Biomedical subjects

K Suda

Publications and source records attributed to K Suda.

At least 199 records · Page 11Linked to original sources

PubMed1992

Incidence of Paneth cells in minute tubular adenomas and adenocarcinomas of the large bowel.

This study attempted to demonstrate the incidence of Paneth cells within large bowel tubular adenoma and adenocarcinoma according to location and macroscopic appearance using minute tumors (up to 5 mm in size). We have shown that Paneth cells were sometimes seen in the early stage of the development of large bowel epithelial neoplasia. According to the macroscopic appearance (elevated or depressed type), in large bowel epithelial neoplasia, there was a statistical difference between the depressed type (32.5%, 14 of 40 cases) and the elevated type (16.6%, 24 of 145 cases) (Chi square analysis, p < 0.05) in the incidence of Paneth cells. Paneth cells were seen more frequently in adenocarcinoma (45.8%, 11 of 24 cases) than in tubular adenoma (16.8%, 27 of 161 cases), with a significant statistical difference (Chi square analysis, p < 0.01). According to location, in both tubular adenoma and adenocarcinoma, Paneth cells were more frequently observed in the proximal colon (tubular adenoma: p < 0.01, adenocarcinoma: p < 0.05, Chi square analysis).

Adenocarcinoma↗

PubMed1992

Solid and papillary epithelial neoplasm of the pancreas: MR imaging and pathologic correlation.

Correlation of magnetic resonance (MR) imaging findings and those at pathologic evaluation was attempted in six cases of solid and papillary epithelial neoplasm of the pancreas. All patients were female, and the mean patient age was 26 years (range, 13-73 years). On T1-weighted spin-echo images, tumors were well demarcated, and areas of high signal intensity were evident within them. At macroscopic examination, these areas corresponded to solid portions with marked hemorrhagic necrosis or cystic portions filled with hemorrhagic debris. In three of four masses surrounded by macroscopically evident fibrous capsules, a rim of low intensity was revealed at T1-weighted imaging. When T1-weighted spin-echo imaging reveals obvious areas of high intensity within a sharply marginated tumor of the pancreas, especially in a young woman, solid and papillary epithelial neoplasm might be a primary diagnostic consideration.

Adolescent↗

PubMed1992

Ca2+ ionophore and phorbol ester stimulate diacylglycerol formation and phosphatidylcholine hydrolysis in rat parotid acinar cells.

We investigated the effects of A23187 and phorbol 12,13-dibutyrate (PDBu) on sn-1,2-diacylglycerol (DAG) accumulation and phosphatidylcholine (PC) hydrolysis in rat parotid acinar cells. Both A23187 and PDBu, in concentration ranges of 0.001-0.1 microM, stimulated DAG accumulation and PC hydrolysis in a time- and concentration-dependent manner. Treatment with A23187 and PDBu stimulated the release of [3H]choline and [3H]phosphocholine into the medium, indicating [3H]PC hydrolysis is due to the activation of phospholipases C and D; however, [3H]phosphatidylethanolamine hydrolysis was not indicated. These releases were unaffected by the addition of glucose 6-phosphate, a phosphatase inhibitor. Staurosporine, a protein kinase C inhibitor, significantly inhibited the DAG accumulation and the PC hydrolysis stimulated by these agents. Combinations of A23187 and PDBu potentiated the stimulatory effect which each of these agents alone had on DAG accumulation and PC hydrolysis. This mode of action was additive but not synergistic. These results suggest that DAG accumulation induced by A23187 and PDBu is related to the PC hydrolysis mediated via the activation of phospholipases C and D, and that it is not related to phosphatidylethanolamine hydrolysis.

Alkaloids↗

PubMed1992

Phorbol ester alters carbachol-stimulated diacylglycerol formation in parotid acinar cells through the hydrolysis of phosphoinositides and phosphatidylcholine.

Incubation of rat parotid acinar cells with phorbol 12,13-dibutyrate (PDBu) resulted in inhibition of carbachol-stimulated formation of sn-1,2-diacylglycerol (DAG). PDBu pretreatment inhibited carbachol-induced turnover of phosphoinositides; this inhibition was indicated by phosphatidylinositol 4,5-bisphosphate breakdown. This pretreatment also attenuated the effect of carbachol on inositol phosphate generation and phosphatidylcholine hydrolysis. These results show that PDBu alters carbachol-stimulated DAG formation through the hydrolysis of phosphoinositides and phosphatidylcholine.

Animals↗

PubMed1992

Successful pancreatojejunal anastomosis for pancreatoduodenectomy.

A series of 100 patients underwent pancreatoduodenectomy for carcinoma of the head of the pancreas (36 patients), the bile duct (19 patients), the gallbladder (14 patients), the papilla of Vater (13 patients), the duodenum (seven patients), the stomach (seven patients) or the colon (one patient), or for chronic pancreatitis (two patients) and adenomyoma of the bile duct (one patient) between October 1983 and December 1990. The operative morbidity and mortality rates were 27 and 6 percent, respectively, and failure of the pancreatojejunal anastomosis was the most common post-operative complication (16 patients). Anastomotic leakage correlated significantly with the quality of the pancreatic remnant and the preoperative technique used (p < 0.01). The leakage rate in 34 patients with fibrotic pancreatic tissue was 5.8 percent (two of 34) and was significantly less than that in 66 patients with a normal pancreatic remnant (21.2 percent). Forty-seven patients underwent direct anastomosis between the main pancreatic duct and the jejunum, using mucosa to mucosa sutures and a pancreatic duct drain tube as well as a single layer of sutures between the pancreatic tissue and the jejunum. Only two patients had a pancreatic fistula (4.2 percent) and the incidence was significantly less than that in 53 patients who received the usual technique of double-layer sutures between the pancreatic remnant and the jejunum without a direct anastomosis to the main pancreatic duct (26.4 percent, p < 0.01).

Adult↗

PubMed1992

Histopathological and immunohistochemical studies on apparently uninvolved areas of pancreas in patients with acute pancreatitis.

Apparently uninvolved areas of the pancreas that were distant from frank parenchymal necrosis in nine patients with acute pancreatitis were histopathologically and immunohistochemically studied. Fibrosis in these areas was observed in seven patients with an illness of 8 days or longer, and it was mainly distributed in the interlobular spaces and accompanied by hemosiderin deposition. Fibrosis was increased and divided into linear and broad types according to the presumed stage of evolution. Fibrosis immunostained it was negative against anti-collagen type I in three patients with an illness of 2 or 3 months was positive against anti--collagen in the interlobular spaces in the two remaining patients, whose illness was of less than 5 days' duration. Fibrosis in the apparently uninvolved areas in patients with acute pancreatitis therefore appears to have developed in relation to acute pancreatitis, and it may consist of type I collagen in longer surviving patients.

Adult↗

PubMed1992

Effects of mitoxantrone in combination with other anticancer agents on a human leukemia cell line.

To investigate the effects of mitoxantrone in combination with other anticancer agents, a human T-cell leukemia cell line, MOLT-3, was incubated for 3 days in the presence of two drugs (mitoxantrone and the combined drug) and cell growth inhibition was determined by assay with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazonium bromide. The effects of drug combinations at doses giving 80% inhibition (ID80) were analyzed by an improved isobologram method. A supra-additive (synergistic) effect was observed for mitoxantrone in combination with amsacrine, cisplatin, or cytosine arabinoside. An additive effect was observed for its combination with bleomycin, doxorubicin, etoposide, 5-fluorouracil, mitomycin C, 6-mercaptopurine, or vincristine. A sub-additive (antagonistic) effect was observed for its combination with methotrexate. These data suggest that mitoxantrone, administered simultaneously with any one of a majority of anticancer agents we studied, is advantageous for cytokilling. Of the anticancer agents tested, amsacrine, cisplatin, and cytosine arabinoside are the most suitable for combination with mitoxantrone, and these combinations are worthy of clinical investigation. Methotrexate in our system is inappropriate for simultaneous administration with mitoxantrone. These data should provide useful information for the establishment of clinical protocols involving mitoxantrone.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Substance P-induced diacylglycerol formation in rat parotid acinar cells.

The mechanisms underlying the ability of substance P, to stimulate the sn-1,2-diacylglycerol (DAG) formation were studied using rat parotid acinar cells. During a 60 s stimulation, 1 microM substance P caused a rapid rise in DAG accumulation at 5 s, whereas a low (0.1 microM) concentration of agonist did not. During long term stimulation for 30 min, DAG accumulation induced by 1 microM substance P reached near maximal levels at 5 min and remained elevated for at least 20 min. In contrast, DAG formation induced by 0.1 microM substance P exhibited a peak at 5 min, gradually declined and returned to near basal levels at 30 min. Furthermore, DAG accumulation in response to substance P at 5 and 20 min increased in a dose-dependent manner. The breakdown of both [32P]phosphatidylinositol 4-monophosphate ([32P]PIP) and [32P]phosphatidylinositol 4,5-bisphosphate ([32P]PIP2) stimulated by 1 microM substance P significantly increased from 5 to 20 min and returned to basal levels by 30 min; however, the breakdown of [32P]PIP2 was greater than that of [32P]PIP. At a low concentration of substance P, [32P]PIP2 breakdown reached maximal levels at 5 min followed by a progressive decrease and returned to basal levels at 30 min, whereas the breakdown of [32P]PIP reached maximal levels at 5 min and returned to near basal levels at 10 min. Both concentrations of substance P caused some [32P]phosphatidylinositol breakdown at 5 min. Changes in [3H]inositol trisphosphate induced by substance P were similar to those in [32P]PIP2. In addition, substance P (1 microM) did not stimulate the release of [3H]choline or [3H]ethanolamine metabolites into the medium. Substance P-induced DAG formation was not inhibited by staurosporine, a protein kinase C inhibitor. These results suggest that DAG formation caused by substance P is closely associated with the hydrolysis of phosphatidylinositides but not that of phosphatidylcholine or phosphatidylethanolamine, and is not regulated by protein kinase C-dependent mechanism(s).

Alkaloids↗

PubMed1991

Protein kinase C-dependent diacylglycerol formation is mediated via Ca2+/calmodulin in parotid cells.

The kinetics of carbachol-induced sn-1,2-diacylglycerol (DAG) formation and the underlying mechanism(s) involved in parotid acinar cells were investigated. Supramaximal concentrations of carbachol for amylase secretion (10 microM) caused a transient rise in DAG levels at 10 s. In contrast, this rapid rise was not elicited by 1 microM carbachol, which is the maximally effective concentration for amylase secretion. Carbachol (10 microM) also increased DAG levels linearly up to 20 min, which were sustained for up to a further 10 min. DAG formation stimulated by 1 microM carbachol was biphasic; the first peak was observed after 5 min and the second after 20 min. DAG formation induced by 0.01-0.1 microM carbachol was concentration-dependent and monophasic, peaking at 5 min. The second peak evoked by carbachol was partly inhibited by Ca2+ deprivation from the extracellular space, whereas the first peak was not. Similar results were obtained in experiments using Ca2+ antagonists such as verapamil and LaCl3. The protein kinase C inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and staurosporine, and a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), significantly inhibited the second DAG peak produced by 1 microM carbachol, but did not alter the first peak. The degree of inhibition of the second peak by these antagonists was comparable. Furthermore, the inhibitory effect of staurosporine and W-7 was concentration-dependent. The A23187-induced accumulation of DAG also was abolished by both staurosporine and W-7. These data indicate that a protein kinase C-dependent mechanism(s) is involved in mediating the second DAG accumulation peak induced by 1 microM carbachol and is mainly regulated by the Ca(2+)-calmodulin complex.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1991

The MAS-encoded processing protease of yeast mitochondria. Interaction of the purified enzyme with signal peptides and a purified precursor protein.

The matrix of yeast mitochondria contains a chelator-sensitive protease that removes matrix-targeting signals from most precursor proteins transported into this compartment. The enzyme consists of two nonidentical subunits that are encoded by the nuclear genes MAS1 and MAS2. With the aid of these cloned genes, we have now overexpressed the active holoenzyme in yeast, purified it in milligram amounts, and studied its biochemical and physical properties. Atomic absorption analysis shows that the purified enzyme lacks significant amounts of zinc, manganese, or cobalt; if none of these metal ions is added during the assay, the enzyme is catalytically inactive but can still cleave substoichiometric amounts of substrate. The amino-terminal sequences of the two mature subunits were determined; comparison with the deduced amino acid sequences of the corresponding precursors revealed that the MAS1 and MAS2 subunits are synthesized with prepeptides composed of 19 and 13 residues, respectively, which have similar sequences. The enzyme is inhibited competitively by chemically synthesized matrix-targeting peptides; the degree of inhibition correlates with the peptides' targeting efficacy. Matrix-targeting peptides containing the cleavage site of the corresponding authentic precursor protein are cleaved correctly by the purified enzyme. A purified artificial precursor protein bound to the holoenzyme can be photocross-linked to the MAS2 subunit.

Amino Acid Sequence↗

PubMed1991

Gross dissection and immunohistochemical studies on branch fusion type of ventral and dorsal pancreatic ducts: a case report.

A case of fusion via two inferior branches between the ventral and dorsal pancreatic ducts was studied both macroscopically and immunohistochemically, based on the organogenesis of the pancreas. Radiologically, the branch fusion seemed to be composed of an inferior branch of the ventral pancreatic duct and an inferior branch of the dorsal pancreatic duct. By mapping pancreatic polypeptide cells in the material obtained by pancreatoduodenectomy, however, the branch was identified as a branch of the dorsal pancreatic duct. Thus, fusion between two inferior branches was not established, but was found to consist of an inferior branch of the dorsal pancreatic duct connected with the ventral pancreatic duct. We therefore challenge the concept of the ansa pancreatica.

Adult↗

PubMed1991

In vivo adaptive control of beta-receptors and adenylate cyclase during short-term heat exposure in rat parotid glands.

1. Adaptation of beta-adrenergic receptors (beta-AR) and adenylate cyclase (AC) in rat parotid glands during short-term heat exposure (33 degrees C) were studied. 2. Heat exposure reduced AC activity in response to isoproterenol (IPR). 3. The number of beta-AR on the cell surface significantly increased after 24 hr but returned to control level after 48 hr. 4. IPR-induced [3H]GDP release was significantly reduced throughout exposure. 5. The data suggest that the major factor which results in the desensitization of AC during short-term heat exposure is a blunted coupling between beta-AR and GTP binding protein(s).

Adaptation, Physiological↗

PubMed1991

Enhanced coupling of adenylate cyclase to lipolysis in permeabilized adipocytes from trained rats.

Digitonin-permeabilized adipocytes were used to study the coupling of adenylate cyclase (AC) to lipolysis in exercise-trained rats. Isoproterenol-(IPR) stimulated lipolysis in permeabilized cells was significantly greater in trained than in control rats. Under essentially identical conditions, the dose-response curve for IPR stimulation of AC activity in the absence of 3-isobutyl-1-methylxanthine was similar in trained and control rats. However, the potency of stimulation by IPR as a percentage of the basal level was greater in trained rats. AC activity and lipolysis in the presence of 3-isobutyl-1-methylxanthine were also significantly greater in trained than in control rats. Least-squares analysis by plotting the log AC vs. lipolysis values showed that the regression coefficient was about three-fold greater in trained than in control rats. The concentration of endogenous adenosine 3',5'-cyclic monophosphate (cAMP) needed to produce a half-maximal lipolytic response was 18.58 and 10.81 pmol.min-1.10(6) cells-1 in control and trained rats, respectively. Thus a positive relationship existed between lipolysis and AC activity, with a tighter coupling in trained rats. Lipolysis in response to exogenous cAMP tended to be greater in trained than in control rats, and the difference was statistically significant for 50 microM and 10 mM cAMP. Our finding support the concept that the major mechanism of enhanced lipolysis in trained rats was an increase in the activity of enzymatic step(s) distal to cAMP.

1-Methyl-3-isobutylxanthine↗

PubMed1991

Peptide contents of neuropeptide Y, vasoactive intestinal polypeptide, and beta-calcitonin gene-related peptide and their messenger ribonucleic acids after dexamethasone treatment in the isolated rat islets of Langerhans.

A number of neuropeptides including neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and beta-calcitonin gene related peptide (beta-CGRP) are known to influence insulin secretion. In order to investigate whether they might have a local autocrine/paracrine effect within the islets of Langerhans we screened isolated islets by Northern blot analysis and RIA for a number of peptides and found evidence for the presence of messenger RNA (mRNA) encoding NPY, VIP, and beta-CGRP. Dexamethasone treatment for 12 days increased the content of NPY, VIP, and beta-CGRP significantly from 1.3 +/- 0.3 to 19.8 +/- 1.6; 0.25 +/- 0.03 to 0.91 +/- 0.1; 2.2 +/- 0.2 to 4.8 +/- 0.1 fmol/islet respectively, mean +/- SEM (n = 4, P less than 0.05) and remained elevated 24 h after recovery. However when the results were normalized and expressed as a ratio of insulin content only NPY and VIP were significantly raised. Five days post treatment VIP was still significantly elevated compared to controls. mRNA for NPY increased 10-fold and for VIP increased 2 1/2 times after dexamethasone whereas mRNA for beta-CGRP was not significantly different from controls. Neither capsaicin nor 6-hydroxydopamine affected islet content or message of NPY, VIP, and beta-CGRP. Immunoreactive NPY and its mRNA were detected in two cultured beta-cell lines, HIT T-15 and RIN m5F cells whereas VIP and beta-CGRP were undetectable. The local islet synthesis of neuropeptides, which are known to influence islet hormone release pharmacologically, suggests the possibility that they may play a role in intraislet paracrine regulation.

Animals↗

PubMed1991

Investigation and characterization of receptors for pituitary adenylate cyclase-activating polypeptide in human brain by radioligand binding and chemical cross-linking.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel peptide of hypothalamic origin which increases adenylate cyclase activity in rat anterior pituitary cell cultures. The 38-amino acid peptide shows a close sequence homology to vasoactive intestinal peptide (VIP). Binding sites for PACAP in membranes from postmortem human brain tissue were studied using [125I]PACAP27 as the radioligand. High specific binding sites (amount of specific binding measured at 0.25 nM [125I]PACAP27 in femtomoles per mg protein +/- SEM; n = 4) were present in hypothalamus (344.5 +/- 13.0), brain stem (343.0 +/- 29.3), cerebellum (292.0 +/- 21.1), cortex (259.6 +/- 19.8), and basal ganglia (259.2 +/- 50.3). Specific binding sites in pituitary, although present, were less abundant (35.0 +/- 8.9). Binding of [125I]PACAP27 was reversible and time, pH, and temperature dependent. Despite the homology with VIP, VIP was a poor inhibitor of [125I]PACAP27 binding (IC50, greater than 1 microM) compared with PACAP27 (IC50, 0.5-1.3 nM) and PACAP38 (IC50, 0.2-1.3 nM). Scatchard plots of [125I]PACAP27 binding showed the presence of both high and lower affinity sites. Chemical cross-linking of PACAP-binding sites revealed that [125I]PACAP27 was bound to polypeptide chains of 67,000 and 48,000 mol wt. Thus, we have demonstrated the presence of PACAP-specific receptors in human brain which are not VIP receptors. This opens the possibility of PACAP functioning as a novel neurotransmitter/neuromodulator in human brain.

Brain↗

PubMed1991

Depletion of islet amyloid polypeptide in the spontaneously diabetic (BB) Wistar rat.

Islet amyloid polypeptide (IAPP) in the pancreas of the spontaneously diabetic (BB) Wistar rat was examined by radioimmunoassay, and IAPP mRNA levels were determined by Northern blotting. IAPP-like immunoreactivity in the diabetic rat pancreas was found to be significantly depleted compared with control (non-diabetic) BB rats (85.9 +/- 5 pmol/g in control rats, n = 8, vs 8.97 +/- 0.9 pmol/g in diabetic rats, n = 5; mean +/- S.E.M.). A similar change in insulin concentrations was found, although insulin was present in approximately 100-fold greater amounts than IAPP. Chromatography of the IAPP immunoreactivity revealed a single molecular form, corresponding to synthetic IAPP. Northern blot analysis of pancreatic RNA (n = 4) revealed that IAPP mRNA in the diabetic group was depleted to 22% of the signal intensity in the control group. Insulin mRNA was dramatically reduced to only 4% of the control group and, in contrast, somatostatin was relatively unaffected, with the diabetic group retaining 86% of signal compared with the controls. This animal model of insulin-dependent diabetes results from severe autoimmune destruction of the beta cell. The extremely low levels of both insulin and its messenger RNA are in agreement with this. These results demonstrate that this pathological state is also associated with a loss of IAPP from the pancreas. Insulin-dependent diabetes is associated with a range of metabolic disturbances. It is possible that the concomitant depletion of IAPP may be a contributory factor in exacerbating the condition.

Amyloid↗

PubMed1991

Endothelin-like immunoreactivity in rat models of diabetes mellitus.

The factors associated with high concentrations of circulating plasma immunoreactive endothelin in patients with diabetes mellitus are unknown. Plasma and tissue (lung and kidney) immunoreactive endothelin levels were therefore measured by radioimmunoassay in three animal models of diabetes mellitus: dexamethasone-treated rats (2 mg/kg per day for 12 days), streptozotocin-treated rats (100 mg/kg, 4 days before being killed) and rats treated with both dexamethasone and streptozotocin. Plasma concentrations of immunoreactive endothelin in the dexamethasone-treated rats (3.13 +/- 0.28 pmol/l, mean +/- S.E.M., n = 15) were significantly (P less than 0.005) higher than those in controls (1.33 +/- 0.18 pmol/l, n = 15), while plasma concentrations of immunoreactive endothelin in streptozotocin-treated rats (n = 8) and rats treated with both dexamethasone and streptozotocin (n = 14) were undetectable (less than 0.5 pmol/l). Fast protein liquid chromatographic analysis of the plasma immunoreactive endothelin of dexamethasone-treated rats showed four peaks: one in the void volume, one eluting before endothelin-3, one eluting after endothelin-3 and before endothelin-1 and one eluting in a position identical with that of endothelin-1. Pulmonary concentrations of immunoreactive endothelin in the three groups of rats with diabetes mellitus were lower (P less than 0.005) but no significant change was found in renal immunoreactive endothelin. These findings indicate that short-term dexamethasone treatment increases plasma levels of immunoreactive endothelin while streptozotocin treatment decreases them. Thus, multiple factors may influence plasma concentrations of immunoreactive endothelin in diabetes mellitus.

Animals↗

PubMed1991

Hyperglycaemia but not hyperinsulinaemia prevents the secretion of glucagon-like peptide-1 (7-36 amide) stimulated by fat ingestion.

The effect of insulin and glucose on fat-induced gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1 (7-36 amide)) was studied in five healthy subjects during continuous glucose infusion (Protocol 1) and during hyperinsulinaemic euglycaemic blood glucose clamp (Protocol 2). In Protocol 1, 50 g fat was orally ingested and glucose was infused at a rate of 0.7 g/kg/h for 2 h continuously from the time of fat ingestion. Either glucose infusion alone or fat ingestion alone was carried out in the same subjects as the control. The release of GIP and GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state. In protocol 2, 50 g of fat was ingested and insulin was infused at a rate of 0.1 U/kg/h with an artificial pancreas system to obtain the normoglycaemic hyperinsulinaemic state. The release of GIP was significantly suppressed in the normoglycaemic hyperinsulinaemic state as well as in the hyperglycaemic hyperinsulinaemic state. However, the release of GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state but not in the euglycaemic hyperinsulinaemic state. Thus, it is concluded that insulin inhibits fat-induced GIP, but not GLP-1 (7-36 amide), secretion and that glucose is likely to inhibit GLP-1 (7-36 amide) secretion.

Adult↗