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Biomedical subjects

S Kitazawa

Publications and source records attributed to S Kitazawa.

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

Usefulness of rapid production model for pancreatic carcinoma in male hamsters.

The rapid production model of pancreatic duct adenocarcinoma established previously in female Syrian hamsters was applied to male hamsters to confirm the efficacy of the "augmentation pressure" procedure and to reveal sex difference in response to this procedure. Hamsters received 70 mg/kg N-nitrosobis (2-oxopropyl) amine (BOP) as an initiation and two cycles of "augmentation pressure" consisting of ethionine on a choline-deficient diet, methionine and BOP and an additional 20 mg/kg BOP and were killed 10 weeks after the beginning of the experiment. During the experimental period, 28% of the hamsters died and severe body weight loss was observed, however, incidence of pancreatic carcinomas reached 50% which is a significantly higher level than that in hamsters which received BOP without "augmentation pressure". A 66.7% yield of cholangiocellular tumors was also observed. The present result indicates that the "augmentation pressure" effected rapid production of pancreatic carcinoma in male hamsters in spite of sex difference in response.

Animals↗
PubMed1990

Enhanced preneoplastic liver lesion development under 'selection pressure' conditions after administration of deoxycholic or lithocholic acid in the initiation phase in rats.

The initiating potential of the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), for rat hepatocarcinogenesis was investigated using the development of hyperplastic nodules and/or glutathione S-transferase placental form (GST-P)-positive liver foci as the end point. Five week old male F344 rats were given either basal diet, or diets containing 0.5% DCA or 0.5% LCA for 3 weeks in conjunction with partial hepatectomy performed midway, followed by a selection regimen consisting of 2 weeks feeding of 0.02% 2-acetylaminofluorene diet and a single gastric intubation of carbon tetrachloride. The animals were then placed on either basal diet or a diet containing 0.05% phenobarbital (PB) for 52 weeks. Significantly higher numbers of hyperplastic liver nodules developed in the DCA-treated rats irrespective of PB promotion as compared with the respective control groups. No such increase was evident in the LCA-treated rats. In contrast, both DCA and LCA treatments enhanced the development of GST-P-positive liver foci with or without subsequent PB promotion. Only one hepatocellular carcinoma was diagnosed in a control group animal. The present data indicate that a short period of feeding of DCA and LCA in the initiation stage in conjunction with partial hepatectomy results in enhanced development of preneoplastic liver lesions under selection pressure conditions with or without subsequent PB promotion. They thus confirm and extend our previous finding of enhanced gamma-glutamyltranspeptidase-positive liver foci development in a short-term assay of DCA and LCA, and suggest that these secondary bile acids either possess possible initiating activity or some other priming effect for rat hepatocarcinogenesis.

Animals↗
PubMed1990

Inhibition of pancreatic hepatocyte induction in hamsters treated sequentially with ethionine, a protein-free diet and then methionine by prior N-nitrosobis-(2-oxopropyl)amine administration.

A 100% yield of pancreatic hepatocytes was induced in pancreas tissues of female hamsters treated with twice-repeated sequential administrations of DL-ethionine (ethionine) together with a protein-free diet and then L-methionine (methionine) for 10 weeks. The cells were also found in 40% of hamsters receiving 20 mg/kg body weight of the pancreatic carcinogen, N-nitrosobis(2-oxopropyl)amine (BOP) given twice at the peak of pancreatic regeneration stimulated by methionine after ethionine-induced cell damage. However, BOP at doses of 30, 70, and 100 mg/kg body weight administered before the occurrence of pancreatic regeneration dose-dependently inhibited their appearance, with reduction of the yield to 40%, 25%, and 8.3% respectively, and BOP per se did not induce any development of pancreatic hepatocytes. Stein iodine staining revealed bile pigments in the induced hamster pancreatic eosinophilic cell populations.

Adenocarcinoma↗
PubMed1990

[An autopsy case of extramural malignant leiomyoblastoma of the stomach with ovarian cancer: an immunohistochemical study].

The subject was an 85-year-old woman, who had been diagnosed as having an ovarian cancer and carcinomatous peritonitis and had been treated conservatively. She subsequently died from respiratory and renal insufficiency, and the autopsy that followed revealed that her pelvic cavity had been filled by a tumorous mass that size of a child's head. Histologically, the tumor was a serous cystadenocarcinoma of the ovary. Moreover another tumor, also the approximate size of a child's head, was found sited extramurally, beneath the posterior wall mucosa of the stomach body. Histological inspection of this tumor revealed a proliferation of round oval, and spindle-shaped tumor cells. A vacuolation of the cytoplasms and karyomitosis to the extent of 10/50 HPF also were observed. Based on the findings of being positive for Vimentin and a negative EMA, this tumor was diagnosed as being a malignant leiomyoblastoma of the stomach smooth muscle. The leioblastoma is a relatively uncommon neoplasm, and recent advances in immunohistochemical staining have indicated that some of these tumors are not only of smooth muscle derivation but also of nerve origin. Therefore, this tumor, given its morphological characteristics, had been generalized in this case as a gastric stromal tumor, and with negative findings for Desmin and S-100 protein, as well as positive for Vimentin.

Aged↗
PubMed1989

A physiological and morphological study of premotor interneurones in the cutaneous reflex pathways in cats.

Implantation of an HRP-pellet into motor nuclei at the T1 segment resulted in retrograde labelling of laminae V-VII neurones densely at C6-C8 in cats. Electrophysiological experiments showed the presence of neurones in this region that received inputs from skin afferents and cortico- and rubrospinal tracts, sent axons descending in the lateral funiculus, and distributed in the motor nucleus at T1. Termination in T1 motor nuclei was also verified by intra-axonal staining with HRP. The input and output properties of these neurones indicated that they can be premotor neurones of skin reflex pathways to T1 motoneurones.

Animals↗
PubMed1989

Functional identification of last-order interneurones of skin reflex pathways in the cat forelimb segments.

Premotor neurones mediating skin reflex actions onto cat forelimb motoneurones at T1 were identified by observing their monosynaptic effects on motoneurones by means of spike-triggered averaging. Both excitatory and inhibitory premotor neurones, with mono- or polysynaptic inputs from skin afferents, were identified at C7 to rostral C8, and were found mostly in laminae V-VI. They received excitatory inputs from corticospinal and rubrospinal tract fibres.

Action Potentials↗
PubMed1989

In situ DNA-RNA hybridization using in vivo bromodeoxyuridine-labeled DNA probe.

An in vivo 5'-bromodeoxyuridine (BrdUrd) labeled DNA probe was used for in situ DNA-RNA hybridization. BrdUrd was incorporated into plasmid DNA by inoculating E. coli with Luria-Bertani (LB) culture medium containing 500 mg/L of BrdUrd. After purification of the plasmid DNA, specific probes of the defined DNA fragments, which contained the cloned insert and short stretches of the vector DNA, were generated by restriction endonuclease. The enzymatic digestion pattern of the BrdUrd-labeled plasmid DNA was the same as that of the non-labeled one. BrdUrd was incorporated in 15%-20% of the total DNA, that is, about 80% of the thymidine was replaced by BrdUrd. Picogram amounts of the BrdUrd-labeled DNA probe itself and the target DNA were detectable on nitrocellulose filters in dot-blot spot and hybridization experiments using a peroxidase/diaminobenzidine combination. The BrdUrd-labeled DNA probe was efficiently hybridized with both single stranded DNA on nitrocellulose filters and cellular mRNA in in situ hybridization experiments. Through the reaction with BrdUrd in single stranded tails, hybridized probes were clearly detectable with fluorescent microscopy using a FITC-conjugated monoclonal anti-BrdUrd antibody. The in vivo labeling method did not require nick translation steps or in vitro DNA polymerase reactions. Sensitive, stable and efficient DNA probes were easily obtainable with this method.

Bromodeoxyuridine↗
PubMed1989

Inhibitory effect of free fatty acids on plasma protein binding of disopyramide in haemodialysis patients.

The plasma (or serum) protein binding of disopyramide (DSP) in five haemodialysis patients was studied using an ultrafiltration technique. There was an increase in the free fraction of DSP in the plasma on dialysis days in comparison to the levels on interdialysis days, which was associated with an elevation of the free fatty acid levels in the plasma together with the increase of the free fraction of DSP. The inhibitory effect of free fatty acids on DSP binding in an in vitro study was enhanced in proportion to their concentrations, and was shown to be due to competition at one binding site by experiments with oleic acid as a representative displacer. Certain endogenous organic acids, such as indoxyl sulphate, 2-hydroxyhippuric acid and hippuric acid, which are characteristically elevated in chronic renal failure, scarcely affected the protein binding of DSP. The findings indicate that free DSP should be monitored in patients with elevated plasma free fatty acid levels, such as those on haemodialysis therapy.

Adult↗
PubMed1989

Possible involvement of arachidonic acid metabolism in phenobarbital promotion of hepatocarcinogenesis.

The effects of inhibitors of arachidonic acid metabolism and antioxidants on the rat liver tumor promotion activity of phenobarbital (PB) were assessed using the enzyme-altered focus as the end-point lesion. Fischer 344 male rats were initiated with N-nitrosodiethylamine (200 mg/kg) and then divided into five groups placed on basal diet, diet containing 0.05% PB, diet containing 0.05% PB plus 0.75%, 1% or 1.5% levels of various inhibitors of arachidonic acid metabolism or antioxidants, or diet containing 1% or 1.5% inhibitors or antioxidants alone for 10 weeks, and then killed. p-Bromophenacyl bromide, an inhibitor of phospholipase A2, significantly inhibited the promotion activity of PB at dose levels of 0.75% and 1.5%, reaching plateau at 0.75%. Both quercetin, an inhibitor of lipoxygenase, and morin, a dual inhibitor of lipoxygenase-cyclooxygenase, significantly reduced the promotion activity of PB at the 1.5% but not 0.75% dose levels. Moreover, acetylsalicylic acid, an inhibitor of cyclooxygenase dose-dependently inhibited the promotion activity of PB. Among the antioxidants investigated, vitamin E did not affect, but n-propyl gallate and ethoxyquin exerted a dose-dependent inhibition of PB promotion. These results are strongly suggestive of an involvement of phospholipase A2, lipoxygenase and cyclooxygenase arachidonic acid metabolic pathways in the mechanisms underlying PB enhancement of hepatocarcinogenesis.

Acetophenones↗
PubMed1989

Cycles of repeated augmentation pressure in rapid production of pancreatic and cholangiocellular carcinomas in hamsters initiated with N-nitrosobis(2-oxopropyl)amine.

We previously reported a rapid production model for pancreatic carcinoma development in Syrian hamsters incorporating the principle of selection by resistance to cytotoxicity. In the present experiment, the efficacy of repeated augmentation pressure with regard to generation of pancreatic lesions in hamsters initiated with N-nitrosobis(2-oxopropyl)amine (BOP) was investigated. Forty-eight female Syrian golden hamsters were divided into four groups according to the frequency of augmentation pressure. Group 1 received 70 mg/kg body weight of BOP and three injections of 20 mg/kg BOP. Groups 2-4 received 70 mg/kg BOP followed by one, two or three cycles of augmentation pressure consisting of dl-ethionine on sugar and salt diet, l-methionine and 20 mg/kg BOP. Hamsters were killed 10 weeks after the beginning of the experiment and the resultant incidences of pancreatic carcinomas from groups 1-4 were 0, 30, 50 and 46.2% respectively, the numbers of pancreatic carcinomas increasing with the frequency of augmentation pressure. A 46.2% yield of cholangiocarcinomas was also observed in group 4. The model should be useful for investigation of potential modulating factors since large numbers of lesions can be induced within a total experimental period of only 10 weeks.

Adenoma, Bile Duct↗
PubMed1989

Inhibitory effect of butylated hydroxyanisole administration on pancreatic carcinogenesis in Syrian hamsters initiated with N-nitrosobis(2-oxopropyl)amine.

The modifying potential of butylated hydroxyanisole (BHA) administration on pancreatic carcinogenesis was evaluated in 70 female Syrian golden hamsters. Groups of animals received saline, 70 mg/kg body weight of N-nitrosobis(2-oxopropyl)amine (BOP) or 70 mg/kg plus 20 mg/kg body weight of BOP followed by basal diet or diet containing 2% BHA from week 3. Although the body weights of hamsters receiving the 2% BHA supplement decreased, caloric restriction was not observed. All hamsters were killed at week 18 and histopathologically examined for lesion development. The incidences of pancreatic carcinomas in hamsters receiving 70 mg/kg plus 20 mg/kg body weight of carcinogen followed by 2% BHA was 7.1%, significantly lower than the 64.3% evident in hamsters given the same doses of BOP followed by basal diet. The total numbers of pancreatic lesions including carcinomas, atypical ductal hyperplasias and ductal hyperplasias and ductular proliferations in the liver were also significantly decreased in animals receiving BOP followed by 2% BHA. The results thus indicate that both pancreatic and cholangiocellular carcinogenesis initiated by BOP in Syrian hamsters can be inhibited by 2% BHA treatment for a relatively short experimental period.

Animals↗
PubMed1989

Intracellular distribution of pancreatic tumor antigen purified from BHP-induced adenocarcinomas in Syrian hamsters.

Pancreatic tumor antigen (PTA) was purified to apparent homogeneity from hamster pancreatic adenocarcinomas by a rapid and simple procedure using column chromatography on Mono P and Superose 6. Amino acid analysis indicated essential similarities between hamster PTA and human pancreatic cancer-associated antigen (PCAA, PCAAc), although differences in the contents of several amino acid residues between the two proteins did suggest species variation. Investigation of the binding pattern of antibody raised against PTA by peroxidase-labeled antibody immunocytochemistry revealed that, whereas PTA is absent or only faintly expressed in normal epithelium, it is very strongly positive in transplantable hamster pancreatic adenocarcinomas induced by nitrosamines. PTA was found to be distributed over the entire surface of neoplastic cells and it was concluded that the presence of PTA on the basolateral surface of malignant pancreatic epithelial cells, where it might have access to the blood circulation, could be one explanation for the observed elevated concentrations of PTA in the serum. PTA is thus a potential marker for hamster neoplastic pancreatobiliary duct-type cells.

Adenocarcinoma↗
PubMed1989

Assessment of clinical application of test-dose concept for theophylline in patients with respiratory failure.

The possibility of clinical application of test-dose concept for theophylline was assessed in 11 patients with serious underlying disease who required theophylline. Based on the pharmacokinetic parameters calculated from the single intravenous aminophylline administration, they received a continuous infusion of aminophylline in order to maintain about 10 micrograms/ml plasma which is considered to be the lowest therapeutic level. Plasma levels during a constant rate infusion were assayed at 6:00, noon, 18:00 and midnight on the 3rd or 4th day after the infusion had started. There were no significant differences among plasma levels at each sampling time, but plasma levels varied ranging from 5.1 to 24.8 micrograms/ml (12.1 +/- 5.5 micrograms/ml: mean +/- S.D.), which values were in disagreement with the predicted value in some cases. The correlations of the theophylline clearance ratio to dose, pH, arterial partial pressures of oxygen (Pao2) and carbon dioxide (Paco2) ratios, which were calculated by dividing the value during continuous infusion by the value at the test dose, were investigated to evaluate which factor largely contributed to the failure of this dosing method. Although the clearance ratio did not correlate to pH and Pao2 ratios, significant negative relationships were observed between the clearance ratio and the dose (p less than 0.05) or Paco2 ratios (p less than 0.02). In other words, the alternation of dose or Paco2 resulted in the change of theophylline clearance. These findings suggest that the test-dose concept should not be used in the seriously ill patients whose theophylline clearance can change easily in relation to dose and/or Paco2 change.

Aged↗
PubMed1989

[Monoclonal antibody to desmosome associated 34 kD protein and immunohistochemical study in relation to the malignancy of transitional cell carcinomas of urinary bladder].

A mouse monoclonal IgG1 antibody (B-11) that recognized desmosomes in some human tissues was isolated and characterized. By Western blotting, B-11 recognized 34 kD protein only in squamous and transitional epithelium. By avidin-biotin complex (ABC) and immunofluorescence method, B-11 was reactive to squamous and transitional epithelium, but was not reactive to simple columnar epithelium from stomach and colon, simple cuboidal epithelium from urinary tubule and thyroid, and pseudostratified ciliated epithelium from trachea and ductus epididymidis. ABC method of B-11 was performed in 47 patients with transitional cell carcinoma of bladder. The higher positive staining was observed in well differentiated (83% in Grade (G) 1, 73% in G2 and 20% in G3), superficial (76% in non-invasive and 20% in invasive) and expansive growth (68% in Infiltration (INF) alpha, 24% in IFN beta and 18% in IFN gamma) carcinomas. 34 kD protein recognized by a new monoclonal antibody (B-11) is a new cell-type-specific desmosomal component which relates to the histological grade, stage and invasive manner of the transitional cell carcinoma of bladder. The transitional cell carcinoma of bladder obtained by operation or surgical biopsy from 47 patients was stained by ABC method using B-11.

Adult↗
PubMed1989

Variations in protein binding of drugs in plasma and serum.

The free fractions of five drugs were determined in plasma treated with EDTA and in serum. The free fractions of phenytoin, sodium valproate, and phenobarbital in serum were significantly higher than in plasma (P less than 0.05). In contrast, the free fractions of carbamazepine and theophylline were significantly lower in serum than in plasma. Although we observed minor differences in the protein patterns obtained with two-dimensional electrophoresis, these did not have an important influence on protein binding. No significant differences were observed between plasma and serum in the physiological data, except for pH. Binding of these drugs by protein was shown to be pH-dependent. We conclude that serum may be better than plasma for determination of the free fraction, because the free fraction in plasma is affected by anticoagulants such as EDTA salts and heparin.

Anticonvulsants↗
PubMed1989

[Two autopsy cases of prune belly syndrome in stillborn and its pathogenesis].

Two autopsy cases of prune belly syndrome are reported. In Japan, 111 cases have been reported. Abdominal muscle deficiency or hypoplasia, urinary tract abnormalities and cryptorchidism are usually recognized. Case 1 was a female stillborn at 33 weeks' gestation and case 2 was a male stillborn at 21 weeks' gestation. Both cases had anomalies of genitourinary and digestive system. There was anatomic obstruction of external urethral orifice in case 1 and overriding urethra in case 2 which meant functional obstruction. In relation to the pathogenesis, we propose the important role of the urethral obstruction, whatever anatomic or functional. Further examination of the lower urinary tract including serial section analysis might be necessary to identify the pathogenesis of prune belly syndrome.

Female↗
PubMed1989

[An autopsied case of malignant paraganglioma of the posterior thoracic cavity].

An autopsied case of a malignant paraganglioma of the posterior thoracic cavity is reported. A 68-year-old man had complained of chest discomfort, and serial examinations revealed a functioning paraganglioma with bone metastasis. After death a pathological examination revealed that the tumors consisted of alveolarly arranged cells and well developed capillary vessels. Numerous neurosecretory granules were observed on viewing by electron microscopy. An immunohistochemical examination showed that most of the tumor cells were positive for NSE, while only a few cells were positive for the S-100 protein. These results indicate that a paraganglioma originating from the aortic sympathetic paraganglia had similar features of a carcinoid and a neuroblastoma.

Adrenal Gland Neoplasms↗