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Biomedical subjects

A Noda

Publications and source records attributed to A Noda.

At least 145 records · Page 8Linked to original sources

Effect of dimethadione derived from repeated oral administration of trimethadione on pancreatic secretion in dogs.

The effect of the weak organic acid of dimethadione (DMO) on secretin-stimulated pancreatic secretion was studied with repeated oral administration of trimethadione (TMO), the precursor of DMO, to dogs at a dose of 10 to 160mg/kg/day for a period of 14 days. The bicarbonate concentration in pancreatic juice at a steady state decreased significantly, reflecting a close correlation with the dose of TMO and DMO concentrations in plasma and pancreatic juice. The maximal decrement from the control of cases of no TMO administration was 18.8 mEq/l (12.1% of the control level). The chloride concentration in pancreatic juice showed a reciprocal relation to the bicarbonate concentration. The sum of both anion concentration was constant, irrespective of the dose of TMO. The average carbon dioxide tension of pancreatic juice in all doses of TMO was lower than that of the control, but differences were not statistically significant. The pH, flow rate, sodium and potassium concentrations in pancreatic juice at a steady state did not differ significantly in relation to the dose of TMO. These findings suggest that repeated oral administration of TMO cause a significant decrease in bicarbonate concentration in pancreatic juice, resulting probably from the buffer action of bicarbonate on protons provided from the undissociated form of DMO.

Administration, Oral↗

Pancreatic excretion of dimethadione and trimethadione by repeated oral administration of trimethadione in dogs.

To examine pancreatic excretion of dimethadione (DMO), a weak organic acid, as well as of its precursor trimethadione (TMO), TMO was given orally to dogs with pancreatic fistulae at a dose of 10-160 mg/kg/day over a period of 14 days. Blood samples were taken once a day during the administration of TMO and for 7 days after discontinuation of the drug. On the 15th day, pancreatic juice was collected under stimulation by secretin (2 Crick-Haper-Raper units/kg/h). DMO concentration in plasma reached a maximal plateau around the 10th day after starting TMO administration, and depended directly on the dose of TMO. Pancreatic excretion of DMO at a steady state closely depended on both the dose of TMO and the DMO concentration in plasma. The pancreatic juice/plasma concentration ratio for DMO exceeded 1.0 at a steady rate and decreased with the increased flow rate. Pancreatic DMO clearance (DMO output/DMO concentration in plasma) increased, depending on the flow rate, the bicarbonate concentration, and pH of pancreatic juice. Pancreatic excretion of TMO was zero or extremely low.

Administration, Oral↗

[Heart rate changes in sleep apnea syndrome].

Sleep apnea syndrome (SAS) is often associated with arrhythmias. The study was performed to clarify the characteristics and mechanisms of the heart rate (HR) changes during and after sleep induced apneas. Thirty-one patients with SAS without definitive heart disease, aged 17-78 years (mean 54.2 years), were examined by electroencephalograms, electrocardiograms, electrooculograms, nasal and oral breathing, thoracic and abdominal respiratory movements and arterial oxygen saturation (SaO2). [Results and Discussion] At the onset of sleep apnea, some showed progressive reductions in HR, followed by abrupt tachycardia on the resumption of breathing. Thirty-one patients with SAS were classified into three Groups (A, B, C). Group A demonstrated that HR changes occurred associated with apnea both in stage REM and in stage non-REM. Group B demonstrated that HR changes occurred associated with apnea only in stage REM. Group C demonstrated that HR changes did not occur associated with apnea. In Group A, apnea frequency and apnea index were higher than those of Group C. In Group A, the lowest SaO2 was lower than that of Group C, total time under 90% of arterial oxygen saturation (SaO2) was longer than that of Group C. There was a good negative correlation between oxygen saturation and HR changes. Further, HR changes were augmented by arousal response. This might be related to the arousal response as well as to the cardiostimulatory effects of hypoxia associated with increased ventilation. The arousability in response to apneas might be important in HR changes. In SAS, the degree of HR changes was related to apnea frequency, apnea index, apnea length and sleep stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of metaphit on phencyclidine and serotonin2 receptors.

We have investigated whether metaphit, a derivative of phencyclidine (PCP) which irreversibly binds to a population of PCP receptor sites in rat brain, blocks PCP-induced head-twitch response which is produced through serotonin2 (5-HT2) receptors, and also whether metaphit decreases the capacity of 5-HT2 receptors. Metaphit (1 mumol/rat) had decreased the intensity of PCP-induced head-twitch response and had depleted both PCP and 5-HT2 receptors by 24 h after administration, but it failed to block 5-HT agonist 5-methoxy-N,N-dimethyltryptamine-induced 5-HT1A receptor-dependent behaviors. These results reconfirmed our hypothesis that PCP and 5-HT2 receptors may have very similar binding sites.

Animals↗

Exoribonuclease activity of purified reverse transcriptase preparations from retroviruses.

Highly purified and commercially available preparations of reverse transcriptases from retroviruses contain a 3' to 5' exoribonuclease activity capable of hydrolyzing synthetic homopolyribonucleotides having a 3'-OH end. The exoribonuclease activity of reverse transcriptase preparations from Rous associated virus-2 was further characterized. This exoribonuclease activity cleaves poly(C) and poly(U) exonucleolytically from the 3'-OH end to produce nucleoside 5'-phosphates. Poly(A), poly(G), circular polyribonucleotide, and double-stranded polyribonucleotide were not hydrolyzed by the activity. This is a novel type of exoribonuclease activity.

Buffers↗

A case of double pylorus accompanied by adrenal adenoma.

We report here a case of double pylorus diagnosed endoscopically in a patient with adrenal adenoma. A 44-yr-old man was found to have double pylorus during examinations for recurrent epigastric pain and obesity. We think that the formation of double pylorus in this case resulted from recurrent peptic ulcer which, in turn, probably was induced by the hypersecretion of endogenous corticosteroids accompanying adrenal adenoma.

Adenoma↗

Quantitative and qualitative characterization of human cancer-associated serum glycoprotein antigens expressing epitopes consisting of sialyl or sialyl-fucosyl type 1 chain.

The levels of carbohydrate antigens having epitopes consisting of type 1 chain (R----Gal beta 1----GlcNAc beta 1----3Gal beta 1----R) in the sera of patients with various malignant and nonmalignant disorders have been investigated with the use of three monoclonal antibodies, N-19-9, FH-7, and FH-9. Serum levels of 2----3 sialylated Lea antigen and 2----6 sialylated Lea antigen, defined respectively by antibodies N-19-9 and FH-7, were found to be frequently high in patients with cancer of the digestive system, particularly pancreatic cancer. High levels of 2----3,2----6 disialylated Lc4 antigen, defined by antibody FH-9, were less frequent in cancer patients when compared with the other two antigens. In patients with nonmalignant disorders, especially renal and autoimmune diseases, serum levels of the two type 1 chain antigens defined by FH-7 and FH-9 were more frequently high than that defined by N-19-9. Molecular weights and other general biochemical characteristics of serum mucin carrying the type 1 chain determinants were not significantly different in cancer patients as compared with patients with nonmalignant disorders. However, the degree of glycosylation of the antigen, as assessed by its solubility in perchloric acid, showed significant differences; i.e., the mucin antigen carrying 2----6 sialylated Lea determinant in the sera of patients with nonmalignant disorders had the highest carbohydrate/protein ratio, followed by the mucin carrying the same determinant in the sera of cancer patients. Mucin antigen carrying 2----3 sialylated Lea antigen or 2----3, 2----6 disialylated Lc4 antigen in cancer patients had the lowest carbohydrate/protein ratio among the four groups tested. Thus, the carbohydrate/protein ratio in the type 1 chain mucin antigens in sera of normal subjects is higher than that in sera of cancer patients (P less than 0.05). This finding is in contrast to previous findings on the mucin antigens carrying the type 2 chain determinant (R. Kannagi et al., Cancer Res., 46: 2619-2626, 1986), in which the mucin antigen in cancer patients was found to have a much higher carbohydrate/protein ratio than that carrying the same antigenic determinants in patients with nonmalignant disorders.

Antibodies, Monoclonal↗

Hydrazine radical formation catalyzed by rat microsomal NADPH-cytochrome P-450 reductase.

Using NADPH-cytochrome P-450 reductase purified from rat liver microsomes, the oxidation of hydrazine to its radical was proved to proceed smoothly. The catalytic effect of NADPH cytochrome P-450 on the radical formation in the hepatic microsomes obtained from phenobarbital-pretreated rats was also supported by the fact that Hz radical formation was stimulated by flavin adenin dinucleotide or methyl viologen and markedly inhibited by superoxide dismutase, however, carbon monoxide showed no effect. Expectedly, anti-NADPH-cytochrome P-450 IgG decreased the radical formation. The present study provides the first evidence for the NADPH-cytochrome P-450 reductase catalyzed oxidation of hydrazine to its radical in the presence of O2 and NADPH.

Animals↗

Glycolipid-directed FH6 monoclonal antibody recognizes high molecular weight glycoprotein antigen carrying sialyl Lex-i determinant in the culture supernatant of PC-9 cells.

The properties of the antigen recognized by monoclonal antibody FH6 have been analyzed. FH6 was originally generated against a glycolipid, i.e. a difucoganglioside isolated from human colonic adenocarcinoma, and specifically reacts with sialyl Lex-i determinant. Several culture supernatants of human carcinoma cell line cells were found to have high levels of FH6-reactive antigen, and PC-9, a human lung carcinoma cell line was used for the analysis. A solid-phase sandwich radioimmunoassay was performed to detect the antigen. The antigenic activity was extractable in 0.6 M PCA or 7% TCA, and was sensitive to mild alkaline treatment and to Pronase digestion. Most of the antigen was eluted in the void volume of a Sepharose CL-2B column, which indicates that its molecular weight is greater than several million. It was eluted from a DEAE-cellulose column at a NaCl concentration in the range of 0.2-0.25 M. The immunoaffinity-purified antigen has a high carbohydrate content of more than 80%. These data indicate that the antigen recognized by FH6 in the culture supernatant of PC-9 is not a glycolipid, but a high molecular weight glycoprotein which could be referred to as a mucin, or a proteoglycan, which contains keratan-sulfate like glycosaminoglycan chains, as judged from the results of the glycosidase treatments.

Antibodies, Monoclonal↗

Macroautoradiographic and densitometric studies of [14C]dimethadione in rats: accumulation of the compound in the pancreas.

Whole-body autoradiographic and densitometric distribution studies were performed on rats to investigate the accumulation of [14C]dimethadione (DMO) in the pancreas. [14C]DMO was intravenously administered at a dose of 167 microCi/0.5 mg/kg. Animals were sacrificed 1, 15, 30, 60 and 180 min after administration of the radioactive compound. The compound was found to rapidly distribute in all body tissues. The distribution pattern of the compound in the pancreas was spotty or linear due to the presence of the radioactive compound in blood of intrapancreatic vessels and in pancreatic ducts at higher levels than parenchyma. The radioactivity of pancreatic ducts became more evident with time, indicating the gradual accumulation of the compound in the ducts. These findings provide morphological evidence that DMO is accumulated in the pancreas and possibly eliminated from pancreatic juice. Densitometry revealed that the levels of radioactive compound in the pancreas were virtually as high as those in the liver and kidney.

Animals↗

Replicon initiation in normal human cells and in ataxia telangiectasia cells: its differential inhibition by cycloheximide and bleomycin.

Treatment of normal human fibroblasts (NHFs) with cycloheximide, which inhibits protein synthesis, resulted in partial inhibition of their DNA synthesis, as determined by incorporation of radioactive thymidine and resistance of the cells to subsequent treatment with bleomycin. The effects of treatments of ataxia telangiectasia fibroblasts (ATFs) with cycloheximide and then bleomycin on their DNA synthesis were very similar to those on DNA synthesis of NHFs. The fact that treatment with bleomycin only caused transient inhibition of DNA synthesis within an hour in NHFs but not ATFs was confirmed. Studies by alkali-density gradient centrifugation showed that the cycloheximide mainly inhibited formation of short fragments of DNA in both NHFs and ATFs, as bleomycin does in NHFs. These findings suggest that these two chemicals both inhibit replicon initiation, and thus provide evidence that the genetic defect in ATFs is related to replicon initiation.

Ataxia Telangiectasia↗

[Effects of ethylcholine mustard aziridinium ion (AF64A) administered intraperitoneally on cholinergic nerves in rat brain].

Rats injected i.p. with AF64A at a dose of 1/3 to 11/25 LD50 showed transient signs of motor disturbance such as ataxia, squatting down and respiratory distress and also longer lasting signs consisting of adipsia, aphagia and loss of body weight. Twenty-four hours after a single injection with AF64A (129 mumol/kg), ACh contents in the cerebral cortex, hippocampus and striatum decreased significantly, and the content in the cerebral cortex still remained at a lowered level even 10 days after injection. When rats received AF64A i.p. with an initial dose of 129 mumol/kg and nine consecutive daily doses of 12.9 mumol/kg and thereafter they were kept with no medication for at least 20 days, the ACh contents in the three brain regions were still significantly reduced. ACh release by electrical stimulation or K+, but not spontaneous release, was significantly reduced in the AF64A treated rats. The T-maze spontaneous alternation behavior in rats treated with AF64A was impaired. The present results indicate that AF64A administered i.p. can induce a long lasting defect in central cholinergic transmission.

Acetylcholine↗

The sign of Leser-Trélat associated with carcinoma of the stomach.

The sign of Leser-Trélat, which refers to the sudden appearance and rapid increase in size and number of seborrheic keratosis associated with a visceral malignant tumor, is very uncommon. This case concerns a 54-yr-old woman presenting with Leser-Trélat's sign associated with advanced gastric cancer. Seborrheic keratosis faded after resection of the tumor, but returned when the cancer recurred. At that time, 24-h urinary excretion of epidermal growth factor determined by radioreceptor assay was slightly elevated. Epidermal growth factor may play a part in the development of Leser-Trélat's sign.

Adenocarcinoma, Mucinous↗

Chronic pancreatitis at early age of onset presenting interesting findings through endoscopic retrograde pancreatography and chemical analysis of nonopaque pancreatic concretion.

This case concerns a 20-year-old male patient with an approximate 10-year history of recurrent and severe abdominal pain radiating to the back. Endoscopic retrograde cholangiopancreatography revealed a short obstructing stenosis of the main pancreatic duct in the head of the pancreas, marked and tortuous dilatation of the prestenotic portion of the main pancreatic duct and its side branches, and a filling defect in the side branch in the body of the gland. Pancreaticojejunostomy was performed to induce decompression of the pancreatic duct. Histology of the pancreas showed advanced chronic pancreatitis. Three nonopaque concretions were obtained at operation. The largest one, which was milky white in appearance and elastic and soft in consistency, proved to be made up of protein. The concretion was rich in acidic amino acids, but poor in basic or aromatic residues. The molar composition of amino acids in the concretion was, in decreasing order, aspartic acid, serine, valine, glycine, and glutamic acid. Powder x-ray diffractometry revealed no crystalline structures.

Adult↗

Dissolution of pancreatic stones by oral trimethadione in a dog experimental model.

Experiments were conducted to develop a dissolution therapy for human pancreatic calculi in a dog experimental model of pancreatic calculi surgically prepared. On plain x-ray films of the abdomen, pancreatic calculi appeared in 19 of 39 dogs within 12 mo after operation. The antiepileptic agent trimethadione was given orally to 13 dogs at a dose of 1.0-1.5 g daily. Pancreatic calculi disappeared in 13 of 15 observations. The scanning electron microscopy, the elemental analysis, and the powder x-ray diffractometry of pancreatic calculi in this model revealed that the calculi closely resembled human pancreatic calculi, consisting mainly of a calcite of calcium carbonate. There was no histologic finding suggesting drug toxicity in the liver, the kidney, and the blood. Pancreatic calculi in 6 control dogs without the treatment neither disappeared nor diminished spontaneously. The oral treatment with trimethadione may have potential for dissolving human pancreatic calculi.

Administration, Oral↗

The roles of different excision-repair mechanisms in the resistance of Micrococcus luteus to UV and chemical mutagens.

M. luteus mutants showing increased sensitivity to both UV and 4-NQO were isolated after the treatment of parental ATCC4698 strain with MNNG. The mutants were also highly sensitive to mitomycin C, cis-platinum, 8-methoxypsoralen (8-MOP) plus near-UV and angelicin plus near-UV in various degrees. The endonuclease activity specific for pyrimidine dimers in UV-irradiated DNA was normally detected in extract of the mutants. With regard to host-cell reactivation ability the mutants fell into two groups. The hcr- mutants lacked the ability to reactivate UV-damaged N6 phage and were resistant to X-rays. The incision of DNA did not occur during incubation after the treatment with angelicin plus near-UV in the hcr- mutants, whereas it occurred in the parental strain. The facts indicate that the hcr- mutants are defective in the incision mechanism which has a wide substrate specificity, similar to the UVRABC nuclease of E. coli. On the other hand, the incision of DNA and the removal of UV-induced thymine dimers from DNA occurred in the hcr- mutants as well as in the parental strain, which is ascribed to the UV endonuclease activity. Compared with the hcr- mutants, hcr+ mutants were highly sensitive to X-rays, like recA- mutants of E. coli.

4-Nitroquinoline-1-oxide↗