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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 703 records · Page 39Linked to original sources

Gametocytogenesis induction by Berenil in cultured Plasmodium falciparum.

Berenil, which is known to inhibit synthesis of nucleic acid, DNA and RNA, and polyamine, induced gametocytogenesis in cultured Plasmodium falciparum, although the mechanism by which Berenil induces gametocytogenesis is unknown. Asexual parasites of a strain of P. falciparum that seldom produce gametocytes in in vitro culture began gametocytogenesis after 2-24 hr treatment with RPMI 1640 medium containing Berenil (final concentration, 0.1-10.0 micrograms/ml) with horse serum. Gametocytogenesis was consistently observed from 3 days after the addition of Berenil to culture. After parasites were cultivated in RPMI 1640 medium containing Berenil (final concentration, 3.0-10.0 micrograms/ml) and concanavalin A with horse serum for 2 hr, Berenil and concanavalin A were removed from culture medium by centrifugation. Nevertheless, induction of gametocytogenesis was observed. The addition of concanavalin A (final concentration, 10 micrograms/ml) to RPMI 1640 medium containing Berenil enhanced the induction of gametocytogenesis by Berenil. However, when RPMI 1640 medium with concanavalin A was used without the addition of Berenil, no gametocytogenesis was observed as in RPMI 1640 medium alone.

Animals↗

Lack of intratumoral heterogeneity in DNA ploidy pattern of hepatocellular carcinoma.

BACKGROUND: From biological and clinical perspectives, it is important to clarify tumor heterogeneity. This study was aimed to investigate whether or not intratumoral heterogeneity of DNA ploidy pattern exists in hepatocellular carcinoma (HCC). METHODS: Using fresh materials resected from 31 untreated patients, DNA ploidy was analyzed at different sites of the same HCC by means of flow cytometry. The tumor size ranged from 1.7 to 25.0 cm. RESULTS: There was no case in which euploid and aneuploid HCCs coexisted in the same tumor. The DNA ploidy pattern was euploid in 15 and aneuploid in 16 instances. Of 15 euploid tumors, the areas analyzed were all diploid in 12 and tetraploid in 2 but diploid/tetraploid in 1. Among 16 aneuploid tumors, the DNA indices (DI) at different sites were similar in 9, but apparently, different aneuploid subclones coexisted in 7 cases. The incidence of DI heterogeneity in aneuploid HCCs was similar between small (< 5 cm) and large (> or = 5 cm) tumors; 3 of 7 (42.9%) versus 4 of 9 (44.4%). CONCLUSIONS: It is assumed that euploid and aneuploid HCCs develop in their own ploidy pattern and that the evolution of aneuploid subpopulations from euploid HCC is rare, but new aneuploid subclones can evolve from aneuploid HCC due to increased instability of its karyotype.

Adult↗

An endothelin ETA receptor antagonist, FR139317, ameliorates cerebral vasospasm in dogs.

The role of endothelin in the pathogenesis of cerebral vasospasm after subarachinoid hemorrhage was investigated by evaluating the effect of FR139317, a novel potent ETA receptor antagonist, on the vasospasm in a canine two-hemorrhage model. Intracisternal administration of FR139317 (0.1 mg) significantly reduced the vasoconstriction of the basilar artery at day 7 (control group, n = 6, 61.6 +/- 4.0%, FR139317 treated group, n = 6, 75.9 +/- 1.5% of basal diameter, p < 0.01). In normal anesthetized dogs, the intracisternal administration of FR139317 did not affect the basal diameter of the basilar artery, blood pressure or heart rate. These results suggest that endothelin plays an important role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, and that FR139317 could be a valuable tool for preventing vasospasm after subarachnoid hemorrhage.

Animals↗

All-or-none shortening of isolated single smooth muscle cells from different organs to acetylcholine.

1. Single smooth muscle cells from the guinea-pig taenia caecum and the fundus of guinea-pig stomach were prepared by collagenase digestion under different, mild conditions. 2. Most of the cells either from taenia caecum or from the fundus of stomach responded repeatedly, showing an all-or-none response to acetylcholine (ACh). 3. The threshold concentrations of ACh were different for the cells of the two tissues. Although individual cells showed an all-or-none response to ACh, the average responses of all the cells were graded, like that of whole tissues. 4. Thus, isolated single smooth muscle cells from different tissues and under different conditions responded to ACh in an all-or-none manner such as the twitch observed in skeletal muscle. 5. These results suggest that the isolation of cells reveals the fundamental characteristics of smooth muscle cells as excitable.

Acetylcholine↗

Rat amygdaloid neuron responses during auditory discrimination.

To investigate amygdaloid contribution to stimulus-affect association and to emotional behavior, single neuron activity was recorded in the basolateral and corticomedial amygdala of the rat amygdala during discrimination of conditioned cue tones associated with positive (glucose and intracranial self-stimulation) and negative (weak electric footshock) unconditioned stimuli. Amygdaloid neurons that responded to two rewarding unconditioned stimuli responded in the same manner to both. Responses to conditioned cue tones and those to rewards were also significantly related, suggesting that amygdaloid neuronal responses to conditioned stimuli are closely related to the affective nature of the corresponding unconditioned stimulation. These might be neuronal functions that underlie stimulus-affect association in the amygdala. In random repeated trials, including acquisition to conditioned cue tones and extinction after acquisition, response plasticity was more evident in basolateral than in corticomedial neurons. Furthermore, more basolateral than corticomedial neurons differentiated glucose and its cue from intracranial self-stimulation and its cue by responding to one but not the other. More basolateral than corticomedial neurons were excited by intracranial self-stimulation and its cue and inhibited by footshock and its cue. The differences between the two nuclear groups suggest that basolateral neurons are more plastic and discriminative, and corticomedial neurons respond indiscriminately to positive and negative unconditioned or conditioned stimuli. The results indicate amygdaloid neuron involvement in stimulus-affect association. Basolateral neurons may be more involved than corticomedial neurons in discriminating and learning conditioned stimuli.

Acoustic Stimulation↗

Neuronal responses in monkey anterior putamen during operant bar-press behavior.

Single neuron activity was recorded in the monkey anterior putamen to compare visuomotor-related responses during operant bar-press behavior with visual discrimination of objects. Of 615 neurons recorded, 9.8% (60/615) responded to the presentation of food during forced delay of access to the bar. Of these 60 neurons, 38 were also tested with nonfood, and 19 of these responded to the nonfood objects regardless of the following movement. The amplitude of the visual-related responses of some differential neurons was graded for different objects to reflect the relative degree of preference for the food presented. However, these responses disappeared in reaction time tasks in which the bar could be accessed for pressing immediately upon presentation of an object. The visual response latency of differential neurons ranged from 50 to 700 ms (mean +/- SD, 386 +/- 211 ms), which was longer than that of the nondifferential responses (207 +/- 204 ms). These results suggest that anterior putamen neurons might participate in estimation of visual information that could be related to forecasting movement.

Animals↗

Effects of energy restriction on age-associated changes of DNA methylation in mouse liver.

DNA methylation is known to change with age in several mammalian species. Here we have examined the effect of dietary energy restriction on this age-associated change in liver DNA of C3H/SHN mice. The total 5-methyldeoxycytidine level in the genome decreased slightly soon after energy restriction started. The effect, however, diminished with time and no appreciable difference was detected at middle and old ages. The degree of methylation at the c-myc gene, on the other hand, was not affected by energy restriction at early periods, but the age-dependent alterations at later ages were repressed. This is a new finding to show that DNA methylation is one of the molecular indices of aging affected by energy restriction. It suggests an importance of DNA methylation in the aging process.

Aging↗

Prostacyclin production in cultured endothelial cells is highly sensitive to low doses of ionizing radiation.

In an attempt to detect if low doses of ionizing radiation affect the physiological function of blood vessels, the effect of prostacyclin production was examined using cultured endothelial cells. Irradiation with 5 cGy suppressed the production to 53% of the levels in unirradiated control cells. The PGI2 production decreased with an increase in the dose, showing a maximal decrease at 100 cGy without further decrease at 200 cGy. The suppressive effect lasted for 15 min after irradiation and disappeared later. Preincubation with alpha-tocopherol abrogated the suppressive effect completely, although preincubation with ascorbic acid showed little effect. These results suggest that low dose irradiation inhibits the prostacyclin production by changing the cellular membranes transiently.

Animals↗

Prevention of radiation-induced bacteraemia by post-treatment with OK-432 and aztreonam.

The effects of combined treatment with OK-432, an immunomodulator prepared from Streptococcus haemolyticus, and aztreonam, a monobactum antibiotic, in the prevention of radiation-induced bacteraemia and mortality were examined in ICR-MCH mice irradiated with 9.5 Gy. The organisms recovered from the irradiated mice were Streptococcus faecalis and Proteus mirabilis. Treatment with aztreonam reduced the incidence of mice infected with Proteus mirabilis (p < 0.01), but it showed no efficacy on Streptococcus faecalis. OK-432 could reduce the frequency of bacteraemia attributed to both organisms (p < 0.05). Combined treatment with OK-432 and aztreonam further decreased the incidence of bacteraemia by both organisms; no organisms were recovered at 14 days following irradiation. The survival rate at 30 days following irradiation was 80% in mice treated with OK-432 plus aztreonam and 55% with OK-432 alone, while it was 0% in the groups treated with aztreonam or saline alone. These results indicated that combined treatment with OK-432 and a suitable antibiotic such as aztreonam is more effective than OK-432 or aztreonam alone.

Animals↗

Biological significance of DNA methylation in the ageing process.

In order to understand the possible importance of DNA methylation in ageing, characteristics of its age-associated changes were examined in mouse and man. The total methylated deoxycytidine level in the genome decreased in the senescent period in mouse liver, but not in mouse brain and human liver. The examination of DNA methylation in each individual gene revealed that only a few genes showed alteration in the senescent phase while many genes change in the maturation period. The alterations were gene- and tissue-specific. Comparison of short-living mouse and long-living man for the age-associated changes of the c-myc gene methylation revealed that the rate of change in mouse was about 20 times faster than that in man. This suggests a deep involvement of DNA methylation in ageing. Further investigations into the causes and consequences of the changes would clarify a basic mechanism of ageing.

Animals↗

Physiological characteristics of spontaneously developed diabetes in male WBN/Kob rat and prevention of development of diabetes by chronic oral administration of synthetic trypsin inhibitor (FOY-305).

The male WBN/Kob rats spontaneously develop diabetes mellitus with age. In this study, we examined how glucose tolerance, potency of insulin release, and histology of the pancreas were changed with age in this model. Furthermore, we examined the effect of FOY-305, a synthetic trypsin inhibitor, on this model. Male WBN/Kob rats were divided into two groups: one group fed on standard pellet diet (STD group) and the other on pellet containing 0.1% FOY-305 (FOY group) for 56 weeks after age 4 weeks. Oral glucose (2 g/kg) tolerance test, histology of the pancreas, and glucose (8.3 mM)- and arginine (10 mM)-stimulated insulin release from the isolated perfused pancreas were examined at 8, 20, 40, and 60 weeks of age in both groups. Pancreatic insulin content was examined at 60 weeks. In the STD group, impairment of glucose tolerance and destruction and fibrosis of pancreatic tissues progressed with age. Glucose-stimulated insulin release was remarkably reduced with age, while arginine-stimulated insulin release was preserved. By contrast, in the FOY group, development of glucose intolerance was delayed and the pancreas showed fewer pathologic changes compared with the STD group. Insulin releases in response to both glucose and arginine were preserved at all ages examined. Total pancreatic insulin content at 60 weeks of age was significantly greater than that of the STD group. The male WBN/Kob rat is a new type of diabetic model that shows a similar pattern of insulin release to that in rat with non-insulin-dependent diabetes mellitus and also shows unique histopathological changes in exocrine pancreas. FOY-305 was effective in preventing the development of diabetes in this model, although its mechanism is still unknown.

Administration, Oral↗

Serum levels of interleukin 6 in patients with pustulosis palmaris et plantaris.

Serum interleukin 6 (IL-6) was measured in patients with pustulosis palmaris et plantaris by a fluorescent sandwich enzyme-linked immunosorbent assay (ELISA) method. Increased production of IL-6 was observed in 8 cases out of 10 showing numerous pustules in their active stage. Six cases were measured before and after tonsillectomy, and statistically significant reduction in the levels of IL-6 paralleled an improvement in the disease activity. It is suggested that IL-6 may be one of the mediators which link tonsillectomy to the activity of pustulosis palmaris et plantaris.

Adult↗

Establishment and characterization of a simian virus 40-immortalized osteoblastic cell line from normal human bone.

We established a human osteoblastic cell line immortalized by simian virus 40 (SV40) in vitro, and designated it SV-HFO. Immunocytochemically, the cells were positive for SV40 large T-antigen, vimentin and osteocalcin, but negative for keratin and epithelial membrane antigen. The cells had characteristic morphologic and ultrastructural features of osteoblasts, produced alkaline phosphatase, and synthesized osteocalcin, the levels of which were elevated by treatment of the cells with 1a,25-dihydroxyvitamin D3. The cells proliferated and showed such osteoblastic properties even under serum-free conditions. The cells grew in soft agar, but did not form tumors when transplanted into athymic nude mice. Karyotypic analysis by the Q-banding technique showed that these cells were of human origin. The SV-HFO cell line is expected to serve as a suitable model for studying metabolism and carcinogenesis in human bone.

Alkaline Phosphatase↗

Varied clinical morphology of HPV-1-induced warts, depending on anatomical factors.

The clinical and histological features of 49 lesions induced by human papillomavirus type 1 (HPV-1) were studied. The majority of cases showed the typical clinical features and location of such lesions. They were usually located on the ventral or lateral surfaces of the hands or feet, and were dome-shaped lesions with a central depression. However, HPV-1-induced lesions located on other body areas displayed different clinical features, such as those of common warts, a digitate wart, and a cutaneous horn. One lesion on a healing burn scar had a herpes-like appearance. As these 49 lesions were induced by the same type of HPV (HPV-1), differences in their clinical features are likely to have been due to host-related factors.

Adolescent↗

1,25-Dihydroxy vitamin D3 stimulation of TGF-beta expression in chick embryonic calvarial bone.

Bone is a highly active producer of the cytokine, transforming growth factor-beta (TGF-beta), which is likely to be functionally involved in the regulation and maintenance of bone development and growth. In addition, bone functions are also regulated by the major calciotropic hormone, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3). This investigation aims to examine the possible relationship between TGF-beta and 1,25(OH)2D3 using an unique calcium-deficient chick embryonic model. By means of long-term culture without the eggshell (shell-less or SL culture), chick embryos may be rendered severely calcium-deficient with gross undermineralization of the skeleton. We have previously observed that the calvaria of these SL embryos develop abnormal chondrogenic phenotype, with production of collagen type II, and elevated TGF-beta expression. Administration of 1,25(OH)2D3 to the SL embryos in vivo on incubation days 10 and 12 (SL + D embryos) resulted in near-normal serum calcium on day 14 and improved calvarial calcification. However, TGF-beta expression in the SL + D calvaria was further increased compared to untreated SL calvaria, when analyzed at both the mRNA and protein levels. Histolocalization of gene expression by immunohistochemistry and in situ hybridization revealed that cells in the less mineralized orbital and temporal zones of the calvarium are particularly affected by the 1,25(OH)2D3 treatment. Interestingly, the increased TGF-beta expression resulting from 1,25(OH)2D3 treatment did not correct the aberrant collagen phenotype in the SL calvaria. These observations suggest that TGF-beta expression by bone cells in situ is stimulated by 1,25(OH)2D3, and that normal cellular differentiation and morphogenesis of the embryonic calvaria are dependent on proper and balanced TGF-beta expression as well as the state of tissue mineralization.

Animals↗