Little response to zoledronic acid in a child of juvenile myelomonocytic leukemia (JMML) harboring the PTPN11 mutation.
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Bone Density Conservation Agents↗
Biomedical subjects
H Yoshihara
Publications and source records attributed to H Yoshihara.
Three-dimensional images for surgical plan of giant sacral schwannoma.
OBJECTIVE: Documentation of three-dimensional (3D) images of a giant sacral schwannoma with intrapelvic expansion. SETTING: Nagoya University, Nagoya, Japan. RESULTS: 3D computed tomography (3D CT) showed a destructed bony region clearly. 3D CT angiography clarified the positional relationship between tumor and iliac arteries. Resection procedure was safely completed based on these 3D evaluations. CONCLUSION: 3D images were helpful to make a surgical plan and to complete this complicated resection combined with sacroiliac reconstruction.
Angiography↗
FK506-associated limbic injury following umbilical cord blood transplantation.
A 5-year-old girl with Ph-positive chronic myelogenous leukemia, who underwent umbilical cord blood transplantation, developed two episodes of electrical status epilepticus while receiving tacrolimus (FK506) then cyclosporin A (CsA), as treatment against graft-versus-host disease. MRI including diffusion weighted MR imaging of the brain revealed abnormalities in the hippocampus and posterior white matter following FK506 and CsA treatment, respectively. While posterior white matter injury has been described with both FK506 and CsA, no previous report describes hippocampal injury from either drug. The MRI changes in the hippocampus in our case suggest possible increased susceptibility to hippocampal injury with FK506.
Child, Preschool↗
De novo malignant transformation of giant cell tumor of bone.
Two cases of malignant lesions are reported, both of which arose secondary to an originally benign giant cell tumor (GCT) of bone. The first case was a typical benign GCT, which occurred in the left proximal tibia of a 31-year-old woman. The tumor was treated by curettage and bone grafting. However, it recurred twice during 15 years of follow-up. The second recurrence showed that the lesion histologically had turned into malignant fibrous histiocytoma. The second case also started as an initially benign GCT that arose in the left distal femur of a 41-year-old man. The patient underwent curettage and bone grafting. The lesion recurred 13 years postoperatively. The histological appearance of the recurrent tumor showed it to be an osteogenic sarcoma. In both patients, radiation and never been given. Malignant transformation has rarely been reported in patients with GCT of bone who have not received radiation treatment.
Adult↗
Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance.
The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-gamma prior to initiation of interferon-alpha treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-alpha treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-gamma (1 MIU/day) was administered daily for 14 days followed by natural IFN-alpha (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-alpha treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-gamma administration, and tended to return to the pretreatment level after the start of IFN-alpha administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN-gamma prior to the initiation of IFN-alpha treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.
Antiviral Agents↗
Significance of serum soluble Fas antigen level in chronic hepatitis C patients treated with interferon: relationship to the therapeutic response.
BACKGROUND AND AIM: Fas system-mediated cytotoxicity is thought to be involved in the development of liver injury in hepatitis C virus (HCV) infection. In this study, we investigated serum soluble Fas antigen levels in chronic hepatitis C patients treated with interferon and their correlation with the therapeutic response. METHODS: The subjects were 67 chronic hepatitis C patients who underwent a 24-week course of alpha-interferon therapy. Patients were categorized into three groups; sustained responders (n = 22), transient responders (n = 24), and non-responders (n = 21), according to changes in the serum alanine aminotransferase level during and after therapy. The viral genotype, viremic level and diversity in the hypervariable region were examined before therapy. Serum soluble Fas antigen levels were assayed by using serum samples taken at the beginning and the end of therapy. RESULTS: In the univariate analysis, serum soluble Fas antigen levels tended to be higher in non-responders (10.0 +/- 3.4 ng/mL) than in sustained responders (8.5 +/- 3.0 ng/mL) and transient responders (8.2 +/- 2.1 ng/mL; P = 0.13 and P < 0.05). The non-response to therapy was observed in eight of the 15 (53%) patients with serum soluble Fas antigen > or = 11 ng/mL, compared with 13 of the 52 (25%) patients with serum soluble Fas antigen < 11 ng/mL (P < 0.05). As for the multivariate analysis, the only significant factor contributing to the sustained response was a low HCV viremic level (P = 0.0046). Significant factors contributing to the non-response were a high serum alanine aminotransferase (P = 0.0407) and a high serum soluble Fas antigen level (P = 0.0483). CONCLUSIONS: High production levels of soluble Fas antigen may be associated with a poor response to interferon therapy in chronic hepatitis C patients.
Adult↗
Histologic analysis of the implanted cartilage in an exact-fit osteochondral transplantation model.
PURPOSE: Osteochondral transplantation is one of the useful treatments for articular cartilage defect. However, the histologic change of the implanted cartilage has not been reported in detail. We investigated the histology of exact-fit osteochondral transplants used to repair articular cartilage defects in an animal model. TYPE OF STUDY: This was a nonrandomized control study using an animal model. METHODS: Sixteen skeletally mature female Japanese white rabbits were used in the study. The region of the femoral groove was selected as the site for the osteochondral defect. A full-thickness cylindrical defect (7 mm in diameter and 7 mm in depth) through the articular cartilage and into the subchondral bone was made using the Osteochondral Autograft Transfer System (Arthrex, Naples, FL). The entire osteochondral fragment was removed and then returned to its original site in the femoral condyle precisely. Thus, the defect was repaired with an autogenous osteochondral transplantation of exactly the same size and configuration as the defect. Specimens were obtained 2, 4, 12, and 24 weeks postoperatively and were analyzed both macroscopically and histologically. RESULTS: Macroscopically, there was smooth continuity of the articular surface and the integration of the graft to the normal host cartilage. However, histologic examination showed that the layer of the grafted cartilage was thicker than that of the normal host cartilage and the extracellular matrix of the implanted cartilage exhibited a stronger staining pattern with safranin-O fast green than the normal cartilage. Cell density was higher in the grafted cartilage, particularly in the middle and the deep zones. Round and polygonal hypertrophic clusters of chondrocytes were observed in the middle and deep zones of the grafted cartilage. CONCLUSIONS: The histologic properties of the exact-fit implanted cartilage were different from that of normal articular cartilage. Further investigation of mechanical and structural properties of grafted cartilage is necessary to verify the long-term effects of osteochondral transplantation.
Animals↗
Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: a retrospective cohort study of 738 patients.
The effect of interferon on the long-term clinical outcome of patients with chronic hepatitis C remains unclear. This study included 594 patients with chronic hepatitis C who received interferon-alpha therapy (Interferon group) and 144 patients with chronic hepatitis C who did not receive interferon (Control group). The patients in the Interferon group were classified into the following three groups based on the response of the serum aminotransaminase level of the patient during and after completion of the therapy protocol: sustained responders (n = 175), transient responders (n = 165), and non-responders (n = 254). The age, sex, serum aminotransaminase level, platelet count, histological staging, hepatitis C virus (HCV) subtype, and HCV concentration at baseline were adjusted with the Cox proportional hazards model. The length of follow-up for assessment of the risk for developing hepatocellular carcinoma (HCC) was 57.2 +/- 13.9 months in the Interferon group and 67.7 +/- 28.7 months in the Control group. Multivariate analysis showed that interferon therapy decreased the risk for developing HCC by 48% compared with that in the Control group (P = 0.064). The older the age, being male, having a low platelet count, and higher histological stage were independent factors associated with the development of HCC. The hazard rate ratio for development of HCC in the sustained responders, transient responders, and non-responders was 0.16 (95% confidence interval [CI]: 0.04-0.62), 0.27 (95% CI: 0. 09-0.79), and 0.74 (95% CI: 0.37-1.48), respectively. During follow-up, 18 patients in the Interferon group died (10 from liver-related diseases) and 17 patients in the Control group died (10 from liver-related diseases). No sustained responder or transient responder in the Interferon group died of liver-related disease. The cumulative survival rates of the Interferon and Control groups were nearly identical during the first 5 years following diagnosis. Thereafter, the cumulative survival rate of the Control group declined, resulting in an 8-year survival rate in the Interferon and Control groups of 97% and 81%, respectively (P = 0. 061). Similar trends were seen in the survival analysis of those who had died of liver disease: the 8-year survival rates of the Interferon and Control groups were 98% and 88%, respectively (P = 0. 32). Our study demonstrated that interferon therapy significantly lowered the incidence of HCC among patients with chronic hepatitis C who showed sustained normalization and among patients who showed transient normalization of the serum aminotransferase level after completion of interferon therapy. The survival analyses and determination of cause of death suggested that interferon therapy improves the long-term survival of chronic hepatitis C patients who respond to this therapy, possibly by decreasing mortality from liver-related diseases.
Antiviral Agents↗
High-frequency ultrasonic wire bonding systems
The vibration characteristics of longitudinal-complex transverse vibration systems with multiple resonance frequencies of 350-980 kHz for ultrasonic wire bonding of IC, LSI or electronic devices were studied. The complex vibration systems can be applied for direct welding of semiconductor tips (face-down bonding, flip-chip bonding) and packaging of electronic devices. A longitudinal-complex transverse vibration bonding system consists of a complex transverse vibration rod, two driving longitudinal transducers 7.0 mm in diameter and a transverse vibration welding tip. The vibration distributions along ceramic and stainless-steel welding tips were measured at up to 980 kHz. A high-frequency vibration system with a height of 20.7 mm and a weight of less than 15 g was obtained.
Journal Article↗
Medical markup language (MML) for XML-based hospital information interchange.
Medical Markup Language (MML) has been developed over the last 6 years in order to create a set of standards by which medical data, within Japan and hopefully worldwide, can be stored, accessed and exchanged in any number of physical locates. The MML version 2.21 is characterized by XML as meta-language, module structure for each document and enhancement of linking function among documents. Data exchange specification has been also added for query and reply. MML instances are composed of MML header and MML body. The MML header includes information for data transmission, while MML body includes several module items. One module item contains two elements: document information and module content. Nine MML module contents are defined at the present time: patient information, health insurance information, diagnosis information, lifestyle information, basic clinic information, particular information at the time of first visit, progress course information, surgery record information and clinical summary information.
Clinical Laboratory Techniques↗
Effect of SOD-mimetic Fe-chlorine e6-Na on the level of brain lipid peroxide of rat fetal brains exposed to reactive oxygen species leading to intrauterine growth retardation.
The influence of oxidative stress in rat brain and liver on intrauterine growth retardation (IUGR) in rat fetuses was examined. Twenty pregnant Wistar rats were used. On the 15th day of pregnancy, uterine artery and vein were ligated bilaterally using a modified Wigglesworth method. On the 21st day of pregnancy, the fetuses were delivered by hysterotomy. Fetal blood was collected by cardiac puncture. Fetal brain and liver were removed for the analysis of lipid peroxide. Sham surgical operations were performed in the control rats. Within the ligated group, a superoxide dismutase mimicking substance, Fe-chlorine e6-Na (FeCNa), was injected intraperitoneally once a day from day 15 of gestation to day 20. Fetal blood, brain, and liver were stored at -70 degrees C until analysis. Control rats received an equivalent volume of saline. In growth-retarded fetuses, both superoxide released from erythrocytes and brain lipid peroxide showed significantly higher levels, but not superoxide dismutase in erythrocytes and liver lipid peroxide. These changes were alleviated by injection of superoxide dismutase-mimicking substance, FeCNa. Rat fetuses with intrauterine growth retardation suffered from a significant oxidative stress in utero. The increase in reactive oxygen species was alleviated by an injection of FeCNa.
Animals↗
Effect of high amniotic fluid pressure on fetal circulation.
The purpose of this study was to investigate the effects of high amniotic fluid pressure (AFP) created by amnioinfusion on fetal circulation. Five pregnant goats whose fetuses had a mean gestational age of 131 +/- 2 days (term 145 days) were used. After a 30 minute control period, 1500 ml of warm saline was infused to the amniotic cavity over a period of 30 minutes. The AFP gradually increased during amnioinfusion and remained 2-3 mmHg above the control level for 3 hours after amnioinfusion. Fetal arterial pH (FpH) tended to decrease, and there was a significant negative correlation between the FpH and AFP (r = -0.723). Fetal arterial pO2 also tended to decrease and negatively correlated to the AFP (r = -0.59). On the other hand, fetal arterial pCO2 tended to increase and positively correlated with the AFP (r = 0.75). Although amnioinfusion is useful for improving the status of a distressed fetus, the fetal condition may be jeopardized at the same time. Therefore, careful monitoring of the AFP and fetal status is recommended during amnioinfusion.
Amniotic Fluid↗
Anti-malarial activity of leaf-extract of hydrangea macrophylla, a common Japanese plant.
To find a new anti-malarial medicine derived from natural resources, we examined the leaves of 13 common Japanese plants in vitro. Among them, a leaf-extract of Hydrangea macrophylla, a common Japanese flower, inhibited the parasitic growth of Plasmodium falciparum. The IC50 of Hydrangea macrophylla leaf extract to Plasmodium falciparum was 0.18 microg/ml. The IC50 to NIH 3T3-3 cells, from a normal mouse cell line, was 7.2 microg/ml. Thus, selective toxicity was 40. For the in vivo test, we inoculated Plasmodium berghei, a rodent malaria parasite, to ddY mice and administered the leaf-extract of Hydrangea macrophylla (3.6 mg/0.2 ml) orally 3 times a day for 3 days. Malaria parasites did not appear in the blood of in the treated mice, but they did appear in the control group on day 3 or 4 after inoculation with the parasites. When leaf extract was administered to 5 mice 2 times a day for 3 days, malaria parasites did not appear in 4 of the mice but did appear in 1 mouse. In addition, the leaf-extract was administered orally 3 times a day for 3 days to Plasmodium berghei infected mice with a parasitemia of 2.7%. In the latter group, malaria parasites disappeared on day 3 after initiating the treatment, but they appeared again after day 5 or 6. Although we could not cure the mice entirely, we confirmed that the Hydrangea macrophylla leaf extract did contain an anti-malarial substance that can be administered orally.
Animals↗
Risk of non-Hodgkin's lymphoma in patients with hepatitis C virus infection.
Hepatitis C virus (HCV) has been suggested to play an etiological role in the development of B-cell non-Hodgkin's lymphoma (NHL) in Italy. However, another study in Scotland questioned increased risk of development of NHL in patients with chronic HCV infection. A total of 2,162 patients admitted to 3 hospitals in Osaka, where the incidence of HCV-related hepatitis is highest in Japan, during the period from 1957 to 1997 were followed up from the date of diagnosis of chronic HCV-related hepatitis until 30 October 1997. Overall, 12,404.5 person-years of observation were accrued with a follow-up period ranging from 0.25 to 40.4 (average 5.74) years. NHL of the B-cell type developed in 4 patients. The interval between onset of chronic HCV and NHL ranged from 6 to 36 (median 13) years. Expected number of cases of NHL in the sex-, age- and calendar year-matched general population was 1.90, which gave a relative risk (RR) of 2.10 (95% confidence interval 0.57-5.38; p = 0.247). Taking the much higher RR for hepatocellular carcinoma among patients with HCV infection into account, chronic HCV infection was considered to be moderately associated with increased risk of NHL.
Adolescent↗
Elective induction of labor at 39 weeks of gestation: a prospective randomized trial.
OBJECTIVE: To clarify the safety of elective induction of labor at 39 weeks of gestation. STUDY DESIGN: Prospective randomized study. SUBJECTS AND METHODS: Uncomplicated nulliparas (N = 194) were randomly assigned at 36 weeks of gestation. Labor was electively induced in 63 women at 39 weeks of gestation in the active management group (I group, N = 98). Spontaneous labor onset was expected with semi-weekly nonstress test (NST) and amniotic fluid index (AFI) by 42 weeks of gestation in the expectant group (E group, N = 96). Perinatal events were compared between the 2 groups. RESULTS: A significantly higher incidence of meconium-stained amnios (19.4% vs 3.2%) and fetal resuscitation (16.7% vs 4.8%) was found in the E group than in the I group. Also, although a significantly higher incidence of epidural analgesia was noted in the I group (89%) than in the E group (54%) (labor onset > or = 39 weeks, N = 72), the duration of the 1st stage was shorter in I group and the duration of the 2nd stage was not significantly different. No other significant difference was noted between the 2 groups in terms of the rate of C-section, blood loss, incidence of pathological FHR, birth weight, Apgar score, umbilical arterial pH, or admission to NICU. CONCLUSION: Active management of labor at 39 weeks could be made as safely as expectant management with modified biophysical profile monitoring.
Adult↗
Effect of sex hormones on oxalate-synthesizing enzymes in male and female rat livers.
PURPOSE: We studied the effect of changes in sex hormones on oxalate metabolism in rats. MATERIALS AND METHODS: Adult male and female rats were administered a precursor of oxalate, and the relationship between dose and urinary oxalate was examined. Levels of sex hormones were varied in rats and glycolate oxidase (GO) and serine pyruvate aminotransferase (SPT) activities were measured under the conditions of being fed tap water or loading with 0.5% ethylene glycol. In addition, urinary oxalate excretion was evaluated. RESULTS: Ethylene glycol and glycolate increased urinary oxalate concentration in male rats dose-dependently but less in female rats. There was almost no change during glycine loading in either male or female rats. GO activity was significantly lower in intact female and gonadectomized male rats. SPT activity was slightly higher in the female than in the male controls. There were no differences in urinary oxalate excretions between male and female rats. During ethylene glycol loading, GO and SPT activities were similar to those with tap water intake. However, urinary oxalate excretion increased to two times the control value in male rats but only slightly increased in female rats. CONCLUSIONS: Sex-related differences exist in the metabolic conversion of glycolate to oxalate in rats, and GO activity is promoted by testosterone. Although difference in GO activity has no physiological effect on oxalate synthesis, GO activity affects urinary oxalate excretion during ethylene glycol loading. We could also conclude that estrogen decreases GO activity in male rats from our results.
Alcohol Oxidoreductases↗
Gene expression of alpha1-6 fucosyltransferase in human hepatoma tissues: a possible implication for increased fucosylation of alpha-fetoprotein.
The 1-6 fucosylated -fetoprotein (AFP) present in serum of patients with hepatocellular carcinoma (HCC) has been employed for the differential clinical diagnosis of HCC from chronic liver diseases. The molecular mechanism by which this alteration occurs, however, remains largely unknown. To address this issue, we purified GDP-L-Fuc:N-acetyl-beta-D-glucosaminide 1-6 fucosyltransferase (1-6 FucT), an enzyme involved in the 1-6 fucosylation of N-glycans from porcine brain, as well as from a human gastric cancer cell line, and cloned their genes. In this study, levels of 1-6 FucT mRNA expression and the activity of this enzyme for 12 human HCC tissues were examined and compared with that in surrounding tissues and normal livers. The mean +/- SD for 1-6 FucT activity was 78 +/- 41 pmol/h/mg in normal control liver, 202 +/- 127 pmol/h/mg in adjacent uninvolved liver tissues (chronic hepatitis: 181 +/- 106 pmol/h/mg; liver cirrhosis: 233 +/- 164 pmol/h/mg), and 195 +/- 72 pmol/h/mg in HCC tissues. The mRNA expression of 1-6 FucT was also enhanced in proportion to enzymatic activity except for a few cases, suggesting that 1-6 FucT expression is increased in chronic liver diseases, especially liver cirrhosis. Transfection of 1-6 FucT gene into cultured rat hepatocytes markedly increased 1-6 FucT activity and led to an increase in lens culinaris agglutinin (LCA) binding proteins in both cell lysates and condition media. When the 1-6 FucT gene was transfected into a human HCC cell line, Hep3B, which originally showed low levels of 1-6 FucT expression, 1-6-fucosylated AFP was dramatically increased in the condition media. Collectively, these results suggest that the enhancement of 1-6 FucT expression increased the fucosylation of several proteins, including AFP, and that the level of 1-6-fucosylated AFP in patients with HCC was in part caused by up-regulation of the 1-6 FucT gene expression.
Adult↗
Interrelationship between alcohol intake, hepatitis C, liver cirrhosis, and hepatocellular carcinoma.
The discovery of a cDNA clone of hepatitis C virus (HCV) genome in 1989 has resulted in numerous reports of high rates of the prevalence of HCV antibody in patients with alcoholic liver disease, in particular, alcoholic liver cirrhosis and hepatocellular carcinoma. Thus, the interaction between alcohol intake and HCV infection has become of great importance. In terms of the effect of alcohol on HCV-RNA levels, the data are controversial; in some reports, alcohol increases HCV-RNA levels, and in the other reports it does not. There are several reports suggesting the possibility of an elevated quasi-species of hypervariable region 1 in the HCV genome caused by alcohol drinking. Recent studies have documented that alcohol intake exaggerates the responsiveness of interferon therapy for chronic hepatitis C; however, its mechanism is still obscure. Several studies have suggested the promoting effect of alcohol on the development of hepatocellular carcinoma in type C liver cirrhosis, which has been similarly observed in type B chronic liver disease, whereas its mechanism is limited to speculations.
Alcohol Drinking↗