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Biomedical subjects

S Arai

Publications and source records attributed to S Arai.

At least 145 records · Page 8Linked to original sources

In vivo antitumor effects of murine interferon-gamma-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascites.

Interferon-gamma-inducing factor/interleukin-18 is a novel cytokine that reportedly augments natural killer (NK) activity in human and mouse peripheral blood mononuclear cell cultures in vitro and has recently been designated IL-18. In this study, IL-18 exhibited significant antitumor effects in BALB/c mice challenged intraperitoneally (i.p.) with syngeneic Meth A sarcoma when administered i.p. on days 1, 2 and 3 after challenge. Intravenous (i.v.) administration also induced antitumor effects in the tumor-bearing mice; however, subcutaneous (s.c.) administration did not. When mice were twice pretreated with 1 microg IL-18 3 days and 6 h before tumor challenge, all mice survived whereas control mice died within 3 weeks of challenge. Inhibitory effects on Meth A cell growth in vitro were not observed with either IL-18 or interferon gamma. The effects of IL-18 pretreatment were abrogated by abolition of NK activity after mice had been injected with anti-asialo GM1 antibody 48 h before and, 24 h and 72 h after tumor challenge. Mice pretreated with IL-18 and surviving tumor challenge resisted rechallenge with Meth A cells but could not reject Ehrlich ascites carcinoma, and spleen cells from the resistant mice, but not control mice, exhibited cytotoxic activity against Meth A cells in vitro after restimulation with mitomycin C-treated Meth A cells for 5 days. The effector cells in the spleen cell preparations from resistant mice appear to be CD4+ cells because cytolytic activity was significantly inhibited after depletion of this subset by monoclonal antibodies and complement. In conclusion, IL-18 exhibits in vivo immunologically (primarily NK) mediated antitumor effects in mice challenged with syngeneic Meth A sarcoma and induces immunological memory and the generation of cytotoxic CD4+ cells.

Animals↗

Association of interleukin-6 in the cerebrospinal fluid during crisis of calf with ammoniated feed syndrome.

Ammoniated feed syndrome (AFS) in cattle is a neurotoxic syndrome caused by feeding specific ammoniated forage. To clarify the pathophysiology of AFS, we examined the association of interleukin-6 (IL-6) in the brain. By feeding milk either from cows fed such ammoniated forage or milk added with 4-methyl-imidazole, newborn calves showed a neurotoxic crisis of hyperexcitability, ataxia, muscle tremor, circling, roaring, epileptoid seizure, sweating and marked fever response. Although these calves had no pathological lesions in the brain, we detected a rise in IL-6 in the cerebrospinal fluid (CSF). Tumor necrosis factor-alpha (TNF-alpha) was not detected in the CSF. In the sera, IL-6 and TNF-alpha hardly changed during the experiment. Administration of recombinant human IL-6 into the lateral ventricle resulted in fever. Thus, we believe IL-6 in the CSF is related to the fever response in newborn calves with AFS.

Acute Disease↗

Transepithelial transport of oligopeptides in the human intestinal cell, Caco-2.

The transepithelial transport of oligopeptides (of more than 4 residues) was studied by using human intestinal Caco-2 cell monolyers. The susceptibility to the brush-border peptidases was observed to be one of the primary factors which decide the transport rate. The apical-to-basolateral transport mechanism was investigated by using bradykinin and GGYR which were resistant to cellular peptidases. The intracellular pathway, probably the adsorptive transcytosis, was suggested to be involved in the transport of bradykinin and its analogues, the transport rate being particularly dependent on the hydrophobic properties of the peptides. On the other hand, the tetrapeptide such as GGYR was suggested to be transported mainly via the paracellular pathway.

Biological Transport↗

Identification of a novel vitamin D response element from the rat genome.

1 alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the active form of vitamin D3, has been thought to be a multifunctional agent. In order to discover novel roles of 1,25-(OH)2D3, we have been looking for new genes that are regulated by 1,25-(OH)2D3. Because the actions of 1,25-(OH)2D3 are mediated through the vitamin D receptor (VDR), that is a DNA binding transcription factor, vitamin D regulated genes should have VDR binding sites in their regulatory regions. In this paper, we describe a novel vitamin D response element (VDRE)-containing sequence, clone 3, which was isolated through binding to VDR. DNA sequence analysis of clone 3 did not reveal any significant similarity with sequences reported previously. Clone 3 had two regions consisting of a direct repeated sequence of AGTTCA motifs, both of which bound to VDR independently. Whereas each direct repeat sequence alone could not mediate transcriptional activation efficiently, with their co-existence there was a strong response to 1,25-(OH)2D3, indicating that these two direct repeated sequences act cooperatively.

Animals↗

Characterization of a gene family encoding cysteine proteinases of Sitophilus zeamais (maize weevil), and analysis of the protein distribution in various tissues including alimentary tract and germ cells.

We have identified and characterized a gene family comprising at least four genes encoding cathepsin L-like cysteine proteinases (SCPs) in Sitophilus zeamais, Coleoptera. A cDNA clone corresponding to a major mRNA species of the gene family in adult insects codes for a cysteine proteinase (CP) of 338 amino acid residues, and two genomic clones code for similar CPs of 331 residues whose COOH-terminal structures are seven amino acids shorter. These three SCPs show high sequence similarity to one another as well as to other insect and mammalian cathepsin L-like proteinases. A polyclonal antibody raised against bacterially expressed SCP was used as a probe to examine the molecular forms and distribution of the enzyme. SCP exists in both proenzyme and mature forms in larvae, pupae, and adults, and the proenzyme converts in vitro into the mature form at acidic pH. Immunohistochemical analysis showed that SCP is present in several tissues including alimentary organs and germ cells. In alimentary organs, SCP is distributed in the gastric caeca, but not the midgut. SCP is also present in genital organs, especially in oocytes and nurse cells, where it exists at high levels. These results indicate that SCP plays a variety of physiological roles including a role in food digestion.

Amino Acid Sequence↗

Characterization and regulation of taurine transport in Caco-2, human intestinal cells.

We characterized the taurine transport system in human intestinal Caco-2 cells and showed that it is subject to adaptive regulation. The activity of taurine transport in Caco-2 cells was evaluated by means of an Na+- and Cl(-)-dependent high-affinity transport system, the characteristics of which were similar to those of the beta-amino acid-specific taurine transport system previously described for various tissues. The activity of taurine transport was down-regulated on culturing in taurine-containing medium. This taurine-induced down-regulation was dependent on both the incubation time with taurine and the concentration of taurine. Hypotaurine and beta-alanine were also capable of inducing this adaptive regulation, whereas alpha-amino acids and gamma-aminoisobutyric acid were not. Kinetic analysis of control and taurine-treated cells suggested that the down-regulation was associated with a decrease in the maximal velocity of taurine transport and also with a decrease in the affinity of the taurine transporter. Cycloheximide treatment weakened the taurine-induced down-regulation. The mRNA level of the taurine transporter (HTAU type) in taurine-treated cells was markedly decreased compared with in control cells. These results indicate that a complex regulatory mechanism is involved in this down-regulation.

Adaptation, Physiological↗

Production of a T-cell clone which reacts with membrane proteins of Acholeplasma laidlawii.

The role of cellular immunity in mycoplasma infection is not completely understood. In this study, we established mycoplasma-specific T-cell clones to evaluate cellular immunity in mycoplasma infection. We developed a T-cell clone (G-10) which was stimulated with Acholeplasma laidlawii. The T-cell clone G-10, CD4+ and T-cell receptor (TCR) alpha beta- recognized the 42- and 65-kilodalton (kDa) membrane proteins of A. laidlawii and responded to A. hippikon. Hence, the application of mycoplasma-specific T cells such as G-10 in animal models may allow the assessment of cellular immune response to mycoplasma infection.

Acholeplasma laidlawii↗

PGE2 inhibits glucose uptake in isolated villous epithelial cells of the ovine small intestine.

This study was designed to clarify whether PGE2 directly inhibits glucose absorption in villous cells. For this purpose, isolated villous epithelial cells of the ovine small intestine were used, and the uptake of 14C-labelled glucose in the absorptive epithelial cells was measured in the presence and absence of 0.2 mM phlorizin or 10 microM PGE2. In isolated villous epithelial cells of the small intestine in sheep, net glucose absorption was reduced by 68.2% in the presence of phlorizin. This result indicates that most of the glucose in ruminants is absorbed by the specific transporter SGLT1, which is sensitive to phlorizin. PGE2 decreased glucose absorption by 26.5% in isolated villous epithelial cells in sheep, although this glucose absorption did not change in the presence of phlorizin. This result clearly indicates the PGE2 inhibits the phlorizin-sensitive glucose absorptive process through direct action on the villous cells of ruminants.

Animals↗

[Functional foods].

This lecture first pinpoints the "tertiary" function of foods which, as opposed to the conventional "primary" and "secondary" functions that are related to nutrition and preference, respectively, is understood to be directly involved in the modulation of our physiological systems such as the immune, endocrine, nervous, circulatory, and digestive systems Insights into this newly defined function are particularly important in that the intake of physiologically functional food factors could be effective in preventing diseases that may be caused by disorders in these systems. Technologically, it has become feasible to design and produce physiologically functional foods (simply, functional foods) that are expected to satisfy in whole or in part our today's demand for disease prevention by eating. Such public expectations are reflected in the activation and development of academic and industrial studies on novel food factors. Meanwhile, a national policy has been established to approve functional foods in terms of "foods for specified health uses" defined by new legislation. Up to now, 78 such items have been approved; the first was a hypoallergenic rice product. Here are highlighted the details of studies on cereal-based functional foods. Other basic and applied studies directed toward the tertiary function of foods, with future perspectives for functional foods, are also discussed.

Edible Grain↗

Effect of UVA on RNA synthesis in isolated chicken liver nuclei.

Little information is available on the effects of UVA (320-400 nm radiation) on transcription. We examined the effect of UVA on RNA synthesis in isolated chicken liver nuclei. Nuclei in air or nitrogen were irradiated with UVA, and the RNA synthesis induced by endogenous RNA polymerase was estimated under conditions in which little or no initiation occurs. Incorporation of [3H]UMP into the acid-insoluble fraction was used as the measure of RNA synthesis in the nuclei. In air the amount of synthesized RNA decreased with increasing UVA fluence. In contrast, in nitrogen UVA had little effect on RNA synthesis. Sodium azide and histidine, which effectively scavenge singlet oxygen (1O2) as well as hydroxyl radicals (.OH), protected the nuclei from inhibition of RNA synthesis; whereas, sodium formate and dimethyl sulfoxide, both of which much more effectively scavenge .OH than 1O2, had no protective effect. These findings provide a strong indication that 1O2 is involved in the inhibition of RNA synthesis. In addition, RNA polymerase II-dependent synthesis (in the nucleoplasm) was much more sensitive to UVA than RNA polymerase I-dependent synthesis (in the nucleolus).

Animals↗

Resistance to UV-irradiation of DNA synthesis in fibroblast cell lines derived from LEC strain rats.

After UV-irradiation, no difference in the survival curves was observed among cell lines derived from LEC strain (LEC) rats and WKAH strain (WKAH) rats. The dose-response curves for inhibition of DNA synthesis in WKAH-derived cells showed a sharp decline at lower doses and a mild decline at higher doses of UV-rays. In contrast, the dose-response curves in LEC-derived cell lines had no sharp component, and were almost identical to the mild component of the curves in WKAH-derived cells. These results show that DNA synthesis in the cell lines of LEC rats was more resistant to UV-irradiation than that of WKAH rats.

Animals↗

Abnormal G1 arrest in the cell lines from LEC strain rats after X-irradiation.

The effect of X-irradiation of cell lines from LEC and WKAH strain rats on a progression of cell cycle was investigated. When WKAH rat cells were exposed to 5 Gy of X-rays and their cell cycle distribution was determined by a flow cytometer, the proportion of S-phase cells decreased and that of G2/M-phase cells increased at 8 hr post-irradiation. At 18 and 24 hr post-irradiation, approximately 80% of the cells appeared in the G1 phase. On the contrary, the proportion of S-phase cells increased and that G1-phase cells decreased in LEC rats during 8-24 hr post-irradiation, compared with that at 0 hr post-irradiation. Thus, radiation-induced delay in the progression from the G1 phase to S phase (G1 arrest) was observed in WKAH rat cells but not in LEC rat cells. In the case of WKAH rat cells, the intensities of the bands of p53 protein increased at 1 and 2 hr after X-irradiation at 5 Gy, compared with those of unirradiated cells and at 0 hr post-irradiation. In contrast, the intensities of the bands were faint and did not significantly increase in LEC rat cells during 0-6 hr incubation after X-irradiation. Present results suggested that the radioresistant DNA synthesis in LEC rat cells is thought to be due to the abnormal G1 arrest following X-irradiation.

Animals↗

Influence of exercise on QT dispersion in ischemic heart disease.

UNLABELLED: QT dispersion (QTd: maximum QT interval-minimum QT interval) is associated with severe cardiac arrhythmia and with abnormal ventricular repolarization. We investigated the influence of exercise on QTd in patients with ischemic heart disease. On standard 12-lead electrocardiograms, QTd was measured before and after treadmill exercise in 7 normal subjects, 17 patients with effort angina pectoris (and > or = 75% stenosis on coronary arteriography), and 33 patients with old myocardial infarction. Bazett's formula was used to obtain the corrected QTd (QTcd). The pre-exercise resting QTcd was 45.9 +/- 10.6, 44.3 +/- 15.2, and 74.8 +/- 28.1 msec in the respective groups, being significantly greater in the infarct group (p < 0.05). The QTcd at 5 min after exercise was respectively 49.3 +/- 9.0, 58.8 +/- 19.9, and 75.4 +/- 30.9 msec (p = 0.0347, infarct vs. controls). The difference in QTcd was significant for the angina group before and after physical exercise (p = 0.0003). There was a significant increase of QTcd after exercise in the angina group whether or not the patients were receiving beta-blockers. The infarct patients without beta-blocker therapy showed an increase of QTcd after exercise, while those receiving beta-blockers showed a decrease. The post-exercise difference between these subgroups was significant (p = 0.0351). CONCLUSIONS: QTcd was significantly increased by exercise in the angina group, possibly reflecting impaired repolarization due to ischemia. Inhibition of the increase in QTd by beta-blockers suggested a possible preventive effect on severe arrhythmias due to nonhomogeneous ventricular repolarization.

Adrenergic beta-Antagonists↗

Subcutaneous fat distribution of the abdomen and buttocks in Japanese women aged 20 to 58 years.

Subcutaneous fat is an essential element in shaping the body of human beings. In this research, skinfold thickness was measured specifically in 33 regions of the human body, including the abdomen and buttocks. Based on our measurements, the subcutaneous fat distribution was assessed for several age groups. The subjects were healthy Japanese women aged 20 to 58 years. Skinfold thickness was measured using the B-mode ultrasound methods, together with anthropometric measurement. A comparison was made between the following five age groups: early 20's, late 20's, 30's, 40's and 50's. The measured values for the early 20's group were used as the standard and the relationship between increase ratio of subcutaneous fat and age was studied. Through our research, we obtained data on the subcutaneous fat distribution in each age group. The largest change was observed between the ages of the early 20's and late 20's. The skinfold thickness measurements of the abdomen and buttocks was consistently around 10 mm for the early 20's, and increased up to 23.8 mm on the rear side section for the late 20's. This result indicates that the increase ratio varied depending on the part of body. Furthermore, the changes in skinfold thickness were different in specific parts of the abdomen and buttocks among different age groups. The difference in skinfold thickness between upper and lower sections of the abdomen also becomes more pronounced with age. Skinfold thickness increased significantly between the early 20's and late 20's. Among the body regions, measurements at the rear side showed the largest change with age; averaging 11.3 mm for the early 20's compared to 33.6 mm for the 50's. The subcutaneous fat distribution on the buttock also showed the differences with age, indicating changes in body shape. Using careful measurements of the abdomen and buttocks, subcutaneous fat distribution among each age group was determined as well as the variation in changes with the aging process.

Abdomen↗

[Successful direct percutaneous transluminal coronary angioplasty in a 91-year-old male with acute myocardial infarction complicating cardiogenic shock].

A 91-year-old male patient was admitted to hospital with acute myocardial infarction complicating cardiogenic shock. An emergency coronary arteriogram showed 99% stenosis at the mid-section of the right coronary artery, and in order to achieve an early recovery direct percutaneous transluminal angioplasty (PTCA) was performed through the brachial artery using a 6 french catheter. The lesion was successfully dilated up to 25% residual stenosis. Hypointention had been sustained during the admission; however, it gradually improved and he was discharged on the 31st hospital day. He has been followed up for 6 months after discharge at the out-patient clinic and has not recurrent ischemic episodes. According to other reports on the use of direct PTCA in the elderly, the postdischarge mortality rate is lower than that with medical therapy or thrombolysis. When cardiogenic shock occurs even in the elderly, direct PTCA should be selected as the first choice of treatment.

Aged↗

[Clinical significant of malassezia furfur specific IgE antibody in atopic dermatitis].

The clinical significance of AlaSTAT (DPC) Specific IgE for Malassezia furfur (Mf) was evaluated by testing the sera of 147 atopic dermatitis (AD) patients. Patients were from 0 to 52 years old, and the prevalence of positive assay results was analyzed by age, class of reactivity, and degree of face and body symptoms. Evaluations of rhinitis, seborrhea as complications and serum total IgE by RIST were included. The prevalence of Mf specific IgE positive sera was lowest in the 0-2 year age group, and increased swiftly in the 3-9 year age group. The older age is, the higher specific IgE antibody for Mf. The prevalence in the 0-2 year age group was significantly different from the other age groups. Although none of the positive results were above AlaSTAT class 2 in the 0-2 year age group, the positive result above AlaSTAT class 2 increased in the 3-9 year age group and was highest in the older age groups, reaching a peak prevalence at age 20 years. A group of age 20 years or older prevalence was significantly different from the 3-9 and 10-19 years old patients. The prevalence of positive did not correlate with face and body symptoms. Adults were more often Mf positive than children. An increasing prevalence of severe face symptoms in adults did correlate with the increased prevalence of Mf specific IgE in the in sera. The AlaSTAT class 3 and 4 results correlated with more severe face symptoms, and complications by seborrhea. The high AlaSTAT class results also corresponded to high total IgE values.

Adolescent↗

[Penetrating brain injury and traumatic aneurysm caused by a nail gun].

A rare case of penetrating brain injury and traumatic aneurysm caused by a nail gun was described. A 45-year-old male was admitted to our hospital on October 13, 1995 due to a penetrating head injury. He had used a nail gun in a suicide attempt. On admission, he presented with moderate consciousness disturbance, right hemiparesis and aphasia. Several small wounds were observed at the bilateral temporal scalp. The skull films showed that there were five nails in the left side and four nails in the right side perforating in the skull. The CT revealed a small hematoma at the left temporal lobe. The cerebral angiograms did not show any particular findings. Under local anesthesia, each nail was extracted carefully. Suddenly, his neurological damage aggravated and the CT showed a massive hematoma in the left temporal lobe. Emergent craniotomy was performed and the hematoma was totally evacuated. Rehabilitation was carried out and he recovered enough to be able to walk. Angiograms four months after the injury revealed the formation of a traumatic aneurysm at the peripheral part of the left middle cerebral artery (cortical cerebral aneurysm). We did not perform a direct operation for the aneurysm since the contrast medium remained in the aneurysm until the late venous phase. This aneurysm disappeared spontaneously after another four months' observation. Although many penetrated head injuries have been previously reported, the present case is the first report of a traumatic aneurysm associated with nail gun injury.

Brain Injuries↗

[Successful open commissurotomy and resection of dysplastic myxomatous tissue on the leaflet edges in a neonate and an early infant with critical aortic stenosis].

A neonate and an early infant with critical aortic stenosis successfully underwent open commissurotomy and resection of dysplastic myxomatous tissue on the leaflet edges using cardiopulmonary bypass. Case 1: A 31-day-old boy admitted to our unit with shock. Echocardiography demonstrated critical aortic stenosis and severe left ventricular dysfunction (EF = 15%). Case 2: A 12-day-old boy suddenly deteriorated and required resuscitation with ventilation and inotropic support. Emergency operation was required in both cases using cardiopulmonary bypass with systemic hypothermia (30 degrees C). In both cases, the aortic valve was bicuspid and dysplastic with gelatinous myxomatous tissue on the leaflet edges. Commissurotomy and resection of myxomatous tissue were performed. Their postoperation courses were uneventful and they have been free from medication at present. These results suggest that aortic commissurotomy and resection of myxomatous tissue under direct vision may be preferable for critical aortic stenosis with dysplastic aortic valve.

Aortic Valve↗