Search PubMed⌕ Search

Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 883 records · Page 49Linked to original sources

Unstable expression of E-cadherin adhesion molecules in metastatic ovarian tumor cells.

E-Cadherin is a member of the cadherin family, which plays a key role in intercellular adhesion in various tumors as well as in normal tissues. Here, we examined the expression of this adhesion molecule in a murine ovarian tumor line OV2944, whose sublines show different degrees of spontaneous metastasis from subcutaneous sites; sublines LM-1 and LM-3 exhibit a low metastatic activity but a variant subline HM-1 has a high metastatic activity. When the expression of E-cadherin in these cells was examined by immunoblot analysis, the highly metastatic HM-1 cells was found to express an extremely small amount of this molecule, as compared with a high level of E-cadherin expression in the weakly metastatic LM-1 and LM-3 cells. Northern blot analysis showed that the amount of tanscripts from the E-cadherin gene is proportional to the amount of proteins detected in these cells. Immunofluorescence staining revealed that cells of the highly metastatic line were heterogeneous, that is, their cultures contained both E-cadherin-positive and negative cells. In contrast, cells of the weakly metastatic lines homogeneously expressed E-cadherin. When the highly metastatic line was subcloned, all the subclones consisted of E-cadherin-positive and negative cells. These results suggest that the expression of E-cadherin gene is not stably controlled in the highly metastatic line.

Animals↗

Ultrastructure of the peri-implant junctional epithelium on single-crystal sapphire endosseous dental implant loaded with functional stress.

To elucidate the ultrastructure of peri-implant junctional epithelium (IJE) on single-crystal sapphire dental implants connected to the adjacent teeth by a metal superstructure, the peri-implant gingivae of ten monkeys were examined using a transmission electron microscope (TEM) at 3, 6 and 12 months after implant insertion. At the time of examination, the ultrastructural features of the IJE were almost identical to those of junctional epithelium (JE) attached to natural teeth, i.e. developed Golgi complexes, rough-surfaced endoplasmic reticulum, numerous free ribosomes and mitochondria. The innermost cells of IJE were attached to the implant surface by means of basal lamina-like structures (500-1000 A in thickness) and hemidesmosomes, but lacked a dental cuticle as seen on teeth. Such epithelial attachment of the IJE was often indistinct or absent at the apical portion of the IJE which terminated at the level of alveolar crest. A continuous basal lamina-like structure was also present along basal cells at the interface between the IJE and gingival connective tissue except at its apical portion.

Aluminum↗

T-cell colony formation in healthy homosexual men without anti-human immunodeficiency virus antibody.

In order to study the abnormal differentiation and proliferation of precursor T cells in homosexual men, a study was made of T-cell colony formation in 15 healthy homosexual men without anti-human immunodeficiency virus (HIV) antibody. The colony forming method used was the one-step monolayer technique using phytohemagglutinin as an inducer. Our results revealed that colony formation was extremely reduced and 3 cases showed no colony growth. However, with the addition of recombinant interleukin 2 to the culture system, the number of colonies increased up to the same level as in heterosexual controls. In addition, the analysis of CD3+, 4+, and 8+ cells of colony component cells revealed a decrease in CD3+ and 4+ cells. However, with the addition of recombinant interleukin 2, the numbers of CD3+ cells distinctly increased. The above results suggest that a disorder in the differentiation and proliferation of precursor T cells in homosexual men might be one of the causes of immunodeficiency.

Adult↗

Binding of sulfonamides to erythrocytes and their components.

Binding of zonisamide, a new antiepileptic sulfonamide derivative, was examined to human erythrocytes, their lysate and their carbonic anhydrase by centrifugation for cells or by ultrafiltration for the others. Scatchard plots revealed that the binding to intact and lysed cells was composed of high- and low-affinity components and that to carbonic anhydrase, of the high-affinity component alone. Parameters for high-affinity binding were similar in all three preparations and those for low-affinity binding were similar in the former two preparations. Dissociation constants for these bindings to erythrocytes were smaller than the dissociation constant for serum albumin. These results may explain the concentration of sulfonamides in red cells, and suggest the participation of cellular protein component(s) in addition to previously known carbonic anhydrase in the binding. Acetazolamide, sulthiame, zonisamide, hydrochlorothiazide and sulfanilamide inhibited carbonic anhydrase in a non-competitive manner to different extents. The Ki values of these sulfonamides were of the order of 0.1--0.2 of their respective Kd values determined by ultrafiltration, suggesting that under the present conditions, physicochemical interactions between sulfonamides and carbonic anhydrase primarily occur at common sites that affect the activity of the enzyme.

Erythrocytes↗

Binding of sulfonamides to erythrocyte proteins and possible drug-drug interaction.

The mode of binding of sulfonamides to erythrocyte proteins and possible drug-drug interaction between those compounds in erythrocytes resulting in changes in tissue levels were studied in rats using zonisamide (a novel antiepileptic agent possessing a sulfonamide group), several other sulfonamides and some antiepileptics without a sulfonamide group. In Michaelis-Menten plottings, the sulfonamide was found to be concentrated into erythrocytes in vitro and in vivo in a saturable high-affinity mode and in a linear low-affinity mode at ordinary therapeutic plasma levels through a simple diffusion process. Concentration in erythrocytes was affected by the presence of albumin in the extracellular medium. The cellular sulfonamide was readily replaced by extracellular sulfonamides in vitro. Even in vivo, erythrocyte levels of zonisamide were lowered by administration of other sulfonamides, although the plasma and tissue levels were not significantly changed since the plasma and tissue compartments of zonisamide were large relative to the erythrocyte compartment at ordinary therapeutic dose levels of zonisamide in animals and man. Therefore, disposition of zonisamide was not significantly influenced by other sulfonamides, but it is suggested that drug-drug interaction affecting the tissue levels may occur for a combination of sulfonamides with extremely different affinities for erythrocytes and low therapeutic plasma levels.

Animals↗

[Urinary alkylphosphate levels as an index of exposure to organophosphorus insecticides in pest control operators].

In pest control operations, organophosphorus compounds (OP) have been sprayed as insecticides, blood cholinesterase (ChE) activities and urinary alkylphosphate levels were measured for both OP-sprayers (n = 102) and non-sprayers (n = 35) in pest control companies, and the relationship between the analytical results and spraying conditions was investigated. Plasma ChE activities of the OP-sprayers and of the non-sprayers, as well as blood cell ChE activities of the OP-sprayers, were significantly lower than those of employees of chemical factories who served as controls (n = 103). Urinary alkylphosphates were not detected in the controls at all but were detected in 83% of the sprayers and in 57% of the non-sprayer employees of pest control companies. A significant negative correlation (r = -0.34, n = 137, p less than 0.01) between the plasma ChE activities and urinary total alkylphosphate levels was observed in employees of pest control companies. In the case of the employees whose urinary total alkylphosphate levels were 0.1 mumol/g creatinine or more, the plasma ChE activities were 25% decreased compared to the control group. The OP-sprayers showed significantly higher urinary total alkylphosphate levels than the non-sprayers. The OP-sprayers were further divided into two groups. One was sprayers engaged in both cockroach- or fly-control and termite-control operations (sprayers I, n = 54) and the other was sprayers engaged in only cockroach- or fly-control operations (sprayer II, n = 48).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Changes of serum thyroid hormone levels induce malformations on early embryogenesis in rats.

The incidence of malformation is increased in infants of hyperthyroid or hypothyroid woman. Although many papers reported that the fetus is insulted from maternal thyroid hormone, the placenta (maternal-fetal barrier) is not yet fully developed before 11.5 days of gestation in rat embryos, suggesting the effect of thyroid hormone on early rat embryogenesis. This study was, therefore, undertaken to investigate whether excess or lack of thyroid hormones would affect early embryogenesis in rat embryo culture. Malformations including open neuropore and microencephaly were observed in 10 of 30 embryos incubated in hyperthyroid serum, and in 12 of 42 cultured in T3-enriched normal serum. Similar malformations were observed on 14 of 42 embryos cultured in hypothyroid serum and in 10 of 30 cultured in hypothyroid serum supplemented with T3. The frequencies of these malformations were significantly higher than in the control embryos (0 in 72 embryos) cultured with normal rat serum. These results suggest that the maternal thyroid status might play an important role for the complication of fetal malformations during early gestational period.

Animals↗

[A questionnaire study on health of taxi drivers--relations to work conditions and daily life].

A questionnaire survey was conducted on 5,523 taxi drivers in Osaka Prefecture to investigate their working conditions and daily life as well as characteristics of their health condition and various effects on health, especially on their cardiovascular system. The major results of this survey were as follows: 1) The rate of subjective symptoms, morbidity rate and rate of poor physical condition over the past year in the taxi drivers were higher than those of the control group. Among the subjective symptoms, the rate of gastrointestinal disorders, fatigue, musculoskeletal system disorders, sensory system disorders, hemorrhoids, etc. was especially high. 2) Work shift, density of work, years of experience in taxi-driving, frequency of fright while driving, pattern of taking meals, way of recuperation on rest days or holidays, obesity, smoking, and intake of coffee and alcohol were found to be factors affecting the health of taxi drivers. 3) Nearly half of the respondents said that they would like to quit or change their job with as much as 62% giving "condition of health" as reason. On the other hand, the rate of heart-related symptoms such as palpitation, and breathlessness did not differ from that of the control group. The possible reason for this deduced from the foregoing results, is that there were some who had changed or quit the job at an early stage for health reasons such as heart trouble and severe physical and mental burden resulting from taxi driving. 4) Many taxi driver are obese and the rate of those with heart-related symptoms was considerably high among those classified as obese. In addition, the results showed that those with longer driving experience tended to be obese.

Adult↗

[Changes in chewing rhythm during repetitive series of mastication in normal adults as a function of time elapsed and the four basic taste stimuli].

Surface EMG activities in the masseter muscle were recorded from 8 healthy men with normal permanent dentition during habitual chewing of a small cube of synthetic cellulose sponge which had absorbed distilled water. Three parameters of chewing rhythm, viz., cycle time, duration, and interval, were shown as the respective averages of 40 measurements of the EMG traces of a masticatory series of 42 consecutive chewing strokes. Twenty-five recording sessions, in each of which the above masticatory series were repeated 10 times in a day with a 5 minutes' recess between each series, were performed on a subject during continuous 25 days. The amount of scatter in the distribution of 25 cycle time values was great at the 1st masticatory series, gradually decreased to reach a node relatively free from the dispersion at the 5th series, and then gradually increased from the 6th to 10th series. The same phenomenon was observed in all 8 subjects, although there was a small difference among them in the number of the series where the node was apparent. The average of 5 cycle time values was used to compare in the same subject the effect of chewing the cellulose sponge which had absorbed one of the 4 basic taste solutions with the effect of chewing that which had absorbed distilled water. The average value while chewing the sponge which had absorbed 1 M saccharose was significantly lower in the subjects who obtained a relatively large average value during distilled water sponge-chewing, whereas it was significantly greater in those who obtained a relatively small average value while chewing the sponge which had absorbed distilled water. The other 3 taste stimuli induced a significant increase in the average value in most subjects.

Adult↗

Effects of brief exposure to insulin-induced hypoglycemic serum during organogenesis in rat embryo culture.

We have previously shown that long-term exposure to medium containing insulin-induced hypoglycemic serum during the early phase of organogenesis can adversely affect embryonic development in rat embryo culture and that these effects were mediated through the interruption of glycolytic flux that constituted the principal pathway at this embryonic stage. Further experiments were performed to examine whether brief exposure to the hypoglycemic medium during critical developmental periods would have adverse effects on embryogenesis during embryo culture not only in normal but also in high glucose concentrations. Rat embryos in the early head-fold stage (9.5 days gestation) were grown in vitro for 48 h until neural tube closure occurred; dysmorphogenic lesions were not elicited in either the basal culture medium containing 6.6 mM glucose (control medium) or the hyperglycemic medium supplemented with glucose at a concentration of 33.3 mM. Hypoglycemic mediums (2.2-2.5 mM glucose) were prepared from the serum of rats given insulin intraperitoneally. Postimplantation embryos (in early neural tube formation) were briefly exposed (1 h) to hypoglycemic medium on day 10.3 of gestation during the basal culture. After exposure to the hypoglycemic medium for 1 h during culture in the control medium, embryos showed minor growth retardation and dysmorphogenic lesions (7.1% open neural pores). Exposure to the hypoglycemic medium for 1 h during culture in hyperglycemic medium suplemented with a subteratogenic concentration of glucose (33.3 mM) resulted in greater growth retardation and increased occurrence of dysmorphogenic lesions (17.3% open neural pores).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

WS-9659 A and B, novel testosterone 5 alpha-reductase inhibitors isolated from a Streptomyces. II. Structural elucidation of WS-9659 A and B.

On the basis of spectroscopic and chemical evidence, the structures of WS-9659 A and B isolated as inhibitors of testosterone 5 alpha-reductase from a Streptomyces have been established as 1 and 2, respectively. The reductase inhibitory activities of the derivatives 5 and 6, and degradation products 3 and 8 were considerably less active and substantially inactive, respectively.

5-alpha Reductase Inhibitors↗

[Left ventricular diastolic flow dynamics in dilated cardiomyopathy: a color flow imaging and pulsed Doppler echocardiographic study].

Left ventricular filling flow was evaluated at the mitral orifice and in the left ventricle (LV) using color flow imaging and pulsed Doppler echocardiography in seven patients with dilated cardiomyopathy (DCM) and 10 normal subjects. Using the apical approach, filling flow in early and late diastole was observed by two-dimensional color and M-mode color flow imaging, and flow velocity patterns at the mitral orifice and in the LV, 3 cm below the orifice, were analyzed by pulsed Doppler echocardiography. Color flow imaging disclosed slower movement of the inflow signals toward the apex in DCM than in the normal. With pulsed Doppler echocardiography, the delay in timing of peak velocity in the LV was distinctly greater in DCM than in the normal, although the mitral inflow velocity did not differ between DCM and the normal. The width of the filling flow, the rate of velocity reduction and the flow velocity in the LV did not differ between DCM and the normal. Thus, in DCM, the timing of filling flow in the LV is clearly delayed compared to the timing at the mitral orifice, and this cannot be explained solely by the mitral flow velocity pattern.

Adult↗