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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 127 records · Page 7Linked to original sources

Comparison of characteristics between patients with GB virus C/hepatitis G virus (GBV-C/HGV) RNA and those with GBV-C/HGV E2-antibody in patients with hemophilia.

We compared characteristics of patients with GB virus C/hepatitis G virus (GBV-C/HGV) RNA to those of patients with GBV-C/HGV E2-antibody. GBV-C/HGV RNA and GBV-C/HGV antibody were assayed in 83 persons with hemophilia using a reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay, respectively. GBV-C/HGV RNA was detected in 19 (22.9%) patients and GBV-C/HGV antibody was detected in 17 (20.5%). The background characteristics between the patient groups did not differ with respect to age, severity of hemophilia based on the frequency of use of blood product, and both the initial age at the first use and years since the first use of blood products. There were no differences in coinfection with hepatitis C virus (HCV) and/or human immunodeficiency virus, except that infection with HCV subtype 1a was more prevalent in patients with GBV-C/HGV RNA (P = 0.0229). Human lymphocyte antigen (HLA) typing was conducted in 18 patients with GBV-C/HGV RNA and 15 patients with GBV-C/HGV E2-antibody; 13 of the patients with GBV-C/HGV antibody had either HLA DQ7, DR15, or DR8, whereas only 4 of the patients with GBV-C/HGV RNA did (P < 0. 001). It is concluded that the presumed age at the time of GBV-C/HGV infection, the frequency of exposure to GBV-C/HGV, and the time since the GBV-C/HGV infection were not associated with recovery from infection with GBV-C/HGV. Coinfection with HCV subtype 1a may be related to persistent GBV-C/HGV viremia, whereas HLA DQ7, DR15, or DR8 may be related to the clearance of GBV-C/HGV after infection.

Adolescent↗

Anisotropic diffusion in kidney: apparent diffusion coefficient measurements for clinical use.

The purpose of this study was to evaluate anisotropy of the kidney by measurements of the apparent diffusion coefficient (ADC) using commercially available magnetic resonance (MR) imaging. Fifty-one consecutive patients underwent diffusion-weighted echoplanar MR imaging of the upper abdomen with five different strengths of motion probing gradients (b = 1.51, 55.3, 36.6, 317, and 932 sec/mm2) applied along the z-axis. Four ADC values for the upper pole and central portion of the kidney were calculated from four different b-value ranges and compared. The ADCs for the kidney calculated in the lower b-value ranges were significantly higher than those in the higher ranges. The ADCs for the upper pole portion were significantly higher than those for the central portion except for one in the highest b-value range. Diffusion in the kidney is anisotropic, probably due to the kidney's radially oriented structures such as renal vessels and tubules.

Anisotropy↗

CD44 is a potential target of amplification within the 11p13 amplicon detected in gastric cancer cell lines.

Classical cytogenetic approaches have revealed many of the chromosomal aberrations that may occur in gastric cancers (GC), although few alterations of specific genes have been identified so far. Genes that affect progression of this disease need to be identified if clinicians are to achieve optimal management of patients with GC. As the first step toward the cloning of gene(s) that may be involved in gastric carcinogenesis, we examined 25 GC cell lines for aberrations in DNA copy number to detect chromosomal gains and losses, as well as gene amplifications, by comparative genomic hybridization (CGH). Our CGH study revealed high-level amplifications in chromosomal regions that had been well defined in GC but also in sites that had not, including 3p24, 5p15, 11p11.2-14, 13q34, 15q26, Xp24, and Xq26-28. The minimal common region at 11p13, within the 11p11.2-14 amplicon, harbors the CD44 gene. Northern and Western blot analyses showed that an alternatively spliced form of CD44, with variant exons 8-10 (CD44E), was overexpressed in all cell lines bearing the 11p13 amplicon. However, cell adhesion activity was no greater in these lines than in cell lines without amplifications at the CD44 locus, suggesting that the major property of upregulated CD44 in these cases might be to transduce signals critically associated with growth and proliferation of the tumor cells.

Blotting, Northern↗

Health surveillance in the population living in a methyl mercury-polluted area over a long period.

It is important to follow up on the health status of inhabitants living in the methyl mercury-polluted area surrounding Minamata City, paying particular attention to diseases not only of the central nervous system but also of other organs. We have been carrying out such concentric studies for more than 10 years. We have previously studied the cause-specific standard mortality ratios in Minamata disease patients and reported that the SMRs for liver disease and renal disease were significantly raised in male and female patients, respectively. It was also found that complications arising from diabetes could be due to the large number of old people among the autopsy cases. The next step was to clarify the actual prevalence and incidence of liver disease, renal disease, and diabetes mellitus epidemiologically among the population in this area. The aim of this study was to determine the actual prevalence of these diseases and complaints, and to investigate the contribution of various risk factors to these diseases in this area. The study was a population-based cross-sectional mass screening survey. A case-control study was designed to estimate the role of various risk factors including methyl mercury exposure for these diseases. A mass multiple health examination survey was performed in 1500 subjects aged 40 years and older in Tsunagi Town, neighboring Minamata City, every summer since 1984. Tsunagi Town is located in a methyl mercury-polluted area and there are 36.9 certified Minamata disease patients per 1000 population. Data concerning liver disease, renal disease, and diabetes mellitus were collected on the basis of urine, hematological, physical, and ultrasonographic examinations. Data on risk factors and subjective complaints were collected by interview and other measures. The prevalence of these diseases was not higher in this methyl mercury-polluted area compared with other areas in Japan, contrary to what was expected based on standard mortality ratios and pathological findings. There were no positive correlations between those diseases and methyl mercury exposure. On the other hand, the population in the polluted area had more and a greater variety of complaints than those in the nonpolluted area. It is possible that not only neurological subjective complaints but also nonspecific complaints of the population in the polluted area might be influenced by past methyl mercury exposure. This health surveillance in the population living in a methyl mercury-polluted area must be maintained in the future.

Aged↗

Efficacy of HSP72 induction in rat liver by orally administered geranylgeranylacetone.

It is well known that heat-shock proteins (HSPs) have a cytoprotective function as "molecular chaperones" when cells are exposed to several stress conditions. Geranylgeranylacetone (GGA) is an antiulcer drug that was developed in Japan and it has recently been reported to induce HSP72 in rat gastric mucosa. In this experiment, we investigated the induction of HSP72 in rat liver in response to oral administration of GGA and assessed its ability to induce tolerance to warm ischemic injury by this approach. We prepared donor rats by orally administering GGA to them and compared HSP72 expression in graft liver, survival rates, and serum TNF-alpha concentrations after liver transplantation with the findings in controls. The survival rates were significantly increased when the livers were obtained from donor rats given GGA. Western blotting revealed expression of HSP72 in graft livers given GGA, and the serum TNF-alpha levels were significantly suppressed in the rats given GGA. Oral administration of GGA induced HSP72 in graft livers, and they were better able to tolerate warm ischemic injury. Oral administration of GGA appears to provide a promising new strategy for preventing ischemia-reperfusion injury.

Administration, Oral↗

Hepatocellular carcinoma effectively treated by intravenous infusion of cisplatin.

We report a rare case of hepatocellular carcinoma (HCC) for which intravenous administration of cisplatin (CDDP) was effective. A 48-year-old woman with recurrent HCC was admitted to our hospital. She had undergone right hepatectomy 1 year previously. A large tumor in the liver and multiple lung metastases were found by computed tomography in June 1995. She was icteric, and titers of serum alpha-fetoprotein (AFP; 214 ng/ml) and protein induced vitamin K absence or antagonist-II (PIVKA-II; 80 AU/ml) were high. According to these findings, she was diagnosed as having nonresectable recurrent HCC with extrahepatic lesions. She was treated by intravenous administration of CDDP. The dose of CDDP was 50 mg and it was infused once a week. One kur of CDDP was 4 weeks, and a total of four kur were administered. We noted that the lung metastases and primary liver tumor resolved after 1 kur of chemotherapy. The levels of serum AFP and PIVKA-II decreased markedly, to 26 ng/ml and <0.07 AU/ml, respectively. A complete response was obtained, and she maintained a good state of health for the next 6 months, until brain metastases occurred. She died 13 months after the initiation of treatment with CDDP. In general, intravenous CDDP cannot be recommended as a single agent for HCC therapy, but CDDP showed good antineoplastic activity in our patient.

Antineoplastic Agents↗

Intraoperative microwave coagulation therapy for large hepatic tumors.

We report new surgical techniques for intraoperative microwave coagulation therapy (IMCT), conducted in three patients with large liver neoplasms with poor liver function or difficult tumor location. Anterolateral thoracotomy was performed for tumors in the right lobe to obtain a good operative field. Four electrode needles were inserted for microwave irradiation, with settings of 60 W, 45 s for coagulation and 1 s for dissociation. Clamping of the hepatoduodenal ligament was performed during IMCT. We began the coagulation at the bottom of the tumor, irradiating the tumor and the surrounding parenchyma to create regional necrosis with a safe margin. With these methods, we treated two women diagnosed with large hepatocellular carcinoma with liver cirrhosis and a man with liver metastasis from rectal cancer. The postoperative course of these patients was uneventful. A marked low-density area was seen in the region of therapy and no enhanced findings were observed on enhanced computed tomography postoperatively. However, in one patient, transcatheter embolization (TAE) was performed 1 month postoperatively because recurrence was noted on the bottom of the tumor. Thus, IMCT destroys the peripheral part of the tumor that may remain viable after TAE, but combination therapy with TAE is preferable, especially when a viable part exists within tumors. IMCT is an active, safe, and nontoxic therapeutic modality for large hepatic tumors, and is particularly applicable in patients with large hepatocellular carcinomas and poor liver function.

Aged↗

Influence of Helicobacter pylori infection on development of stress-induced gastric mucosal injury.

Immediately after the Great Hanshin Earthquake in Kobe in 1995, the recurrence rate of peptic ulcer in patients infected with Helicobacter pylori was higher than that in patients in whom H. pylori had been eradicated. We evaluated the influence of H. pylori infection on stress-induced gastric mucosal injury in Mongolian gerbils and C57BL/6 mice. These animals were immersed in water for 30, 120, and 720 min 12 weeks after inoculation with H. pylori, and then killed to assess gastric mucosal damage, and to measure cytokine production (interleukin [IL]-1beta, IL-4, IL-6, and IL-10; interferon [IFN]-gamma; and tumor necrosis factor [TNF]-alpha) in the gastric tissue of the mice. The stress treatment for 30 min resulted in a significantly higher bleeding rate and bleeding index among infected gerbils and mice compared with results in uninfected animals. Conversely, the bleeding and ulcer indexes were significantly higher in uninfected gerbils after 720 min of the stress treatment than in infected gerbils. Prior to the stress treatment, gastric IL-1beta and IFN-gamma production was significantly higher in the infected group than in the uninfected group. After 120 min of the stress treatment, TNF-alpha production was increased in the infected group, and IL-1beta and IL-10 production was increased in the uninfected group. However, the production of these cytokines showed no change at 30 min of the stress treatment. These results suggest that H. pylori infection influences the development of gastric mucosal injury in the early phase of stress exposure; cytokines do not play a major role in this process.

Animals↗

Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin.

Increased expression of matrix metalloproteinases, particularly gelatinase B (MMP-9), has been described in the lungs in pulmonary fibrosis. Intratracheal bleomycin is often used experimentally to produce lesions resembling human fibrosing alveolitis. To assess the role of gelatinase B in bleomycin-induced fibrosing alveolitis, we instilled bleomycin intratracheally into gelatinase B-deficient mice and gelatinase B+/+ littermates. Twenty-one days after bleomycin the two groups of mice were indistinguishable in terms of pulmonary histology and total lung collagen and elastin. However, the lungs of gelatinase B-deficient mice showed minimal alveolar bronchiolization, whereas bronchiolization was prominent in the lungs of gelatinase B+/+ mice. Gelatinase B was identified immunohistochemically in terminal bronchiolar cells and bronchiolized cells 7 and 14 days after bleomycin in gelatinase B+/+ mice, and whole lung gelatinase B mRNA was increased at the same times. Many bronchiolized cells displayed Clara cell features by electron microscopy. Some bronchiolized cells stained with antibody to helix transcription factor 4, a factor associated with the ciliated cell phenotype. Thus, fibrosing alveolitis develops after intratracheal bleomycin irrespective of gelatinase B. However, gelatinase B is required for alveolar bronchiolization, perhaps by facilitating migration of Clara cells and other bronchiolar cells into the regions of alveolar injury.

Animals↗

Inhibitory mechanisms in hypoxic respiratory depression studied in an in vitro preparation.

A medullary-spinal cord preparation without the pons isolated from the neonatal rat was used to investigate the role of inhibitory neurotransmitters in the respiratory depression induced by hypoxia (hypoxic respiratory depression; HRD). The burst frequency (C(4)-f) and peak amplitudes of the integrated activity of the C(4) roots (integral C(4)) and of the hypoglossal nerve (integral XII) were recorded. A marked decrease in C(4)-f (to 36+/-6% of control, P<0. 05) with no change in the peak amplitudes of integral C(4) or integral XII was observed 17-21 min after superfusion with hypoxic CSF bubbled with 5% CO(2) in N(2). Antagonists of GABA(A) (bicuculline; 10 microM), GABA(B) (phaclofen; 0.2-0.5 mM), glycine (strychnine; 10 mM), adenosine (aminophylline; 100 mM) or opioid (naloxone; 1 mM) receptors were added to the bathing solution to block inhibitory synaptic transmission. Among these antagonists, only strychnine and naloxone alleviated HRD reducing the decline in C(4)-f to 57+/-11 and 53+/-6%, respectively (P<0.05). Posthypoxic neural arrest (PHNA) following resumption of oxygenation was shortened by the application of aminophylline, strychnine or naloxone (by 91+/-17, 96+/-25 and 40+/-6 s, respectively, P<0.05). These findings indicate that the reduction in the frequency component of HRD depends on glycinergic and opioid-mediated neuronal inhibition in an in vitro medullary spinal cord preparation. It was also observed that the duration of PHNA was positively correlated with the severity of the fall in C(4)-f (r=0.60, P<0.01).

Animals↗

Respiratory neural activity responses to chemical stimuli in newborn rats: reversible transition from normal to 'secondary' rhythm during asphyxia and its implication for 'respiratory like' activity of isolated medullary preparation.

To clarify a possible origin of 'respiratory like' rhythmic activities observed in in vitro brainstem preparation, the phrenic (Phr) and cranial nerve (XII or IX) inspiratory activities were analyzed in halothane-anesthetized, vagotomized and artificially ventilated newborn (2--6 days after birth) and young adult rats (30--50 days) during altered chemical stimuli and prolonged asphyxia at 25 degrees C. The newborn rat showed regular rhythmic inspiratory discharges of short duration, and their responses to CO(2) and hypoxia did not differ from those seen in adult rats. In the newborn rat the Phr and cranial nerve inspiratory discharges increased first, then respiratory frequency decreased and finally ceased completely for approximately 1--2 min during asphyxia. Thereafter, 'secondary' rhythmic inspiratory activity emerged at a slower rate with decremental inspiratory discharge profile, which persisted for a period more than 40 min of asphyxia. A normal respiratory activity recovered after resumption of artificial ventilation. Though young adult rats exhibited similar sequential changes in respiratory activity during asphyxia, the 'secondary' rhythmic activity persisted for a period of several min only. The pattern of 'secondary' respiratory activity corresponded well with that of rhythmic activities seen in the isolated medullary block preparation of newborn rat. 'Respiratory like' activity found in isolated medullary preparations of newborn animals may arise from a mechanism that generates 'secondary' (or so called 'gasping' type) rhythmic inspiratory activity during prolonged asphyxia in in vivo preparations.

Age Factors↗

Impact load transmission of the knee joint-influence of leg alignment and the role of meniscus and articular cartilage.

OBJECTIVE: The objective of this study was to evaluate load transmission in the cancellous bone of the tibia under static and impact load.BACKGROUND. Abnormal transmission of loads may result in osteoarthritis and fractures. However, the role of the cancellous bone in these processes is not well understood.METHODS. The compressive stresses in the subchondral bone, epiphysis and diaphysis of the tibia of porcine knees were measured under static and impact load using mini-pressure transducers. The tests were performed using a drop-tower type testing machine in neutral, varus and valgus alignments. Tests were repeated after meniscectomy and again after removing the articular cartilage.RESULTS. In the intact knee in all alignments, the highest stress on the medial side was found in the epiphysis, and in the subchondral bone on the lateral side. After meniscectomy, a significant increase was observed in the stress in the subchondral bone on both sides. After the articular cartilage was also removed, the stress in the subchondral bone increased again, but slightly.CONCLUSION. The importance of the meniscus in load transmission is supported by this study. The contribution of the articular cartilage to load transmission is less than that of the meniscus.Relevance. The patterns of static and dynamic load transmission observed in this study correlate with the sites of insufficiency fractures of the medial tibial plateau and traumatic lateral tibial plateau fractures observed clinically. Examination of the load transmission is key to a more complete understanding of the causes of osteoarthritis and tibial plateau fractures.

Analysis of Variance↗