of contractile elements.

Animals↗

PubMed1996

Structure-activity relationship of a novel K+ channel opener, KRN4884, and related compounds in porcine coronary artery.

1. KRN4884 (5-amino-N-[2-(2-chlorophenyl) ethyl]-N'-cyano-3-pyridinecarboxamidine), Ki3005 (5-deamino KRN4884), Ki5624 (2-dechloro KRN4884) and Ki1769 (5-deamino-2-dechloro KRN4884) produced concentration-dependent relaxations in isolated porcine coronary arteries contracted by 25 mM KC1. The order of relaxant potency was KRN4884 > Ki3005 > Ki5624 > Ki1769. 2. The relaxation induced by these compounds was antagonized by glibenclamide; they had almost no effect on coronary arteries contracted by 60 mM KC1. 3. The present results suggest that these pyridinecarboxamidine derivatives have vasodilating ability based on a K+ channel opening action, and that both the amino groups in the pyridine nucleus and the chlorine atom in the benzene nucleus in pyridinecarboxamidine are important for their potency as a K+ channel opener.

Animals↗