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Biomedical subjects

H Sakamoto

Publications and source records attributed to H Sakamoto.

At least 253 records · Page 14Linked to original sources

In vivo malignant phenotype of hst-1-transfected cells regulated by paracrine endothelial cell growth stimulation by HST-1.

The hst-1 gene product, one of the fibroblast growth factor family proteins, has transforming and angiogenic activities. The BALB/c 3T3 cell line was transfected with an expression vector harboring human hst-1 cDNA and the malignant properties of two stably transfected clones, TC-1 and TC-2, were examined. The stimulating activity of TC-1-conditioned medium for endothelial cell DNA synthesis was approximately four times stronger than that of TC-2-conditioned medium and correlated with hst-1 mRNA expression levels. Other than endothelial cell growth stimulation, these two clones had similar typical in vitro transformed properties, with identical doubling times and morphological changes. When nude mice were injected s.c. with these clones, TC-1 cells revealed faster tumor formation and growth, compared to TC-2 cells which had less potential to promote endothelial cell growth. Furthermore, the life span of mice injected i.v. with TC-1 cells was shorter than those with TC-2 cells, resulting from progressive tumor growth in the lungs. This advanced malignant in vivo behavior of TC-1 cells may be mediated by the high angiogenic potential of TC-1 cells secreting larger amounts of HST-1 compared to TC-2 cells, suggesting that angiogenesis contributes to malignant progression of tumors.

Journal Article↗

Developmental changes in the NGF content in the brain of young, growing, low-birth-weight rats.

The NGF content in each region of the brain of four-week-old rats was ranked in the decreasing order of cerebral cortex, hippocampus, cerebellum, midbrain/diencephalon, and pons/medulla oblongata, and the NGF concentration, in the decreasing order of hippocampus, cerebral cortex, cerebellum, midbrain/diencephalon, and pons/medulla oblongata in both AFD and SFD groups. The NGF content and concentration in the cerebral cortex were about the same value at each age between those in the AFD and SFD groups. Those in the hippocampus were a little higher in the SFD group than in the AFD group at the ages of three and four weeks, unlike those in the other regions, where the values for the cerebellum, midbrain/diencephalon and pons/medulla oblongata tended to be somewhat higher in the AFD group than in the SFD group. The NGF concentrations in the hippocampus and cerebral cortex increased with growth: the concentration in the hippocampus at four weeks of age was about 4-fold of that at one week in the AFD group and about 5.7-fold of that at one week in the SFD group; and likewise the concentration in the cerebral cortex at four weeks of age was about 5.3-fold in the AFD group and about 7-fold in the SFD group. The NGF concentrations in the cerebellum decreased, and those in midbrain/diencephalon and pons/medulla oblongata hardly changed with growth in either AFD or SFD group. From these results NGF may have stronger implications for the neuronal growth in the hippocampus compared with those in the lower brain regions of the SFD rats.

Animals↗

Pseudoxanthoma elasticum-like papillary dermal elastolysis: report of four Japanese cases and an immunohistochemical study of elastin and fibrillin-1.

We report four patients with pseudoxanthoma elasticum-like papillary dermal elastolysis (PDE). Multiple small papules on the neck, clinically resembling pseudoxanthoma elasticum, and loss of the elastic fibre network in the papillary dermis were found in each case. Immunohistochemical staining for elastin and fibrillin-1 in one patient demonstrated the disappearance of elastin and fibrillin-1 in the papillary dermis. Site-matched normal skins of the elderly showed intact elastin but a lack of fibrillin-1 in the papillary dermis. The younger normal skins revealed intact elastin and fibrillin-1. The results suggest that fibrillin-1 is absent from the papillary dermis of the normal-appearing neck skin of the elderly and that the primary defect in PDE may be in elastin rather than in fibrillin-1.

Adult↗

Surface expression and release of soluble forms of CD8 and CD23 in CD40- and IL-4-activated mononuclear cells from patients with Graves' disease (GD).

We investigated the effect of T cell-dependent B cell activation on the surface expression and release of the soluble forms of CD8 and CD23 by peripheral blood mononuclear cells (PBMC) obtained from patients with GD, versus patients with Hashimoto's thyroiditis, and normal controls. Incubating the PBMC with anti-CD40 MoAbs and IL-4 increased the soluble CD23 levels in cells from all three groups. An increase in the number of CD23+ cells was observed in the PBMC from the patients with GD, but not in PBMC from Hashimoto's thyroiditis or controls. Less soluble CD8 was released from anti-CD40 antibody and IL-4-stimulated PBMC obtained from patients with GD relative to those from the controls. In addition, the number of CD8+ cells was significantly reduced in stimulated PBMC from the GD patients relative to those from controls. Incubation of PBMC with anti-CD40 antibody plus IL-4 did not affect the proportions of CD4+, CD20+, Fas+ CD4+, and Fas+ CD8+ cells. The addition of T3 to cultured PBMC from controls did not reproduce the changes in CD23+ and CD8+ cells noted in the samples froin GD patients. Thus, T cell-dependent B cell activation, mediated by a CD40 pathway, may reduce the number of CD8+ cells, causing exacerbation of GD.

Adult↗

The clinical role of specific IgE and IgG4 antibodies in patients having immunotherapy for seasonal allergic rhinitis.

This study was designed to investigate the clinical role of specific IgG4 and IgE responses in patients during immunotherapy for seasonal allergy. The study included 109 patients with seasonal allergic rhinitis due to Japanese cedar pollens. They were divided into the control group and the immunotherapy group. Serum samples were obtained at the start of immunotherapy, before the pollen season and during the season, to determine serum specific IgE and IgG4. In the control group specific IgE was significantly increased, but specific IgG4 was not changed during the pollen season. In the immunotherapy group specific IgE was not significantly increased, but specific IgG4 was significantly increased during the season. In the patients having immunotherapy for 2 years or less, the seasonal increase in specific IgG4 related to the magnitude of the clinical effect. In the patients having immunotherapy for 3 years or more, the seasonal increase in specific IgE related to the magnitude of the clinical effect. In conclusion, the specific IgG4 response and specific IgE response during the pollen season make a significant contribution to the clinical effect of immunotherapy. However, modulation of specific IgE and IgG4 responses out of the pollen season was unlikely to be an important phenomenon related to the clinical effect of immunotherapy.

Adolescent↗

Ten-year follow-up study of allergen-specific immunoglobulin E and immunoglobulin G4, soluble interleukin-2 receptor, interleukin-4, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in serum of patients on immunotherapy for perennial allergic rhinitis.

Recent double-blind placebo-controlled trials for perennial allergic rhinitis have all clearly shown the efficacy of immunotherapy. Although several mechanisms for the clinical efficacy of immunotherapy have been proposed, the exact mechanisms related to the clinical effect still remain unclear. Since immunotherapy is a form of systemic treatment and its clinical benefit is likely to be, at least in part, a consequence of its systemic effects on different phases of immunological events, our study focused exclusively on several immunological parameters in serum. A total of 47 patients with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective study. Venous blood was collected for determination of specific immunoglobulin (Ig)E, specific IgG4, soluble interleukin-2 receptor (IL-2R), interleukin-4 (IL-4), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1), six times from 20 untreated patients and 27 patients on immunotherapy, at enrolment, and 1, 2, 3, 5, and 10 years after enrollment. No specific IgE, IgG4, soluble IL-2R, IL-4 and soluble ICAM-1 levels changed significantly for a span of 10 years in the untreated patients. By contrast, immunotherapy affected serum levels of specific IgE, specific IgG4, soluble IL-2R, IL-4 and soluble ICAM-1, but not of soluble VCAM-1. The rates of increase in specific IgG4 and the rates of decrease in soluble IL-2R were correlated with the rates of decrease in symptom scores during the first 3 years, but not 5 and 10 years after the course of immunotherapy. On the other hand, the rates of decrease in specific IgE, IL-4 and soluble ICAM-1 were significantly correlated with the rates of decrease in symptom scores at 5 and 10 years, but not during the first 3 years. Each immunological modulation by immunotherapy was likely to be involved in the working mechanism related to clinical efficacy at different phases of immunotherapy.

Adolescent↗

Effects of 4 hours magnesium sulfate infusion on fetal heart rate variability and reactivity in a goat model.

Effects of magnesium sulfate were investigated on fetal heart rate (FHR) baseline, variability, and reactivity in goats. Six chronically catheterized fetuses of Japanese Saanen goat at 125 to 130 days' gestation (term = 147 days) were used. Magnesium sulfate was directly infused to the fetuses. Short-term variability and long-term variability were obtained according to Huey et al. The baseline, reactivity, short-term variability and long-term variability of the FHR were compared between those receiving magnesium sulfate infusions and those receiving vehicle infusions without magnesium sulfate for 4 hr. Two-way analysis of variance (ANOVA) and Duncan's multiple range test was applied for statistical significance. Four hours magnesium sulfate infusion significantly increased fetal plasma concentration of magnesium from 2.4-6.6 mg/dL, without significant changes in fetal respiratory gases and pH values. The baseline FHR was significantly decreased by magnesium infusion compared with that receiving vehicle infusion. The incidence of acceleration, short-term variability, and long-term variability during the fourth hour of magnesium infusion was also significantly decreased compared to a controlled infusion. The time spent by high amplitude phase of short-term variability and that of long-term variability were also significantly reduced. Significant correlation was obtained between the magnesium concentration and incidence of acceleration at fourth hour of magnesium infusion. Four hours infusion of magnesium sulfate significantly decreases baseline FHR, short-term variability, long-term variability, and reactivity in fetal goats at 0.85 gestation.

Animals↗

Seasonal rise in interleukin-4 during pollen season is related to seasonal rise in specific IgE for pollens but not for mites.

Since IL-4 plays a key role in inducing and increasing the generation of not only primary polyclonal but also secondary specific IgE responses by B lymphocytes, a seasonal increase in IL-4 is likely to be involved in such seasonal rises in specific IgE in seasonal allergic rhinitis. The first aim of this study was to investigate the possible seasonal increase in serum IL-4 in patients with seasonal allergic rhinitis due to Japanese cedar pollens. If serum IL-4 increases in response to seasonal pollen exposure and is responsible for the seasonal increase in pollen-specific IgE in sera, this increase in IL-4 might theoretically affect specific IgE synthesis for other allergens. The second aim was to investigate the effect of natural pollen exposure on serum concentrations of house dust mite-specific IgE in patients who have seasonal allergic rhinitis and concurrent perennial allergic rhinitis due to house dust mites. This study included 55 adult patients with seasonal and perennial allergic rhinitis due to Japanese cedar pollens and Dermatophagoides farinae (D. farinae). Venous blood was collected twice from each patient, before and during the cedar pollen season 1996, to determine IL-4, cedar pollen-specific IgE and D. farinae-specific IgE in sera. Both IL-4 and pollen-specific IgE in sera were significantly increased during the pollen season, and the seasonal increase rate in pollen-specific IgE was significantly correlated with the seasonal increase rate in IL-4. By contrast, D. farinae-specific IgE was not changed during the pollen season in these patients. In conclusion, an elevation of IL-4 in sera during the pollen season may play an important part in the seasonal rise in pollen-specific IgE, and enhancement of specific IgE synthesis is likely to need not only an increase in IL-4 but also an increase in the number and/or capacity of specific IgE-secreting B cells.

Adolescent↗

Soluble vascular cell adhesion molecule-1 in perennial allergic rhinitis.

Since the expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells plays a central part in the selective recruitment of eosinophils into allergic inflammatory lesions, VCAM-1 may be a key molecule in allergic inflammatory diseases. Soluble forms of VCAM-1 (sVCAM-1) have recently been identified in the circulation, but there is limited published information on levels of sVCAM-1 in the circulation. If the levels of sVCAM-1 vary between patients with allergic diseases and normal controls, this variance would be very useful to investigate the state of the allergic disease and underlying inflammation. This study investigated the serum sVCAM-1 level in patients with perennial allergic rhinitis (rhinitis group) in comparison with non-atopic healthy volunteers (control group). No significant difference in the serum sVCAM-1 level was seen between the two groups (p = 0.4342). However, the serum sVCAM-1 levels in the severe rhinitis group were significantly higher than those in both the control group (p = 0.0067) and the mild rhinitis group (p = 0.0015), whereas no significant difference was observed between the mild rhinitis group and the control group (p = 0.1113). In addition, the serum levels of sVCAM-1 were significantly correlated with the nasal symptoms in the rhinitis group (rs = 0.486, p < 0.0001). In conclusion, serum concentrations of sVCAM-1 are increased in patients with severe perennial allergic rhinitis, and measurement of sVCAM-1 concentrations in sera is likely to be a useful tool for investigation of the severity of allergic rhinitis and underlying inflammatory reactions.

Animals↗

Interleukin-6 and tumour necrosis factor alpha synthesized by cholesteatoma cells affect mucociliary function in the eustachian tube.

The aims of this study were to investigate the possible synthesis of IL-6 and TNF-alpha by cholesteatoma cells in culture and the effect of IL-6 and TNF-alpha produced by cultured cholesteatoma cells on the function of the mucociliary system in the tubotympanum. Cholesteatoma cells were collected from 10 patients, and the medium supernatants in which cholesteatoma cells or normal human epidermoid cells had been cultured for 48 h were collected. The concentrations of IL-6 and TNF-alpha in the supernatants were measured by enzyme-linked immunosorbent assays. The effect of the culture supernatants on ciliary activity was examined using an in vitro experimental system. The supernatants were injected into the tympanic cavities of guinea pigs, and mucociliary clearance time of the Eustachian tube was determined according to our dye transport technique 24 h after the intratympanic injection. Human cholesteatoma cells produced larger amounts of IL-6 and TNF-alpha than normal human epidermoid cells. The supernatants of cholesteatoma cells compromised ciliary activity and mucociliary clearance of the Eustachian tube in the guinea pigs. The effects of the supernatants of cholesteatoma cells on the ciliary activity and mucociliary clearance were correlated with the concentration of IL-6 and TNF-alpha in the supernatants. In conclusion, cholesteatoma cells can produce IL-6 and TNF-alpha, which are able to compromise the mucociliary function in the tubotympanum. IL-6 and TNF-alpha produced in middle ear cholesteatoma might aggravate the disease by the wide range of their biological activities on the mucociliary system, the proliferation of cholesteatoma cells and the bone metabolism.

Adult↗

Fluorine-18 fluorodeoxyglucose positron emission tomography imaging of parotid mass lesions.

Using X-ray CT or magnetic resonance imaging (MRI), fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) studies were performed in 28 patients with parotid lesions. All lesions except two showed higher accumulation of FDG than normal parotid gland. High accumulation was found in all of 5 carcinomas, all of 6 Warthin's tumors, and 8 of 12 pleomorphic adenomas, with standardized uptake values (SUVs) over 3.0. The mean SUVs of carcinomas, Warthin's tumors, and pleomorphic adenomas were 5.92 +/- 2.05, 7.03 +/- 2.49, and 4.07 +/- 1.55, respectively. On the other hand, all 5 inflammatory lesions demonstrated low accumulation, with mean SUVs of 1.66 +/- 0.89. It is thus difficult to differentiate malignant from benign parotid lesions by SUV on FDG-PET.

Adult↗

Effects of thyroid hormone on catecholamine and its metabolite concentrations in rat cardiac muscle and cerebral cortex.

Clinical and experimental data suggest that thyroid hormone affects the actions of catecholamine (CA). However, the serum or tissue levels of CA during thyroid disorders have not been well defined. Accordingly, we investigated the levels of CA and their metabolites in the cardiac muscle, the cerebral cortex, and the plasma of rats with hyperthyroidism and hypothyroidism versus euthyroid animals. The Neurochem analyzer system (ESA, Inc., Bedford, MA) was used in such determinations. The cardiac muscles of hyperthyroid rats exhibited a 16% decrease in the levels of 1-dopa, 3-methoxytyramine (3-MT) and homovanillic acid (HVA) as compared with those in euthyroid rats. The levels of norepinephrine (NE) in cardiac muscle of these rats increased significantly (5.2-fold) relative to the levels in euthyroid rats. NE was undetectable in the cardiac muscles of the hypothyroid rats. Epinephrine (E) and dopamine (DA) were not detected in the cardiac muscles of the rats with either thyroid disorder. Levels of E and 3,4-dihydroxymandelic acid (DOPEG) were detected only in the cerebral cortex of hyperthyroid rats. The cerebral cortex levels of 3-methyoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), metanephrine (MN), and homovanillic acid (HVA) were all significantly increased in the hyperthyroid versus the euthyroid rats. The cerebral cortex levels of DA, NE, normetanephrine (NMN), and VMA in the hyperthyroid rats all showed a significant decrease. Levels of NE, NMN, and DOPAC in the cerebral cortex increased significantly in the hypothyroid rats. The level of VMA was undetectable in cerebral cortex of such animals. Data from studies on cardiac muscle and cerebral cortex indicate that the changes in CA and CA metabolites are responsible in part for the cardiovascular and the central nervous system symptoms observed in hyperthyroidism and hypothyroidism.

Animals↗

Immunotherapy decreases seasonal rise in serum-soluble CD23 in seasonal allergic rhinitis.

There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of potentiating IgE synthesis, but the in vivo physiologic significance remains to be established. This study investigated the seasonal changes in sCD23 in patients with seasonal allergic rhinitis. It included 112 adult patients with seasonal allergic rhinitis due to Japanese cedar pollens and 20 nonatopic healthy volunteers. The 64 patients of the pharmacotherapy group were treated with nonsedating antihistamine tablets alone throughout the pollen season and the remaining 48 patients of the immunotherapy group continued to be treated with immunotherapy. Serum concentrations of sCD23 were measured in each patient, before and during the pollen season of 1996, by a sandwich enzyme-linked immunosorbent assay. The serum levels of sCD23 in the pharmacotherapy group before the pollen season were significantly higher than those in the nonatopic group (P = .0130) and those in the immunotherapy group (P = .0316). Seasonal increase in sCD23 was significant in the pharmacotherapy group, irrespective of the clinical response (P < .0001). By contrast, sCD23 was not significantly increased in the good responders to immunotherapy (P = .1826), but was significantly increased in the poor responders to immunotherapy (P = .0052). A significant correlation between seasonal increase in rate in specific IgE and seasonal increase in rate in sCD23 was confirmed in both the pharmacotherapy group (rs = 0.321, P = .0107) and the immunotherapy group (rs = 0.474, P = .0012). In conclusion, seasonal rise in sCD23 is associated with and is probably involved in seasonal rise in specific IgE in patients with seasonal allergic rhinitis, and successful immunotherapy is capable of blunting seasonal increase in sCD23, thus resulting in attenuation of seasonal increase in specific IgE and clinical benefits during the pollen season.

Adult↗

Bilateral dissecting aneurysms of the vertebral arteries resulting in subarachnoid hemorrhage: case report.

OBJECTIVE AND IMPORTANCE: We present the case of a patient with bilateral dissecting aneurysms of the vertebral arteries resulting in subarachnoid hemorrhage. CLINICAL PRESENTATION: A 44-year-old man suffered a sudden onset of severe occipital headache and nausea and then dysphasia caused by subarachnoid hemorrhage. A computed tomographic scan demonstrated right side dominant subarachnoid hemorrhage mainly in the posterior fossa. Angiography revealed bilateral, vertebral dissecting aneurysms. The right aneurysm was larger and had a bleb-like protrusion, which strongly suggested a causative lesion of the subarachnoid hemorrhage. Six months later, the patient was referred to our hospital for further evaluation and treatment. INTERVENTION: The ruptured right aneurysm was trapped surgically through a lateral suboccipital approach. The patient's postoperative course was unremarkable, and he was discharged on the 14th day after surgery. However, postoperative angiography demonstrated slight enlargement of the left nonruptured aneurysm. Four months after surgery, the patient developed brain stem ischemic symptoms. The angiography conducted at that time showed further enlargement of the left aneurysm. Five months after surgery, fatal rupture of the left aneurysm occurred. CONCLUSION: These results indicate that sacrifice of the unilateral vertebral artery may result in an enlargement of the contralateral nonruptured aneurysm and may thus be dangerous in the case of a patient with bilateral dissecting aneurysms.

Adult↗

Moyamoya disease and pregnancy: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Many female patients with moyamoya disease are of childbearing years, including those who were diagnosed before entering their childbearing years. However, there have been no extensive reviews of the management of pregnancy and delivery in association with moyamoya disease. The purpose of this report is to describe the case of a patient with moyamoya disease complicated by pregnancy and to review the literature on other such cases. CLINICAL PRESENTATION AND INTERVENTION: We report a 23-year-old primipara with moyamoya disease who delivered uneventfully by cesarean section under spinal anesthesia at 38 weeks of gestation. In the literature, 30 cases were reported of patients who had been diagnosed with moyamoya disease before pregnancy and delivery, and 23 patients who were symptomatic and were diagnosed for the first time with moyamoya disease in association with pregnancy. CONCLUSION: There is no evidence that pregnancy increases the risk of cerebrovascular accident or that bypass surgery decreases its risk. Poor prognosis of the patient or the newborn is mostly caused by cerebral hemorrhage and not by cerebral ischemia. It is important to control blood pressure and especially to avoid toxemia during pregnancy. Either cesarean section or vaginal delivery can be accomplished safely. Any anesthetic method can be used, provided special attention is given to avoiding hypocapnia, hypotension, and hypertension. Oral contraceptives should be avoided.

Adult↗

Inhibitory effect of tomato juice on rat urinary bladder carcinogenesis after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation.

The effects of tomato juice on urinary bladder carcinogenesis were studied in male Fischer 344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. The animals (6 weeks old) were given 0.05% BBN in their drinking water for 8 weeks, followed by diluted tomato juice for 12 weeks, and killed at 20 weeks after the beginning of the experiment. Lycopene concentrations in the livers of rats given tomato juice were elevated. Histopathological analysis of urinary bladder lesions revealed the numbers, but not incidences, of urinary bladder transitional cell carcinomas (TCCs) to be decreased in the group given tomato juice. No influence on the incidence of simple and nodullopapillary hyperplasias, invasion or differentiation of TCC was noted. These results indicate that tomato juice, presumably the contained lycopene and other anti-oxidants in combination, exerts an inhibitory effect on the development of TCCs in the rat urinary bladder.

Animals↗