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Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 595 records · Page 33Linked to original sources

A feasibility study of the SDI test for the evaluation of gastrointestinal cancer sensitivity to anticancer drugs.

The succinic dehydrogenase inhibition (SDI) test has been widely used to evaluate the sensitivity of cancer cells to anticancer agents. Recently, the techniques for tissue culture have progressed; the ability to make formazan has improved with the use of methylthiazol tetrazolium bromide (MTT) instead of triphenyl tetrazolium chloride (TTC) in this assay. Therefore, we modified the SDI test in order to evaluate the drug response to gastrointestinal cancer and applied it in a clinical study. In this assay, the optimal concentration levels of mytomycin-C and Adriamycin for the clinical materials are 10 micrograms/ml, that is, 10 times higher than for the cancer cell line, and that of Cisplatin is 30 micrograms/ml, for Cisplatin is unstable in the culture medium. To evaluate its antitumor effect, it was found necessary to expose the cancer cells to 5-fluorouracil (5-FU) for 3 days. We applied this assay for the clinical materials; the evaluable rate of this assay is 83.3%. The peculiarity of this assay is its high evaluable rate. These results suggest that this test may be useful for clinical application.

Animals↗

Photodynamic therapy for rat pituitary tumor in vitro and in vivo using pheophorbide-a and white light.

This is the first report on the use of photodynamic therapy (PDT) for rat pituitary tumor in vivo. Rat pituitary tumor (GH3) cells were cultured, GH3 tumor was subcutaneously implanted in nude mice, and pheophorbide-a (Ph-a) and white light were prepared. Photocytotoxicity proportional to Ph-a concentration, intensity of irradiation, and incubation time was observed in vitro. Despite the delay in the disappearance of Ph-a from the tumor, Ph-a in the pituitary gland rapidly decreased after intravenous administration in vivo. Through PDT, the tumor grossly disappeared, the plasma levels of rat growth hormone secreted from the tumor also remarkably decreased, and the development of giantism was inhibited. These results indicate that PDT is effective against rat pituitary tumor.

Animals↗

Suppressive effect of SUN1165 on supraventricular tachycardia.

The electrophysiologic properties of SUN1165 and its suppressive effect on supraventricular tachycardia were assessed in 14 patients, nine with atrioventricular reentrant tachycardia (AVRT) and five with atrioventricular nodal reentrant tachycardia (AVNRT). This new agent prolonged the PR interval and QRS duration but did not alter the QT interval or the corrected QT interval. It did not alter the sinus cycle length or sinus node recovery time. The drug prolonged the AH interval, HV interval, and intraatrial conduction time but did not change the effective refractory periods of the right atrium or right ventricle. SUN1165 prevented the induction of tachycardia in six of nine patients with AVRT by a complete retrograde block of the accessory pathway and prevented AVNRT in four of five patients by a complete retrograde block of the fast atrioventricular nodal pathway as well. We conclude that SUN1165 is very effective in preventing AVRT or AVNRT. Larger studies with more patients are warranted.

Administration, Oral↗

Hymenolepis nana: immunity against oncosphere challenge in mice previously given viable or non-viable oncospheres of H. nana, H. diminuta, H. microstoma and Taenia taeniaeformis.

When mice, previously given oral inoculation with viable oncospheres of the heterologous cestode species (Hymenolepis diminuta, H. microstoma, Taenia taeniaeformis) and the homologous one (H. nana), were challenged with oncospheres of H. nana 4 days after the primary inoculation, they showed strong and complete resistance to H. nana challenge, respectively. However, the resistance was not evoked in mice given either infective eggs of Toxocara canis or non-viable oncospheres of all cestode species examined. Congenitally athymic nude mice given viable oncospheres did not show any resistance to H. nana either. Eosinophil infiltration around cysticercoids of H. nana in the intestinal villi appeared to be more prominent in mice previously given viable oncospheres of H. diminuta than in mice given non-viable oncospheres or PBS only. Some of the eosinophils in the villus harboring cysticercoid(s) of H. nana invaded the epithelia in the former, whereas all eosinophils remained in the lamina propria in the latter. There was almost no eosinophil infiltration in nude mice. Microscopic observations revealed that oncospheres of H. diminuta, which require beetles as the intermediate host like H. microstoma, could invade the mouse intestinal tissue. Therefore, it is strongly suggested that the strong cross resistance to H. nana in mice, induced by oncospheres of all heterologous cestode species, is thymus-dependent and due to oncospheral invasion into the intestinal tissue of mice.

Animals↗

Vaccination against Taenia taeniaeformis infection in rats using a recombinant protein and preliminary analysis of the induced antibody response.

Primary screening of a cDNA expression library of Taenia taeniaeformis oncospheres in lambda gt11 bacteriophage was carried out using rabbit anti-T, taeniaeformis oncosphere serum affinity-purified from oncosphere pellets. From approximately 1.6 x 10(5) plaques, 21 single clones that were positive with the affinity-purified antibodies were isolated. Sibling analysis revealed that 17 clones out of the 21 could be assigned to five different antigen families. Only family 1 was strongly recognized by a serum prepared in a rabbit against a partially purified host-protective oncosphere antigen fraction. The fragments of lambda DNA were inserted into a pGEX plasmid vector that encodes glutathione S-transferase (GST) of Schistosoma japonicum. Clones designated TtO-18, -49.53 (family 1), 46 (family 2), 15 (family 3), 40 (family 4) and 66 (family 5) were established as subclones in pGEX-1 plasmid vectors which produced GST fusion proteins. All GST fusion proteins were soluble and recognized by anti-GST and anti-TtO sera. Three vaccination experiments with these fusion proteins using specific-pathogen-free Wistar rats revealed that all three fusion proteins of family 1 were exclusively effective against T. taeniaeformis oncosphere challenge with approximately 95% and 91% reductions in cystic metacestode and total metacestode recoveries, respectively. Rats vaccinated with fusion proteins of family 1 produced antibodies which reacted with a 21-kDa oncosphere antigen component which appeared to be a major oncosphere stage-specific antigen.

Animals↗

Identification of rabbit uterine cervical procollagenase activator as rabbit matrix metalloproteinase 3 (stromelysin).

1. We previously reported an endogenous activator of procollagenase from the culture medium of rabbit uterine cervical fibroblasts (Ishibashi et al. (1987) Biochem. J. 241, 527-534). 2. Similar activator was also purified and characterized from rabbit synovial fibroblasts (Vater et al. (1983) J. biol. Chem. 258, 9374-9382), but its mode of activation of procollagenase was reported to be different from that of purified activator from uterine cervical fibroblasts. 3. Here we report the comparative studies of the two activators of procollagenase and demonstrate that they are identified as matrix metalloproteinase 3 (stromelysin) by their immunological and functional criteria. The specific role of the activator in procollagenase activation is also described.

Animals↗

A comparison of central nervous lesions directly induced by Escherichia coli lipopolysaccharide in piglets, calves, rabbits and mice.

To evaluate the role of endotoxin during Gram-negative bacterial meningitis, the nervous lesions of piglets, calves, rabbits and mice were compared by direct inoculation of Escherichia coli lipopolysaccharide into the central nervous system. Suppurative leptomeningitis was induced in piglets by small doses of lipopolysaccharide. Mice also had a mild suppurative inflammation in the leptomeninges. In contrast, calves showed suppurative pachymeningitis, but no lesions in the leptomeninges. Leptomeningeal inflammation was not induced in rabbits. Induction of the leptomeningitis by endotoxin was compared with sensitivity to intravenous or intraperitoneal endotoxin in these species.

Animals↗

Calmodulin antagonists differentiate between Ni(2+)- and Mn(2+)-stimulated phosphatase activity of calcineurin.

The interaction of calmodulin antagonists with a phosphoprotein phosphatase, calcineurin, was investigated using para-nitrophenyl phosphate (pNPP) as a substrate. Calmidazolium, a potent calmodulin antagonist, inhibited the Ni(2+)-stimulated calmodulin-independent phosphatase activity to much the same extent as it did the Ca2+/calmodulin-stimulated activity. Other calmodulin antagonists, such as trifluoperazine, thioridazine, and W-7, also inhibited the Ni(2+)-stimulated phosphatase activity. On the other hand, calmidazolium only weakly and partially inhibited the Mn(2+)-stimulated phosphatase activity and the other calmodulin antagonists examined increased the Mn(2+)-stimulated activity, in the absence of calmodulin. With the addition of an equimolar amount, as to the inhibited holoenzyme, of the purified B subunit of calcineurin, the Ni(2+)-stimulated phosphatase activity recovered from 38 to 63% of the control level in the presence of 5 microM calmidazolium. When the amount of additional B subunit was increased, the phosphatase activity recovered to 94% of the control level, thereby implying that calmidazolium inhibits the Ni(2+)-stimulated phosphatase activity by interacting with the B subunit, in the absence of calmodulin. The Mn(2+)-stimulated phosphatase activity also recovered from the inhibition by calmidazolium, but a much larger amount of the B subunit was necessary for the recovery. These results indicate that the Ni(2+)- and Mn(2+)-stimulated activities of calcineurin are differentially affected by calmodulin antagonists and that the B subunit plays a crucial role in the expression of the Ni(2+)-stimulated phosphatase activity.

4-Nitrophenylphosphatase↗

Normolipemic papuloeruptive Xanthomatosis in an infant.

A 8-month-old boy showed several yellow to brownish yellow, papular and/or nodular eruptions predominantly on the face. Initial clinical and histologic findings indicated possible juvenile xanthogranuloma or papular xanthoma. Since his second year, the papulonodular lesions have gradually merged into large confluent plaques, particularly on the face, nape, and axillae. Consequently, it was considered that his condition had terminated in diffuse plane xanthoma. Serum lipid panels showed normolipemia. Finally, a diagnosis of papuloeruptive xanthomatosis with normal lipid metabolism and no associated systemic disorders was made. The patient's papulonodular lesions have continued to involute spontaneously since the age of three.

Facial Dermatoses↗

Induction of signet ring cell carcinomas in X-irradiated hypocatalasemic mice (C3H/Cbs).

The stomach region of hypocatalasemic mice of both sexes was X-irradiated once with a dose of 20 Gy. Thirteen months after the irradiation, 3 out of 13 (20%) males and 2 out of 9 (15%) females were observed to have developed signet ring cell carcinomas in the glandular stomach. This finding was statistically significant (P less than 0.01 in males and P less than 0.05 in females) compared to a total absence of similar tumors in the non-irradiated controls. Local invasion of malignant tumors into muscle and subserosal layers was observed, but no metastatic tumors were found in distant organs.

Acatalasia↗

Estrogen receptor levels and tumor growth in a series of pituitary clonal cell lines in rats.

Four kinds of in vitro clonal pituitary tumor cell lines named MtT/Se, MtT/SM, MtT/S and MtT/E, each of which shows different sensitivity to estrogen on proliferation, were inoculated into fat pad of ovariectomized rats and estrogen-loaded ovariectomized rats at 10(5) and 10(6) cells/site. They formed tumor with average latency ranging from 30 to 71 in ovariectomized rats and 13 to 63 days in estrogenized rats inoculated with 10(6) cells. MtT/Se was highly sensitive to estrogen for growth, and MtT/SM also grew well in estrogenized rats. With MtT/S and MtT/E, there was no significant shortening of average tumor latency in estrogenized rats. In vivo, the cytosolic estrogen receptor (ER) levels of MtT/Se, SM, S and E were measured to be 452 +/- 66, 370 +/- 115, 260 +/- 16 and 83 +/- 8 fmol/mg protein, respectively. In vitro, however, the lowest ER level was noted in MtT/Se. Histologically, all four tumors grown in rats were composed of homogeneous round cells, and MtT/Se contained particularly large nucleated cells. In MtT/E, the cells appeared to be changing into fibromatous cells. Three cell lines except MtT/E maintained the function of hormonal secretion in vivo as well as in vitro. Serum GH level was increased in rats with MtT/Se and MtT/S. Increased levels of both prolactin and growth hormone were measured in sera of rats with MtT/SM. Increases of hormones as well as tumor sizes were promoted by the estrogen.

Animals↗

Stimulatory effects of retinoic acid on tumor growth and serum insulin-like growth factor-1 in rats bearing estrogen-responsive pituitary tumor MtT/Se.

MtT/Se is one of 4 cell lines derived from an estrogen-dependent pituitary tumor, MtT/F84. The main difference between these tumor types is that MtT/F84 secretes both growth hormone (GH) and prolactin (PRL) whereas MtT/Se secretes only GH. MtT/Se grew slowly in ovariectomized (ovex) rats, but tumor growth was much faster in estrogen-treated ovex rats. Effects of dietary retinoic acid (RA) on tumor growth, serum GH and insulin-like growth factor-1 (IGF-1) levels were examined in ovex rats. Latency of tumor growth was shortened, and tumor take and weight were promoted by all-trans RA both in the presence and absence of exogenous estrogen. Serum GH and IGF-1 levels became increased in tumor-bearing rats whereas PRL levels remained unchanged. Serum IGF-1 levels exhibited a good correlation with tumor weights (r = 0.84). Our results suggest a close relationship between increase of tumor weight and stimulation of serum IGF-1 level by RA in tumor-bearing rats.

Animals↗

Radiation damage in soft X-ray microscopy of live mammalian cells.

When specimens are observed by soft X-ray microscopy, they always absorb many photons, causing radiation damage at the imaged site. The problems of radiation damage were studied in view of the principle of image formation; absorption contrast, scattering (holography), or phase contrast. In all cases, photons with a wavelength of 1-10 nm interact with the specimen mainly through the photoelectric effect followed by the transfer of energy to the imaging site either directly (absorption imaging) or indirectly (holography or phase contrast). This absorbed energy will cause structural changes to the imaging site. From a review of the literature the absorbed dose is estimated to be as high as 10(7) Gy when the expected resolution of the specimen (1-10 microns thick) is 10 nm. This dose is far in excess of the amount required for cells to be able to survive when live mammalian cells are exposed. The levels of radiation effects were extrapolated to the estimated absorbed dose from the reported values for cell survival, chromosome aberrations, and DNA strand breaks with respect to observations on mammalian chromosomes. The extrapolated results show that some damage will occur in every 10 x 10-nm (expected resolution) size unit. Although these studies focused only on the effects on mammalian chromosomes, the present results are more or less common phenomena in the observation of biological specimens. Hence, the results suggest that dynamic observations will be difficult. On the other hand, a time-scale study of the effects of radiation on structural integrity suggests that single-shot imaging with short-pulsed (probably shorter than a few milliseconds) X-rays may be appropriate for the observation of intact live biological specimens in the hydrated condition, before they have deteriorated.

Cell Survival↗

Glucocorticoid stimulates melanogenesis and tyrosinase gene expression in B16 melanoma cells.

Effects of dexamethasone on melanogenesis and tyrosinase mRNA levels were determined in B16/F10 melanoma cells. Melanin content of B16 cells increased in a dose-dependent manner by the addition of dexamethasone to the culture medium. After 72 hr exposure, dexamethasone (10(-6) M) produced a 2.4-fold increase in melanin content. Northern blot analysis revealed that tyrosinase mRNA level also increased by the addition of dexamethasone to the culture medium. After 24 hr exposure, dexamethasone (10(-6) M) caused a 1.8-fold increase in tyrosinase mRNA levels. A tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) decreased tyrosinase mRNA level at 30 nM concentration. Dexamethasone antagonized this TPA-mediated decrease in tyrosinase mRNA. It is suggested that glucocorticoids are involved in the regulation of tyrosinase activity at the transcriptional level.

Animals↗

[Mycological and clinical study of cryptococcosis in Yokohama City University Hospital during the period from 1965 to 1989].

Among patients examined at the Central Laboratory of Yokohama City University Hospital over the 25 years from 1965 to 1989, those whose clinical samples showed Cryptococcus were studied in greater detail. The following findings were obtained. Of 16 patients who were found to have cryptococcosis, 14 (87.5%) were treated at the department of internal medicine, and one each at the departments of neurosurgery and dermatology. A study of these patients in terms of clinical type revealed 10 patients (62.5%) with meningitis, two with pneumonia and one with sepsis. The remaining three patients had complicated diseases: meningitis with sepsis, pneumonia with cutaneous cryptococcosis, or pleuritis with sepsis. Underlying disease, including liver cirrhosis, leukemia, multiple myeloma, malignant lymphoma and collagen disease, was found in 6 patients (37.5%), who were all from the department of internal medicine. All patients but one were given antimycotic agents. They were treated by a combination therapy except for three patients who received single amphotericin B (AMPH) therapy. The most frequent combination was AMPH + 5-flucytosine (5-FC), which was found in 7 cases. Seven patients (43.4%) died, three males and four females. Analysis of these cases in terms of clinical type revealed meningitis in four, and pneumonia, sepsis, or pleuritis complicated with sepsis in the remaining three patients. Four patients (57.1%) had underlying diseases. In addition, eleven strains isolated from the specimens were examined for serotypes and minimum inhibitory concentration (MIC) using three types of antimycotic agents. Serotypes of Cryptococcus neoformans were all A and the MIC was 0.1-0.39 micrograms/ml for AMPH, 0.05-0.2 micrograms/ml for 5-FC and 0.2-0.78 micrograms/ml for miconazole (MCZ).

Adolescent↗

Effects of H2-receptor antagonists on matrix metalloproteinases in rat gastric tissues with acetic acid-induced ulcer.

To investigate the destructive process of connective tissues in gastric ulcer, both collagenolytic and gelatinolytic activities were examined in the homogenates of rat acetic acid-induced gastric ulcer, a typical model of chronic ulcer. Gelatinolytic activity in the ulcerous lesion was significantly higher than that in the normal tissue. However, collagenase was not detected in both normal and ulcerated tissues either by the enzyme assay or by the immunoblotting. By gelatin-gel-zymographic analyses, the gelatinolytic activity was found to be composed of a number of species, mainly 60-, 72- and 92-kDa, all of which were inhibited by ethylenediaminetetraacetic acid. Among the induced matrix metalloproteinases, one crossreacted with a sheep anti-(rabbit prostromelysin)antibody. Thus, in chronic gastric ulcer, it is likely that several metalloproteinases participate in degradation of connective tissue matrices including components of basement membranes. The elevated levels of gelatinolytic activities in the ulcerous tissues and ulcer index were significantly suppressed by treating the animals with famotidine or a new H2-receptor antagonist, 3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2- butenylamino]-3-cyclobutene-1,2-dione hydrochloride (IT-066).

Acetates↗

[The relationship between dividing properties of scored tablets and dynamic characteristics of powder].

The relationship between dividing properties of the scored tablet and dynamic characteristics of the powder was investigated for proving the effects of physical characteristics of the powder on dividing properties of the scored tablet. Lactose, microcrystalline cellulose, corn starch, synthetic aluminum silicate and Perfiller were used as excipients. The dynamic characteristics of the powder, such as tensile strength (T), cohesive force (C), angle of friction (delta), flow factor (FF), shear index (n), C/T(K) and constants of Kawakita's equation of tapping compaction (a, 1/b) were measured. No correlations between coefficient of variation of divided tablet weight and each dynamic characteristics of the powder were found. However, from the result of the multiple regression analysis, multiple regression equation containing C and a as variables was obtained. Then a significant correlation was obtained between coefficient of variation of divided tablet weight and C/a, and also between logarithms of dividing strength of scored tablets and C/a. As a result, coefficient of variation of divided tablet weight decreased and dividing strength of scored tablets increased with decreasing C/a value.

Chemical Phenomena↗