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Biomedical subjects

F Sasaki

Publications and source records attributed to F Sasaki.

At least 91 records · Page 5Linked to original sources

Internalization of styryl dye FM1-43 in the hair cells of lateral line organs in Xenopus larvae.

We used a fluorescent dye, FM1-43 to investigate mechanotransduction mechanisms in the hair cells of lateral line organs of Xenopus larvae. FM1-43 specifically labeled the hair cells. The photo-oxidation technique was performed with election microscopy to examine the labeling sites and their mechanisms. The results showed that the labeling sites were mitochondria and rough endoplasmic reticulum throughout the cytoplasm. Endocytic activity of the hair cells was limited to endosomes and small granules located at the apical part of the cells. Blockers of the mechanosensitive cation channel (neomycin, gentamicin, streptomycin, and amiloride) effectively inhibited FM1-43 labeling. One of the blockers, amiloride, was found to bind to hair cells when its fluorescence was examined. Divalent cations such as Mg2+ and Ca2+, but not monovalent cations such as Na+ and K+, inhibited FM1-43 labeling when they were added in excess amounts. These results suggest that FM1-43 internalizes hair cells via the putative mechanosensitive cation channel in the plasma membrane.

Amiloride↗

Pneumonitis during interferon and/or herbal drug therapy in patients with chronic active hepatitis.

We report four cases of acute pneumonitis due either to interferon, or a herbal drug, "Sho-saiko-to", or both in combination, in patients with chronic active hepatitis, focusing on its pathogenesis and response to prednisolone therapy. These cases shared common clinical features: fever, dry cough, dyspnoea, hypoxaemia, diffuse infiltrates both on chest radiography and chest computed tomography, restrictive pulmonary functional impairment, and alveolitis on examination of transbronchial lung biopsy, all of which suggest acute interstitial pneumonia. Furthermore, lymphocytosis was observed in association with the dominant CD8+ T-cell subset in bronchoalveolar lavage fluid. A lymphocyte stimulation test using peripheral blood was positive to interferon in one case and to Sho-saiko-to in another. All patients responded to oral prednisolone therapy. Peripheral soluble interleukin-2 receptor levels decreased in parallel with improvement in the clinical course. All patients were free of symptoms with a follow-up of 1-3 yrs. We conclude that interferon- and/or Sho-saiko-to-induced acute pneumonitis may be due to allergic-immunological mechanisms rather than toxicity, and that peripheral levels of soluble interleukin-2 receptor appear to be good markers of disease activity.

Adult↗

Effects of maternal uninephrectomy on the development of the proximal tubule in fetal rat kidney: morphometrical study.

The kidneys of fetal rats from uninephrectomized mothers were investigated morphometrically on days 18, 20, and 22 of gestation. Maternal uninephrectomy was performed on day 5. On days 20 and 22, the proximal tubular cell height in fetuses from uninephrectomized mothers was significantly lower than that in fetuses from sham-operated mothers. The luminal diameter, length and total volume of the proximal tubule were significantly larger in fetuses from uninephrectomized mothers than in those from sham-operated mothers. The total glomerular volume of mature type in fetuses from uninephrectomized mothers was significantly larger than that in fetuses from sham-operated mothers. On day 18, maternal uninephrectomy caused no significant difference in any kind of parameters used for the proximal tubule, but induced an increase in the total glomerular volume of immature type. These results suggest that maternal uninephrectomy stimulates morphological development of the proximal tubule in the fetal kidney.

Animals↗

Very low incidence rates of community-acquired hepatitis C virus infection in company employees, long-term inpatients, and blood donors in Japan.

To assess the contemporary rate of hepatitis C virus (HCV) propagation in Japanese community, we conducted a sentinel study on three groups of people: company employees, long-term inpatients, and blood donors. A total of 3079 company employees negative for anti-HCV were followed thereafter, and seroconversion to anti-HCV was found in 5 per 5786 person-years. None of them was positive for HCV RNA. In the group of 703 long-term inpatients (25 of whom were initially positive for anti-HCV) none showed seroconversion to anti-HCV per 2712 person-years. As for 114,266 repeated blood donors who were initially antibody-negative, 227 became anti-HCV positive later. Of these seroconverted donors, 83 were found to have anti-HCV with titers of 2(6) or greater. HCV RNA was positive in only 3 of them. Thus, the incidence rates of acquired HCV viremia in these three groups were 0 for both company employees and long-term inpatients, and 1.78 (95% C.I.: 0.37-5.19) per 100,000 person-years in blood donors. These results suggest that community-acquired HCV infection is now rare in Japan, and that even if it occurred it hardly leads to persistent viremia.

Adolescent↗

[Immunodeficiency with thymoma (Good's syndrome) similar to sino-bronchial syndrome].

A 58-year-old man was admitted to our hospital because of recurrent pulmonary infections that began three years previously. Laboratory data showed hypogammaglobulinemia and a chest computed tomogram showed diffuse bilateral micronodular shadows and an anterior mediastinal tumor. Immunodeficiency with thymoma (Good's syndrome) was diagnosed. After undergoing a thymectomy, he received intravenous gamma-globulin injections once a month for prophylaxis. Good's syndrome occurs rarely in Japan. A solid tumor-like shadow is not necessarily observed in routine chest X-ray studies, and hypogammaglobulinemia is one sign of this syndrome. The hypogammaglobulinemia of Good's syndrome should be carefully differentiated from that of other immunodeficiency diseases such as common variable immunodeficiency, the acquired immunodeficiency syndrome, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and multiple myeloma (non-secretory type).

Agammaglobulinemia↗

DNA localization in nuclear fragments of apoptotic ameloblasts using anti-DNA immunoelectron microscopy: programmed cell death of ameloblasts.

Ameloblasts responsible for tooth enamel formation are classified into two different phases: secretion and maturation. At the transition between these secretion and maturation stages, a considerable number of cells die. In this study, we examined the morphology of degenerating ameloblasts by conventional electron microscopy, and DNA cleavage in degenerating ameloblast nuclei by the in situ terminal transferase assay. The results suggest that apoptosis (programmed cell death) in ameloblasts, including DNA ligation is induced at the transitional stage. The nuclear fragments, chromatin condensation and DNA relocation in apoptotic nuclei were examined quantitatively by post-embedding anti-DNA immunogold electron microscopy and the in situ terminal transferase assay combined with electron microscopy. Numerical analysis revealed that immunogold labeling density in the condensed chromatin of apoptotic nuclei was comparable on the average to that in the perinuclear heterochromatin of normal nuclei, and that individual apoptotic nuclear fragments exhibited highly variable to that of normal heterochromatin, to fragments with densities twice as high as that of normal heterochromatin. The in situ terminal transferase assay combined with electron microscopy detected DNA ends exposed by ultrathin sectioning as well as DNA cleavage by a putative endonuclease. In conclusion, the state of the DNA, including its ligation and degeneration, changes gradually during chromatin condensation and nuclear fragmentation of apoptosis.

Ameloblasts↗

Fulminant hepatitis caused by a hepatitis B virus core region variant strain.

We studied the viral genome of a hepatitis B viral strain isolated from a patient with fulminant hepatitis. The patient was followed from prior to the rise in transaminases until she recovered. The precore and core regions of the viral strains were sequenced before and after the illness via the polymerase chain reaction and subcloning methods. Prior to her clinical illness, a strain with precore wild-type sequence and core mutations corresponding to amino acid residues 77 and 113 was noted in large quantities. With the onset of hepatitis, this core variant completely disappeared. Very low titers of precore and core wild or partial core deletion strains remained 1 month later. The core variants described may have contributed to the severe host immune reaction, fulminant hepatitis and immune-mediated viral clearance. Such variants appeared to have been eliminated, and wild and core-deleted virus that lacked the peculiar mutations remained.

Acute Disease↗

Transmission of hepatitis C virus from mothers to infants: its frequency and risk factors revisited.

A total of 16,714 pregnant Japanese women were tested for antibodies against hepatitis C virus (HCV), and 163 (0.98%) were positive. None of these were infected with human immunodeficiency virus-1 (HIV-1). We conducted a prospective study to discover the rate of HCV infection in babies born to mothers who were HCV RNA-positive but had no evidence for hepatitis (so called "asymptomatic carriers"), and only 2 (2.3%) of 87 such babies became infected during follow-up. This rate was considerably lower than those from other reports which included mothers with clinically overt chronic hepatitis C. We conducted another study to follow babies born to mothers with chronic hepatitis C, and found two babies infected. All of the four infected babies were born to mothers who had HCV RNA in their circulations around delivery at high titers (greater than 5.0 x 10(6) Eq/ml by branched DNA assay). This confirmed the previous finding that virus load was an important risk factor. In addition, we found three families where mother-to-infant HCV transmission was suspected in a retrospective study by indexing HCV-infected pediatric patients. Throughout the seven families, siblings of infected babies were free from HCV infection, suggesting that maternal infection of HCV owes much to chance. Breast milk feeding was not regarded as a risk factor. We also assessed the prevalence of anti-HCV antibody among 6-year old children, and only 10 of 10,446 (0.1%) were positive, suggesting low frequency of HCV infection during the period from birth to this age.

Carrier State↗

Bronchial arterial response to contrast medium.

RATIONALE AND OBJECTIVES: Contrast agents have been shown to produce vasodilatory responses in several vascular beds. To our knowledge, however, their effect on the bronchial vasculature has not been examined. Clinically, contrast-induced bronchial vasodilation could potentially exacerbate life-threatening pulmonary hemorrhage during bronchial angiography for hemoptysis. In the current study, we systematically measured the bronchial vasodilatory response to diatrizoate meglumine 66% and diatrizoate sodium 10% (MD-76) and examined whether vasodilation would be mediated by nitric oxide (NO). METHODS: We measured bronchial blood flow in seven anesthetized, ventilated, open-chested sheep using an ultrasonic flow probe placed around the bronchial artery. Bronchial blood flow was recorded before and after injection of 2 ml MD-76 into the bronchial artery. The protocol was repeated after 20 min infusion of N omega-nitro-L-arginine (L-NA; 10(-2) mol/l), an NO-synthase inhibitor, into the bronchial artery. RESULTS: There was a 45 +/- 8 ml/min increase (p < .01) in bronchial blood flow after injection of MD-76, which was reduced to 20 +/- 6 ml/min (p < .01) after infusion of L-NA. CONCLUSION: Bronchial arterial injection of MD-76 results in a consistent increase in bronchial blood flow that is mediated partly by NO.

Animals↗

Effects of chronic treatment with carvedilol on abnormalities of endothelium-dependent relaxation and structure of endothelium in resistance arteries of SHRSP.

1. This study investigated the effects of chronic treatment with carvedilol, a beta-blocking agent with an alpha-blocking activity, on blood pressure, endothelium-dependent relaxation and the endothelial structure of the mesenteric resistance artery in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Chronic treatment with carvedilol at a dose range of 30-120 mg/kg per day lowered systolic blood pressure of SHRSP from 234.9 +/- 3.3 to 198.7 +/- 3.1 mmHg at 16 weeks of age. 3. Acetylcholine-induced endothelium-dependent relaxation was impaired in the mesenteric artery from SHRSP and high concentrations of acetylcholine produced contractions. The impairment of the relaxation was abolished in the presence of indomethacin. Carvedilol treatment improved the impairment in the preparation from SHRSP. The structural abnormality of endothelium was observed in the preparation from SHRSP. The abnormality could be prevented by the antihypertensive treatment. 4. These results suggest that the impairment of endothelium-dependent relaxation in the preparation from SHRSP is due to the corelease of an endothelium-derived contracting factor which is considered to be a product of cyclo-oxygenase pathway of arachidonic acid cascade and that the impairment can be prevented by the antihypertensive treatment with carvedilol.

Acetylcholine↗

Leukotoxin, 9,10-epoxy-12-octadecenoate inhibits mitochondrial respiration of isolated perfused rat lung.

To investigate how mitochondrial function was affected in leukotoxin (Lx)-,9,10-epoxy-12-octadecenoate-induced lung injury, lung mitochondria were extracted from isolated perfused rat lung with or without Lx-induced edematous injury. In the lung treated with 30 mumol of Lx, the mitochondrial respiration rate in states 3 and 4 significantly decreased (without mitochondrial uncoupling) concomitantly with increased release of lactate dehydrogenase (LDH), a parameter for cellular damage, into the perfusate and decreased ATP content in the lung tissue compared with those of untreated lung. Moreover, 30 mumol of Lx resulted in significant inhibition of cytochrome-c oxidase activity (vs. vehicle control). In contrast, lower doses of Lx (10 mumol) caused lung edema and cellular damage without evidence for mitochondrial dysfunction. We also examined cellular and mitochondrial damage in hydrostatic lung edema. Such edema showed neither suppressed mitochondrial respiration nor elevated LDH activity in perfusate, although lung wet weight increased as much as it did after 30 mumol Lx treatment. Our results suggest that the ex vivo mitochondrial dysfunction is one of the secondary (vs. initial augmented permeability) but specific manifestations of toxicity of Lx, and together with the previous reports, the ex vivo damaging effect of Lx against mitochondria may be ascribed not to its direct action on mitochondria but to Lx-derived cellular mechanism(s).

Adenine Nucleotides↗

Endogenous nitric oxide influences acetylcholine-induced bronchovascular dilation in sheep.

To test whether endogenous endothelial nitric oxide (NO) influences baseline bronchial vascular tone and mediates acetylcholine (ACh)-induced bronchial vascular dilation and/or modulates bronchoconstriction in ovine airways, we studied anesthetized ventilated open-chest sheep and measured bronchial blood flow (Qbr) and pulmonary resistance (RL). In six sheep we measured the response of Qbr and RL to the dose of ACh required to produce 50% of the maximal increase in Qbr at baseline during infusion of the NO synthase inhibitor NG-nitro-L-arginine (L-NNA; 10(-2) M). Infusion of L-NNA decreased both the baseline Qbr (28 +/- 13 to 8 +/- 2 ml/min, P < 0.01) and the change in Qbr (delta Qbr) from the baseline value (84 +/- 42 to 33 +/- 18 ml/min, P < 0.05). There was no difference in baseline RL or in the response of RL to ACh at any time. In another six sheep, phenylephrine (5 x 10(-6) to 5 x 10(-7) M) decreased baseline Qbr (22 +/- 6 to 10 +/- 3 ml/min, P < 0.05) but not delta Qbr (62 +/- 13 to 66 +/- 21 ml/min, not significant). Infusion of L-NNA in these sheep decreased the baseline Qbr to a similar extent (11 +/- 5 ml/min) and also decreased delta Qbr (42 +/- 16 ml/min, P < 0.05). We conclude that endogenous endothelial NO influences baseline vascular tone and ACh-induced vasodilation of the ovine bronchial vasculature but has no effect on baseline RL or ACh-induced bronchoconstriction.

Acetylcholine↗

Morphometry on proximal tubule of the kidney in rat pups from uninephrectomized mothers.

Effects of maternal uninephrectomy in rats, which was performed on day 5 of gestation, on development of proximal renal tubule of the pups were morphometrically investigated. One day after birth, both the proximal tubular length per unit volume (1 mm3) of whole kidney and total proximal tubular volume in the neonates from uninephrectomized mothers were significantly larger than those in the neonates from sham-operated mothers. Six weeks after birth, no significant differences in parameters of the kidney were observed between the pups from uninephrectomized and sham-operated mothers. These results suggest that maternal uninephrectomy in the rat accelerates the development of proximal renal tubule in the fetus and that the renotropic activity is not lasting during postnatal development of the kidney.

Aging↗

[Chemosensitivity test for thyroid cancer by in vitro MTT assay].

In vitro MTT assay was applied for examining chemosensitivity with 50 thyroid cancers; 47 papillary cancers, 1 follicular cancer, 1 anaplastic cancers, and 1 medullary cancer. Anticancer drugs examined were 5-fluorouracil (5-FU), cisplatin (CDDP), adriamycin (ADM), etoposide (VP-16) and ifosfamide (IFO) (active type). Their efficacy was as follows: 5-FU 0%, CDDP 40.9%, ADM 0%, VP-16 5.3%, IFO 48.5%. Anaplastic cancer and medullary cancer showed no sensitivity to all tested drugs. We compared the chemosensitivity between cancer tissue and normal tissue. CDDP was more effective in cancer tissue than in normal tissue. Chemosensitivity of CDDP depended on the drug concentration but 5-FU did not. CDDP and IFO might be useful against human differentiated thyroid cancer.

Antineoplastic Agents↗

[Primary hyperparathyroidism in young patients].

Five young patients with primary hyperparathyroidism were treated in our hospital. Male to female ratio was 3 to 2 and the mean age was 12.2 years old. Hypercalcemia due to a single adenoma of the parathyroid gland was found in all cases. They showed various clinical symptoms, such as abdominal pain, nausea, convulsions and disturbance of walking. Parathyroid tumors usually could be easily identified with ultrasonography or CT scan or thyroid subtraction scintigraphy. But in two cases parathyroid tumor was not found during operation. Angiography and/or venous sampling were performed and they showed the right localization.

Adolescent↗