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Biomedical subjects

T Hosono

Publications and source records attributed to T Hosono.

At least 55 records · Page 3Linked to original sources

Pharmacological studies on Puerariae flos III: protective effects of kakkalide on ethanol-induced lethality and acute hepatic injury in mice.

Kakkalide, one of the major isoflavonoid components of Puerariae flos, has been investigated for its effect on ethanol-induced intoxication and on hepatic injury, including hyperglycaemia, in mice. Kakkalide reduced mortality associated with administration of ethanol. At doses of 100 and 200 mg kg-1 the effect of kakkalide was significant. The same dose of kakkalide prevented increased serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activity. At a dose of 200 mg kg-1 it also counteracted ethanol-induced elevation of glucose levels. These results suggest that kakkalide might be useful for counteracting the effects of alcohol and might be effective for treating hepatic injury.

Acute Disease↗

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level.

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.

Animals↗

Translational augmentation of pro-matrix metalloproteinase 3 (prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)-1 mRNAs induced by epidermal growth factor in human uterine cervical fibroblasts.

The mechanisms by which epidermal growth factor (EGF) enhances the production of pro-matrix metalloproteinase 3 (proMMP-3/prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)-1 were investigated using human uterine cervical fibroblasts. The treatment of the cells with EGF for 24 h resulted in about 5-6-fold increase in the production of proMMP-3 and TIMP-1 compared with the untreated control cells. This increase was accompanied by an increase of proMMP-3 and TIMP-1 mRNAs. However, an about 3- and 2-fold increase in the production of proMMP-3 and TIMP-1, respectively, was observed as early as 1 h after the treatment of the cells with EGF, and it was not accompanied by any apparent increase in proMMP-3 and TIMP-1 mRNAs. This early effect of EGF on the enhanced production of proMMP-3 and TIMP-1 was not inhibited by actinomycin D, even though actinomycin D inhibited the synthesis of the total RNA in both the EGF-treated and untreated cells. These results indicate that EGF enhances the apparent production of proMMP-3 and TIMP-1 by two mechanisms: one by the accelerated translation of their mRNAs; and the other by the enhanced transcription of their genes. The former event takes place much earlier than the latter.

Cells, Cultured↗

Translational augmentation of pro-matrix metalloproteinase 3 (prostromelysin 1) and a tissue inhibitor of metalloproteinases (TIMP)-1 mRNAs by epidermal growth factor and transforming growth factor alpha, but not by interleukin 1 alpha or 12-O-tetradecanoylphorbol 13-acetate in human uterine cervical fibroblasts: the possible involvement of an atypical protein kinase C.

We have previously reported that epidermal growth factor (EGF) augments the translation of pro-matrix metalloproteinase 3 (proMMP-3/prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)-1 mRNAs during the first 1-h treatment of human uterine cervical fibroblasts (Hosono, T. et al., FEBS Lett., 381, 115-118, (1996)). In this report, we have investigated the effect of interleukin 1 alpha (IL-1 alpha) and 12-O-tetradecanoylphorbol 13-acetate (TPA), potent stimulators of proMMPs and TIMP-1 production, on the translation of proMMP-3 and TIMP-1 mRNAs. When human uterine cervical fibroblasts were treated with IL-1 alpha or TPA for 2h, their translations were not augmented, whereas the steady-state levels of proMMP-3 and TIMP-1 mRNAs in the cells treated with these stimuli for 24 h were increased 13.3- and 1.3-fold by IL-1 alpha and 52.5- and 5.7-fold by TPA, respectively. By contrast, transforming growth factor alpha(TGF alpha), which also binds to EGF-receptor, enhanced their production as early as 2 h after treatment, indicating that growth factors that bind to EGF-receptor are likely to be involved in the translational enhancement of proMMP-3 and TIMP-1 mRNAs. EGF partially translocated cytoplasmic protein kinase C (PKC) to plasma membrane, but the PKC down-regulation induced by 100nM TPA did not diminish the EGF-mediated translational augmentation of proMMP-3 and TIMP-1 mRNAs. In contrast, the PKC inhibitor of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) effectively suppressed the translational regulation of proMMP-3 and TIMP-1 in a dose-dependent manner during the first 2-h treatment with EGF. These results suggest that EGF and TGF alpha, but not IL-1 alpha and TPA, specifically augment the translation of proMMP-3 and TIMP-1 mRNAs and accelerate their accumulation without modifying their transcripts during the first 1-2 h treatment of human uterine cervical fibroblasts. This translational augmentation is suggested to be mediated by a TPA-insensitive atypical PKC subclass in the PKC family.

Cervix Uteri↗

Warm and cold signals from the preoptic area: which contribute more to the control of shivering in rats?

1. To find out whether the thermosensitive neurones in the preoptic area that control shivering are predominantly warm or cold sensitive, we tested the effects of injecting the excitatory amino acid L-glutamate at various sites in and adjacent to the preoptic area of anaesthetized rats shivering at ambient temperatures of 15-21 degrees C. 2. L-Glutamate injections (0.2 mM in 0.5-1.0 microliter), as well as preoptic warming and electrical stimulation, suppressed shivering, whereas control saline injections had no effect. Effective sites were restricted to the anterior part of the preoptic area, and a tenfold lower concentration of L-glutamate did not influence shivering. 3. Injections of procaine (0.2 M) into the sites where L-glutamate suppressed shivering did not affect strong shivering activity, but facilitated shivering in three out of seven cases when shivering was weak or absent at higher ambient temperatures (25-30 degrees C). 4. L-Glutamate injections, as well as preoptic warming and electrical stimulation, also elicited vasodilatation of the paw skin and the tail. Procaine elicited vasoconstriction when it was applied during vasodilatation induced by local preoptic warming. 5. These results indicate that the contribution of the preoptic area to the control of shivering and vasomotion is influenced more by signals from warm-sensitive neurones than by signals from cold-sensitive neurones.

Animals↗

Hypothalamic network for thermoregulatory shivering.

Warming one side of a rat's preoptic area and anterior hypothalamus (POAH) suppresses shivering on both sides of the body, and the present study evaluated the extent to which signals mediating this suppression cross the midline within and below the POAH. Hind paw shivering during unilateral POAH thermal stimulation was measured for rats in which the POAH had been midsagittally transected and for rats in which one side of the hypothalamus had been coronally transected just caudal to the POAH. In midsagittally transected rats, unilateral warming on either side of the POAH suppressed shivering equally on both sides of the body. In unilaterally transected rats, POAH warming on the transected side did not affect shivering, but warming the intact side suppressed shivering equally on both sides of the body. When a unilateral transection of only the lateral part of the hypothalamus included the medial forebrain bundle, the effect was the same as that of a unilateral transection of the whole hypothalamus. These results indicate that no information controlling shivering is exchanged between the left and right POAH and that efferent signals from the POAH, descending through the medial forebrain bundle, cross the midline somewhere below the hypothalamus to innervate both sides of the body equally.

Animals↗

Hypothalamic network for thermoregulatory vasomotor control.

Warming one side of a rat's preoptic area and anterior hypothalamus (POAH) causes skin vasodilation on both sides of the body, and the present study evaluated the extent to which signals mediating this vasodilation cross the midline within and below the POAH. Hind paw vasomotion during unilateral POAH thermal or electrical stimulation was measured for rats in which the POAH had been midsagittally transected and for rats in which one side of the hypothalamus had been coronally transected just below the POAH. In midsagittally transected rats, unilateral POAH thermal or electrical stimulation produced bilateral paw vasodilation, but the ipsilateral dilation occurred at a hypothalamic temperature lower than that at which contralateral dilation occurred. In the unilaterally transected rats, unilateral POAH warming produced bilateral vasodilation and, regardless of which side of the POAH was warmed, the threshold stimulus temperature was always lower for vasodilation on the intact side. Unilateral transection of a part of the hypothalamus that included the medial forebrain bundle had the same effect as did unilateral transection of the whole hypothalamus. Information controlling thermoregulatory vasomotion thus crosses the midline both within and below the POAH. Although efferent signals descending through the medial forebrain bundle innervate skin blood vessels on both sides of the body, this innervation is stronger on the ipsilateral side.

Animals↗

Antineutrophil cytoplasmic autoantibodies in 6 patients with renal failure and systemic sclerosis.

OBJECTIVE: To elucidate the distribution and frequency of antineutrophil cytoplasmic autoantibodies (ANCA) in systemic sclerosis. METHODS: Patient sera were analyzed by indirect immunofluorescence and by enzyme linked immunosorbent assay. RESULTS: High titers for perinuclear ANCA correlated with rapid deterioration of renal function. Patients were normotensive with normal plasma renin levels, but anemia, pulmonary hemorrhage and thrombocytopenia were problematic. All patients had anti-myeloperoxidase antibodies and some had anti-nRNP, anti-DNA, anti-Sm and LE cell antibodies. Outcome was poor except for one patient treated by plasmapheresis and cyclophosphamide. CONCLUSION: A renal specific subset of systemic sclerosis is suggested.

Acute Kidney Injury↗

Involvement of protein kinase C in the interleukin 1 alpha-induced gene expression of matrix metalloproteinases and tissue inhibitor-1 of metalloproteinases (TIMP-1) in human uterine cervical fibroblasts.

The role of protein kinase C in the interleukin 1 (IL-1)-mediated production of pro-matrix metalloproteinases (proMMPs) and tissue inhibitor-1 of metalloproteinases (TIMP-1) in human uterine cervical fibro-blasts has been investigated. IL-1 and a protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA) augmented the production of proMMP-1 (interstitial procollagenase), proMMP-3 (prostromelysin-1) and TIMP-1, but their effects were inhibited by the protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine in a dose-dependent manner. The suppressive effect of H-7 and staurosporine on the IL-1-induced production of proMMPs-1 and -3 and TIMP-1 resulted from the decrease in the steady-state levels of their mRNAs. When protein kinase C was down-regulated by treating the cells with a high level of TPA, the inductive effect of IL-1 upon proMMP-3 production was reduced considerably. These results indicate that protein kinase C mediates the IL-1-induced production of proMMPs-1 and -3 and TIMP-1 at the pretranslational level in human uterine cervical fibroblasts. On the other hand, neither IL-1 nor TPA modulated the production of proMMP-2 (progelatinase A). Both IL-1 and TPA also accelerated the production of prostaglandin E2 (PGE2) by cervical fibroblasts. However, the treatment of the cells with staurosporine in the presence of IL-1 or TPA further augmented PGE2 synthesis, suggesting that the increased synthesis of PGE2 by IL-1 treatment is mediated via signalling pathways distinct from those of proMMPs-1 and -3 and TIMP-1.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Pharmacological studies on small peptide fraction derived from soybean. The effects of small peptide fraction derived from soybean on fatigue, obesity and glycemia in mice].

The present research was an attempt to determine the pharmacological actions as for anti-fatigue, anti-obesity and hypoglycemia of small peptide isolated from soybean in mice. Small peptide administration prevented the decrease in sporting movement induced by concussion stress for 3 h in mice. In addition, it should be noted that the recovery rate of fatigue in 60 min after small peptide administration was over one hundred percentage in comparison with that after pretreatment, while the equivalent dose administration of amino acid mixture with the same small peptide amino acid composition did not prevent the decrease in sporting movement. In gold-thioglucose (500 mg/kg (i.p.))-induced obese mouse body weight gain, liver weight and body lipid level around uterine were significantly reduced by the chronic oral administration of small peptide (200, 1000 mg/kg). Administration in 1000 mg per kg of small peptide significantly lowered hyperglycemia in 30 and 120 min after glucose (3 g/kg (p.o.)) administration, whereas the equivalent amino acid mixture showed no effect. In conclusion, it suggested that small peptide isolated from soybean might have some pharmacological effects of anti-fatigue, anti-obesity, and hypoglycemia.

Animals↗

[Administration of human AT-III in a case of lupus anticoagulant positive pregnancy].

A 26-year-old pregnant woman was diagnosed as having both lupus anticoagulant (LA) and anticardiolipin antibody (ACA). Her previous pregnancy ended in intrauterine fetal death at 27 weeks' gestation. During the present pregnancy she was treated with aspirin, dipiridamole, predonisolone, and heparin. At 24 weeks, fetal growth became retarded, accompanied by markedly decreased activities of AT-III, protein C, plasminogen and alpha 2-plasmin inhibitor. Supplement of human AT-III led both to prolongation of the gestational period and improvement of fetal growth. The pregnancy ended in cesarean section because of signs of fetal distress at 30 weeks. The infant was a 1025-g male with Apgar scores of 5 and 9 at one and five minutes, respectively, and is healthy. The mother developed DIC after surgery, but recovered after therapy. In this case, TAT, alpha 2PI-plasmin complex, FDP Ddimer, FPB beta 15-42, L-FDP showed little correlation with the clinical course.

Adult↗

Risk factors for developmental disorders in infants born to women with Graves disease.

OBJECTIVE: To identify risk factors for disorders of fetal growth and thyroid function in the presence of maternal Graves disease. METHODS: Two hundred thirty pregnancies in gravidas with Graves disease were analyzed. Maternal thyroid status was evaluated by serum free thyroxine (T4) or free T4 index, TSH, and TSH-receptor antibody; personal history of thyrotoxicosis and total dose of antithyroid drugs during pregnancy were also noted. Neonatal thyroid function was assessed at birth and on the fifth day after birth. RESULTS: Fifteen neonates (6.5%) were small for gestational age (SGA), and this occurrence was significantly associated with thyrotoxicosis lasting for 30 weeks or more of pregnancy, TSH-receptor antibody level of 30% or more at delivery, history of Graves disease of 10 years or longer, and onset of Graves disease before 20 years of age. However, no significant correlation was found between maternal thyroid hormone level and SGA neonates. Thyroid dysfunction developed in 38 infants (16.5%), of whom only four were SGA; development of this dysfunction was significantly related to the mother's total dose of antithyroid drugs, duration of thyrotoxicosis in pregnancy, and/or TSH-receptor antibody level at delivery. CONCLUSIONS: Duration of maternal Graves disease or thyrotoxicosis, either mild chemical or overt, in pregnancy is significantly associated with SGA neonates. Neonatal thyroid dysfunction is associated with the maternal thyroid condition, especially the serum TSH-receptor antibody level.

Adult↗

[Prenatal evaluation of the platelet counts in the fetuses and the neonates of the mothers complicated with idiopathic thrombocytopenic purpura].

We investigated 25 pregnancies with ITP. The results were as follows. 1. The platelet counts of the maternal blood just before delivery were not correlated with those of the cord blood. 2. It was suggested that the maternal PAIgG value just before delivery could foretell the onset of neonatal thrombocytopenic purpura. 3. The platelet counts in fetal scalp blood were correlated with those of the cord blood, but falsely lower platelet counts were found in the fetal scalp samples. 4. We saw 5 cases of percutaneous umbilical blood sampling (PUBS) in pregnancies with ITP. PUBS was found to be a useful and safe method. The indications for PUBS and fetal platelet transfusion in pregnancy with ITP are discussed.

Cesarean Section↗

[Growth of endometrial cancer and hormone].

Proliferation and differentiation of the normal endometrium are orderly regulated by female sex steroid hormones. In this connection, development and growth of endometrial cancer have also thought to be controlled in part by sex steroid hormones. Furthermore, some of the sex steroid hormones, progesterone, for example, are used as therapeutic agents in the management of endometrial cancer. The role of estrogen as a promotion factor of endometrial cancer is understood by unopposed estrogen hypothesis, and relative excess of estrogen unopposed by gestagen is regarded as an important factor for the development of endometrial cancer. High dose administration of gestagen has been used as a therapeutic agent of endometrial cancer over these three decades, and now the oral administration of medroxyprogesterone acetate (MPA) is mainstay, with response rate of approximately 30%. However, recently some cases with serious side effect, mainly thrombosis, have been reported. These cases should be regarded as a grave warning to easy usage of MPA. Therefore, the search for more effective and safe way for clinical application have to be requested; for example, clarification of the precise mechanism of anti-tumor effect of MPA on endometrial cancer or development of new hormonal therapeutic agents. Moreover, basic research in the field of cancer and hormone may create a new era in cancer therapy in the future.

Aged↗

[Right ventricular flow dynamics in the early neonatal period assessed by pulsed Doppler echocardiography].

Right ventricular hemodynamic changes in the early neonatal period were observed by pulsed Doppler echocardiography in 45 neonates free of organic cardiac disease. Subjects consisted of 19 male and 26 female infants who were categorized by delivery as 22 normals, seven breech presentations, eight vacuum delivery and eight Cesarean section. Asphyxia was present at birth in 11 cases. Echocardiography was performed at 0, 1, 3, 5 and 30 days of age. The pulmonary flow pattern was recorded using the suprasternal long-axis view as a reference, and the maximum pulmonary flow velocity (PaV), acceleration time (AcT) and right ventricular ejection time (RVET) were measured. Mean pulmonary arterial pressure (MPAP) was estimated from the AcT and AcT/RVET ratio, according to Kitabatake et al. The tricuspid flow pattern was recorded with the four-chamber view as a reference, and the peak velocities of rapid filling (R) and atrial filling (A), and the A/R ratio were measured. The A/R ratio of tricuspid flow decreased with age in days and no significant differences were observed on each successive day, but there were significant differences between 0 and 3, 5 and 8 days of age. There were no significant differences by age in days in the maximum velocity of pulmonary blood flow, and the mean value was 74.9 +/- 3.0 cm/sec. The estimated MPAP was maximum at 0 day of age, declined gradually until 5 days of age, and was unchanged thereafter. No significant differences were found according to the type of delivery. Transient tricuspid regurgitation (TR) was detected in nine infants comprised of seven asphyxic infants and two of breech presentations. In these infants with TR, significantly higher estimates of MPAP were observed as compared with those without TR, and the A/R ratio of tricuspid flow was also higher among the infants with TR. These results indicate that the data obtained by this study reflect well acute hemodynamic changes in the early neonatal period in normal infants, and it can be applied for assessing cardiopulmonary disease, as well.

Blood Flow Velocity↗

[Retrograde metastasis of hepatocellular carcinoma with an interesting lesion of the stomach--a case report].

A 48-year-old man with hepatocellular carcinoma (HCC) showing tumor emboli in the portal vein and a typical retrograde metastasis via the portal vessels, is reported. Metastatic lesions were localized only in the veins of the lesser omentum, stomach, lower esophagus, pancreas, left hemidiaphragm and left adrenal gland, due to the hemodynamic alteration of the portal blood flow caused by liver cirrhosis and HCC. No metastatic lesion was found in the lung, Kidney, bone or intestine. As gastric metastasis Borrmann I, II, III and submusal tumor types were reported, but the present case revealed hard fold-like lesions, as it were, hard white varices.

Carcinoma, Hepatocellular↗