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Biomedical subjects

M Shiba

Publications and source records attributed to M Shiba.

At least 109 records · Page 6Linked to original sources

The effects of formaldehyde gas in a flow-through rat tracheal implant system.

A flow-through rat tracheal implant system is described which permits the quantitative and repetitive exposure of respiratory epithelia to test gaseous substances. To investigate the acute toxicity of formaldehyde gas with this new system, open-ended rat tracheal implants were exposed to the gas for 1 h twice a week for up to 8 weeks. The formaldehyde gas was gene-rated from paraformaldehyde, mixed with humidified air and introduced into the lumens of the tracheal implants through microbore tubing. Concentrations of 4.1 +/- 0.9, 8.1 +/- 1.2 or 12.7 +/- 1.5 ppm, were introduced into the trachea by passing an airstream moving at 50, 225 or 475 ml/min, respectively, over the paraformaldehyde heated to 42 degrees C. These formaldehyde concentrations induced mucociliary hypertrophy and increasing amounts of atrophic, transitional and metaplastic epithelia in the tracheal mucosa.

Animals↗

Randomized controlled trial of transfer factor immunochemotherapy as an adjunct to surgical treatment for primary adenocarcinoma of the lung.

A total of 102 patients were studied in a randomized controlled trail to evaluate the clinical effect of transfer factor (TF) for primary resected adenocarcinoma of the lung. The TF and Control groups consisted of 50 and 52 randomly chosen patients, respectively. However, 6 and 5 patients were excluded from both groups for various reasons, therefore the total of cases eligible for evaluation were 44 and 47 in the TF and Control groups, respectively. The clinical features of both groups were similar. The survival of the TF group was significantly better than that of Controls in Stage I cases (p less than 0.05), however, there was no significant difference in patients in Stages II, III and IV. Significant differences were found between the TF and Control groups in curative resection cases (p less than 0.05), however, no significant difference was seen in either the relatively curative resection or noncurative resection groups. TF seems to inhibit postoperative recurrence and appears to be an effective postoperative adjuvant immunotherapeutic for primary resected adenocarcinoma of the lung, especially at the relatively early stages.

Adenocarcinoma↗

Lectin-binding sites in preneoplastic and neoplastic lesions of human and rodent respiratory tracts.

The localization of fluorescein-labeled lectins, i.e., concanavalin A (Con A), Ricinus communis-120 (RCA), and wheat-germ agglutinin (WGA), were studied histologically in F344 rat epithelial lesions produced in the course of chemical carcinogenesis. WGA could not be demonstrated in these lesions. Although all lesions showed positive-binding sites when high concentrations of either Con A or RCA were used, a dilution study showed that the epithelial lesions had different affinities for lectins. With both Con A and RCA, dysplastic and neoplastic lesions showed the strongest intensity of fluorescence and squamous metaplasia showed the weakest. Normal and hyperplastic epithelia showed intermediate intensity. In the dilution study, RCA showed eight times more affinity and Con A showed two times more affinity for dysplastic and neoplastic epithelia than for normal or hyperplastic epithelium. Similar affinity patterns were observed in human lesions and tumors. With Con A, 58% of tumors showed much stronger fluorescence than did normal epithelium, and 44% of the tumors showed positive fluorescence with RCA. Although both lectins exhibited a stronger affinity for all the dysplastic-neoplastic lesions than for normal or hyperplastic epithelium, RCA proved to be the most adequate marker for preneoplastic lesions.

9,10-Dimethyl-1,2-benzanthracene↗

An open-ended rat tracheal implant model: toxic effects of formaldehyde on the respiratory epithelium.

An open-ended rat tracheal implant model was developed to permit quantitative and repetitive exposure of respiratory epithelia to test substances of a variety of physical forms. To investigate the acute toxicity of formaldehyde with this new model, tracheas were exposed to formaldehyde solutions twice a week, for up to 12 weeks. At the higher formaldehyde concentrations (1.0, 0.6, 0.3%) the tracheal lumens became obstructed by granulation tissue. At the lower concentrations (0.2, 0.1, 0.01%), the appearance of flattened and atrophic epithelium as well as hyperplasia and squamous metaplasia were observed. The extent of these epithelial alterations was, for the most part, formaldehyde dose-dependent.

Animals↗

Variation of gamma glutamyl transpeptidase activity and lectin binding in the course of carcinogenesis of the respiratory tract epithelium.

Gamma glutamyl transpeptidase (GGT) activity and fluorescein-labeled lectins Concanavalin A (Con A) and Ricinus communis-120 binding sites were studied in lesions produced by 7,12-dimethylbenz[a]anthracene during chemical carcinogenesis using syngeneic heterotopic rat tracheal transplants. Although all types of lesions showed positive GGT activity and lectin binding, prominent differences were observed between the different types of lesions. Compared with regular squamous metaplasia, dysplastic-neoplastic lesions showed much stronger reaction for GGT and lectins; normal and hyperplastic mucociliary epithelium showed intermediate reactions. Although the relationship between keratinization, cell surface changes, GGT activity and lectin binding are not completely clear, lectins seem to be good markers of dysplastic and neoplastic lesions of the respiratory tract epithelium.

9,10-Dimethyl-1,2-benzanthracene↗

[Effect of eel calcitonin derivative (elcatonin) in osteoporosis].

Calcitonin has been considered to be useful in the treatment of osteoporosis due to its remarkable suppressive action on bone resorption as well as its putative stimulative effect on bone formation. However, its usefullness, especially the effect for decreasing the loss of bone mass in osteoporosis has not been proved substantially. We have studied this point using eel calcitonin derivative, elcatonin , in relatively low doses with and without calcium supplement. Bone mass was evaluated by microdensitometry of the roentgenograms of the second metacarpal bone. One hundred and thirty cases of postmenopausal and senile osteoporotics were divided into the following four groups and studied for six months: A) calcium and elcatonin treated group, B) calcium treated group, C) elcatonin treated group, D) control group. Elcatonin was administered intramuscularly 10 units once a week, and calcium was given 700 mg for every day. The results of metacarpal densitometry revealed the signs of significant increase of the bone mass in the calcium and elcatonin treated (A) group compared with the control (D) group, while the changes in the other groups (B and C) were not significant. It was shown that elcatonin had the significant analgesic effect for the back pain in the patients. Serum iPTH was not increased and the antibody for elcatonin was not detected in elcatonin treated patients. Although the study period is rather short, necessitating further studies, at present, our study suggests that the use of calcitonin with calcium supplements had the place in the treatment of osteoporosis.

Absorptiometry, Photon↗

Effect of carcinogen release rate on the incidence of preneoplastic and neoplastic lesions of the respiratory tract epithelium in rats.

Inbred F34 rat tracheal transplants were exposed to 7,12-dimethylbenz[a]anthracene (DMBA) delivered at different release rates for intraluminal pellets made of various matrices to study the effect of carcinogen dose rate on the induction of lesions in the epithelium. These matrices were beeswax, beeswax-stearyl alcohol, and beeswax-cholesterol. In addition, DMBA absorbed onto carbon particles was dispersed in beeswax-stearyl alcohol. The fastest release was obtained from beeswax pellets from which 99% of the carcinogen (198 micrograms) was released in 4 weeks, and the slowest release was from DMBA absorbed on carbon at a ratio of 1:9 from which only 56% (113 micrograms) was released in 16 weeks. Morphometry of histologic sections showed marked differences in the percentage of luminal surface covered by dysplastic-neoplastic epithelium (i.e., 7.5% in the tracheas exposed to the fastest releasing pellets and 46.3% in the tracheas exposed to the slowest releasing pellets). An inverse linear correlation was found between the cumulative amount of DMBA relased from the different pellet matrices of 2 weeks and the incidence of dysplastic plus neoplastic lesions of tracheal epithelium at 16 weeks. The results indicate that lower doses of carcinogen delivered slowly are more effective in producing dysplastic plus neoplastic lesions than hgher doses delivered rapidly.

9,10-Dimethyl-1,2-benzanthracene↗

Propagation of normal human epithelial cell populations using an in vivo culture system. Description and applications.

A new model using xenotransplanted human epithelia was developed for the study of toxic and carcinogenic effects of chemicals. Epithelial cells from the respiratory tract of 4 male and 3 female premature and fullterm fetuses were enzymatically removed and inoculated into deepithelialized rat tracheas. These were sealed at both ends and transplanted subcutaneously into nude mice. After 3-4 weeks, a normal mucociliary epithelium covered the tracheal lumen. At this stage the epithelial cells could be isolated again and transplanted into new denuded rat tracheas. This passaging could be repeated up to six times, each permitting an amplification factor of approximately 3. Tracheal transplants containing cells of human origin (in vivo Passages 2-4) were treated with 7,12-dimethylbenz(a)anthracene. Hyperplasias, squamous metaplasias, and dysplasias were seen 1-8 weeks after initiation of treatment, indicating that the responses of human and rodent epithelial cells to polycyclic aromatic hydrocarbons are similar. Initial experiments with skin and esophageal epithelia suggest that other covering epithelia could also be used in this fashion for evaluation of toxicants and carcinogens that are likely to come into contact with these tissues.

9,10-Dimethyl-1,2-benzanthracene↗

Red cell preservation and removal system of purine derivatives.

The new preservative containing high concentrations of adenine (8 mM), inosine (40 mM) and other chemicals which was indicated by Nakao et al., was applied to the preservation of red cell concentrates. Moreover, the system for the removal of purine derivatives (adenine, inosine and hypoxanthine) added and produced in stored samples was developed, using bead activated charcoal coated with the blood-compatible polymer (Hydron). Over 90% of purine derivatives in the medium and erythrocytes were removed by Hydron-coated bead activated charcoal (HAC) column. The recovery of erythrocytes by HAC column treatment was over 98%.

2,3-Diphosphoglycerate↗