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Biomedical subjects

M Otsuki

Publications and source records attributed to M Otsuki.

At least 271 records · Page 15Linked to original sources
PubMed1985

[The disorder of vitamin D metabolism in patients with liver cirrhosis].

Liver cirrhosis (LC) is often associated with osteomalacia and osteoporosis. Since it has been shown that serum levels of 25 hydroxy vitamin D (25-OH-D) are reduced in LC, defective hepatic hydroxylation of vitamin D has been postulated to be responsible for the low serum 25-OH-D levels and skeletal demineralization. This study was designed, therefore, to determine serum 25-OH-D and 1 alpha, 25-(OH)2-D levels in patients with LC. Further, the response of serum 1 alpha, 25-(OH)2-D to a single oral dose of 1 alpha-OH-D3 (2 micrograms) was investigated. In 5 patients with severe decompensated LC and 3 patients with compensated LC, serum 25-OH-D and 1 alpha, 25-(OH)2-D levels were respectively measured by the modified method of Belsey and by that of Eisman. Serum 25-OH-D in patients with compensated and decompensated LC was significantly higher than that in normals. Serum levels of 1 alpha, 25-(OH)2-D in patients with decompensated LC were significantly lower than those in patients with compensated LC and normals. After a single oral administration of 1 alpha-OH-D3 at a dose of 2 micrograms, the 1 alpha, 25-(OH)2-D rose in each patient within 6h, reaching the maximum levels at 12h. The percent increase over the basal value in decompensated LC was similar to that in compensated LC.(ABSTRACT TRUNCATED AT 250 WORDS)

Dihydroxycholecalciferols↗
PubMed1985

Exocrine pancreatic function in rats after acute trypsin inhibitor treatment.

A single oral dose of synthetic trypsin inhibitor (TI, 20 mg/100 g) was given to rats by orogastric tube 6, 12, 18, or 24 hr before the removal of the pancreas and the preparation of isolated perfused pancreas. TI treatment induced no significant changes in body weight and total amount of DNA content in the pancreas, but pancreatic wet weight, total pancreatic protein and amylase, and the concentration of total protein and amylase relative to DNA were significantly decreased at 6 or 12 hr posttreatment, with a partial return toward control values at 18-24 hr after TI treatment. In isolated perfused pancreas, basal amylase output was similar in the control and in all 4 groups of TI-pretreated rats, while basal rate of flow of pancreatic juice was significantly increased at 12-24 hr posttreatment. Caerulein (0.1 ng/ml; 64 pM) stimulated pancreatic juice flow was greatly increased in rats pretreated with TI 12-24 hr earlier. In contrast, caerulein-stimulated amylase output was significantly lower in TI-pretreated groups compared with the control. However, when amylase output was related to the total content in the pancreas, the secretory responsiveness for amylase release was significantly higher in rats at 6-18 hr posttreatment compared with the control. The present study indicates that a single oral administration of TI modulates biological response to caerulein in the isolated perfused pancreas. The enhanced responsiveness of amylase release to subsequent stimulation is seen in early periods, while that of pancreatic juice flow is observed in late periods.

Amylases↗
PubMed1985

Comparative inhibitory effects of pirenzepine and atropine on cholinergic stimulation of exocrine and endocrine rat pancreas.

The effects of pirenzepine on carbamylcholine-stimulated exocrine and endocrine pancreatic functions were compared with those of atropine in both the isolated pancreatic acini and the isolated perfused pancreas of rats. In the isolated acini pirenzepine and atropine produced a concentration-dependent inhibition of amylase secretion initiated by carbamylcholine. This inhibition resulted in a rightward shift in the dose-response curve for carbamylcholine-stimulated amylase secretion without altering the maximal increase in amylase secretion. Pirenzepine was, however, approximately 300 times less potent than atropine in inhibiting the stimulated amylase release. A similar difference in potency was observed with respect to carbamylcholine stimulation of pancreatic juice, amylase, and insulin release from the isolated perfused pancreas. The maximal inhibitory concentration of pirenzepine on a maximal effective concentration of pirenzepine on a maximal effective concentration of carbamylcholine for stimulating pancreatic exocrine secretion was 10 microM, whereas that of atropine was 30 nM. The present data define the pirenzepine receptors in the exocrine and endocrine pancreas as low-affinity-type receptors.

Amylases↗
PubMed1985

Relationship between the severity of diabetes mellitus and pancreatic exocrine dysfunction in rats.

The relationship between the severity of diabetes mellitus and pancreatic exocrine function was investigated in rats made diabetic by injecting 3 different doses of streptozotocin (30, 45 or 60 mg/kg body weight). The expected correlation was obtained between the dose of streptozotocin and degree of elevation of blood glucose and decrease in pancreatic insulin content. Pancreatic amylase content of the diabetic rats was less than that of control rats and was in parallel with less values in pancreatic insulin content. On the other hand, trypsinogen content of diabetic rats was greater than that of control. Basal and caerulein-stimulated flow rates of pancreatic juice and protein output were similar in the control and in all 3 groups of diabetic rats. In contrast, there was a graded response of amylase and trypsinogen, depending upon the content of each enzyme in the pancreas. Both basal and caerulein-stimulated amylase outputs from diabetic rat pancreas were significantly reduced in parallel with the severity of diabetic state, but were similar to those from the control rats when related to the total pancreatic content. The present findings indicate that pancreatic exocrine dysfunction in diabetes mellitus is closely related to the severity of the disease, but the secretory dynamics in the perfused pancreas are not altered.

Amylases↗
PubMed1985

Interaction of caerulein, glucose, and amino acids on insulin secretion from the perfused rat pancreas.

The effect of caerulein on insulin response to graded amounts of glucose from the isolated perfused rat pancreas was investigated in the presence or absence of an amino acids mixture. Caerulein at a concentration of 0.1 ng/ml which is a submaximal concentration for an effect on exocrine pancreatic secretion potentiated insulin responses to glucose concentrations less than 200 mg/dl, but produced no further increase when added to a glucose stimulus over a 200 mg/dl. However, in the presence of amino acids the insulin response to 200 mg/dl glucose was significantly potentiated by the stimulation of 0.1 ng/ml caerulein. The effectiveness of caerulein as an insulinotropic agent depended on the glucose concentration only when amino acids were present. These results indicate that caerulein, at a concentration which stimulate pancreatic exocrine secretion, has a synergistic effect on insulin response to glucose and amino acids and therefore raises the possibility that endogenously released CCK may contribute to the entero-insular axis.

Amino Acids↗
PubMed1985

The intermediate filaments in human hepatocytes.

The intermediate filaments (IFs) in human hepatocytes were studied in biopsy specimens from patients with minimal histological changes. They were clearly visualized three-dimensionally by using polyethylene-glycol-embedding method after washing out cellular organelles and other components of cytoskeletons with a solution containing 0.15% Triton X-100 and saponin 0.5 mg/ml. We demonstrated that IFs were distributed throughout the cytoplasm in a meshwork fashion, attached to the junctional complex, encircled the bile canalicular lumen, and were directly attached to nucleus. Even after extensive washout of cytoplasmic structures, hepatocytes did not collapse, with the nuclei situated at due places in the cells. These findings may support the view that IFs play a role in nuclear positioning and in keeping the cytoplasmic space in human hepatocytes.

Adolescent↗
PubMed1985

Endotoxemia in liver diseases: detection by a quantitative assay using chromogenic substrate with perchloric acid pretreatment.

With a quantitative blood endotoxin assay using a chromogenic substrate with a perchloric acid pretreatment (PCA-LCT), endotoxemia in various liver diseases was studied. With PCA-LCT, recovery of added endotoxin in human plasma was nearly 90%, as evidenced by an intra- and inter-assay coefficients of variation of 5.7% and 11%, respectively. Because the recovery of endotoxin was not affected in severely icteric plasmas, PCA-LCT proved to be applicable to patients with liver diseases where various degree of jaundice exist. In none of the plasmas from patients with chronic hepatitis, acute hepatitis without hepatic failure or liver cirrhosis without ascites did the endotoxin level exceed the normal range of less than 5 pg/ml. With the presence of ascites, however, endotoxemia became detectable, but at low levels and not in all cases. At the stage of hepatic failure complicated with renal failure or disseminated intravascular coagulation, endotoxemia was more frequent and endotoxin concentration greater. It is uncertain, at present, whether endotoxemia itself is deteriorating factor in hepatic failure or is merely concomitant phenomenon resulting from Kupffer cell failure.

Ascites↗
PubMed1985

Three-dimensional structure of cytoskeletal system in human hepatocytes viewed by polyethylene-glycol-embedding method.

In an attempt to demonstrate the three-dimensional cytoskeletal system of human hepatocytes, we used two kinds of tissue processing. In one, specimens were immediately fixed with 1% glutaraldehyde, saponin 0.5 mg/ml, and tannic acid 2 mg/ml (procedure A) and in the other, cytoplasmic matrix and organelles were washed out with a solution containing saponin 0.5 mg/ml and 0.15% Triton X-100, followed by fixation with glutaraldehyde (procedure B). The specimens were embedded in polyethylene glycol, sectioned at 500 nm, critical point-dried and observed in a TEM. With procedure A, a fine lattice was shown to spread throughout the cytoplasm so as to connect plasma membranes with cytoplasmic organelles, condensed around the bile canaliculi. With procedure B, microfilaments, microtubules and intermediate filaments could be clearly visualized three-dimensionally instead of the lattice structure. At a higher magnification, microvilli of canaliculus were found to contain a core microfilament which were enmeshed in a pericanalicular filament plexus. This plexus looking like the terminal web of intestinal epithelia, encircled the canaliculus and was attached to the zonula adherens. Outside the plexus, intermediate filament network was shown attached to the desmosome. These morphological findings indicated that the cytoskeleton of human hepatocytes is composed of microfilaments, microtubules, intermediate filaments and the fine lattice structure, suggesting that the bile canaliculi could contract in vivo.

Actin Cytoskeleton↗
PubMed1984

Serum pancreatic secretory trypsin inhibitor in pancreatic disease.

The clinical usefulness of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic diseases was evaluated. The mean serum PSTI level of 41 healthy normal persons was 9.4 ng/ml (ranging from 5.2 to 16.7 ng/ml). Serum PSTI levels were abnormally raised in all patients with acute pancreatitis ranging from 35.0 to 4500 ng/ml, but were almost within normal range in patients with chronic pancreatitis, pancreatic cyst, acute abdominal emergencies such as perforated ulcer and intestinal obstruction, and macroamylasemia. There was no correlation between serum PSTI levels and total or pancreatic-type isoamylase activity. Patients with acute pancreatitis in whom the elevation of serum PSTI was transient and occurred after that of serum amylase activity had relatively mild symptoms and recovered along with normalization of serum PSTI levels. On the other hand, patients whose serum PSTI values became increased coincidentally with serum amylase activity and remained elevated, had severe clinical symptoms and unfavorable clinical outcome. Of 2 patients who underwent partial pancreatectomy, the serum PSTI level increased markedly in one who developed postoperative pancreatitis but not in the other without pancreatitis. In contrast to patients with acute pancreatitis, the serum response to the secretin stimulation in patients with chronic pancreatitis, was only small and transient, reaching the maximum at 10 min after administration of secretin. These results suggest that measurement of serum PSTI concentration may be useful in the diagnosis of acute pancreatitis and that the degree of rise and the duration of the elevated levels of serum PSTI are closely related to the severity of acute pancreatitis.

Acute Disease↗
PubMed1984

Exocrine and endocrine secretion from isolated perfused rat pancreas with islet cell tumors induced by streptozotocin and nicotinamide.

Pancreatic exocrine and endocrine function in the rat with islet cell tumors induced by streptozotocin and nicotinamide was studied in the in vitro isolated perfused pancreas. The tumor-bearing pancreas secreted significant amounts of insulin even at 2.8 mM glucose stimulation. Further, insulin response to 8.3 mM glucose stimulation was greater in the tumor-bearing pancreas than in the control. Not only endocrine, but also exocrine, disorders were found in the rat pancreas bearing islet cell tumors. In contrast to the increased response of insulin, amylase output in response to 0.1 ng/ml cerulein was significantly lower in the tumor-bearing than in the control pancreas, although there was no difference in pancreatic juice flows from both groups. These results suggest that enzyme secretory function of the pancreas with islet cell tumors may be suppressed in the presence of some interrelationship between the exocrine and endocrine portion of the pancreas with islet cell tumors.

Adenoma, Islet Cell↗
PubMed1984

Amylase inhibitor from wheat: its action and clinical application.

The electrophoretic and column chromatographic characteristics of an amylase inhibitor of wheat origin were investigated. Further, the clinical usefulness of this inhibitor for determining the ratio of pancreatic to salivary isoamylase activity in serum was evaluated. Amylase inhibitor inhibits the action of salivary alpha-amylase by making an amylase-inhibitor complex, which is easily separated into its individual component during electrophoresis with full recovery of amylase activity. Using the specific inhibitory effect of this inhibitor on salivary alpha-amylase activity, the ratio of pancreatic to salivary isoamylase activity (P/S) in serum was determined. There was a good correlation in P/S ratio in serum between the results obtained with the inhibitor method and those with electrophoretic method. The P/S ratio in sera from patients with acute pancreatitis was over 8.0, whereas that in sera from patients with salivary-type hyperamylasemia such as mumps, pulmonary diseases and following surgery was less than 0.1. However, hyperamylasemia due to macroamylase or renal failure could not be identified by the inhibitor method.

Amylases↗
PubMed1984

Effect of short-term peroral administration of synthetic trypsin inhibitor on endocrine secretion in the isolated perfused rat pancreas.

The effects of peroral treatment with synthetic trypsin inhibitor on endocrine secretion in response to four different stimuli were investigated in the isolated perfused rat pancreas. After 10 days' treatment pancreatic wet weights and protein and amylase contents in the pancreas were significantly increased. On the other hand, total contents of IRI and IRG in the T.I.-treated and control pancreas were nearly the same. In spite of the lack of alteration in hormone contents, a lower initial phase of IRI response to 8.3 mM glucose, glucose plus 0.1 ng/ml caerulein or 20 mM arginine was observed in the T.I.-treated pancreas. Furthermore, the IRI response to 10 mM theophylline was both slower and the most reduced in the T.I.-treated pancreas. From these observations, it is suggested that short-term peroral administration of synthetic trypsin inhibitor not only has no trophic effect on pancreatic B-cell and A-cell in the rat but also may affect some pathway of insulin secretion from the B-cell to reduce IRI responses to secretagogues.

Amylases↗
PubMed1984

Amylase secretion by isolated pancreatic acini after acute cholecystokinin treatment in vivo.

A single dose of synthetic cholecystokinin octapeptide (CCK8, 5 micrograms/kg) in a depot carrier was injected subcutaneously into rats 2 and 14 h before the removal of the pancreas and the preparation of isolated pancreatic acini. CCK8 treatment induced no significant change in body weight or total amount of pancreatic DNA, but pancreatic weight, total pancreatic protein and amylase, and the concentration of amylase and total protein relative to DNA were significantly decreased. In acini prepared from CCK8-pretreated rats, responsiveness to maximal and supramaximal concentrations of CCK8 was significantly increased, irrespective of whether the amount of amylase released was expressed relative to DNA or calculated as a percentage of the acinar content. The dose-response curves for CCK8 were similarly shaped in both CCK8-pretreated and control rats but shifted threefold toward higher concentrations of CCK8 2 or 14 h after CCK8 treatment. Specific 125I-CCK binding was significantly increased only for high-affinity binding sites. Although these observations suggest that alterations in pancreatic amylase release could be due to changes at the cholecystokinin receptor, the secretory responsiveness to maximal and supramaximal concentrations of carbachol was also increased without any change in the sensitivity. Moreover, in contrast to the cholecystokinin receptor, there was no change in the number of muscarinic receptors or in their affinity for either agonists or antagonists measured with [3H]quinuclidinyl benzilate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Morphologic study of cytoskeletal systems of mouse hepatocytes using polyethylene glycol-embedding method.

SM mouse livers extracted by immersion in 1% Triton X-100, or in 1% Triton X-100 followed by 0.3 M KI were studied electron microscopically using the polyethylene glycol-embedding method. After extraction with 1% Triton X-100, almost all the structural components of hepatocytes remained intact and cytoplasmic filaments could be seen three-dimensionally by using stereopairs of micrographs. It was difficult, however, to discriminate microfilaments, intermediate-sized filaments and microtubules from one anoter in these specimes . By immersion in 1% Triton X-100 followed by 0.3 M KI, hepatocytes were extracted remaining only plasma membranes, vesicles and filaments. These filaments were approximately 10 nm in diameter, that is intermediate in size. They were branched and were connected with plasma membranes, especilly at desmosomes. The combination method of immersion extraction and PEG-embedding seems to be suitable for the electron microscopic observation of the cytoskeleton of cells in situ.

Animals↗
PubMed1984

Diabetes in the rat is associated with a reversible postreceptor defect in cholecystokinin action.

Diabetes in the rat is associated with a selective decrease in the sensitivity of pancreatic acini to the secretagogue cholecystokinin. In these animals the concentration of cholecystokinin-33 that maximally stimulates amylase release from isolated pancreatic acini shifts from 300 pM in normal animals to 1 nM in animals made diabetic with streptozotocin. To evaluate the role of the cholecystokinin receptor in this loss of sensitivity, specific 125I-cholecystokinin-33 binding to its receptors on acini was measured. When compared with controls, acini from diabetic rats bound more cholecystokinin at all hormone concentrations. In diabetes, the total cholecystokinin binding capacity of acini increased from 157 fmol/mg to 362 fmol/mg acinar protein. Moreover, the amount of cholecystokinin bound at a maximally stimulating cholecystokinin concentration increased fourfold from 11 to 44 fmol/mg acinar protein. When diabetes was reversed by treatment with insulin, both the altered secretory responses and the increased binding of 125I-cholecystokinin returned to normal. These data indicate, therefore, that the decreased sensitivity of pancreatic acini from diabetic rats is due to an impaired ability of receptor bound cholecystokinin to initiate its cellular response.

Amylases↗